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PubMed2026

Promoter Methylation of HOXA5 and NDRG2 in Multiple Myeloma Patients with Renal Impairment.

Renal impairment (RI) is frequently caused by multiple myeloma (MM), which makes clinical care more difficult if renal function deteriorates or renal failure develops. Thus, in this investigation, we looked at the relationship between HOXA5&NDRG2 promoter methylation in MM patients and evaluated their prognostic potential in predicting RI risk in MM patients. This study included 60 control volunteers and 120 MM patients. The promoter methylations of HOXA5&NDRG2 were quantitatively evaluated by real-time PCR (qPCR) after the extraction of gDNA from whole blood and then treated with bisulfite. The promoter methylation percentages of HOXA5&NDRG2 were significantly increased in MM patients (77.16 ± 2.43&45.49 ± 2.16;p < 0.05) when compared to controls (4.47 ± 0.61&3.33 ± 0.31,respectively), in stage II&III patients when compared to stage I patients and in patients with age ≥ 60 years when compared to patients with age < 60 years. While only the methylation percentage of NDRG2 promoter was significantly increased in MM patients with RI (53.61 ± 3.21,p < 0.05) when compared to MM patients without RI (37.37 ± 2.04). Results obtained from ROC curve revealed that both HOXA5&NDRG2 promoter methylation were good diagnostic tools for MM. The NDRG2 promoter methylation was good prognostic biomarker could predict renal while HOXA5 promoter in the prediction of MM staging. The Kaplan-Meier survival test showed that patients with higher HOXA5&NDRG2 promoter methylation had a shorter OS and a worse prognosis. Only NDRG2 promoter hypermethylation was significantly associated with the risk of RI development in MM patients. HOXA5&NDRG2 promoter hypermethylation may have roles in the molecular etiology of MM and could be used as a treatment regimen.

Humans↗

PubMed2026

Genetic Diversity of BK Polyomavirus Among Renal Transplant Recipients in Yunnan, China.

BK polyomavirus (BKV) infection, a common complication following kidney transplantation, can lead to BKV-associated nephropathy (BKVN). Molecular genetic studies have classified BKV into four genotypes (I-IV); however, comprehensive molecular characterization of BKV strains circulating in China remains limited. This study aimed to elucidate the predominant subtypes and clinical infection characteristics of BKV strains among kidney transplant recipients in Yunnan, a province in southwestern China. PCR-amplified BKV DNA sequences from kidney transplant recipients were aligned with reference strains and subjected to phylogenetic analysis. The viral VP1 gene was successfully amplified from 180 participants, spanning 16 ethnic groups. Genotype I was the predominant viral strain (56.66%, 102/180), followed by genotype IV (43.33%, 78/180), while genotypes II and III were not detected. Among genotypic subtypes, IVc-1 was most prevalent (40.0%, 72/180), followed by Ic (38.3%, 69/180) and Ib-1 (18.3%, 33/180). IVa-1 and IVa-2 were rare, identified in only 0.6% (n = 1) and 2.2% (n = 4) of cases, respectively. No significant differences in sex, age, BKVN incidence, BK viremia, or viruria were observed between patients with BKV-I and BKV-IV infections. Among the five confirmed BKVN cases, two were genotyped as subtype Ic, one as Ib-1, and two as IVc-1. Clinical phenotypes were also comparable between patients with BKV-I and BKV-IV infections. This study represents the largest single-center sequencing analysis of BKV in kidney transplant recipients in China, offering a valuable genomic resource for future research.

Humans↗

PubMed2026

The Role of Small Segmental Duplications in Generating Identical Isoforms Through Alternative Splicing Sites.

Alternative splicing plays a crucial role in expanding proteomic diversity but can also generate identical isoforms under certain conditions. While mutually exclusive splicing of tandem exons has occasionally been reported to produce identical isoforms, the extent to which other splicing events contribute to this phenomenon remains unclear. In this study, we demonstrate that alternative 5' and 3' splice site selection can also lead to the formation of identical isoforms, providing an additional type of splicing event for functional redundancy in transcriptomes. To address this, we analyzed reference genome annotations from 15 plant species, including Arabidopsis thaliana and wheat (Triticum aestivum), obtained from the RefSeq database. Identical isoforms were computationally defined as transcripts with distinct exon-intron structures but identical coding sequences. Our analysis reveals that the majority of alternative 5' and 3' fragments originate from small segmental duplications, suggesting that sequence repetition within gene regions facilitates the emergence of such splicing patterns. We also observed differences in the annotated 5' UTRs of some identical isoforms. However, since the alternative splicing sites themselves were not located within UTRs, these differences may reflect annotation uncertainty rather than genuine AS-derived variation. Given that UTR predictions in reference databases are not always precise, such observations should be interpreted cautiously. Expression analysis using an isoform-specific k-mer approach confirmed that identical isoforms can be differentially regulated. These findings suggest that, beyond expanding protein diversity, alternative splicing can also generate redundant isoforms that are differentially expressed at the RNA level, indicating potential regulatory roles. By elucidating the structural and regulatory factors contributing to the formation and retention of identical isoforms, our study provides new insights into the evolutionary and functional significance of alternative splicing in plants.

Alternative Splicing↗

PubMed2026

Boosting domestic wastewater treatment with quorum signal-augmented heterotrophic nitrification-aerobic denitrification bacterial-algal aerobic granular sludge.

The aerobic bacterial-algal granular sludge (ABGS) enhanced with heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria, as a novel symbiotic technology, exhibits fluctuating treatment efficiency and unstable performance primarily due to the unstable symbiotic relationship. This study proposes an innovative approach to strengthening the bacteria-algae symbiosis by introducing exogenous signaling molecules. Concurrently, high-throughput, correlation analysis of environmental factors and metagenomic sequencing techniques are employed to elucidate the enhancement mechanisms of the signaling molecules. The results demonstrate that signaling molecule enhancement boosted total nitrogen (TN) removal efficiency by 24.51 % in the bacteria-algae symbiotic system (X1). Scanning electron microscopy (SEM) characterization revealed that the addition of signaling molecules resulted in more compact aerobic granular sludge (AGS) and markedly improved stability. High-throughput sequencing showed signaling molecules enriched denitrifying bacteria (Hydrogenophaga, Pseudoxanthomonas, Thauera, Zoogloea) and organic-degrading Desulfomicrobium, optimizing microbial diversity and enhancing nitrogen/organic removal. Correlation analysis of environmental factors indicate that the addition of C8-HSL facilitates the enrichment and functional activation of specific genera. Metagenomic analysis revealed that signaling molecules enhanced the system's denitrification performance by modulating gene expression and associated metabolic pathways. Quantitative polymerase chain reaction (qPCR) analysis further confirmed that the signaling molecules upregulated the expression of the napA, nirK, and nirS genes. An increased abundance of the napA gene facilitated aerobic denitrification (NO₃⁻-N→NO₂⁻-N), while upregulated abundance of the nirK and nirS genes accelerated nitrite reduction (NO₂⁻-N→N₂). This study aims to provide theoretical and practical foundations for implementing advanced bacteria-algae symbiotic technologies.

Denitrification↗

PubMed2026

Effects of umbilical cord mesenchymal stem cell-derived exosomes on periodontal ligament stem cells: An exploratory study.

OBJECTIVE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) at two osteogenic induction stages (undifferentiated and late-stage) differentially affect periodontal ligament stem cells (PDLSCs), and to explore the potential molecular basis. DESIGN: UCMSCs and PDLSCs were isolated and cultured. Exosomes were harvested from undifferentiated UCMSCs (Exo-D0) and UCMSCs after 14 days of osteogenic induction (Exo-D14). PDLSCs were treated with both exosome types. Proliferation and migration were analyzed using EdU and scratch assays, the latter under serum-free conditions. Early osteogenic differentiation was assessed by alkaline phosphatase staining and quantitative reverse transcription PCR (qRT-PCR). Differentially expressed miRNAs were identified by high-throughput sequencing and further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: Both exosome types promoted PDLSC migration. Exo-D0 enhanced early osteogenic differentiation, whereas Exo-D14 enhanced proliferation but reduced early osteogenic marker expression. Sequencing identified 21 differentially expressed miRNAs (13 upregulated, 8 downregulated). Bioinformatic prediction suggested that the putative target genes were enriched in Ras signal transduction, regulation of kinase activity, and focal adhesion, and further predicted significant enrichment in the MAPK, Ras, and PI3K-Akt signaling pathways, which are central to cell proliferation and osteogenic differentiation. CONCLUSIONS: Exosomes from undifferentiated and osteogenically induced UCMSCs exerted distinct effects on PDLSCs, potentially associated with differentially packaged miRNAs. These findings offer a basis for hypotheses about exosome-mediated mechanisms and support matching exosome sources to the intended therapeutic outcome as potential cell-free strategies for periodontal tissue regeneration and alveolar bone repair.

Humans↗

PubMed2026

Antagonistic regulation by mango MiSPL9a and MiSPL9b regulates flowering time, drought and salt stress in Arabidopsis.

SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, which are unique to plants, contain a highly conserved SBP domain that regulates gene expression by binding to downstream targets. They play critical roles in various biological processes, especially in the regulation of flowering in plants. In this study, two SPL-like genes (MiSPL9a and MiSPL9b) were identified from mango genomic and transcriptomic data, and their sequence, expression and function were further analyzed. Sequence analysis revealed that MiSPL9a and MiSPL9b have open reading frames of 1173 bp and 1158 bp, respectively, with slight differences in the number of cis-regulatory elements within their promoter regions. Expression analysis under stress conditions revealed distinct patterns: MiSPL9a expression significantly differed under drought stress but did not significantly differ under salt stress, whereas MiSPL9b expression responded significantly to salt stress but changed minimally under drought stress. Phenotypic analysis of the transgenic Arabidopsis lines revealed that MiSPL9a overexpression delayed flowering, whereas MiSPL9b overexpression promoted early flowering. Under stress conditions, compared with wild-type plants, MiSPL9a-overexpressing plants presented increased drought tolerance but did not significantly differ. In contrast, MiSPL9b-overexpressing plants were sensitive to salt stress, with no notable phenotypic differences observed under drought conditions. Physiological assays revealed that under drought stress, MiSPL9a transgenic plants presented significantly reduced levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and increased proline (Pro) content and superoxide dismutase (SOD) activity. Under salt stress, MiSPL9b transgenic plants presented opposite trends in terms of these physiological markers. In summary, both MiSPL9a and MiSPL9b are involved in the regulation of plant flowering time and stress responses, but their functions differ.

Arabidopsis↗

PubMed2026

Molecular characterization and biological characteristics of a highly pathogenic recombinant ALV-J strain (HUE2023) with cross-clade gp85 recombination.

Avian leukosis virus subgroup J (ALV-J) has undergone extensive diversification into phylogenetically distinct clades, yet whether recombination between these clades within the gp85 envelope glycoprotein generates variants with altered pathogenicity has received little direct investigation. A field strain (HUE2023) was recovered from breeding roosters displaying vascular tumors. The viral genome was sequenced and subjected to phylogenetic and recombination analyses. The three-dimensional structure of gp85 was predicted with AlphaFold3; electrostatic surface potentials and surface hydrophobicity were computed using the Adaptive Poisson-Boltzmann Solver and the Eisenberg hydrophobicity scale, respectively. Pathogenicity and immunosuppressive effects were assessed in Hy-Line Brown chickens. Recombination analysis revealed that HUE2023 is an inter-clade recombinant derived from Clade 1.1 (major parent: JS14NT01) and Clade 1.2 (minor parent: JS09GY3). A single-residue deletion at position 61 within receptor-binding domain 1 (RBD-1), unique to the recombinant, induced a localized conformational rearrangement that generated a concentrated electronegative surface patch and a contiguous hydrophobic pocket not observed in either parental gp85. Animal challenge showed that HUE2023 is highly pathogenic: female chickens in the high-dose group reached only 61% survival and displayed significant growth retardation (P < 0.05) together with marked immunosuppression. The recombination in the RBD-1 led to local conformational rearrangement, resulting in a concentrated and negatively charged surface area as well as a continuous hydrophobic pocket, which were never present in any of the parental gp85 sequences. These results indicate that gp85 recombination across clades can yield variants with fundamentally altered receptor-binding surfaces and argue for integrating structural surveillance into ALV-J monitoring programmes.

Animals↗

PubMed2026

Comparative analysis of lipopolysaccharide lipid A structure and its biosynthetic genes in the plant-associated bacteria Brucella cytisi and Brucella lupini.

The genus Brucella comprises important human and animal pathogens, as well as numerous environmental and symbiotic species. Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, plays a crucial role in bacterial physiology and host interactions. In this study, the structures of lipid A, the hydrophobic anchor of lipopolysaccharide, isolated from two plant-associated strains, Brucella cytisi ESC1ᵀ and Brucella lupini LUP21ᵀ, were presented. Lipid A preparations were structurally characterized using chemical methods, MALDI-TOF mass spectrometry, and nuclear magnetic resonance spectroscopy. The obtained results indicated that both lipid A molecules have almost identical structures. Their sugar backbones consist exclusively of 2,3-diamino-2,3-dideoxy-d-glucose (d-GlcpN3N). Phosphate residues were connected to distal and proximal GlcpN3N in approximately half of the lipid A molecules. Fatty acid analysis revealed the presence of C14:0 (3-OH), C16:0 (3-OH), and traces of C18:0 (3-OH). All of these were primary fatty substituents of the sugar backbone and were amide-linked residues. Lactobacillic acid C19:0cyc and 27-hydroxyoctacosanoic acid (C28:0 (27-OH)) were found as ester-linked secondary acyl residues. In turn, C28:0 (27-OH) was partly esterified by a 3-hydroxybutyroyl residue. Two unsubstituted 3-hydroxyfatty acids were linked exclusively to the proximal d-GlcpN3N residue. It was pointed out that sequences of putative genes encoding enzymes required for lipid A biosynthesis and genes encoding specific enzymes involved in structural modifications of lipid A occurring in the genomes of both bacterial species are almost identical. The high sequence similarity of these proteins reflects the observed similarities in the lipid A structures in both investigated Brucella species.

Brucella↗

PubMed2026

Dosimetric Parameters of the Heart and Its Substructures in Predicting Cardiac Events or Survival in Patients With Lung Cancer After Radiation Therapy: A Systematic Review and Meta-analysis.

The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in patients with lung cancer remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. A total of 80 studies, including 21,645 patients, were analyzed. Of these, 25 studies reported CEs, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: (1) left anterior descending (LAD) V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses, were significantly associated with ischemic events. (2) Multiple CS parameters were associated with different arrhythmia subtypes. (3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion. (4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. (5) We also identified several thresholds with potential predictive values, such as LAD V15 <10% for MACE, left pulmonary vein (LPV) V55 <2%, and right pulmonary vein (RPV) V10 <54% for atrial fibrillation (AF), right atrium (RA) V60 <0.03 cc for non-AF supraventricular tachyarrhythmia, and left main artery (LMA) V10 ≥1 cc for bradyarrhythmia. This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.

Humans↗

PubMed2026

Antennal transcriptome analysis of chemosensory proteins in the raspberry weevil, Aegorhinus superciliosus (Coleoptera: Curculionidae).

Aegorhinus superciliosus (Coleoptera: Curculionidae) is a polyphagous pest of economic importance in southern Chile, the chemical ecology of which remains poorly characterized. Across insect species, chemosensory proteins, including odorant receptors (ORs), gustatory receptors (GRs), ionotropic receptors (IRs), odorant-binding proteins (OBPs), chemosensory proteins (CSPs), and sensory neuron membrane proteins (SNMPs), mediate the detection of chemical cues involved in host selection, reproduction, and other ecologically relevant behaviors. In this study, the antennal transcriptome of adult A. superciliosus was sequenced and analyzed using a de novo RNA-seq approach. Three independent biological replicates per sex were used for RNA-seq, and the same number of independent biological replicates was used for RT-qPCR validation; sequencing yielded 147,409,936 high-quality reads after quality filtering. A total of 112 candidate chemosensory genes were identified, comprising 43 ORs, 34 OBPs, 10 CSPs, 18 IRs, 5 GRs, and 2 SNMPs. Phylogenetic analyses assigned these candidate proteins to established clades, providing a comparative framework for functional inference for ORs and OBPs. Sex- and tissue-biased expression analyses revealed that several ORs, including AsupOR4, AsupOR19, and AsupOBP13, exhibit antennal enrichment and sex-specific expression patterns. Notably, AsupOR19 and AsupOBP13 displayed strong female-biased expression. In addition, transcripts of selected ORs and OBPs were detected in non-antennal tissues, such as the rostrum and legs, suggesting potential functional versatility beyond canonical olfaction. Together, these findings represent the first molecular identification of the chemosensory repertoire of A. superciliosus. This study establishes a foundation for reverse chemical ecology approaches aimed at identifying behaviorally active volatile organic compounds (VOCs) toward environmentally sustainable strategies for integrated pest management.

Animals↗

PubMed2026

Ossicle occurrence characteristics and related molecular mechanisms in the sea cucumber Apostichopus japonicus.

To investigate the morphogenetic pattern and molecular mechanism of ossicle formation in the sea cucumber Apostichopus japonicus, this study systematically examined the morphological development and temporal sequence of spicules using the NaClO maceration method, in-situ squash preparation and microscopic observation. Comparative transcriptome sequencing was performed between doliolaria and pentactula larvae to screen differentially expressed genes (DEGs) related to ossicles formation, followed by pathway enrichment analysis. The function of the candidate key gene papilin-like was verified using siRNA-mediated gene silencing. The results were as follows: 1) Ossicles of A. japonicus first appeared at the late auricularia stage, initiating as X-shaped ossicles at the base of the oral tentacles. The number of X-shaped ossicles increased dramatically during the doliolaria stage. X-shaped ossicles were gradually replaced by table-shaped and rosette-shaped ossicles at the pentactula stage, suggesting that X-shaped ossicles may differentiate into these two ossicle types. The morphology of table-shaped ossicles showed a "simple-complex-simple" pattern with development. 2) Key genes related to ossicles formation, including CA1, COL1A2, and papilin-like, were identified by transcriptome analysis. After papilin-like knockdown, abnormal morphologies were observed in table-shaped ossicles of 1-year-old A. japonicus, such as spine-like protrusions on the outer margin of the disc and loss of table legs, confirming its crucial roles in maintaining ossicle morphology. This study clarified the morphological development pattern of ossicles in A. japonicus and identified a key regulatory gene (papilin-like) involved in ossicle morphogenesis, providing preliminary insights into the underlying molecular regulatory mechanism. These findings enrich our understanding on ossicles formation in echinoderms, and provide important morphological and molecular biological information for further studies on the developmental mechanism of ossicles in A. japonicus.

Animals↗

PubMed2026

Robot-assisted versus manual percutaneous vascular interventions across vascular territories: a systematic review and meta-analysis.

Robot-assisted percutaneous vascular intervention (R-PVI) has expanded beyond coronary procedures, but previous reviews were largely coronary-focused and observational. Recent randomized controlled trials (RCTs) warrant broader reassessment of R-PVI versus manual percutaneous vascular intervention (M-PVI) across vascular territories. PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from database inception to January 31, 2026, following PRISMA guidelines. RCTs and observational studies including ≥10 adult patients in total were eligible. Comparative studies informed primary analyses, while single-arm studies provided supportive evidence. Primary outcomes were clinical success rate and major adverse cardiovascular/cerebrovascular events (MACE) rate. Secondary outcomes included mortality rate, technical success rate, procedural time metrics, contrast volume, and radiation exposure. Random-effects models were used. Forty studies were included: 3 RCTs, 10 comparative observational studies, and 27 single-arm observational studies, comprising 3,870 patients undergoing R-PVI and 1,142 undergoing M-PVI. Comparative analyses showed similar clinical success rates (RR 1.00, P = 0.46), MACE rates (RR 0.72, P = 0.43), and mortality. Single-arm pooled estimates for clinical and technical success were 98.76% and 96.09%, respectively. R-PVI prolonged total procedure time overall (MD 15.92 min, P = 0.01), with consistent increases in the neurovascular, RCT, and non-RCT subgroups. Fluoroscopy time was also longer (MD 1.91 min, P = 0.04), mainly in the RCT subgroup (MD 2.83 min, P = 0.001). In contrast, intravascular intervention time was unchanged overall and in RCTs, but was prolonged in non-RCTs (MD 8.72 min, P = 0.006). Operator radiation exposure was markedly reduced (MD -33.97 μSv, P < 0.001), whereas patient radiation exposure and contrast volume were similar. R-PVI appears feasible and safe across selected vascular procedures. Its clearest benefit is reduced operator radiation exposure, whereas lower whole-procedure efficiency remains its main limitation.

Humans↗

PubMed2026

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H₂O₂-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans↗

PubMed2026

Ecr positively regulates activity of the PhoQ/PhoP signalling system in Klebsiella pneumoniae.

BACKGROUND: The rising prevalence of polymyxin resistance in multidrug-resistant Klebsiella pneumoniae presents a critical situation with limited therapeutic options. METHODS: Methods Genomic sequencing of 15 clinical polymyxin-resistant K. pneumoniae strains with multidrug resistance revealed that MgrB inactivation, predominantly disrupted by insertion sequences (ISs) in the IS1, IS4, and IS5 families, was the leading cause of polymyxin resistance. Comparative transcriptomics of wild-type, ΔmgrB, and ΔmgrBΔphoP were performed to elucidate the MgrB-PhoPQ regulatory network. RESULTS: This study conducted a system-wide analysis of the regulatory network and identified a species-specific PhoPQ regulon in K. pneumoniae.Beyond the classical MgrB-PhoPQ-ArnBCADTEF pathway, we identified a previously unannotated PhoPQ-regulated gene, 144 bp LN739_RS09850, encoding an Ecr homologue from Enterobacter cloacae. This protein has been reported to confer colistin heteroresistance, with the underlying mechanism not yet functionally validated. This study revealed that overexpression of Ecr homologues decreased colistin susceptibility in both K. pneumoniae and E. cloacae, but this phenotype was abolished upon phoP deletion, confirming PhoP's essential role. Consistent with this dependency, comparative transcriptomics of Ecr-overexpressing K. pneumoniae vs. control revealed significant upregulation of mgrB, phoPQ, arnBCADTE, and pmrD. Two-hybrid bacterial assays further demonstrated direct Ecr-PhoQ interaction. Electrophoretic mobility shift assay confirmed that PhoP directly binds to the ecr promoter in vitro, and a β-galactosidase reporter assay demonstrated that PhoP enhanced ecr promoter activity, indicating that PhoP regulates ecr expression by directly controlling its transcription. CONCLUSION: Collectively, these findings suggest that PhoP may directly activate the transcription of Ecr, with Ecr feedback activating the PhoPQ system via interaction with PhoQ, leading to induction of the arn operon and consequent polymyxin resistance.

Klebsiella pneumoniae↗

PubMed2026

Single-organ proteomics in Drosophila melanogaster larva.

The combination of genetic accessibility, organ complexity, evolutionary conservation, and cost-efficiency makes Drosophila melanogaster (Dm) a well-known model system for biomedical and fundamental biological research. Proteomic analysis of single organs enables the identification and quantification of proteins expressed in specific organs. This will help to uncover specific biological functions and unique protein profiles that are not detectable in whole-organism analyses. In this study we have isolated single organs form Dm larvae, and we have performed a deep proteomics mapping by following a minimal manipulation preparation procedure. The combined dataset across all organs comprised 9132 identified proteins. As anticipated, principal component analysis (PCA) revealed clear separation between the proteomes of most organs, confirming distinct protein profiles. These findings demonstrate the applicability of the sample preparation strategy for high-resolution proteomic characterization of individual organs in Drosophila. Given the extensive genetic tools available for this model organism, our approach has the potential to open new avenues for proteomic studies in Drosophila melanogaster and any other biological systems where the sample amount is limiting. SIGNIFICANCE STATEMENT: Drosophila melanogaster is a well-known model system for biomedical and fundamental biological research that serves as a valuable in vivo model organism due to its high degree of evolutionary conservation with higher vertebrates, tractable genetics, and logistical efficiency. However, the proteome of Drosophila at single organ level has been elusive to date, due to several factors like low sensitivity of previous generation mass spectrometers and sample preparation procedures, difficult isolation of some organs. In this study we have applied a compilation of advanced methods including minimal sample manipulation together with simple, straightforward and efficient protein extraction and digestion methods. Obtained peptides were minimally handled to be analyzed by applying specific and sensitive nLC methods coupled on-line to state-of-the-art MS/MS system. Altogether, the applied strategy allowed us to get the first single organ study to date for this animal. These datasets represent a significative resource for future genomic, transcriptomic and proteomic studies in Drosophila, as multi-omic integration requires deep proteomics to translate data into functional biochemistry, and serves as a critical bridge and an indispensable standalone resource across the genomic, transcriptomic, and proteomic landscapes.

Animals↗

PubMed2026

Assessment of Genetic Diversity and Population Structure on Azadirachta indica A. Juss. in an Urban Metropolitan: Ahmedabad, India.

Azadirachta indica (A. indica) A. Juss., commonly known as Neem, is a valuable multipurpose tree with profound medicinal properties and socioeconomic importance, widely recognized since ancient Ayurvedic times. Despite its prominence, knowledge about its genetic diversity within the metropolitan area of Ahmedabad is limited. This study marks the first in-depth exploration of the genetic diversity and population structure of A. indica in Ahmedabad. The authenticity of the species was validated through DNA barcoding, and a Geographical Information System (GIS) was used to collect the samples. A total of 35 A. indica accessions were analyzed using five Inter Simple Sequence Repeat (ISSR) primers. Genetic diversity and population structure were evaluated using Inter Simple Sequence Repeat (ISSR) markers through polymorphism assessment, clustering, ordination, and Bayesian population structure analyses. ISSRs revealed a high level of polymorphism (75.66%), indicating substantial genetic variability among accessions. An analysis of genetic diversity indices revealed low to moderate diversity (Hs = 0.14, Ht = 0.217, I = 0.217). Analysis of Molecular Variance (AMOVA) analysis depicted 81% variation within the population and 19% among the population. Low to moderate genetic differentiation (Gst = 0.319) and moderate gene flow (Nm = 1.06) indicated that urban development has not hindered gene flow among populations. Mantel's test revealed a weak but significant correlation between genetic and geographic distances, suggesting limited isolation by distance. The estimated ΔK using STRUCTURE exhibited two subpopulations, representing two gene pools for A. indica accessions (K = 2). Collectively, these patterns indicate that urbanization has not severely disrupted genetic connectivity in A. indica, reflecting its resilience and adaptive potential in a metropolitan environment. These findings provide pivotal knowledge for further understanding the genetic diversity and population structure of A. indica in one of the fastest-growing cities in India, which can be utilized for new breeding programmes, sustainable development and future conservation strategies around the globe.

India↗

PubMed2026

Integrated phytochemical and bioactivity profiling of Xanthium strumarium fruits from Korea and China: Implications for origin-specific quality specification.

BACKGROUND: Geographic origin influences the phytochemical composition and biological activities of medicinal plant resources. Xanthium strumarium L. (XS) fruit is widely used in East Asian traditional medicine. However, current pharmacopeial standards primarily recognize Chinese-derived material, despite the availability and traditional use of XS in Korea. To address this gap and support origin-informed quality specification, we compared fruits from Korea (XS-K) and China (XS-C) using chloroplast genome sequencing, targeted phytochemical profiling (high-performance liquid chromatography (HPLC) for selected phenolics and gas chromatography-flame ionization detection (GC-FID) for fatty acids and phytosterols, and multivariate chemometric analysis. RESULTS: Chloroplast genome analysis revealed high overall similarity but localized divergence around the rpoC2 locus and a greater mutation burden in XS-C, supporting origin-associated genomic differentiation. Phytochemical profiling revealed distinct origin-dependent metabolic signatures. XS-K showed higher levels of phytosterols, chlorogenic acid, 4,5-dicaffeoylquinic acid (4,5-DCQ), and xanthatin was detected only in XS-K, whereas XS-C exhibited greater abundance of total fatty acids, particularly oleic acid. Unsupervised clustering and log2 fold-change ranking confirmed clear compositional separation, and variable importance in projection (VIP) analysis identified chlorogenic acid, β-sitosterol, oleic acid, 4,5-DCQ, and xanthatin as major discriminators between origins. Bioactivity assays demonstrated that XS-K exerted stronger antioxidant effects in ABTS, DPPH and FRAP assays, stronger skin-related enzyme inhibition, and greater antibacterial activity against Staphylococcus aureus, consistent with its enriched phenolic and sterol profile. CONCLUSION: Together, chloroplast sequence variation, targeted metabolite quantification, and screening bioassays consistently distinguished XS-K from XS-C. These findings support the use of candidate markers for the origin-based authentication and quality control of XS fruit-derived ingredients. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fruit↗

PubMed2025

The wider erection angle in hypospadias: A neglected feature affecting surgical outcomes.

INTRODUCTION: Penile curvature often accompanies hypospadias, and numerous techniques have been described for its correction; however, in some cases, an abnormal erection angle may also be present, further exacerbating the perception of curvature. OBJECTIVE: This study investigates the significance of the erection angle in hypospadias cases and its correlation with the severity of the anomaly. STUDY DESIGN: A retrospective analysis of intraoperative photographs of hypospadias cases operated between 2019 and 2023 was performed. Erection angle was measured with a digital goniometer during a full artificial erection. Erection angles in proximal and distal hypospadias cases were analyzed and compared to data from Kinsey's subgroups representing healthy male erection angles. RESULTS: This study involved images of 68 patients, with 31 having proximal and 37 distal hypospadias. The median age of the whole group was 11 months (6-156, IQR 9). Median erection angle was 91 (63-119, IQR 11) for distal cases, whereas it was 96 (75-138, IQR 21) for proximal cases. The difference was statistically significant (p = 0.009). The erection angle distribution in our cohort, including both proximal and distal hypospadias cases, skewed toward wider angles, highlighting a distinct pattern compared to data constituted by Kinsey and Sparling. DISCUSSION: Our findings indicate that the erection angle in hypospadias is significantly wider in proximal cases, suggesting a correlation between erection angle and severity of the hypospadias. While we acknowledge the limitation of comparing our prepubertal cohort with Kinsey's adult data, the absence of evidence suggesting significant post-pubertal changes in erection angle justifies this approach. Additionally, the use of digital images for angle assessment is not a standardized technique in hypospadias evaluation; these images were initially captured for curvature assessment. Despite these limitations, our study provides novel insights into seldom mentioned association with hypospadias - a wide erection angle, emphasizing the need for further research on its implications for surgical planning and long-term outcomes. CONCLUSION: This study introduces a wider erection angle as an additional characteristic of hypospadias particularly pronounced in proximal cases. To our knowledge, this is the first focused investigation on addressing this aspect of the condition. It emphasizes the need for further research on adults with wide post-repair erection angles to explore its long-term impact on sexual function and aesthetics.

Humans↗