Larch shoot blight, caused by the fungus Neofusicoccum laricinum, threatens larch (Larix spp.) forests across northeastern China, jeopardizing both timber productivity and ecological stability. This study aimed to investigate the genomic diversity, population structure, and potential adaptive mechanisms of N. laricinum across contrasting climatic regions. To achieve this, we conducted whole-genome resequencing of 23 N. laricinum isolates collected from three major provinces-Heilongjiang, Inner Mongolia, and Jilin-that represent distinct climatic zones ranging from cold-temperate to relatively warmer regions. We identified ~219.1 K genetic variants, offering a detailed portrait of the pathogen's genomic diversity. Population structure analyses, including principal component analysis and phylogenetic tree, revealed clear genetic differentiation aligning with geographic origin and climate. Functional annotation (GO and KEGG) highlighted enrichment in metabolic, stress-response, and membrane transport pathways, suggesting potential adaptation to varied temperature regimes and environmental pressures. Moreover, region-specific variants-particularly missense and stop-gain mutations-were linked to genes involved in ATP binding, oxidoreductase activity, and cell division, underscoring the fungus's capacity for rapid adaptation. Collectively, these findings fill a critical gap in the population genetics of N. laricinum and lay a foundation for future disease management strategies to larch shoot blight under changing climatic conditions.

A virulent bacteriophage, P12L, infecting hypermucoviscous Klebsiella pneumoniae of capsule-type K2 was characterized. The phage was found to have podovirus-like morphology, with an icosahedral head and a short tail. It exhibited efficient adsorption with a burst size of 183 PFU/cell. The viral genome is a linear dsDNA molecule that is 42,343 bp in length and contains 62 putative open reading frames (ORFs). It lacks genes associated with drug resistance or virulence factors and encodes two predicted domains associated with depolymerase activity. Because depolymerase can degrade polysaccharide capsules and promote efficient phage-host interactions, phage P12L shows potential as a biocontrol agent.

Climate change poses significant challenges to global agriculture, with elevated atmospheric CO2 (eCO2) concentrations and increased frequency of droughts affecting crop productivity. Understanding how economically important crops like sugarcane respond to these combined stresses is essential for developing resilient cultivars. This study explores the effects of eCO2 and drought stress on sugarcane growth and cell wall composition. Sugarcane plants were cultivated under CO2 treatments (390 ppm and 780 ppm) and subjected to drought stress. Leaf biomass, cell wall composition, and global transcriptome sequencing were analyzed. eCO2 (780 ppm) significantly increased leaf biomass by 64%, attributed to enhanced photosynthesis and water-use efficiency. Conversely, drought reduced leaf biomass by 45%, highlighting sugarcane's sensitivity to water scarcity. When both conditions were combined, eCO2 mitigated drought's negative impact, maintaining biomass at levels comparable to ambient conditions. Despite notable changes in biomass, cell wall biomass was only slightly affected. Under drought, a 14% reduction in cell wall biomass was observed alongside compositional changes, including reduced arabinosylation in glucuronoarabinoxylan (GAX). This alteration, supported by decreased xylan arabinosyl transferase (XAT) expression and reduced arabinose content, suggests stronger associations between GAX and cellulose, potentially enhancing drought tolerance by modifying cell wall rigidity and flexibility. Under eCO2, cell wall composition was altered, with reductions in glucose and uronic acid in specific fractions, indicating decreased mixed-linkage glucan (MLG) and pectin. These changes likely increased cell wall flexibility, supporting rapid growth. Combined eCO2 and drought treatments amplified specific modifications, such as enhanced fucosylation of xyloglucan (XG) and potential MLG expansion, both linked to stress adaptation. Overall, the findings underscore the critical role of cell wall plasticity in sugarcane's response to abiotic stress. While eCO2 boosted growth and partially alleviated drought effects, structural changes in cell wall composition under these conditions further contribute to stress resilience, emphasizing the adaptive mechanisms of sugarcane to environmental challenges. This is the first report in which eCO2, and drought are combined to evaluate the response of sugarcane to the impact of climate changes.

Cassava, Manihot esculenta Crantz, is the main raw material used in starch production in China. However, due to the small planting scale and high demand in China, large-scale imports are needed. To improve cassava yield and to meet China's needs, we examine the agronomic traits of root weight, root number, and root length-to-width ratio per plant. By constructing two semi-sibling genetic maps and using years of data for quantitative trait locus (QTL) localization, we compare two population mapping results to screen co-located 15 QTLs, and transcriptome analysis to explore candidate genes related to these traits. We found OsWRKY78 in rice to be homologous to candidate gene Manes.03G051300, which can regulate rice stem elongation and seed size, and Manes.18G023500 to be homologous to MeMYB108, which can reduce leaf shedding and regulate cassava biomass. Through QTL mapping, we identify key genes related to yield traits that can be used in cassava molecular breeding to improve cassava yield.

The burgeoning field of aquaculture has become a pivotal contributor to global food security and economic growth, presently surpassing capture fisheries in aquatic animal production as evidenced by recent statistics. However, the dense fish populations inherent in aquaculture systems exacerbate abiotic stressors and promote pathogenic spread, posing a risk to sustainability and yield. This study delves into the transformative potential of metagenomics, a method that directly retrieves genetic material from environmental samples, in elucidating microbial dynamics within aquaculture ecosystems. Our findings affirm that metagenomics, bolstered by tools in big data analytics, bioinformatics, and machine learning, can significantly enhance the precision of microbial assessment and pathogen detection. Furthermore, we explore quantum computing's emergent role, which promises unparalleled efficiency in data processing and model construction, poised to address the limitations of conventional computational techniques. Distinct from metabarcoding, metagenomics offers an expansive, unbiased profile of microbial biodiversity, revolutionizing our capacity to monitor, predict, and manage aquaculture systems with high accuracy and adaptability. Despite the challenges of computational demands and variability in data standardization, this study advocates for continued technological integration, thereby fostering resilient and sustainable aquaculture practices in a climate of escalating global food requirements.

Many cancer risk variants are located within enhancer regions and lack sufficient molecular interpretation. Here, we constructed the first comprehensive atlas of enhancer RNA (eRNA)-mediated genetic effects from 28 033 RNA sequencing samples across 11 606 individuals, identifying 21 073 eRNA quantitative trait loci (eRNA-QTLs) significantly associated with eRNA expression. Mechanistically, eRNA-QTLs frequently altered binding motifs of transcription factors. In addition, 28.48% of cancer risk variants are strongly colocalized with eRNA-QTLs. A pan-cancer eRNA-based transcriptome-wide association study is conducted across 23 major cancer types, identifying 626 significant cancer susceptibility eRNAs predicted to modulate cancer risk via eRNA, from which 54.90% of the eRNA target genes are overlooked by traditional gene expression studies, and most are essential for cancer cell proliferation. As proof of principle validation, the enhancer functionality of two newly identified susceptibility eRNAs, CCND1e and SNAPC1e, is confirmed through CRISPR inhibition and shRNA-mediated knockdown, resulting in a marked decrease in the expression of their respective target genes, consequently suppressing the proliferation of prostate cancer cells. The study underscores the essential role of eRNA in unveiling new cancer susceptibility genes and establishes a strong framework for enhancing our understanding of human cancer etiology.

Glioblastoma (GBM) is the most common primary brain malignancy. Few neoantigens have been tested in trials as the cancer vaccine against GBM.

To better understand the neoantigen landscape and its associated tumor microenvironment (TME) for the optimized vaccine design of our initiated GBM trial, we apply the integrative multi-omics approach to comprehensively profile the mutation, HLA typing, TCR/BCR repertoire, immune cell components on the tumor tissue and peripheral blood mononuclear cell (PMBC) specimen of 24 GBM patients.

On average, 148 mutated genes and 200 mutated sites per patient were identified, with no predominant mutated sites and genes in this cohort. Diversified HLA genotypes and expression rate across A, B, and C alleles, with A30:01&A11:01, B13:02, and C06:02, as the most frequent genotypes at respective alleles. Clustered CDR3 of TCR/BCR existed in tumor tissue with decreased richness compared with PMBC. NK and Th1 cells were revealed as the predominant immune cells within the tumor microenvironment (TME). Neoantigens were feasible predicted and designed for each patient, with an average number of 107. Very few neoantigens were shared by more than two patients and no dominant neoantigen could be identified. A minimum of 11-peptide bulk was required to cover this 24-patient cohort, guaranteeing each patient could have at least one neoantigen.

In summary, our data reveals a heterogeneous landscape of the neoantigen and its associated immune TME of GBM, based on which a peptide bulk is feasibly developed to cover these patients as a cohort.

This study evaluated the in vitro and in silico probiotic potential and technological characteristics of Lacticaseibacillus rhamnosus MW019593 isolated from Algerian cow's milk. Safety was verified by the absence of hemolytic activity, biogenic amine production, and antibiotic sensitivity. Functional probiotic properties of L. rhamnosus MW019593 included moderate inhibition of gastrointestinal pathogens such as Salmonella, Listeria, Clostridioides, and Escherichia coli, tolerance to pH 2-3 and up to 1% bile salts, 46.4% hydrophobicity, 42.4% autoaggregation, and 12.9% adhesion to Caco-2/TC7 cells without cytotoxicity. The ability to form biofilms with a thickness of 23.7 µm, comparable to L. rhamnosus ATCC 53103, was observed using confocal microscopy. Technologically, L. rhamnosus MW019593 and ATCC 53103 showed similar growth profiles and biomass yields, reaching approximately 5 × 109 CFU/mL with a 63% yield after lyophilization. No significant difference in strain viability was noted at 4 °C and - 20 °C, which are suitable temperatures to maintain their viability for 3 months. Whole genome sequencing (WGS) was conducted on L. rhamnosus MW019593, followed by comprehensive in silico genomic analysis. Taxonomic validation using average nucleotide identity (ANI) and genome-to-genome distance hybridization (GGDH) confirmed the strain's affiliation to this species. Gene screening revealed the absence of virulence and antibiotic resistance genes, while beneficial genes, including those for bacteriocin production, were identified. These findings, supported by the demonstrated safety, functional, and technological properties of the strain, highlight its promising potential for food and therapeutic applications, pending in vivo validation.

Broussonetia papyrifera is a deciduous tree with significant economic and medicinal value. It demonstrates notable physiological adaptability to mining areas with severe manganese contamination and is a pioneering species in the field of ecological restoration. Flavonoids are vital secondary metabolites that improve plant resilience to environmental stresses. In the study presented herein, immature and mature fruits of B. papyrifera grown in normal and high manganese environments were used as the test materials. B. papyrifera fruit was subjected to transcriptome sequencing via high-throughput sequencing technology to analyze its flavonoid metabolic pathways and related genes. Transcriptome sequencing identified a total of 46,072 unigenes, with an average length of 1248 bp and a percentage of Q30 bases ranging from 92.45 to 93.17%. Furthermore, 31,792 unigenes (69% of the total) were annotated using eight databases, including the GO and KEGG. Analysis of KEGG metabolic pathways and flavonoid content trends in B. papyrifera fruits revealed four unigenes with strong links to the flavonoid biosynthesis pathway under manganese stress: flavone 3-hydroxylase, flavonoids 3',5'-O-methyltransferase, chalcone synthase, and flavonol synthase. These unigenes may play important roles in regulating flavonoid synthesis in B. papyrifera fruits under manganese stress. This study lays the groundwork for functional gene research in B. papyrifera.

Few cohorts have study populations large enough to conduct molecular analysis of ex vivo lung tissue for genomic analyses. Transcriptome imputation is a non-invasive alternative with many potential applications. We present a novel transcriptome-imputation method called the Lung Gene Expression and Network Imputation Engine (LungGENIE) that uses principal components from blood gene-expression levels in a linear regression model to predict lung tissue-specific gene-expression.

We use paired blood and lung RNA sequencing data from the Genotype-Tissue Expression (GTEx) project to train LungGENIE models. We replicate model performance in a unique dataset, where we generated RNA sequencing data from paired lung and blood samples available through the SUNY Upstate Biorepository (SUBR). We further demonstrate proof-of-concept application of LungGENIE models in an independent blood RNA sequencing data from the Genetic Epidemiology of COPD (COPDGene) study.

We show that LungGENIE prediction accuracies have higher correlation to measured lung tissue expression compared to existing cis-expression quantitative trait loci-based methods (median Pearson's r = 0.25, IQR 0.19-0.32), with close to half of the reliably predicted transcripts being replicated in the testing dataset. Finally, we demonstrate significant correlation of differential expression results in chronic obstructive pulmonary disease (COPD) from imputed lung tissue gene-expression and differential expression results experimentally determined from lung tissue.

Our results demonstrate that LungGENIE provides complementary results to existing expression quantitative trait loci-based methods and outperforms direct blood to lung results across internal cross-validation, external replication, and proof-of-concept in an independent dataset. Taken together, we establish LungGENIE as a tool with many potential applications in the study of lung diseases.

Sof Umer Cave is an unexplored extreme environment that hosts novel microbes and potential genetic resources. Microbiomes from caves have been genetically adapted to produce various bioactive metabolites, allowing them to survive and tolerate harsh conditions. However, the biosynthesis-related gene cluster signatures in the microbiomes of Sof Umer Cave have not been explored. Therefore, high-throughput shotgun sequencing was used to explore biosynthesis-related gene clusters (BGCs) in the microbiomes of Sof Umer Cave. The GeneAll DNA Soil Mini Kit was used to extract high-molecular-weight DNA from homogenized samples, and the purified DNA was sequenced using a NovaSeq PE150. According to the Micro-RN database, the most common microbial genera in Sof Umer Cave are Protobacteria, Actinobacteria, Verrucomicrobiota, and Cyanobacteria. The biosynthesis-related gene clusters were annotated and classified, and the BGCs were predicted using antiSMASH and NAPDOS1. A total of 460 putative regions of BGCs encoding a wide range of secondary metabolites were identified, including RiPP (47.82%), terpene (19.57%), NRPS (13.04%), hybrid (2.18%), and other newly annotated (10.87%) compounds. Additionally, the NAPDOS pipeline identified a calcium-dependent antibiotic gene cluster from Streptomyces coelicolor, an actinomycin gene cluster from Streptomyces chrysomallus, and a bleomycin gene cluster from Streptomyces verticillus. These findings highlight the untapped biosynthetic potential of the Sof Umer Cave microbiome, as well as its potential for the discovery of natural products.

N6-methyladenosine (m6A) methylation is a key epigenetic modification that can modulate gene expression and strongly affect mammalian developmental processes. However, the genome-wide methylation of long non-coding RNAs (lncRNAs) and its implications for the development of skeletal muscle remain poorly understood. Bovine skeletal muscle samples from five developmental stages were analyzed in this study to establish lncRNA methylome and transcriptomic maps.

Globally, 59.67% of lncRNAs in skeletal muscle with m6A modifications, and this percentage decreased progressively during development. lncRNA expression levels were positively associated with the number of m6A peaks, with lncRNAs possessing 3 or more peaks showing significantly higher expression levels than those with 1 or 2 peaks. Specific lncRNAs involved in skeletal muscle development were identified through two analytical approaches. The first approach employed weighted gene co-expression network analysis (WGCNA) of transcriptomic data to identify correlations between annotated lncRNAs and growth-related traits, resulting in 21 candidate hub lncRNAs. The intersection of these 21 hub lncRNAs with 151 differentially methylated lncRNAs (DM-lncRNAs) identified 10 shared candidate lncRNAs. The second approach integrated MeRIP-seq and RNA-seq data to identify 36 lncRNAs that were both differentially m6A modified and differentially expressed (dme-lncRNAs). GO and KEGG enrichment analyses of cis-target genes associated with these dme-lncRNAs identified eight candidate lncRNAs. Combining the results from the two approaches identified 16 key m6A-modified lncRNAs likely involved in skeletal muscle development.

These findings highlight the regulatory and functional significance of dynamic lncRNA methylation in skeletal muscle development.

Essential fatty acids could regulate inflammation, especially n-3 PUFA (n-3 polyunsaturated fatty acids), which are considered to have a protective effect to inhibit neuroinflammation. Peony seed oil is one of the most abundant n-3 PUFAs in oils. but the mechanism of peony seed oil affecting inflammation in mice brains is still lacking convincing evidence. Sixty male C57BL/6J mice were randomly allocated into four groups: D-gal (D-galactose) induced model group, FO (D-gal + fish oil), PSO (D-gal + peony seed oil). After 10 weeks, the fatty acid composition in liver and brain tissues and potentially related genes were examined. Docosahexaenoic acid (DHA) was significantly higher, while arachidonic acid (AA) was significantly lower in both in the PSO and FO groups than that in the model group in the brain and liver. In the PSO and FO groups, the relative mRNA levels of Fads1/2, Elovl2, and Acaa1a were significantly up-regulated, but Acox1 and Acox3 were significantly down-regulated compared to the model group. In the PSO and FO groups, the relative protein levels of PPARG, RXRA, and IL-10 were significantly up-regulated, and the expressions of AGERs, TNF-α, PLA2, and PGF2α were significantly down-regulated compared to the model group. The phosphorylation-tau of total tau protein ratio was significantly lower in the PSO and FO groups than in the model group. Peony seed oil, rich in n-3 PUFA, inhibited neuroinflammation and rescued the disruption of alternative splicing of the Mapt gene by activating the PPAR/RXR signaling pathway and promoting n-3/n-6 biosynthesis.

Obesity is a growing global epidemic. The composition of the intestinal microbiota can be influenced by several factors. Studies highlight the role of intestinal bacteria in the pathophysiology of obesity. So, the objective of this study was to investigate whether the use of probiotics, together with healthy lifestyle habits, contributes to weight reduction in obese individuals by analyzing the intestinal microbiota profile.

A prospective study was carried out with 45 adults with obesity. Participants underwent guidance on healthy lifestyle habits, received a probiotic component containing different microbiological strains and were followed for 60 days. Clinical parameters, body composition, biochemical analysis, and intestinal microbiota assessment were performed before and after treatment. After 60 days, it was observed that the bacterial strains present in the probiotic were present in the patients' intestinal microbiota. Participants also showed improvements in physical activity, sleep quality, and anxiety management, as well as changes in some eating habits, such as a reduction in the consumption of processed foods and a significant increase in water intake.

A reduction in BMI, fasting glucose, insulin, HOMA-IR, LDL cholesterol, and triglycerides was observed, in addition to an increase in HDL cholesterol, improvement in bowel movement frequency, and stool consistency. Analysis of the intestinal microbiota revealed an increase in microbial diversity and a better balance between the bacterial phyla Firmicutes and Bacteroidetes.

The changes related to improving the composition of the intestinal microbiota, dietary habits, increased physical activity, reduced anxiety, and better sleep quality have significantly contributed to weight loss and improvements in physiological parameters in obese individuals.

Mycobacteriophages are viruses that specifically infect bacteria of the Mycobacterium genus. A substantial collection of mycobacteriophages has been isolated and characterized, offering valuable insights into their diversity and evolution. This collection also holds significant potential for therapeutic applications, particularly as an alternative to antibiotics in combating drug-resistant bacterial strains. In this study, we report the isolation and characterization of a new mycobacteriophage, Vic9, using Mycobacterium smegmatis mc (2)155 as the host strain. Vic9 has been classified within the B2 subcluster of the B cluster. Morphological analysis revealed that Vic9 has a structure typical of siphophages from this subcluster and forms characteristic plaques. The phage adsorbs onto host strain cells within 30 min, and according to one-step growth experiments, its latent period lasts about 90 min, followed by a growth period of 150 min, with an average yield of approximately 68 phage particles per infected cell. In host range experiments, Vic9 efficiently lysed the host strain and also exhibited the ability to lyse M. tuberculosis H37Rv, albeit with a low efficiency of plating (EOP ≈ 2 × 10-5), a typical feature of B2 phages. No lysis was observed in other tested mycobacterial species. The genome of Vic9 comprises 67,543 bp of double-stranded DNA and encodes 89 open reading frames. Our analysis revealed unique features in Vic9, despite its close relationship to other B2 subcluster phages, highlighting its distinct characteristics even among closely related phages. Particularly noteworthy was the discovery of a distinct 435 bp sequence within the gene cluster responsible for queuosine biosynthesis, as well as a recombination event within the structural cassette region (Vic_0033-Vic_0035) among members of the B1, B2, and B3 subclusters. These genetic features are of interest for further research, as they may reveal new mechanisms of phage-bacteria interactions and their potential for developing novel phage therapy methods.

The combined use of lytic bacteriophages with antibiotics is currently being explored as a strategy to enhance the effectiveness of infectious disease therapies, including those caused by Staphylococcus aureus. In this study, we investigated the synergistic potential of bacteriophage vB_SauM-515A1 (Herelleviridae family) and the first-line antibiotic linezolid against the methicillin-resistant S. aureus strain SA0413Rev. A checkerboard assay revealed a significant synergistic effect against planktonic cells (FIC = 0.225): a combination of 1/8 MIC of linezolid and 0.01 MOI of the bacteriophage completely inhibited bacterial growth. However, the impact on biofilm-associated cells depended on the treatment sequence. Sequential administration resulted in antagonism, while simultaneous application demonstrated a synergistic effect, as confirmed through scanning electron microscopy. Transcriptomic analysis of S. aureus SA0413Rev under the combined influence of linezolid (1/4 MIC) and bacteriophage vB_SauM-515A1 (10 MOI) predominantly reflected changes associated with productive bacteriophage infection, including alterations in nucleotide metabolism, activation of prophage regions, and virulence factors. Furthermore, both agents affected energy and carbon metabolism. These findings contribute to the development of combination therapy approaches for infections caused by S. aureus and highlight the importance of optimizing treatment conditions for maximal therapeutic efficacy.

While a considerable number of viruses have been recently discovered in hematophagous insects, there remains insufficient research on virus diversity and their association with phytophagous insect hosts. In this study, we conducted a systematic investigation of the RNA virome in the small brown planthopper (SBPH), Laodelphax striatellus, an important vector of plant viruses. We successfully identified a total of 22 RNA viruses, including 17 novel viruses, from various families. These viruses were prevalent and abundant in SBPH populations, originating from the lab or field, with +ssRNA viruses composing the core SBPH viruses. Subsequent analysis revealed that the overall abundance of RNA viruses in SBPH remained relatively consistent across different developmental stages of the insects, although the titers of individual viruses varied among different insect tissues. This indicates a delicate balance between the viruses and their insect hosts. Interestingly, cross-species experiments confidently indicated that certain SBPH viruses could successfully infect and replicate in two other rice planthopper species (the brown planthopper and the white-backed planthopper) through microinjection. In conclusion, this study provides valuable insights into the RNA virome and its adaptability in a phytophagous insect, contributing to a better understanding of the intimate relationship between viruses and host insects.

In the last decade, advances in the next-generation sequencing technology have unveiled a vast diversity of viruses in insects, particularly RNA viruses in hematophagous insects. However, research on virus diversity and their association with phytophagous insect hosts remains insufficient. This study presents a comprehensive analysis of the RNA virome in the small brown planthopper (SBPH), Laodelphax striatellus, a critical vector of plant viruses. The results indicated that the +ssRNA viruses, especially picorna-like viruses, comprised the core RNA viruses of SBPH that were prevalent in both laboratory and field populations. Moreover, a delicate balance was observed between the viruses and insect hosts. Significantly, some RNA viruses of SBPH could successfully infect and replicate in two other rice planthopper species belonging to different genera. This study provides valuable insights into the RNA virome and its adaptability in a phytophagous insect.

Heat stress (HS) can affect the physiology and metabolism of animals. HS-induced intestinal inflammation in pigs is a common disease, causing severe diarrhea, that can result in substantial economic losses to the pig industry, but the molecular mechanisms and pathogenicity of this disease are not fully understood. The objective of this study was to identify the differentially expressed genes (DEGs) and long noncoding RNAs (DELs) related to inflammation in the colon tissues of pigs under constant (1, 7, and 14 days) HS.

LncRNA and targeted gene interaction networks were constructed. GO annotation and KEGG pathway analyses were subsequently performed to determine the functions of the DEGs and DELs. The results revealed 57, 212, and 54 DEGs and 87, 79, and 55 DELs in the CON/H01, CON/H07, and CON/H14 groups, respectively. KRT85, CLDN1, S100A12, TM7SF2, CCN1, NR4A1, and several lncRNAs may be involved in regulating the development of intestinal inflammation. GO analysis indicated that the DEGs and DELs were enriched in a series of biological processes involved in the innate immune response, RAGE receptor binding, and positive regulation of the ERK1 and ERK2 cascades. KEGG pathways related to inflammation, such as the tight junction (TJ) and MAPK signaling pathways, were enriched in DEGs and DELs.

This study have expanded the knowledge about colon inflammation-related genes and lncRNA biology in pigs under HS; analyzed the the lncRNA‒mRNA interaction for HS-induced intestinal inflammation. These results may provide some references for our understanding of the molecular mechanism of the intestinal response to HS in pig.

Lonicera japonica is a well-known medicinal plant, and the Damaohua cultivar is one of the oldest known honeysuckle cultivars in China. The 155,151 bp chloroplast genome of this cultivar was obtained through Illumina sequencing. The genome includes a pair of inverted repeats (IRa and IRb; 23,789 bp each), a large single-copy region (88,924 bp), and a small single-copy (SSC) region (18,649 bp). In total, 127 unique genes were identified: 80 protein-coding, 39 tRNA, and 8 rRNA genes. Only ycf3 contained two introns. Eighty-nine large repetitive sequences and 54 simple sequence repeats were detected. Fifty potential RNA editing sites were predicted. Adaptive evolution analysis revealed that infA, matK, petB, petD, rbcL, rpl16, rpl2, rps3, ycf1, and ycf2 were positively selected, possibly reflecting the specific environmental adaptations of this cultivar. Sequence alignment and analysis revealed several candidate fragments for Lonicera species identification, such as the intergenic regions rpoB-petN, rbcL-accD, and psaA-ycf3. The IR region boundary and phylogenetic analysis revealed that the L. japonica cv. Damaohua chloroplast genome was most closely related to the L. japonica genome, but there were five distinct differences between the two. There are four sites with high variability between L. japonica and L. japonica cv. Damaohua with nucleotide variability (Pi) greater than 0.002, including rps2-rpoC2, atpB-rbcL, ycf1, and ycf1-trnN GUU. The differences between L. japonica and L. japonica cv. Damaohua were further confirmed by the single nucleotide polymorphism sites between these two species. Therefore, this study revealed that the chloroplast genome can serve as a universal super barcode for plant identification, which can identify differences and help distinguish Lonicera japonica from related species. An understanding of Lonicera japonica cv. Damaohua chloroplast genomics and a comparative analysis of Lonicera species will provide a scientific basis for breeding, species identification, systematic evolution analysis, and chloroplast genetic engineering research on medicinal honeysuckle plants.

Base editing technologies enable programmable single-nucleotide changes in target DNA without double-stranded DNA breaks. Adenine base editors (ABEs) allow precise conversion of adenine (A) to guanine (G). However, limited availability of optimized deaminases as well as their variable efficiencies across different target sequences can limit the ability of ABEs to achieve effective adenine editing. Here, we explored the use of a TurboCas9 nickase in an ABE to improve its genome editing activity. The resulting TurboABE exhibits amplified editing efficiency on a variety of adenine target sites without increasing off-target editing in DNA and RNA. An interesting feature of TurboABE is its ability to significantly improve the editing frequency at bases with normally inefficient editing rates in the editing window of each target DNA. Development of improved ABEs provides new possibilities for precise genetic modification of genes in living cells.

The antimicrobial resistance crisis along with challenges of antimicrobial discovery revealed the vital necessity to develop new antibiotics. Many of the animal proline-rich antimicrobial peptides (PrAMPs) inhibit the process of bacterial translation. Genome projects allowed to identify immune-related genes encoding animal host defense peptides. Here, using genome mining approach, we discovered a family of proline-rich cathelicidins, named rumicidins. The genes encoding these peptides are widespread among ruminant mammals. Biochemical studies indicated that rumicidins effectively inhibited the elongation stage of bacterial translation. The cryo-EM structure of the Escherichia coli 70S ribosome in complex with one of the representatives of the family revealed that the binding site of rumicidins span the ribosomal A-site cleft and the nascent peptide exit tunnel interacting with its constriction point by the conservative Trp23-Phe24 dyad. Bacterial resistance to rumicidins is mediated by knockout of the SbmA transporter or modification of the MacAB-TolC efflux pump. A wide spectrum of antibacterial activity, a high efficacy in the animal infection model, and lack of adverse effects towards human cells in vitro make rumicidins promising molecular scaffolds for development of ribosome-targeting antibiotics.

Endocrine disrupting chemicals (EDCs) such as bisphenol S (BPS) are xenobiotic compounds that can disrupt endocrine signaling due to steric similarities to endogenous hormones. EDCs have been shown to induce disruptions in normal epigenetic programming (epimutations) and differentially expressed genes (DEGs) that predispose disease states. Most interestingly, the prevalence of epimutations following exposure to many EDCs persists over multiple generations. Many studies have described direct and prolonged effects of EDC exposure in animal models, but many questions remain about molecular mechanisms by which EDC-induced epimutations are introduced or subsequently propagated, whether there are cell type-specific susceptibilities to the same EDC, and whether this correlates with differential expression of relevant hormone receptors. We exposed cultured pluripotent (iPS), somatic (Sertoli and granulosa), and primordial germ cell-like (PGCLC) cells to BPS and found that differential incidences of BPS-induced epimutations and DEGs correlated with differential expression of relevant hormone receptors inducing epimutations near relevant hormone response elements in somatic and pluripotent, but not germ cell types. Most interestingly, we found that when iPS cells were exposed to BPS and then induced to differentiate into PGCLCs, the prevalence of epimutations and DEGs was largely retained, however, >90% of the specific epimutations and DEGs were replaced by novel epimutations and DEGs. These results suggest a unique mechanism by which an EDC-induced epimutated state may be propagated transgenerationally.

Cardiac metabolism ensures a continuous ATP supply, primarily using fatty acids in a healthy state and favoring glucose in pathological conditions. Pyruvate kinase muscle (PKM) controls the final step of glycolysis, with PKM1 being the main isoform in the heart. PKM2, elevated in various heart diseases, has been suggested to play a protective role in cardiac stress, but its function in basal cardiac metabolism remains unclear. We examined hearts from global PKM2 knockout (PKM2-/-) mice and found reduced intracellular glucose. Isotopic tracing of U-13C glucose revealed a shift to biosynthetic pathways in PKM2-/- cardiomyocytes. Total ATP content was two-thirds lower in PKM2-/- hearts, and functional analysis indicated reduced mitochondrial oxygen consumption. Total reactive oxygen species (ROS) and mitochondrial superoxide were also increased in PKM2-/- cardiomyocytes. Intriguingly, PKM2-/- hearts had preserved ejection fraction compared to controls. Mechanistically, increased calcium/calmodulin-dependent kinase II activity and phospholamban phosphorylation may contribute to higher sarcoendoplasmic reticulum calcium ATPase 2 pump activity in PKM2-/- hearts. Loss of PKM2 led to altered glucose metabolism, diminished mitochondrial function, and increased ROS in cardiomyocytes. These data suggest that cardiac PKM2 acts as an important rheostat to maintain ATP levels while limiting oxidative stress. Although loss of PKM2 did not impair baseline contractility, its absence may make hearts more sensitive to environmental stress or injury.

Cellular senescence is a diverse phenotype characterised by permanent cell cycle arrest and an associated secretory phenotype (SASP) which includes inflammatory cytokines. Typically, senescent cells are removed by the immune system, but this process becomes dysregulated with age causing senescent cells to accumulate and induce chronic inflammatory signalling. Identifying senescent cells is challenging due to senescence phenotype heterogeneity, and senotherapy often requires a combinatorial approach. Here we systematically collected 119 transcriptomic datasets related to human fibroblasts, forming an online database describing the relevant variables for each study allowing users to filter for variables and genes of interest. Our own analysis of the database identified 28 genes significantly up- or downregulated across four senescence types (DNA damage induced senescence (DDIS), oncogene induced senescence (OIS), replicative senescence, and bystander induced senescence) compared to proliferating controls. We also found gene expression patterns of conventional senescence markers were highly specific and reliable for different senescence inducers, cell lines, and timepoints. Our comprehensive data supported several observations made in existing studies using single datasets, including stronger p53 signalling in DDIS compared to OIS. However, contrary to some early observations, both p16 and p21 mRNA levels rise quickly, depending on senescence type, and persist for at least 8-11 days. Additionally, little evidence was found to support an initial TGFβ-centric SASP. To support our transcriptomic analysis, we computationally modelled temporal protein changes of select core senescence proteins during DDIS and OIS, as well as perform knockdown interventions. We conclude that while universal biomarkers of senescence are difficult to identify, conventional senescence markers follow predictable profiles and construction of a framework for studying senescence could lead to more reproducible data and understanding of senescence heterogeneity.

In clinical practice, imaging manifestations of diffuse lung parenchymal lesions are common and indicative of various diseases, making differential diagnosis difficult. Some of these lesions are eventually diagnosed as lung cancer.

Because respiratory microorganisms play an important role in lung cancer development, we searched for microbial markers that could predict the risk of lung cancer by retrospectively analyzing the lower respiratory tract (LRT) microbiome of 158 patients who were hospitalized in the First Affiliated Hospital of Guangzhou Medical University (March 2021-March 2023) with diffuse lung parenchymal lesions. The final diagnosis was lung cancer in 21 cases, lung infection in 93 cases, and other conditions (other than malignancy and infections) in 44 cases. The patient's clinical characteristics and the results of metagenomic next-generation sequencing of bronchoalveolar lavage fluid (BALF) were analyzed.

Body mass index (BMI) and LRT microbial diversity (Shannon, Simpson, species richness, and Choa1 index) were significantly lower (P< 0.001, respectively) and Lactobacillus acidophilus relative abundance in the LRT was significantly higher (P< 0.001) in patients with lung cancer. The relative abundance of L. acidophilus in BALF combined with BMI was a good predictor of lung cancer risk (area under the curve = 0.985, accuracy = 98.46%, sensitivity = 95.24%, and specificity = 100.00%; P< 0.001).

Our study showed that an imbalance in the component ratio of the microbial community, diminished microbial diversity, and the presence of specific microbial markers in the LRT predicted lung cancer risk in patients with imaging manifestations of diffuse lung parenchymal lesions.

New β-lactam-β-lactamase inhibitor combinations represent last-resort antibiotics to treat infections caused by multidrug-resistant Pseudomonas aeruginosa. Carbapenemase gene acquisition can limit their spectrum of activity, and reports of resistance toward these new molecules are increasing. In this multi-center study, we evaluated the prevalence of resistance to ceftazidime-avibactam (CZA) and comparators among P. aeruginosa clinical isolates from bloodstream infections, hospital-acquired or ventilator-associated pneumonia, and urinary tract infections, circulating in Southern Italy. We also investigated the clonality and content of relevant β-lactam resistance mechanisms of CZA-resistant (CZAR) isolates. A total of 120 P. aeruginosa isolates were collected. CZA was among the most active β-lactams, retaining susceptibility in the 81.7% of cases, preceded by cefiderocol (95.8%) and followed by ceftolozane-tazobactam (79.2%), meropenem-vaborbactam (76.1%), imipenem-relebactam (75%), and aztreonam (69.6%). Among non-β-lactams, colistin and amikacin were active against 100% and 85.8% of isolates respectively. In CZAR strains subjected to whole-genome sequencing (n = 18), resistance was mainly due to the expression of metallo-β-lactamases (66.6% VIM-type and 5.5% FIM-1), followed by PER-1 (16.6%) and GES-1 (5.5%) extended-spectrum β-lactamases, mostly carried by international high-risk clones (ST111 and ST235). Of note, two strains producing the PER-1 enzyme were resistant to all β-lactams, including cefiderocol. In conclusion, the CZA resistance rate among P. aeruginosa clinical isolates in Southern Italy remained low. CZAR isolates were mostly metallo-β-lactamases producers and belonging to ST111 and ST253 epidemic clones. It is important to implement robust surveillance systems to monitor emergence of new resistance mechanisms and to limit the spread of P. aeruginosa high-risk clones.

Multidrug-resistant Pseudomonas aeruginosa infections are a growing threat due to the limited therapeutic options available. Ceftazidime-avibactam (CZA) is among the last-resort antibiotics for the treatment of difficult-to-treat P. aeruginosa infections, although resistance due to the acquisition of transferable β-lactamase genes is increasing. With this work, we report that CZA represents a highly active antipseudomonal β-lactam compound (after cefiderocol), and that metallo-β-lactamases (VIM-type) and extended-spectrum β-lactamases (GES and PER-type) production is the major factor underlying CZA resistance in isolates from Southern Italian hospitals. In addition, we reported that such resistance mechanisms were mainly carried by the international high-risk clones ST111 and ST235.

Rat models are valuable tools to study the lung microbiota in diseases. Yet the impacts of different lung parts, young and mature adult stages, and the different batches of the same conditions on the healthy rat lung microbiome have not been investigated.

The rat lung microbiome was analyzed to clarify the lung part-dependent and age-dependent differences and to evaluate the effects of several 'batch environmental factors' on normal rats, after eliminating potential contamination.

The results showed that the contamination could be identified and excluded. The lung microbiome from left and right lung parts was very similar so one representative part could be used in the microbiome study. There were significantly different lung microbial communities between the young and mature adult groups, and also between the different feeding batches groups of the same repetitive feeding conditions, but a common lung microbiota characterized by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria as the most dominant phyla were present in all adult rats. It indicated that the experiment under the same condition of the same rats batch was needed to compare the difference in the lung microbiota and repeated experiments were necessary to confirm the results.

These data represented that the lung bacterial communities were dynamic and rapidly susceptible to environmental influence, clustered strongly by age or different feeding batches but similar in the different lung tissue parts. This study improved the basic understanding of the potential effects on the lung microbiome of healthy rats.

Cyprinid herpesvirus 2 (CyHV-2) is the pathogen of herpesviral hematopoietic necrosis (HVHN), causing the severe economic losses in farmed gibel carp (Carassius gibelio). Further exploration of the genome structure and potential molecular pathogenesis of CyHV-2 through complete genome sequencing, comparative genomics, and molecular characterization is required. Herein, the genome of a CyHV-2 YC-01 strain isolated from diseased gibel carp collected in Yancheng, Jiangsu Province, China was sequenced, then we analyzed the genomic structure, genetic properties, and molecular characterization. First, the complete YC-01 genome comprises 275,367 bp without terminal repeat (TR) regions, with 151 potential open reading frames (ORFs). Second, compared with other representative published strains of the genus Cyvirus, several evident variations are found in YC-01, particularly the orientation and position of ORF25 and ORF25B. ORF107 and ORF156 are considered as potential molecular genetic markers for YC-01. ORF55 (encoding thymidine kinase) might be used to distinguish YC-01 and ST-J1 from other CyHV-2 isolates. Third, phylogenetically, YC-01 clusters with the members of the genus Cyvirus (together with the other six CyHV-2 isolates). Fourth, 43 putative proteins are predicted to be functional and are mainly divided into five categories. Several conserved motifs are found in nucleotide, amino acid, and promoter sequences including cis-acting elements identification of YC-01. Finally, the potential virulence factors and linear B cell epitopes of CyHV-2 are predicted to supply possibilities for designing novel vaccines rationally. Our results provide insights for further understanding genomic structure, genetic evolution, and potential molecular mechanisms of CyHV-2.

Fish skeletal muscle is composed of well-defined fiber types. In order to identify potential candidate genes affecting muscle growth and development under epigenetic regulation. Bisulfite sequencing was utilized to analyze and compare the muscle DNA methylation profiles of Larimichthys crocea inhabiting different environments. The results revealed that DNA methylation in L. crocea was predominantly CG methylation, with 2,396 differentially methylated regions (DMRs) identified through comparisons among different populations. The largest difference in methylation was observed between the ZhouShan and JinMen wild populations, suggesting that L. crocea may have undergone selection and domestication. Additionally, GO and KEGG enrichment analysis of differentially methylated genes (DMGs) revealed 626 enriched GO functional categories, including various muscle-related genes such as myh10, myf5, myf6, ndufv1, klhl31, map3k4, syn2b, sostdc1a, bag4, and hsp90ab. However, significant enrichment in KEGG pathways was observed only in the JinMen and XiangShan populations of L. crocea. Therefore, this study provides a theoretical foundation for a better understanding of the epigenetic regulation of skeletal muscle growth and development in L. crocea under different environmental conditions.

Allergic rhinitis (AR) is a complex disease in which gene-environment interactions contribute to its pathogenesis. Epigenetic modifications, such as N6-methyladenosine (m6A) modification of mRNA, play important roles in regulating gene expression in multiple physiological and pathological processes. However, the function of m6A modification in AR and the inflammatory response is poorly understood.

We used the ovalbumin (OVA) and aluminum hydroxide to induce an AR mouse model. Nasal symptoms, histopathology, and serum cytokines were examined. We performed combined m6A and RNA sequencing to analyze changes in m6A modification profiles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and methylated RNA immunoprecipitation sequencing qPCR (MeRIP-qPCR) were used to verify differential methylation of mRNAs and the m6A methylation level. Knockdown or inhibition of Alkbh5 in nasal mucosa of mice was mediated by lentiviral infection or IOX1 treatment.

We showed that m6A was enriched in a group of genes involved in MAPK signaling pathway. Moreover, we identified a MAPK pathway involving Map3k8, Erk2, and Nfκb1 that may play a role in the disrupted inflammatory response associated with nasal inflammation. The m6A eraser, Alkbh5, was highly expressed in the nasal mucosa of AR model mice. Furthermore, knockdown of Alkbh5 expression by lentiviral infection resulted in high MAPK pathway activity and a significant nasal mucosa inflammatory response. Our findings indicate that ALKBH5-mediated m6A dysregulation likely contributes to a nasal inflammatory response via the MAPK pathway.

Together, our data show that m6A dysregulation mediated by ALKBH5, is likely to contribute to inflammation of the nasal mucosa via the MAPK signaling pathway, suggesting that ALKBH5 is a potential biomarker for AR treatment.

Bladder cancer is one of the leading causes of cancer-related mortality in the urinary system. Understanding genomic information is important in the treatment and prognosis of bladder cancer, but the current method used to identify mutations is time-consuming and labor-intensive. There are now many novel and convenient ways to predict cancerous genomics from pathological slides. However, the publicly available datasets are limited, especially for Asian populations. In this study, we developed a dataset consisting of 75 Asian cases of bladder cancers and 112 Whole-Slide Images with one to two images obtained for each patient. This dataset provides information on the most frequently and clinically significant mutated genes derived by whole-exome sequencing in these patients. This dataset will facilitate exploration and development of novel diagnostic and therapeutic technologies for bladder cancer.

Breast cancer (BC) is the most common cancer among women and a major cause of death from cancer. The role of estrogen and progestins, including synthetic hormones like R5020, in the development of BC has been highlighted in numerous studies. In our study, we employed machine learning and advanced bioinformatics to identify genes that could serve as diagnostic markers for BC. We thoroughly analyzed the transcriptomic data of two BC cell lines, T47D and UDC4, and performed differential gene expression analysis. We also conducted functional enrichment analysis to understand the biological functions influenced by these genes. Our study identified several diagnostic genes strongly associated with BC, including MIR6728, ENO1-IT1, ENO1-AS1, RNU6-304P, HMGN2P17, RP3-477M7.5, RP3-477M7.6, and CA6. The genes MIR6728, ENO1-IT1, ENO1-AS1, and HMGN2P17 are involved in cancer control, glycolysis, and DNA-related processes, while CA6 is associated with apoptosis and cancer development. These genes could potentially serve as predictors for BC, paving the way for more precise diagnostic methods and personalized treatment plans. This research enhances our understanding of BC and offers promising avenues for improving patient care in the future.

The white spot syndrome virus (WSSV) is a causative agent of white spot disease (WSD) in crustaceans, especially in cultivated black tiger shrimp (Penaeus monodon), leading to significant economic losses in the aquaculture sector. The present study describes four whole genome sequences of WSSV obtained from coastal regions of Bangladesh.

Trichoderma species are known for their mycoparasitic activity against phytopathogenic fungi that cause significant economic losses in agriculture. During mycoparasitism, Trichoderma spp. recognize molecules produced by the host fungus and release secondary metabolites and hydrolytic enzymes to kill and degrade the host's cell wall. Here, we explored the participation of the Trichoderma atroviride RNAi machinery in the interaction with six phytopathogenic fungi of economic importance. We determined that both Argonaute-3 and Dicer-2 play an essential role during mycoparasitism. Using an RNA-Seq approach, we identified that perception, detox, and cell wall degradation depend on the T. atroviride-RNAi when interacting with Alternaria alternata, Rhizoctonia solani AG2, and R. solani AG5. Furthermore, we constructed a gene co-expression network that provides evidence of two gene modules regulated by RNAi, which play crucial roles in essential processes during mycoparasitism. In addition, based on small RNA-seq, we conclude that siRNAs regulate amino acid and carbon metabolism and communication during the Trichoderma-host interaction. Interestingly, our data suggest that siRNAs might regulate allorecognition (het) and transport genes in a cross-species manner. Thus, these results reveal a fine-tuned regulation in T. atroviride dependent on siRNAs that is essential during the biocontrol of phytopathogenic fungi, showing a greater complexity of this process than previously established.IMPORTANCEThere is an increasing need for plant disease control without chemical pesticides to avoid environmental pollution and resistance, and the health risks associated with the application of pesticides are increasing. Employing Trichoderma species in agriculture to control fungal diseases is an alternative plant protection strategy that overcomes these issues without utilizing chemical fungicides. Therefore, understanding the biocontrol mechanisms used by Trichoderma species to antagonize other fungi is critical. Although there has been extensive research about the mechanisms involved in the mycoparasitic capability of Trichoderma species, there are still unsolved questions related to how Trichoderma regulates recognition, attack, and defense mechanisms during interaction with a fungal host. In this work, we report that the Argonaute and Dicer components of the RNAi machinery and the small RNAs they process are essential for gene regulation during mycoparasitism by Trichoderma atroviride.