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Cardiorespiratory training for people with stroke.

RATIONALE: Low levels of cardiorespiratory fitness are common after stroke and are associated with post-stroke disability and increased risk of secondary stroke. Cardiorespiratory training interventions aim to increase cardiorespiratory fitness, improve physical function, reduce disability, and help prevent future strokes. Clinical guidelines recommend exercise as part of lifestyle modification for secondary prevention, and strongly recommend exercise for rehabilitation. This review is one of three reviews that were originally a single review on physical fitness training for stroke. OBJECTIVES: The primary objective of this review was to determine whether cardiorespiratory training after stroke has an effect on death, disability, adverse events, risk factors, fitness, walking, and indices of physical function when compared to a non-exercise control. SEARCH METHODS: In April 2025, we searched nine bibliographic databases and two trials registers to identify studies for inclusion in the review. We checked reference lists, tracked citations, and contacted experts. ELIGIBILITY CRITERIA: We included randomised controlled trials comparing cardiorespiratory training interventions with usual care, no intervention, or a non-exercise intervention in people with stroke. OUTCOMES: Our critical outcomes were death, disability, adverse events, risk factors, fitness, walking, and indices of physical function, assessed at the end of the intervention and the end of the longest follow-up. RISK OF BIAS: We used the Cochrane RoB 1 tool to assess the risk of bias in the included studies. SYNTHESIS METHODS: The studies evaluated different comparisons (e.g. cardiorespiratory training versus no intervention/waiting list control or versus attention control or versus usual care), which we synthesised into a single comparison: cardiorespiratory training versus control. We used random-effects meta-analysis on arm-level data (risk difference (RD) for dichotomous data, and mean difference (MD) or standardised mean difference (SMD) for continuous data, with 95% confidence intervals (CIs)). For outcome data that we did not meta-analyse, we followed Synthesis Without Meta-analysis (SWiM) guidance. We used GRADE to assess the certainty of the evidence for critical outcomes. INCLUDED STUDIES: We included 53 studies (2672 participants, with an average age of 61.9 years). Most studies recruited ambulatory participants in the early subacute (7 days to 3 months) or chronic (> 6 months) phases of recovery. Exercise duration recommendations were met in 49 studies, and frequency recommendations in 48. Twenty-eight studies lacked balanced exposure between groups. Programme duration was 12 weeks or more in 16 studies (maximum: 24 weeks). Sixteen studies had a post-intervention follow-up period (12 weeks to 12 months from baseline). One study planned a six-month follow-up but did not report it. SYNTHESIS OF RESULTS: Cardiorespiratory training does not increase or decrease deaths at the end of intervention (RD 0.00, 95% CI -0.01 to 0.01; 36 studies, 1563 participants; high-certainty evidence) or the end of follow-up (RD -0.00, 95% CI -0.02 to 0.02; 10 studies, 713 participants; high-certainty evidence). Cardiorespiratory training may improve indices of disability slightly at the end of intervention (SMD 0.35, 95% CI 0.12 to 0.57; 17 studies, 1073 participants; very low-certainty evidence), but the evidence is very uncertain. Re-expressed using the Barthel Index (0 to 20), the equivalent effect is MD 1.68, 95% CI 0.59 to 2.74. It is unclear if the effect is clinically meaningful (the minimal clinically important difference (MCID) is +1.85). The effect is unclear at the end of follow-up (SMD -0.14, 95% CI -0.36 to 0.08; 5 studies, 347 participants; low-certainty evidence). Cardiorespiratory training does not increase or decrease the incidence of secondary cardiovascular or cerebrovascular events at the end of intervention (RD -0.00, 95% CI -0.03 to 0.02; 8 studies, 544 participants; high-certainty evidence) and probably does not affect them at the end of follow-up (RD -0.02, 95% CI -0.08 to 0.04; 4 studies, 412 participants; moderate-certainty evidence). It is very uncertain whether cardiorespiratory training affects systolic blood pressure (mmHg) at the end of intervention (MD -2.12, 95% CI -5.81 to 1.57; 9 studies, 535 participants; very low-certainty evidence) (MCID -2 mmHg) or follow-up (MD 0.93, 95% CI -4.30 to 6.16; 3 studies, 155 participants; very low-certainty evidence); the 95% CIs include the MCID. Cardiorespiratory training probably results in a slight improvement in cardiorespiratory fitness (VO2 ml/kg/min) at the end of intervention (MD 2.37, 95% CI 1.39 to 3.36; 13 studies, 608 participants; moderate-certainty evidence); it is unclear if the effect is clinically meaningful (MCID +3.5 ml/kg/min). The effect may be similar at the end of follow-up (MD 2.76, 95% CI 1.36 to 4.16; 5 studies, 237 participants; low-certainty evidence). Subgroup analysis favoured longer interventions. Cardiorespiratory training probably results in a slight increase in comfortable walking speed (metres per second) at the end of intervention (MD 0.08, 95% CI 0.04 to 0.12; 16 studies, 647 participants; moderate-certainty evidence), but the effect is not clinically meaningful (MCID +0.13). The effect is unclear at the end of follow-up (MD 0.02, 95% CI -0.05 to 0.10; 3 studies, 182 participants; low-certainty evidence). Cardiorespiratory training may improve indices of balance at the end of intervention (SMD 0.31, 95% CI 0.15 to 0.47; 18 studies, 772 participants; very low-certainty evidence), but the evidence is very uncertain. Re-expressing using the Berg Balance Scale, the equivalent effect is MD 2.09, 95% CI 1.10 to 3.07; and it is unclear if it is clinically meaningful (MCID of +2). The effect is unclear at the end of follow-up (MD 0.90, 95% CI -1.32 to 3.12; 6 studies, 253 participants; low-certainty evidence). Overall, our certainty about the evidence is limited for most outcomes by imprecision (small number of studies and participants) or risks of bias (e.g. imbalanced exposure doses) or both. AUTHORS' CONCLUSIONS: Cardiorespiratory training after stroke does not affect mortality or the incidence of secondary events at the end of the aerobic exercise training programme or end of follow-up. It may increase fitness, reduce disability, increase walking speed, and improve balance at the end of intervention, but it is unclear if these improvements are clinically meaningful. Further well-designed randomised trials are needed to fully understand the potential benefits and long-term effects of cardiorespiratory training and the optimal exercise prescription. FUNDING: No dedicated funding REGISTRATION: Protocol (and previous versions) available via DOI 10.1002/14651858.CD003316.

Humans↗

Strategies to improve recruitment to randomised trials.

BACKGROUND: Recruiting participants to randomised controlled trials (RCTs) is challenging. Identifying effective recruitment strategies would benefit health research: poor recruitment leads to underpowered trials, reducing the reliability of findings and increasing the risk of wasted resources, ethical concerns, and trial failure. Evidence to inform recruitment strategies is increasingly generated through Studies Within A Trial (SWATs), which are methodological studies embedded within host RCTs. This is an update of a review last published in 2018. OBJECTIVES: Primary: to quantify the effects of strategies to improve recruitment of participants to RCTs. Secondary: to evaluate recruitment strategies' cost-effectiveness and impact on retention, and the equity, diversity, and inclusion (EDI) characteristics of recruited participants. SEARCH METHODS: We used MEDLINE, Embase, and six other databases to identify the studies included in the review. We also sought unpublished recruitment SWATs through social media and targeted email dissemination to trial methodology networks. The latest search date was 16 February 2023. SELECTION CRITERIA: We included randomised SWATs evaluating trial recruitment strategies embedded in healthcare and non-healthcare trials. We excluded quasi-randomised, hypothetical, questionnaire-only, retention-only, or clinician incentive studies. DATA COLLECTION AND ANALYSIS: Primary outcome: proportion of eligible participants or centres recruited. SECONDARY OUTCOMES: cost-effectiveness, retention rates, and EDI characteristics of included participants. We conducted random-effects meta-analysis for strategies evaluated in at least two studies; otherwise, we synthesised results narratively. We reported effects as risk differences (RDs) with 95% confidence intervals (CIs), and assessed between-trial heterogeneity. We used GRADE to assess the certainty of evidence for the primary outcome. We expressed cost-effectiveness as the incremental cost per additional participant recruited in pounds sterling (GBP). MAIN RESULTS: We identified 91 eligible studies (53 new to this update), providing 94 comparisons and involving at least 176,747 participants. Eighty-one studies involved strategies aimed at trial participants, while 10 evaluated strategies aimed at recruiters. All were healthcare studies. We found 65 recruitment strategies; 49 were evaluated in a single study. Only five strategies were supported by high-certainty evidence according to GRADE criteria, and we focus on these strategies in the summary below. Open-label trials versus blinded, placebo trials. Open-label trials recruited more participants than blinded trials (RD 10%, 95% CI 8% to 12%; 3 studies, 9004 participants), corresponding to approximately 10 additional participants per 100 approached. The studies involved mostly women in the UK and Estonia. No cost or retention data were reported. Telephone reminder versus no telephone reminder. Telephone reminders to people who did not respond to an initial postal invitation boosted recruitment by 6% (95% CI 3% to 9%; 2 studies, 1450 participants), in trials with low underlying recruitment (we are less certain for trials with over 10% recruitment). The studies involved people with a mean age of 58 years in Canada and Norway. No cost or retention data were reported. Recruitment primer letter versus no letter. Pre-recruitment letters and leaflets designed to encourage participation made little or no difference to recruitment (absolute improvement 1%, 95% CI -1% to 2%; 2 studies, 5376 participants), and were associated with increased costs compared to not sending a primer (incremental cost: GBP 2.08). The studies involved mostly older white people in the UK and Ireland. Multimedia information via a digital link/QR code plus paper participant information leaflet (PIL) versus paper PIL alone. This made little or no difference to recruitment (absolute improvement 0%, 95% CI -1% to 1%; 7 studies, 11,612 participants) and retention (absolute improvement 0%, 95% CI -2% to 3%; 5 studies, 7403 participants), and increased costs compared to not including multimedia information (incremental cost: GBP 0.78). The studies involved people in the UK. Optimised, user-tested PIL versus standard PIL. Optimising participant information leaflets (e.g. through user-testing the leaflet with the target population to shape its content, format, and appearance) made little or no difference to recruitment: absolute improvement was 0% (95% CI 0% to 1%; 6 studies, 27,805 participants). The studies involved people in the UK. Only one study reported EDI data; participants were mostly older women. No cost or retention data were reported. We had moderate-certainty evidence for 13 other strategies; confidence was often reduced because the results came from single studies. Seven strategies involved changes to how potential participants received information; four involved changes to trial conduct; one targeted the recruiter or recruitment site; and one tested non-monetary incentives. We had much less confidence in the other 47 comparisons because the studies had design flaws, were single studies, or had very uncertain results. Costs were reported in only 17 of 91 studies. Strategy impact on retention was reported in 15 studies. All but one study (99%) were from high-income countries. The most reported demographics were age (49 studies), sex (32 studies), gender (27 studies), and education level (16 studies). AUTHORS' CONCLUSIONS: The evidence on strategies to improve trial recruitment remains broad but lacks depth. Of 65 strategies evaluated, only five were supported by high-certainty evidence. Open-label trial designs and telephone reminders to non-responders increased recruitment, while optimised participant information leaflets, recruitment primer letters, and multimedia information provided alongside a paper participant information leaflet had little or no effect. Reporting of participant characteristics was poor, limiting assessment of equity, diversity, and inclusion across most studies. Evidence is heavily skewed toward high-income countries. Future research must prioritise evaluations in low-to-middle-income settings and consistently report cost, retention, and EDI outcomes. We strongly urge the methodology research community to strengthen the evidence base by prioritising replications of existing strategies over the development and testing of new ones. FUNDING: National Institute for Health and Care Research (Advanced Fellowship, Adwoa Parker, reference:NIHR302256). Health Research Board, Republic of Ireland, Evidence Synthesis Ireland (grant ESI-2021-001) REGISTRATION: This review updates an earlier Cochrane review, which was first published in 2002 and subsequently updated in 2007, 2010, and 2018. Previous versions of the review and their protocols are available at: https://doi.org/10.1002/14651858.MR000013.pub2 https://doi.org/10.1002/14651858.MR000013.pub3 https://doi.org/10.1002/14651858.MR000013.pub4 https://doi.org/10.1002/14651858.MR000013.pub5 https://doi.org/10.1002/14651858.MR000013.pub6.

Randomized Controlled Trials as Topic↗

Untangling the Arisaema enigma: Investigating the complex evolutionary history and species relationships in North American Arisaema.

PREMISE: The evolutionary history of morphologically variable plant groups is often obscured by cryptic diversity, morphological convergence, and limited genetic data. Arisaema, a diverse genus within Araceae, exemplifies these challenges. Although some taxonomic treatments recognize only two species of North American Arisaema (A. dracontium and A. triphyllum), other studies have identified morphologically distinct groups within both taxa. Here, we reconstructed evolutionary relationships in North American Arisaema, assessed genetic structure and admixture, and tested the monophyly of proposed species. METHODS: We used 2b-RAD sequencing to generate genome-wide SNP data for 146 samples from 31 populations across the eastern United States. Phylogenetic relationships were inferred using maximum-likelihood and Bayesian approaches. Population structure and admixture were assessed using the program structure and principal component analysis (PCA). RESULTS: Both the Arisaema triphyllum and A. dracontium complexes formed well-supported monophyletic groups. Within the A. dracontium complex, we recovered three monophyletic lineages: A. dracontium, A. calciphilum, and A. macrospathum. In the A. triphyllum complex, A. quinatum, A. stewardsonii, and A. allegheniense consistently formed distinct groups. Relationships between A. pusillum and A. acuminatum, and among A. triphyllum s.s., A. purpurascens, and A. striatum were less clearly resolved, likely due to recent or incomplete divergence, gene flow, or polyploidy. CONCLUSIONS: The results support the monophyly of multiple newly proposed taxa within North American Arisaema, but additional sampling across the species' ranges is needed to fully resolve species boundaries. Our study provides the first evolutionary framework for this group, providing a foundation for future ecological, taxonomic, and conservation research in the genus.

Araceae↗

Substrate-Dependent Crosslinking by the Cytochrome P450 From Aminopyruvatide Biosynthesis.

Cytochrome P450s catalyze an array of reactions including crosslinking of aromatic side chains in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs). ApyO is a cytochrome P450 that forms a C─C bond between two tyrosines in a YLY motif in the substrate ApyA, the precursor peptide of the RiPP aminopyruvatide. We utilized cell-free translation to generate ApyA variants and probe the substrate tolerance of ApyO. Through AlphaFold-based modelling and in vitro assays, we show that ApyO accepts the 10 C-terminal residues of ApyA and requires a conserved Arg/Lys in the substrate. Inspired by substrate sequences in orthologous biosynthetic gene clusters, we substituted one of the tyrosine residues with a tryptophan and observed that ApyO catalyzed formation of an N─C bond between the indole of Trp and Cε2 of Tyr. ApyO unexpectedly catalyzed formation of a C─O bond between the two tyrosine residues when we substituted the leucine residue in the YLY motif with tyrosine or tryptophan. A peptide containing a biaryl linkage and C-terminal aminopyruvate displayed sub-nanomolar inhibition of select proteases, with the aminopyruvate group critical for activity. Overall, this study demonstrates plasticity in the manner of macrocyclization catalyzed by the P450 ApyO.

biosynthesis↗

Timing matters: Impact of covalent BTK inhibitor dose modifications on outcomes in chronic lymphocytic leukemia/small lymphocytic leukemia-A 7-year real-world study.

BACKGROUND: Covalent BTK inhibitors (cBTKis) are the cornerstone of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) therapy, yet real-world data on dose modifications and their differential impact on long-term outcomes remain incompletely defined. This study investigated the incidence, timing, and the effectiveness of drug switching in a real-world CLL cohort. METHODS: In this 7-year retrospective real-world study, 324 CLL/SLL patients treated at a specialized Shanghai outpatient clinic (April 2018-April 2025; median follow-up, 42 months) were analyzed. Dose modifications were classified as dose interruption (DI) or dose reduction (DR). Their prognostic impact on progression-free (PFS) and overall survival (OS) was assessed by Kaplan-Meier analysis and multivariate Cox regression. RESULTS: The 42-month PFS rate was 70.2%. Of 324 patients, 229 (70.7%) experienced dose reductions or interruptions; infections were the predominant cause (61.9%). The full-dose (FD) group (n&#xa0;=&#xa0;90) demonstrated superior 4-year PFS (93% vs. 58%, p&#xa0;<&#xa0;.001) and OS (98% vs. 76%, p =&#xa0;.007). Early modifications (0-3 months) were independent predictors of inferior PFS (hazard ratio [HR], 3.93, p =&#xa0;.008) and OS (HR,&#xa0;3.29, p =&#xa0;.014). Prolonged DI (>14 days) was associated with inferior PFS (HR,&#xa0;2.64) and OS (HR,&#xa0;2.15), whereas DR and short DI (&#x2264;14 days) had negligible impact. Early (0-3 months) prolonged DI was devastating&#xa0;(3-year PFS, 41.2%; HR,&#xa0;3.84, p&#xa0;<&#xa0;.001). cBTKi switching (n&#xa0;=&#xa0;82; 100% nonprogression-driven) shortened DI (median, 6 vs. 14 days) and was independently associated with superior OS (HR,&#xa0;0.34, p =&#xa0;.018) and PFS (HR,&#xa0;0.36, p =&#xa0;.022). CONCLUSIONS: Early prolonged DI is the dominant adverse prognostic factor in cBTKi-treated CLL/SLL. Proactive switching minimizes treatment gaps and improves survival, supporting a timing-aware, DI- versus DR-informed approach to dose management.

Humans↗

Effect of demographic characteristics on the outcome of prostate cancer salvage radiotherapy: Analysis from a randomized controlled trial.

BACKGROUND: This study investigated the impact of advanced molecular imaging, race, socioeconomic status, and metabolic dysregulation on the outcome of salvage radiotherapy (sRT) for prostate cancer recurrence in a clinical trial setting. METHODS: The authors randomized post-prostatectomy men with detectable prostate-specific antigen to sRT guided by conventional imaging (arm A) or 18F-fluciclovine-positron emission tomography/computed tomography (arm B) and followed them up for up to 48 months to determine failure-free survival (FFS). The authors computed socioeconomic status (SES) and allostatic load (AL) scores to quantify socioeconomic status and level of metabolic dysregulation. They stratified patients by race as African American men (AAM) versus men of other races (MOR) and compared FFS between them using the z-test. RESULTS: Eighty-one (AAM&#xa0;=&#xa0;29, MOR&#xa0;=&#xa0;52) and 76 (AAM&#xa0;=&#xa0;26, MOR&#xa0;=&#xa0;50) men completed per-protocol sRT in arms A and B, respectively. Across study arms, AAM showed a higher FFS rate than MOR (72.8% [95% CI, 53.8%-85.0%] vs. 58.7% [95% CI, 46.6%-68.9%]; p&#xa0;=&#xa0;.002). In arm A, FFS rate was better for AAM than MOR, (64.0% [95% CI, 34.4%-82.9%] vs. 45.3% [95% CI, 28.8%-60.4%]; p&#xa0;=&#xa0;.008). In arm B, FFS improved for both groups but less so for AAM, (81.5% [95% CI, 57.2%-92.7%] vs. 73.0% [95% CI, 56.3%-84.1%]; p&#xa0;=&#xa0;.131). The authors found lower SES scores and higher AL scores for AAM in both study arms than MOR. CONCLUSION: Despite lower socioeconomic status and higher burden of metabolic dysregulation, in a clinical trial setting that controls for disparities in health care access, AAM have a more favorable sRT outcome than MOR.

Humans↗

A systematic review of international/national guidelines for the management of nasopharyngeal carcinoma: Convergence and divergence of recommendations.

Increasing numbers of clinical practice guidelines have been published by international/national groups for nasopharyngeal carcinoma (NPC), providing valuable references for clinicians in making evidence-based decisions on treatment. However, there are substantial discrepancies in various recommendations, leading to uncertainties in choosing the optimal strategies. The authors systematically searched databases and organizational websites for NPC guidelines published between January 2000 and November 2025. All identified guidelines underwent quality appraisal; in total, 26 clinical practice guidelines rated recommended for use were included. The recommendations covering all management aspects (diagnosis, staging, radiotherapy, systemic therapy, follow-up surveillance, biomarkers, and salvage of recurrent/metastatic diseases) were summarized and comparatively analyzed for consistency and disparities. Strong consensus exists for diagnostic workup, staging systems, and induction chemotherapy plus concurrent chemoradiotherapy for advanced disease, whereas marked disparities exist on radiotherapy details, particularly target volume delineation, elective coverage extent, and dose specifications. Although systemic therapy strategies for different stage groups were mostly consistent, substantial disparities exist in alternative options and treatment details. This first comprehensive systematic synthesis of international NPC guidelines provides a practical reference for clinicians to understand all recommendations and select optimal options based on local resources and expertise while identifying current controversies that demand future research for further standardization and harmonization.

Humans↗

Pangenome of Streptomyces sampsonii and Relatives Highlights Horizontal Gene Transfer and Secondary Metabolism in Environmental Adaptation and Ecological Significance.

Streptomyces sampsonii is a promising biocontrol bacterium, but its genomic basis of adaptation and secondary metabolism remains unclear. Here, we present a chromosome-level genome assembly of S. sampsonii (7.20&#x2009;Mb, 6015 protein-coding genes) and perform comparative analyses with 95 related Streptomyces species. Phylogenomic and synteny analyses revealed its closest relationship with S. albidoflavus, while extensive structural variations distinguished more distant lineages. Pangenome analysis uncovered 84,178 gene clusters, with pan_shell and pan_cloud genes predominantly enriched in xenobiotic biodegradation, metabolism, and antibiotic biosynthesis, highlighting their roles in ecological adaptation and biocontrol potential. Biosynthetic gene cluster (BGC) analysis identified numerous NRPS, PKS, and terpene pathways, many of which belong to pan_shell and pan_cloud regions, suggesting dynamic evolutionary origins. We further detected 66,260 horizontally transferred (HGT) genes, including 438 in BGCs, underscoring HGT as a major driver of metabolic innovation. Together, these findings provide novel insights into the genomic diversity, adaptive capacity, and secondary metabolic potential of S. sampsonii and its close relatives.

BGCs↗

Elucidating the In&#xa0;Vitro Adverse Effect of Functionalized Single-Walled Carbon Nanotubes Against Breast Cancer Cells at the Proteomics Level.

The tremendous therapeutic potential of carbon-based nanomaterials (CNMs) has been limited by inconsistent data regarding the nanotoxicity assessment. Although a bulk of studies have been performed to assess the in&#xa0;vitro cytotoxicity mechanism of CNMs, the exact factors responsible for the cytotoxicity of CNMs have not been fully understood. With the rapid advancement of mass spectrometry technologies, proteomics has emerged as a powerful strategy for systematically investigating the molecular and cellular mechanisms underlying toxicity induced by nanomaterials. This study examined the in&#xa0;vitro cytotoxicity of single-walled carbon nanotubes (SWCNTs) in human MCF-7 breast cancer cells by conducting a comparative proteome-level analysis using mass spectrometry. Initially, the characterized SWCNTs were incubated with MCF-7 cells for 3, 6, and 24&#x2009;h. Proteins were subsequently extracted from each treatment group and subjected to nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) analysis. The relative abundance of the identified proteins was determined by comparison with the control group, and differential expression patterns, including upregulated and downregulated proteins, were assessed. A total of 3482 unique protein groups were identified across all exposure periods. Among these, 3466 protein groups were detected following 3&#x2009;h of exposure, 3469 following 6&#x2009;h of exposure, and 3480 following 24&#x2009;h of exposure. Compared with the control group, the identified differentially expressed proteins exhibited fold changes ranging from 2-fold to 20-fold across the incubation periods. In total, 70 proteins were found to be significantly regulated following SWCNT exposure. Of the differentially expressed proteins, 45 were significantly upregulated, whereas 25 were significantly downregulated. Visualization of these regulations over time was shown in a heatmap of log2-transformed fold-change values to explore time-specific proteomic alterations. Functional enrichment analysis of these proteins also showed that the regulated proteins were significantly associated with Reactome pathways, including ER-to-Golgi anterograde transport, Golgi-to-ER retrograde transport, COPI-mediated vesicle trafficking, regulation of insulin-like growth factor transport and uptake by insulin-like growth factor-binding proteins, protein metabolism, and posttranslational protein modification. Furthermore, a systematic comparison of previous studies within the present findings was provided to situate our study within the broader context of understanding CNT-induced cellular toxicity. Collectively, these findings provided an important proteomic evidence of the adverse effects of SWCNTs on MCF-7 cells. Furthermore, this study showed a comprehensive proteomic landscape of cellular responses to SWCNT exposure, contributing to a better understanding of the molecular mechanisms underlying SWCNT-induced cytotoxicity and bridging the gap between protein regulation and the resulting cellular responses. In this study, we characterized the proteomic landscape of MCF-7 cells following SWCNT exposure, revealing molecular mechanisms associated with cellular responses and cytotoxicity. The identified differentially expressed proteins established a link between altered protein regulation and SWCNT-induced cellular effects. Moreover, these proteins need to be further validated in different cell models and would potentially represent promising candidates for the identification of novel molecular targets involved in SWCNT-induced cytotoxicity.

MCF&#x2010;7 cells↗

Somatic Mitochondrial-Nuclear DNA Transfer in Lymphoproliferative Disorders.

INTRODUCTION: Somatic mitochondrial-nuclear DNA transfer (SMNT) is a process by which mitochondrial DNA (mtDNA), of varying sizes, integrate into the nuclear genome and has been previously reported in solid tumours. METHODS: EuroClonality-NGS DNA Capture sequencing data from 755 lymphoid malignancies and 59 lymphoid cell lines were analysed for SMNT-associated structural variants. RESULTS: Five malignancies (0.66%) harboured SMNTs, predominantly involving IGH genes, with one PTEN gene disruption identified. Breakpoint features supported non-homologous end joining-mediated integration. CONCLUSION: SMNTs are rare but recurrent events in lymphoid malignancies and may represent stable clonal markers for minimal residual disease monitoring. TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.

Journal Article↗

Cooccurrence of Homologous Recombination Deficiency and Mismatch Repair Deficiency in Colorectal Cancer.

Homologous recombination deficiency (HRD) in colorectal cancer (CRC) remains largely unexplored. In contrast, mismatch repair deficiency (dMMR) occurs in &#x223c;15% of patients with CRC. Although HRD and dMMR have historically been regarded as mutually exclusive, emerging evidence suggests that this mutual exclusivity may not be absolute. Here, we conducted a retrospective cohort study utilizing genomic and transcriptomic data to define HRD status in a Chinese dMMR CRC cohort (n&#xa0;=&#xa0;99). Multiple machine learning approaches were employed to analyze the expression profiles of these tumors and to develop a classifier distinguishing HRD from homologous recombination proficiency (HRP) in dMMR CRCs. In the Chinese dMMR CRC cohort, 66% of tumors were classified as HRD. Compared with the HRP group, the HRD group had a significantly higher tumor mutational burden and better outcomes. The derived expression signature, comprising eight genes, successfully predicted HRD status in dMMR tumors with high accuracy in the training set (AUC&#xa0;=&#xa0;0.88, Na&#xef;ve Bayes) and the test set (AUC&#xa0;=&#xa0;0.87). In this study, a subset of dMMR CRC tumors with co-occurring HRD was identified, which may have potential implications for patient stratification and the application of targeted therapies, such as PARP inhibitors, in this molecular subgroup.

colorectal cancer↗

Application of Omics Technologies for Cowpea Improvement.

Cowpea (Vigna unguiculata) is a vital crop for food security, nutrition, and climate resilience in sub-Saharan African and other semi-arid regions. However, its improvement is constrained by the complexity of polygenic traits such as drought tolerance, pest resistance, and seed quality. Conventional breeding, while foundational, remains insufficient to address these challenges at the required pace. Recent advances in multi-omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, provide new opportunities to dissect complex traits, identify candidate genes, and accelerate the development of resilient, high-yielding cultivars. This review presents a critical synthesis of current applications of omics technologies in cowpea improvement, highlighting their contributions to stress adaptation, nutritional enhancement, and precision breeding. The review also examines key technical and institutional constraints limiting the adoption of omics-assisted breeding in cowpea, including inadequate research infrastructure, challenges in multi-omics data integration, and limited technical capacity across breeding programs in sub-Saharan Africa. It discusses strategies to address these barriers through regional collaboration, investment in bioinformatics capacity, and the integration of computational approaches into breeding pipelines. Overall, the review concludes that combining multi-omics technologies with artificial intelligence and machine learning has strong potential to improve genotype-phenotype prediction, accelerate breeding decisions, and support the development of climate-resilient and nutritionally enhanced cowpea cultivars.

cowpea↗

Integrating Biobanking Into Conservation Practice: The Development and Impact of the EAZA Biobank.

Zoological biobanks are becoming essential tools in conservation, offering a means to preserve genetic material and support in situ population management amid accelerating biodiversity loss. With rapid advances in genomics, cryopreservation, and assisted reproduction technologies, biobanks enable a proactive approach to providing insurance against genetic erosion and facilitating future research, supplementation, and genetic rescue. However, to be effective, zoological biobanks must be purposefully designed, strategically integrated into conservation frameworks such as the Convention on Biological Diversity (CBD) Kunming-Montreal Global Biodiversity Framework (KMGBF), and regularly evaluated for coverage and impact. Using the EAZA Biobank as an example, we outline the structure, development, and collaborative foundations that have enabled its rapid growth, built on community support and conservation impact. Leveraging EAZA's institutional network and data-sharing platforms such as ZIMS, the Biobank employs a decentralized, four-hub model of zoological institutions storing samples. A gap analysis, integrating threat status, breeding programs, genomic data repositories, and phylogenetic diversity, highlights current sampling strengths and deficiencies and guides future collection priorities. The integration of specimen-specific genomic data and the EAZA Biobank Cryonetwork of institutions with expertise in storing and generating gametes and cell lines will expand the Biobank's role in population management and conservation. Zoological biobanks must now evolve alongside advances in biotechnology and genomics. Sample collection strategies should serve conservation needs and anticipate future applications in genomics, cryobiology, and conservation medicine, linking biospecimens with the wealth of data generated from them. This approach should be scalable beyond EAZA, forming the foundation of a global standardized biobanking framework. Ultimately, zoological biobanks are not merely repositories of the past-they are essential infrastructures shaping the future potential of species conservation.

EAZA↗

Recurrent and niche-specific functional bacteriome of maize hybrid revealed by integrated metabarcoding and culturomics.

The plant microbiome plays a pivotal role in plant survival in natural habitats by facilitating nutrient acquisition, stress adaptation, and disease suppression, while also offering opportunities to enhance crop productivity and climate resilience. However, the distribution of persistent and culturable bacteriome across maize-associated niches and their functional potential remain poorly resolved. This study integrated metagenomic next-generation sequencing (mNGS-based metabarcoding) and culturomics to characterise the maize-associated bacteriome of bulk soil, rhizoplane, phylloplane, and cob of the maize hybrid PHM-1 under contrasting cropping and tillage systems, and to identify recurrent and agriculturally promising bacteriome components. The bacteriome exhibited pronounced niche-specific structuring, whereas overall bacterial community composition did not differ significantly across cropping and tillage treatments (ANOSIM, R&#x2009;=&#x2009;0.038, p&#x2009;=&#x2009;0.306). Proteobacteria predominated in the culturable bacteriome (69-84%; mean, 76.2%) but accounted for only 1% of the total bacteriome, whereas Patescibacteria and Firmicutes were relatively enriched. Niche-specific dominance was evident, with Pantoea accounting for 40.79% of the total and 56.27% of the culturable phylloplane bacteriome under cereal monocropping, while Serratia represented 31.59% and 59.40% of the total and culturable cob bacteriomes, respectively. Across niches, mNGS captured substantially greater bacteriome diversity, particularly uncultured and unidentified taxa in soil-associated compartments, whereas culturomics recovered a narrower but functionally accessible fraction. Culturomics yielded 99 isolates representing 32 species across 12 genera, including six genera shared with the mNGS-derived recurrent bacteriome: Bacillus, Enterobacter, Pantoea, Pseudomonas, Serratia, and Stenotrophomonas. Functional screening identified strong biocontrol and plant-beneficial traits among core-associated isolates. Pseudomonas oryzihabitans ZM-DL-PA10 inhibited Rhizoctonia solani, Macrophomina phaseolina, and Bipolaris maydis by up to 40.6%, 43.9%, and 45.2%, respectively, through secreted and volatile metabolites; exhibited P, K, and Zn solubilisation; and produced IAA and siderophores. It also recorded the lowest B. maydis disease index (ADI) of 1.00. Pantoea ananatis ZM-BH-EA4 showed 52.4% and 68.5% inhibition of R. solani and B. maydis, respectively, through volatile metabolites. Collectively, the integration of mNGS and culturomics revealed a strongly compartmentalised maize bacteriome and identified recurrent, culturable, and functionally promising bacterial taxa, providing a targeted resource for microbiome-based crop protection and climate-resilient maize production.

Zea mays↗

Hybrid genome assembly of&#xa0;Penicillium oxalicum&#xa0;UV4 delineates cryptic secondary metabolite pathways and robust lignocellulolytic potential.

Penicillium oxalicum is a saprophytic fungus well-known for its hydrolytic potential; however, little is known about its metabolic flexibility and secondary metabolite biosynthesis, especially in isolates from underrepresented areas. In this study, we sequenced the genomic DNA of Penicillium oxalicum UV4 using Illumina and Oxford Nanopore platforms, generating a high-quality hybrid genome assembly of 30.28 Mb. The genome features 7,944 predicted genes (7,747 protein-coding sequences and 197 tRNAs) and demonstrates high completeness (99.0% BUSCO). Genomic analysis revealed 40 Biosynthetic Gene Clusters (BGCs), including distant orthologs of the Alternaria phytotoxin ACT-toxin II and the mycotoxin alternariol, as well as a putative clavaric acid-like biosynthetic cluster. Further investigation revealed an expanded CAZyme repertoire comprising 150 secreted proteins, featuring an AA16 lytic polysaccharide monooxygenase and putative multi-domain architectures, such as a pectin methylesterase-polygalacturonase fusion. This comprehensive genomic profiling highlights the dynamic metabolic capacity of P. oxalicum UV4, establishing it as a highly promising candidate for bio-refining studies and the discovery of cryptic bioactive metabolites.

Penicillium↗

Salinimicrobium molybdatiresistens sp. nov., a novel molybdate-resistant and selenite-reducing bacterium isolated from river silt.

Strain TH3T was isolated from the river bottom silt collected in Hengshui, Hebei Province, China. The bacterium is a yellow-pigmented, rod-shaped, Gram-staining negative and aerobic organism. It was able to grow between 10 and 37&#xa0;&#xb0;C (optimum 30&#xa0;&#xb0;C), at pH values from 5.0 to 9.0 (optimum pH 7.0), and tolerated NaCl concentrations ranging from 0 to 13% (w/v, optimum 2%). The 16&#xa0;S rRNA gene sequence of strain TH3T was found to be most closely related to Salinimicrobium sediminilitoris ASW11-47T (99.7%). Nevertheless, genome comparison revealed the relatedness indices below species delineation thresholds: digital DNA-DNA hybridization was 49.7%, and average nucleotide identity was 93.2%, and average amino acid identity was 94.2% compared to Salinimicrobium sediminilitoris ASW11-47T. Strain TH3T had a genome size of 3.7&#xa0;Mb and a DNA G&#x2009;+&#x2009;C content of 41.0%. The major fatty acids observed for strain TH3T (&#x2265;&#x2009;5%) were iso-C14:0, iso-C15:0, anteiso-C15:0, iso-C16:0, iso-C16:0 3-OH, iso-C17:0 3-OH, and summed feature 3. The polar lipid composition included phosphatidylethanolamine, one unidentified phospholipid, two aminolipids, along with five unknown lipids. The sole respiratory quinone in strain TH3T was menaquinone-6. In addition, strain TH3T was highly resistant to molybdate (500 mM) and selenite (20 mM), and could completely reduce 1 mM selenite to red elemental SeNPs within 3 d. Strain TH3T contains several putative selenite-reducing genes, including sodA, serA, serC, cysH, deoC, tktA, and pdhC. Based on polyphasic characterization, strain TH3T was found to be a novel species in the genus Salinimicrobium, and the proposed name is Salinimicrobium molybdatiresistens sp. nov. The type strain is TH3T (=&#x2009;GDMCC 1.3399T&#x2009;=&#x2009;JCM 35713T).

Rivers↗

Characterization of culturable endophytes and microbial communities in the rhizosphere and pitcher fluid of the carnivorous plant Nepenthes khasiana.

Endophytes colonize plant tissues through roots and shoots without causing harm and can move throughout the plant via its vascular system. However, little is known about culturable endophytes, particularly bacteria, in pitcher plants, and their possible entry through pitcher fluid remains unexplored. To address this gap, we isolated endophytes from the pitcher plant Nepenthes khasiana, and performed metagenomic analysis of its rhizospheric soil and pitcher fluid, from which bacteria and fungi were also isolated, to investigate the possible origin of these endophytes. We found that culturable endophytic bacteria were predominantly associated with roots and seeds, whereas endophytic fungi were more abundant across the N. khasiana pitcher. Although most endophytes were restricted to specific tissues, some exhibited a broader distribution across nearly the entire plant. Several OTUs from the rhizospheric soil matched endophytes at the genus level, including some that were also detected in the pitcher fluid. Specifically, three bacterial genera - Enterobacter, Staphylococcus and Bacillus - and one fungal genus, Cladosporium, detected in the pitcher fluid, matched the isolated endophytes. These findings suggest that endophytes in N. khasiana most likely originate from the rhizosphere, with possible migration into the pitcher fluid.

Rhizosphere↗