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PubMed2026

Ribosome stalling position, spacing, and A-site occupancy impact translation and cotranslational mRNA decay in plants.

Ribosomes can pause during mRNA translation, but what causes pausing, how pauses affect protein production, and whether they trigger cotranslational mRNA decay are poorly understood in plants. Here, we investigate the causes and consequences of ribosome pausing in Arabidopsis and maize. This is accomplished by sizing, mapping, and quantifying footprints of individual ribosomes (monosomes) and closely spaced ribosome pairs (disomes) at single-codon resolution on open reading frames (ORFs). Ribosome footprinting was combined with 5'P-degradome-seq to examine the coincidence of pausing with cotranslational decay under control conditions and brief hypoxia in Arabidopsis. The data resolve two monosome conformations and three disome configurations. These include monosomes with a vacant or occupied A-site and disomes that have collided or are separated by one or two codons. Pausing is prevalent at initiation, termination, and di-Proline codons. Di-Proline pauses do not trigger cotranslational decay but appear important in cotranslational protein processing. Brief hypoxia induces stalling of A-site vacant ribosomes at Aspartate codons, often coinciding with 5'P peaks, indicating that rate-limiting decoding can trigger cotranslational mRNA decay. Notably, actively transcribed and translated hypoxia-response mRNAs accumulate 1- to 2-codon-separated disomes and are actively degraded. Comparative analysis of footprints in the two species reveals ribosome conformations and codon-specific pausing can be conserved or lineage-specific, as exemplified by pausing at di-Prolines and on Conserved Peptide upstream ORFs. In sum, the stalling of ribosomes at specific codons, coupled with ribosome A-site occupancy and disome spacing, modulates protein production and cotranslational mRNA decay in plants.

Ribosomes↗

PubMed2026

Mineral-driven molecular signatures of energy metabolism underpin sperm motility in buffalo.

The success of spermatogenesis depends on the interplay of various biomolecules that ultimately determine sperm quality. In this study, RNA-seq analysis of frozen-thawed buffalo sperm (n = 8) revealed the presence of 263 mineral-associated genes (>1 FPKM) in high (n = 4) and 181 in low motile (n = 4) sperm groups. Among these, 177 mineral-associated genes were commonly expressed between them, and the majority were upregulated (>1 fold), LOC102391588 (ncRNA; 37-fold), ZNF699 (26.5-fold), MYZAP (13-fold), etc., in the high motile group. The expression of selected mineral-associated genes was validated. The top enriched functions in commonly expressed genes were regulation of transcription by RNA polymerase II (FDR: 4.7 × 10⁻2; ZNF331, ZNF692, ZNF180, etc.), followed by spermatogenesis (FDR: 2.9 × 10⁻2; CALR3, ADAM18, ADAM29, etc.), proton transmembrane transport (FDR: 4.0 × 10⁻2; ATP6V0E1, ATP1A4, ATP6V1B2, etc.) and flagellated sperm motility (FDR: 2.3 × 10⁻1; CATSPERD, EFCAB6, CABS1, etc.). Additionally, the chromatin remodeling pathway (FDR: 3 × 10⁻2; PTP4A1, PPM1A, DUSP1, etc.) emerged as the most significant and may suggest that these minerals influence genome packaging and sperm functionality. Mineral-associated genes were predominantly associated with zinc (49%), followed by calcium (20%), phosphorus (10%), iron (5%), sodium (2%), potassium (2%), copper (1%) and other trace elements (11%). Although the current study uses frozen-thawed sperm, the findings indicate that mineral-associated genes are crucial for promoting membrane stability, energy production, motility and chromatin integrity, which may contribute to the superior fertilizing ability of sperm.

Animals↗

PubMed2026

An oxidative stress - and immunotherapy-related six-gene signature defines immune subtypes and predicts prognosis and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Oxidative stress and the tumor immune microenvironment jointly shape hepatocellular carcinoma (HCC) progression and response to immunotherapy, yet integrated biomarkers linking these processes are lacking. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify oxidative stress- and immunotherapyrelated differentially expressed genes (OSIRDEGs). Functional enrichment, weighted gene co-expression network analysis (WGCNA) and LASSO-Cox regression were used to construct a prognostic signature. Consensus clustering, TIDE, CIBERSORT and ssGSEA characterized immune phenotypes. Somatic mutation, copy-number and drug-response data were integrated to assess genomic alterations and drug sensitivity. Expression of model genes was validated by qRT-PCR and western blotting in HCC cell lines. RESULTS: We identified 24 OSIRDEGs enriched in cell-cycle and mitotic pathways. WGCNA intersection yielded 18 module genes, from which a six-gene signature (BUB1B, CDKN2A, CENPE, HMMR, PTTG1, SPP1) was derived. The signature robustly stratified patients into high- and low-risk groups with significantly different progression-free and disease-free survival in both TCGA-LIHC and GSE14520. Based on signature expression, two molecular subtypes were defined, exhibiting distinct survival, immune landscapes and predicted immunotherapy responsiveness. Model genes harbored recurrent alterations and showed significant correlations with anticancer agents. All six genes were upregulated at mRNA and protein levels in metastatic HCC cell lines versus normal hepatocytes. CONCLUSIONS: We systematically explored the landscape of OSIRDEGs in HCC, and proposed a validated six-gene signature that refines prognostic stratification, delineates immunerelevant HCC subtypes and highlights candidate biomarkers for therapeutic selection and mechanistic investigation.

Humans↗

PubMed2026

Transcriptomic insights into the coordinated regulation of signaling, apoptosis, immunity, and metabolism during Sinonovacula constricta larval metamorphosis.

Metamorphosis is a critical ontogenetic transition for marine bivalves, marking the shift from planktonic to benthic lifestyles, where successful transformation dictates survival. The razor clam Sinonovacula constricta is economically important; however, low larval metamorphosis rates remain a major bottleneck in seedling production. To elucidate the mechanisms governing this process, we performed a comparative transcriptome analysis of S. constricta larvae at pre- and post-metamorphosis stages using Illumina sequencing. A total of 3701 differentially expressed genes (DEGs) were identified, including 3254 up-regulated and 447 down-regulated genes. Functional annotation of the respective top 20 significantly up-regulated and down-regulated DEGs indicated their potential pivotal roles in signal transduction (e.g., up-regulated: CAV1, CHRNA2; down-regulated: APP, NOTCH1), cellular proliferation and differentiation (e.g., up-regulated: TUBA, EGF1; down-regulated: KIF23, TTC25), transcriptional and epigenetic regulation (e.g., up-regulated: NFIL3; down-regulated: OVO, HMX1), substance transport (e.g., up-regulated: LRP2, LRP1B; down-regulated: SLC51A, Slc33a1), substance metabolism (e.g., up-regulated: CPK3, CYP26A1; down-regulated: RDMT1, ADAC), immunomodulation (e.g., up-regulated: CPN2, CRISP2), and protein homeostasis (e.g., up-regulated: HSP27, NAS-27). Functional enrichment analysis further revealed that DEGs were significantly enriched in pathways related to signal transduction and developmental regulation (e.g., Ras, TNF), cell death and homeostasis (e.g., apoptosis), immune responses (e.g., Toll-like receptor), energy metabolism (e.g., lipid), cardiovascular related (e.g., Fluid shear stress), cell junction and architecture (e.g., Tight junction), and infectious disease (e.g., measles). These results suggest a synergistic interplay between signaling, apoptosis, immunity, and metabolism during S. constricta metamorphosis. This study advances our understanding of marine bivalve metamorphosis and offers candidate genes for further mechanistic studies.

Animals↗

PubMed2026

Integrative machine learning and transcriptomic analysis reveals molecular mechanisms underlying low survival rate in larval Chinese Bahaba (Bahaba taipingensis).

Chinese Bahaba (Bahaba taipingensis) is a Class I protected marine fish endemic to China. Low larvae survival during artificial breeding severely hinder population recovery. To investigate the molecular mechanism of high mortality in larval fish, this study performed RNA-seq on liver from naturally deceased (ND) and mass-dead (MD) individuals, combined with least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms to screen for core signature genes. A total of 873 differentially expressed genes (DEGs) were identified, including 112 upregulated and 761 downregulated genes. GO and KEGG enrichment analyses revealed significant enrichment in amino acid metabolism disorders, one‑carbon folate pool impairment, PPAR signaling abnormalities, ECM-receptor interaction, focal adhesion pathway, indicating widespread metabolic suppression accompanied by extracellular matrix remodeling and signaling disturbances in the livers of MD fish. MAD pre-filtering combined with dual machine learning algorithms yielded 18 robust core signature genes, among which SLC38A4, MMP1, FADD, FKBP5, and APOB were consistently identified as high-frequency core genes by both algorithms. SLC38A4 exhibited the highest importance score in the RF model and was significantly downregulated, making it the primary molecule distinguishing ND from MD phenotypes. ROC curve analysis showed that both models achieved an AUC of 1.000 (95% CI lower bound: 0.610), confirming the precise discriminatory ability of the core genes. GSEA further demonstrated significant enrichment of this core gene set in ND samples. This study provides the first systematic elucidation of the molecular mechanisms underlying liver dysfunction in low survival rate B. taipingensis, characterized by amino acid transport impairment, metabolic reprogramming, and structural remodeling, offering theoretical foundations for health assessment, early mortality risk warning, and artificial breeding conservation of this species.

Animals↗

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

The impact of routine traffic encounters that include procedural justice on police perceptions.

OBJECTIVES: Despite procedural justice in police-citizen interactions being widely studied, there is limited research regarding police perceptions of these interactions. This study addresses this by exploring police perceptions of two different types of random breath test (RBT) - standard and procedurally just - in an experimental trial. Officers were asked to report on whether they believe that their RBT interaction with drivers and riders changed behaviour, developed more positive perceptions of police and resulted in slower travel. Additionally, they were asked if they thought that the RBT interaction took too long. METHODS: This study was a six month randomised control trial with two operational conditions: a control condition with a standard (n = 18 days) and an experimental condition with a procedurally just (n = 17 days) RBT. Police officers completed post-operation surveys (n = 80). RESULTS: Police officers incorporating the principles of procedural justice into RBT had limited impact on officer perceptions. However, those officers who were more open to innovation believed that the interaction would result in more positive perceptions of police. Police officers who believed that their RBTs with motorcycle riders would make a difference perceived that the riders would both change their behaviour and travel more slowly after the interaction. There were no differences in perceived interaction length by police officers across both conditions. CONCLUSIONS: This study has shown that police officer openness to innovation has an important role to play in police officers having more positive perceptions regarding the outcomes of RBT interactions. As such police organisations should undertake activities, such as training, to improve innovation. The lack of perceived differences in RBT length between standard and procedurally just interactions suggests that these enhanced interactions can be implemented without concerns that police officers believe that they 'take too long'.

Humans↗

PubMed2026

Accelerated Diagnostic Pathways for Suspected Acute Coronary Syndrome in Practice: A Randomized Trial of 0/1-Hour vs 0/3-Hour Troponin Testing.

BACKGROUND: For suspected acute coronary syndrome (ACS), guidelines recommend using high-sensitivity troponins (hs-cTn) in accelerated diagnostic pathways (ADPs) with 0/1-hour recommended over 0/3-hour ADP. However, implementation of these ADPs, with universal use of hs-cTns, has not been directly compared in randomized trials OBJECTIVES: This study sought to compare the efficiency and safety of the European Society of Cardiology (ESC) 0/1-hour and a 0/3-hour ADP when implemented in real-world clinical practice. METHODS: This pragmatic, randomized, noninferiority implementation trial compared the safety and efficiency of clinician decision making using these 2 pathways. To prevent incorporation bias, an independent hs-cTnI was used for formal adjudication using the fourth universal definition of myocardial infarction (MI). Efficiency was judged by the proportion of patients discharged within 4 hours. The safety endpoint was major adverse cardiac events (MACE) within 30 days (adjudicated index or representation type 1 MI, cardiovascular death, and urgent coronary revascularization) for those who were considered not to have ACS and discharged. The noninferiority margin, for absolute difference in sensitivity, between the ESC 0/1-hour and the 0/3-hour ADP was set at 3%, assessed with a 1-sided 97.5% CI. RESULTS: From December 2021 to July 2024, of 13,983 screened 3,543 individual patients with suspected ACS were recruited and consented from 2 major emergency departments in North-West England, with 100% follow-up achieved for all representations to any national hospital. The median age was 60 years (IQR: 49.5-70.5 years), 53% were men, 6.7%, and 7.6% had adjudicated index type 1 MI and MACE within 30 days, respectively. The turnaround time from sample to result for central laboratory hs-cTnT was 81 minutes (IQR: 69-101 minutes). The proportion of patients discharged within 4 hours was relatively low and did not differ substantially (21.8% vs 19.2%, P = 0.07). In addition, the 0/1-hour pathway was noninferior for safety, in patients discharged, compared with the 0/3-hour pathway, absolute difference in sensitivity was +4.2% (1-sided 97.5% CI: -2.5) in favor of the 0/1-hour pathway. The calculated sensitivities were 93.7% (95% CI: 88.4%-97.1%) vs 89.5% (95% CI: 82.7%-94.3%), respectively. CONCLUSIONS: Implementation of the ESC 0/1-hour pathway failed to discharge significantly more patients within 4 hours of presentation compared with the 0/3-hour ADP. In addition, The ESC 0/1-hour was noninferior to the 0/3-hour hs-cTn pathway for safety of discharge, although safety for both pathways was less than that imputed by observational studies. This trial demonstrates that perceived benefits to emergency department efficiency of a reduced sampling interval are mitigated by central laboratory turnaround times as well as system constraints. (Pragmatic Randomised Trial of the ESC 0/1 Versus 0/3 Hour Troponin Pathway [MACROS2]; NCT05322395).

Acute Coronary Syndrome↗

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

Integrated transcriptomic and metabolomic analyses provide new insights into the response of black rockfish (Sebastes schlegelii) larvae to temperature fluctuations.

Sebastes schlegelii usually encounter elevated and fluctuating water temperatures near its upper thermal limit in summer, yet the hepatic responses of larvae to repeated temperature fluctuation regimes remain unclear. To address this question, S. schlegelii larvae were exposed for 8 days to four thermal regimes: constant 18 °C (CT), constant 28 °C (HT), intermittent cooling from 18 to 8 °C followed by recovery to 18 °C (FL), and intermittent warming from 18 to 28 °C followed by recovery to 18 °C (FH). Survival rate was evaluated, and integrated liver transcriptomic and metabolomic analyses were performed. Final survival rates were 96.67% in the CT group, 97.78% in the FL group, and 77.78% in the FH group. Survival rate in the HT group (38.89%) was significantly lower than that in the other three groups (P < 0.05). HTvsCT, FLvsCT, FHvsCT, and FHvsHT comparisons identified 2598, 1207, 622, and 2404 differentially expressed genes and 627, 606, 690, and 610 differential metabolites, respectively. KEGG enrichment analyses of DEGs and SDMs in HTvsCT highlighted HSP-mediated proteostasis, endoplasmic-reticulum protein processing, branched-chain and sulfur amino acid metabolism, glutathione metabolism, and central carbon metabolism, with upregulated hsp90aa1, bckdha, gclc, and pfkp and reduced levels of branched-chain amino acids and methionine. Compared with HT, FH showed attenuated disturbances in proteostasis, amino acid and redox regulation, and central carbon metabolism, together with recovery-associated glycerophospholipid turnover. FL primarily induced polyunsaturated fatty acid (PUFA)-related membrane lipid remodeling. These findings indicate that hepatic responses differed between continuous high-temperature exposure and temperature fluctuations and between fluctuation regimes.

Animals↗

PubMed2026

Maternal vaccination with RSVpreF and risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

BACKGROUND: A bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) was approved in the United States in August 2023 for use during pregnancy to prevent infant RSV-associated lower respiratory tract disease. The pivotal phase 3 trial identified a numerical imbalance in hypertensive disorders of pregnancy (HDP) that did not reach statistical significance; postmarketing observational studies have since reported inconsistent findings. We conducted a systematic review and meta-analysis to assess this association. METHODS: We searched MEDLINE, Embase, CENTRAL, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception to Jan 26, 2026, for randomized controlled trials (RCTs) and observational studies comparing HDP outcomes in RSVpreF-vaccinated versus unvaccinated or placebo-receiving pregnant individuals. Unadjusted risk ratios (RRs) were pooled using a random-effects model; adjusted estimates from observational studies were pooled separately by inverse variance methods. This study is registered with PROSPERO (CRD420251026835). RESULTS: Nine studies were included (3 RCTs, 6 retrospective cohort studies; n = 148,267). RSVpreF vaccination was associated with a small but statistically significant increase in overall HDP risk (RR 1·08, 95% CI 1·02-1·13; p = 0·004; I2 = 44%), driven by the observational studies group (1·08, 1·02-1·14; I2 = 61%); RCTs showed a directionally consistent but non-significant RR (1·12, 0·87-1·43; I2 = 0%). The association was attributable to gestational hypertension, with no significant association for preeclampsia/eclampsia. CONCLUSION: Maternal RSVpreF vaccination was associated with a small increase in HDP attributable to gestational hypertension and driven primarily by observational studies, in which residual confounding remains possible. The benefits of infant RSV prevention remain substantial, and these findings support continued postmarketing surveillance and informed shared decision-making.

Humans↗

PubMed2026

The association between prenatal PM2.5 constituent exposure and gestational diabetes mellitus: Exploratory analysis of the potential modifying role of thyroid hormones.

The associations of PM2.5 constituents with blood glucose and GDM remain unclear, and the interplay between PM2.5 exposure and thyroid hormone levels in relation to GDM has not been well characterized. This retrospective cohort study included 1314 pregnant women with data collected through multiple methods. A generalized linear model analyzed PM2.5-glucose links, logistic regression assessed pollutant-GDM associations, and stratified analyses explored these relationships at different thyroid hormone levels. In the study population, first-trimester exposure to SO42- and BC correlated positively with FBG, as did PM2.5 and its components in the second trimester. First-trimester SO4²⁻ exposure (OR=1.26, 95% CI: 1.06, 1.51) and second-trimester exposures to PM2.5 (OR=1.67, 95% CI: 1.19, 2.35), NO3⁻ (OR=1.34, 95% CI: 1.06, 1.68), and NH4⁺ (OR=1.33, 95% CI: 1.06, 1.65) were associated with increased GDM risk. Stratified analyses showed that second-trimester BC and OM were positively correlated with FBG in the high-TSH and low-FT4 strata, respectively. In addition, first-trimester exposure to SO42- (high TSH: OR = 1.42, 95% CI: 1.10, 1.84; low FT4: OR = 1.35, 95% CI: 1.05, 1.74) and to PM2.5 (high TSH: OR = 1.93, 95% CI: 1.14, 3.27; low FT4: OR = 1.82, 95% CI: 1.46, 2.25) in the second trimester were associated with higher odds of GDM. These findings show that PM2.5 exposure was associated with glucose dysregulation and GDM in pregnant women differently by trimester and component. Across the separate TSH- and FT4-stratified analyses, women in the high-TSH and low-FT4 strata, respectively, appeared to show greater susceptibility to air pollution-related GDM. These subgroup findings should therefore be interpreted as exploratory and require validation in future studies.

Effect modification↗

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

A contextual activity score (CAS) for inferring ADAR-associated transcriptional activity across RNA-seq, single-cell, and spatial transcriptomics.

BACKGROUND AND OBJECTIVE: Adenosine-to-inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), is a widespread modification involved in neural function, immune regulation, and cancer. The Alu Editing Index (AEI) is the standard metric to estimate ADAR activity but requires raw sequencing reads and is poorly suited for single-cell and spatial transcriptomic data. This study aimed to develop an alternative framework for inferring ADAR-associated transcriptional activity from gene expression data across diverse transcriptomic technologies. METHODS: We developed the Contextual Activity Score (CAS), a framework based on transcriptional signatures from ADAR perturbation experiments. Context-specific signatures were generated for human neurons, mouse neurons, and cancer models to infer ADAR1 and ADAR2 activity. CAS was computed from normalized gene expression matrices using regulon-based enrichment analysis. Performance was evaluated by comparing with the Alu Editing Index across bulk RNA sequencing datasets, simulated sequencing depths, and library preparation protocols. RESULTS: CAS showed strong concordance with the Alu Editing Index across multiple datasets, while remaining robust to reduced sequencing depth and different library protocols. Unlike the Alu Editing Index, CAS can be applied to single-cell and spatial transcriptomic data and enables the independent assessment of ADAR2 activity. In cancer and neuronal contexts, CAS captured biologically meaningful variations in ADAR-associated transcriptional activity at sample, cell-type, and spatial levels. CONCLUSION: CAS provides a scalable approach applicable across multiple RNA-seq protocols for estimating ADAR-associated transcriptional activity using gene expression data. This method, implemented in an open-source R package for broad adoption, expands the ability to study ADAR-associated transcriptional activity across transcriptomic modalities where direct editing quantification is challenging, such as single-cell and spatial transcriptomics.

Adenosine Deaminase↗

PubMed2026

Transcriptomic and RNAi analyses reveal chloride channel 3-associated osmoregulation in Litopenaeus vannamei under low-salinity stress.

Chloride channels and transporters are important for cellular volume regulation and salinity adaptation in euryhaline crustaceans, yet the intestinal transcriptional relationship between plasma-membrane and intracellular chloride pathways remains unclear in Litopenaeus vannamei. In this study, RNA interference of anoctamin 1 (ANO1) was combined with intestinal transcriptome sequencing under the production-relevant low-salinity condition of salinity 3. ANO1 silencing produced a focused transcriptional response, with 16 differentially expressed genes (DEGs) identified (11 upregulated and 5 downregulated). Functional enrichment indicated that these genes were associated with transporter activity, cytoskeletal organization, extracellular matrix-receptor interaction, membrane lipid metabolism, and vesicular processes. Notably, a transcript encoding chloride channel protein 3 (CLC-3) was significantly upregulated following ANO1 knockdown, suggesting a potential transcriptional relationship between ANO1 and CLC-3 in chloride homeostasis. Based on this finding, CLC-3 was selected for full-length cDNA cloning, sequence characterization, salinity-gradient expression analysis, and RNAi-based functional assessment. The cloned CLC-3 cDNA was 2883 bp in length and encoded an 850 amino acid protein containing a conserved voltage-gated chloride channel (Voltage-CLC) domain and two cystathionine β-synthase domains. Phylogenetic analysis placed LvCLC-3 within the intracellular CLC-c clade, and tissue distribution analysis showed the highest CLC-3 expression in the intestine. Intestinal CLC-3 expression responded nonlinearly to salinity variation, peaking at salinity 20. Under salinity 3, CLC-3 knockdown reduced ANO1, Na+/K+-ATPase alpha subunit, and Na+-K+-2Cl- cotransporter transcript levels, whereas glutamate-gated chloride channel expression increased. Mild hepatopancreatic structural alterations were also observed after CLC-3 knockdown. These findings suggest that CLC-3 is a salinity-responsive intracellular chloride-transporter candidate associated with intestinal ion-transport-related transcriptional responses after ANO1 suppression in L. vannamei, although the underlying physiological mechanism requires further validation.

Animals↗

PubMed2026

Regional genomic analysis of lineage distribution and transferable multidrug resistance among chicken-associated Salmonella Kentucky isolates in China.

Salmonella enterica serovar Kentucky is an important multidrug-resistant foodborne pathogen in the poultry meat supply chain. Although recent broader genomic studies have elucidated the population structure and epidemiological significance of major lineages in China (e.g., ST198 and ST314), the regional dynamics within local poultry supply chains remain insufficiently characterized. In this study, 31 chicken meat-derived isolates from Shanghai and 39 publicly available genomes from China were analyzed using antimicrobial susceptibility testing, whole-genome sequencing, phylogenetic analysis, conjugation experiments, and complete sequencing of representative plasmids. This enabled a systematic characterization of the molecular epidemiological features of the population and the mechanisms underlying resistance dissemination. Population genomic analysis revealed a lineage composition markedly different from the global epidemiological pattern: ST314 was the predominant sequence type among the Shanghai chicken-derived isolates (74.2%), whereas the internationally recognized high-risk clone ST198 accounted for only 25.8% of the local isolates. However, risk stratification analysis indicated that although ST198 was detected less frequently, it carried a significantly greater burden of acquired resistance genes and therefore represented a higher-risk resistant lineage. Functional and structural validation further elucidated the molecular basis of resistance dissemination within this high-risk lineage. Conjugation experiments confirmed the co-transfer of a multidrug resistance module carrying blaTEM-1 and blaCTX-M-267 to the recipient strain Escherichia coli J53. Complete plasmid analysis revealed that these two β-lactam resistance genes were co-localized on a 242-kb transferable plasmid flanked by Tn1331, Tn3, and multiple transposase-associated elements, thereby providing a structural basis for their horizontal transfer. This study provides important molecular epidemiological evidence for lineage-specific surveillance and risk-stratified control of resistant Salmonella in the poultry meat supply chain and further underscores the need for continuous monitoring of mobile genetic elements within a One Health framework.

Animals↗

PubMed2026

Single-cell transcriptome revealed the aberrant keratinocytes activation in antigen presentation in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD), a common chronic inflammatory skin disease, has been extensively studied using single-cell genomics. However, keratinocytes, as key effector cells in AD, have underlying mechanisms remain incompletely understood and require further investigation. METHODS: We integrated single-cell transcriptomic data from skin tissues of healthy controls, chronic active AD patients, spontaneously healed AD (SHAD) patients, and an ovalbumin-induced AD mouse model. The study particularly emphasized the gene expression and cellular dynamics of keratinocytes across the different groups, as well as their interactions with immune cells. RESULTS: Compared to healthy controls, we observed significant changes in the keratinocyte transcriptome, cellular state, and keratinocyte-immune cell ligand-receptor interactions in AD skin, particularly the marked activation of genes involved in antigen processing and presentation. Interestingly, such gene activation was not observed in keratinocytes from the ovalbumin-induced AD mouse model, despite its phenotype closely resembling human AD. Furthermore, in SHAD, we identified a recovery of both the ligand-receptor interaction patterns and antigen processing and presentation genes, accompanied by a notable shift in the transcriptome. This involved a significant downregulation of genes related to cytoplasmic transcription and oxidative phosphorylation. Notably, this pattern was not observed in the self-healing mouse model following the removal of ovalbumin stimulation. CONCLUSION: Our results suggest that the persistent activation of antigen processing and presentation pathways in keratinocytes may be a key driver of chronic inflammation in AD. Therefore, redirecting anti-allergic therapeutic strategies from solely targeting immune cells to targeting of keratinocyte-mediated antigen presentation may offer a more effective approach. Furthermore, we raise concerns about the use of ovalbumin-induced mouse models to recapitulate human chronic AD, as the underlying mechanisms may differ significantly.

Dermatitis, Atopic↗

PubMed2026

Proteomic insights into hepatic responses to high soybean meal inclusion with citric acid supplementation in hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus) juveniles.

This study evaluated the growth performance and hepatic proteomic responses of juvenile hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus) juveniles fed diets containing 30% or 40% soybean meal (SBM), with or without 3% citric acid supplementation, and compared with a fishmeal (FM) control diet over a 10-week feeding trial. Fish fed 30% SBM (LSBM) showed a final body weight comparable to the FM group, whereas fish fed 40% SBM (HSBM) recorded significantly reduced growth and net protein utilization (NPU) (p < 0.05). Supplementation of citric acid in the 40% SBM diet (HSBM + CA) significantly improved NPU and partially restored growth relative to HSBM. LC-MS/MS based quantitative proteomics identified 1544 hepatic proteins and showed clear dietary segregation. Differentially expressed proteins were predominantly associated with reduced abundance of proteins involved in lipid metabolism, amino acid metabolism, pyruvate metabolism, and the tricarboxylic cycle across all SBM diets, suggesting a shift in oxidative metabolic capacity. In contrast, LSBM induced upregulation of spliceosome-associated proteins and RNA processing components, suggesting adaptive post-transcriptional regulation under moderate SBM inclusion. In contrast, HSBM exhibited greater reduction in metabolic protein abundance without comparable upregulation of adaptive regulatory components, coinciding with reduced nutrient retention. Protein-protein interaction analysis further confirms the correlation between the regulation of spliceosomal clusters and mitochondrial lipid-catabolic modules. Citric acid supplementation did not markedly reverse hepatic metabolic protein changes but improved protein retention. Data are available via ProteomeXchange with identifier PXD081994. These findings suggest a tolerance limit between 30% and 40% SBM inclusion, with 30% inducing adaptive hepatic proteomic responses compatible with maintained growth performance.

Animals↗