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PubMed2026

CL16019, A Combination of Cissus quadrangularis and Boswellia serrata Extracts Promotes the Healing of Distal Radius Fractures: A Multicentric, Randomized, Open-Label Study.

OBJECTIVE: Distal radius fracture (DRF) is the most frequent injury to the upper limb. Complications include nonunion, wrist stiffness and instability, local discomfort, and tendon irritation. The purpose of the current open-label clinical study was to evaluate the safety, efficacy, and tolerability of CL16019, an herbal formulation of Cissus quadrangularis and Boswellia serrata extract, in accelerating fracture healing in volunteers with DRFs. METHODS: Fifty participants (both male and female; age: 30-50 years) with type I, IIA, or IIB DRFs (as per Lidstrom classification) were equally randomized and treated with standard treatment (ST) or ST + CL16019 for 60 days. The primary efficacy outcome was the radiographical bone fracture healing rate as scored by the Radius Union Scoring System (RUSS). Pain, swelling, and tenderness were among the clinical characteristics evaluated using the visual analog scale (VAS). Wrist function improvements were assessed using the Patient-Rated Wrist Evaluation Questionnaire (PRWEQ). The intergroup and intragroup results were analyzed using a paired t-test and an analysis of covariance model, respectively. RESULTS: The RUSS scores for the ST and ST + CL16019 groups at the end of the trial were 5.54 ± 1.77 and 7.96 ± 0.20, respectively, with a p-value <0.0001. In addition, the CL16019 volunteers showed substantial (p < 0.05) declines in their VAS and PRWEQ scores. The ST + CL16019 group demonstrated higher Physician Global Assessment and Subject Global Assessment scores. CONCLUSIONS: Supplementation of CL16019 along with standard therapy was found to enhance the bone fracture healing rate, possibly by accelerating the callus formation rate and enhancing cortical bridging. These findings imply that CL16019 might be a good adjunctive in addition to ST for the faster healing of DRFs. The trial was registered with the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2021/12/039006, on December 29, 2021.

Humans↗

PubMed2026

Implementation factors shaping British Columbia's drug decriminalization pilot: A systematic review with narrative synthesis.

BACKGROUND: In January 2023, British Columbia (BC) became the first Canadian province to implement a legally sanctioned drug decriminalization policy, removing criminal penalties for adults possessing 2.5 g or less of opioids, cocaine, methamphetamine, and MDMA. Introduced as a three-year pilot, it aimed to reframe substance use as a public health issue, reduce stigma, and improve health and social service engagement. Criminal penalties were reintroduced for drug possession in most public spaces in May 2024, and the pilot ended in January 2026. Its termination has been interpreted as policy failure; this review aimed to examine how the pilot was implemented in practice and to identify factors that shaped its operationalization and early implementation-relevant outcomes. METHODS: We conducted a systematic review with narrative synthesis of peer-reviewed literature examining implementation-relevant aspects of BC's decriminalization pilot. Six databases were searched (January-February 2026) for studies published May 31, 2022-February 1, 2026. The protocol was registered in PROSPERO (CRD420251271694). RESULTS: Twenty-seven studies were included. Four cross-cutting implementation barriers were identified: pilot design features, public and cross-sector communication gaps, limited frontline training, and insufficient funding and infrastructure. Design features included the 2.5 g possession threshold, misalignment with real-world drug use patterns; the three-year timeframe, which constrained system-level effects; and the May 2024 amendment, which introduced additional instability. The pilot was implemented without commensurate investment in harm reduction, treatment, or housing infrastructure, within already constrained systems. CONCLUSION: BC's decriminalization pilot suggests the effects of legal reform are shaped by implementation context. Early outcomes may reflect design features, institutional readiness, and system capacity rather than legal change alone; longer-term impacts remain uncertain. Future reforms should align legal change with coordinated implementation, operational guidance, public communication, and adequate service infrastructure.

British Columbia↗

PubMed2026

Tigecycline-resistant Staphylococcus in waiting pens of a pig slaughterhouse: genomic insights into a food safety alert.

BACKGROUND: The waiting pens of slaughterhouses represent a critical control point in the 'farm-to-fork' continuum, yet their role in the emergence and dissemination of antimicrobial resistance remains understudied. This study investigated tigecycline-resistant Staphylococcus (TRS) in these high-risk zones to assess their prevalence, resistance mechanisms, and transmission dynamics. METHODS: 400 samples were collected from the waiting pens of a pig slaughterhouse in Guangzhou, China. Antimicrobial susceptibility testing, whole-genome sequencing, phylogenetic analysis, and molecular cloning were employed to characterize resistance mechanisms and transmission patterns. RESULTS: 78 TRS strains were isolated and classified into three species, including S. borealis, S. ureilyticus, and S. pasteuri. These isolates exhibited multidrug-resistant phenotypes and carried new mutations in rpsJ and tet(M), which were functionally confirmed to reduce tigecycline susceptibility. Phylogenetic evidence demonstrated clonal transmission between pig farms and the slaughterhouse. The tet(M) gene was located within Staphylococcal cassette chromosome mec elements mediated by IS257, while tet(L) was carried by plasmids formed through IS256/IS257-mediated recombination. CONCLUSIONS: Waiting pens serve as crucial reservoirs for the amplification and dissemination of antimicrobial resistance. Our findings underscore the urgent need for enhanced biosecurity measures, improved waste management, and routine molecular surveillance in these high-risk zones to mitigate the spread of resistance along the food production chain.

Animals↗

PubMed2026

Safety and efficacy of distal versus conventional radial artery cannulation for invasive blood pressure monitoring: a systematic review and meta-analysis.

To compare the safety and effectiveness of distal radial artery (DRA) versus conventional radial artery (CRA) catheterization for invasive arterial blood pressure monitoring. This meta-analysis followed PRISMA guidelines. Randomized controlled trials published up to December 30, 2025 were systematically searched in PubMed, Embase, Web of Science, the Cochrane Library, CINAHL, CNKI, Wanfang, VIP, and SinoMed. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Meta-analyses were conducted using Review Manager 5.4 and Stata 18.0, and evidence quality was evaluated with the GRADE system. 12 randomized controlled trials (RCTs) involving 1,790 participants were included. For the primary outcomes, compared with CRA, DRA was associated with lower incidences of haematoma (RR = 0.42, 95% CI: 0.24-0.73), catheter blockage (RR = 0.33, 95% CI: 0.14-0.81), and bleeding (RR = 0.25, 95% CI: 0.11-0.59), but a longer catheter insertion time (MD = 26.89, 95% CI: 5.28-48.50). For the secondary outcomes, DRA was associated with a shorter haemostasis time and reduced waveform instability, with no significant differences in first-attempt success rate or pain scores. Subgroup analysis showed a higher first-attempt success rate in patients aged ≤ 65 years (RR = 1.14, 95% CI: 1.02-1.28). DRA catheterization for invasive arterial blood pressure monitoring appears to be associated with fewer complications and more stable arterial waveform acquisition than CRA catheterization, despite a longer insertion time. DRA may represent a feasible alternative in surgical and intensive care settings; however, further high-quality studies are needed to confirm its long-term safety and generalizability.

Humans↗

PubMed2026

Genome-wide characterization of the TGF-β superfamily identifies bmp15, gdf9, and gsdf as sex-biased candidate regulators of gonadal differentiation in the synchronous hermaphrodite Plectropomus leopardus.

The transforming growth factor-β (TGF-β) superfamily plays conserved roles in vertebrate reproduction and gonadal sex differentiation. However, its genomic repertoire and sex-biased expression patterns remain unclear in the leopard coral grouper (Plectropomus leopardus), a species with synchronous hermaphroditism. Here, we performed a genome-wide identification of the TGF-β superfamily, identifying 42 genes from the chromosome-level genome. Phylogenetic and synteny analyses indicated that segmental duplication under purifying selection contributed to family expansion. Expression profiling across multiple tissues and four gonadal developmental stages (undifferentiated, 120 dph; early differentiated, 15 months; mature testis, 3 years; mature ovary, 3 years) identified eight gonad-enriched genes, among which bmp15 and gdf9 exhibited pronounced female-biased expression, with transcripts localized exclusively to the oocyte cytoplasm, particularly in stage II-III oocytes. In contrast, gsdf showed male-biased expression and was localized in spermatogenic cells of the testis. These reciprocal expression patterns indicate that bmp15/gdf9 and gsdf are candidate factors associated with gonadal sex differentiation. Our study provides the first comprehensive characterization of the TGF-β superfamily in P. leopardus and highlights bmp15, gdf9, and gsdf as candidate sex-differentiation factors in this hermaphroditic species.

Animals↗

PubMed2026

A genome-wide coverage-based pipeline for the identification of host-derived candidate DNA biomarkers from cell-free blood.

We have created a new data-analysis pipeline for the discovery of host-specific candidate DNA biomarkers derived from sequencing data of cell-free blood. Unlike approaches that rely on specific molecular or genetic signatures, our method leverages the coverage distribution of cell-free DNA sequences mapped to a reference genome, applying statistical analyses to identify informative short genomic regions for biomarker discovery. The pipeline is applicable to diverse diseases and can be used to analyze cell-free DNA sequences from plasma or serum to identify candidate biomarkers that are characteristic of disease states in mammals. Core functionalities were developed in Java and integrated with open-source software tools for the preprocessing of raw sequencing data, complemented by Python scripts for the machine-learning analysis and statistical validation. The pipeline is designed for HPC use and users can access the pipeline through a Galaxy workflow, which offers a user-friendly web interface for input selection prior to execution and analysis progress monitoring. Performance tests, carried out using duplicate sets of COVID-19 samples and controls, showed linear scalability of execution time with an increasing dataset size, as well as a substantial reduction in execution time through parallelized computation, whereby each HPC node is used to process the data of one chromosome. Further statistical tests confirmed the quality of the pipeline's results by showing that the set of identified candidate biomarkers remained stable across varying dataset sizes.

Biomarkers↗

PubMed2026

Genome-guided stage- and tissue-resolved transcriptome analysis of Serrodes campana identifies sex-biased antennal expression and candidate chemosensory-related genes.

Serrodes campana is an erebid moth of ecological and forestry relevance; its larvae are mainly associated with the soapberry tree, Sapindus mukorossi, whereas adults exhibit fruit-piercing behavior. However, stage- and tissue-resolved transcriptomic resources for this species remain limited. Here, using a chromosome-level reference genome, we performed a genome-guided transcriptome analysis of S. campana based on 12 RNA-seq libraries representing major developmental stages and key adult tissues. Global transcriptomic analyses revealed pronounced transcriptional differentiation across developmental stages and tissue types. Tissue-enriched gene sets and functional enrichment analyses identified distinct molecular signatures associated with developmental, sensory, and pheromone-associated tissues. Comparative analysis of female and male antennae further revealed sex-biased expression of several candidate chemosensory-related genes. Among 153 curated chemosensory-related candidate genes, most odorant receptor genes showed strong antennal enrichment, whereas other major chemosensory gene families displayed broader but still tissue-preferential expression patterns. In addition, an exploratory comparison of female terminal abdominal gland tissue and male terminal abdominal coremata revealed divergent expression profiles and highlighted candidate genes potentially associated with pheromone-related physiology, reproduction, and tissue-specific signaling. Together, this study provides the first genome-guided stage- and tissue-resolved transcriptomic resource for S. campana and offers a useful foundation for future studies of chemosensory detection, sex-biased gene expression, and pheromone-associated biology in this species.

Animals↗

PubMed2026

Reference genome of the Californian trapdoor spider Aptostichus stephencolberti Bond 2008 (Araneae: Mygalomorphae: Euctenizidae).

We present a reference genome assembly for the trapdoor spider Aptostichus stephencolberti. This species, described in 2008, is endemic to the highly fragmented coastal dune habitats of Northern California from Monterey to the San Francisco Bay Area. Trapdoor spiders are ideal taxa for landscape scale genomic studies owing to their extreme site fidelity and limited dispersal capabilities; these same characteristics make them prone to extinction. Genomic studies of species like A. stephencolberti can reveal novel areas of endemism and high conservation value that may not be evident in species with wider ranges and greater dispersal capabilities. As part of the California Conservation Genomics Project, we constructed the A. stephencolberti reference genome from high quality long-read sequences, scaffolded with proximity ligation Omni-C data. The primary assembly comprises 551 scaffolds spanning 3.63 Gbp, a scaffold N50 of 62.2 Mbp and BUSCO completeness of 95.6%. We estimate 52 chromosomes yet find no (TTAGG)n telomer repeats. Expanding the telomeric repeat search finds an ancestral loss of the repeat from all spiders. Automated annotation using the NCBI refseq pipeline and RNAseq data from whole adults finds 14,067 genes with a BUSCO annotation completeness of 95.56%. Repeat annotation identified 77% of the genome to be interspersed repeats. This resource, the first for family Euctenizidae will facilitate future study and resulting conservation actions of A. stephencolberti and other Aptostichus sp. populations associated with the rapidly changing California coastal dune ecosystem.

Aptostichus stephencolberti↗

PubMed2026

Outcomes of stereotactic radiosurgery for spine multiple myeloma-a systematic review.

Spinal involvement in multiple myeloma (MM) commonly results in pain, vertebral instability, epidural spinal cord compression, and neurological deficits. Although conventional external beam radiation therapy (EBRT) remains the standard radiation modality because of the radiosensitive nature of MM, stereotactic radiosurgery (SRS) has emerged as a highly conformal treatment option capable of delivering focal high-dose radiation while sparing adjacent spinal cord structures and uninvolved bone marrow. This systematic review evaluated the clinical outcomes and safety profile of SRS for spinal MM. A systematic review of the literature was performed to identify studies evaluating SRS for spinal MM. Extracted variables included patient demographics, tumor characteristics, treatment parameters, radiographic outcomes, pain response, neurological outcomes, local control, overall survival, and adverse events. Three retrospective studies comprising 133 patients and 181 treated spinal lesions met the inclusion criteria. Median patient age ranged from 59 to 65 years, with a slight male predominance across studies. Thoracic spine lesions represented the most treated region (55.5-67.7%). Median prescribed SRS dose was 14-16 Gy, predominantly delivered in a single fraction. Median follow-up ranged from 11.2 to 27.8 months. Local control rates ranged from 89.4 to 100%, with 6- and 12-month local control rates of 94% and 91%, respectively, in one study. Pain improvement was reported in 41-88% of treated patients/sites, with a median time to pain relief of 1.6 months in one cohort. Neurological improvement occurred in 56-71.4% of patients with preexisting deficits. Reported adverse events included vertebral compression fractures, fracture progression, pain flare, and tracheoesophageal fistula. De novo vertebral fractures ranged from 3.6 to 7%, while fracture progression ranged from 14 to 18%. SRS appears to provide excellent local control and meaningful pain and neurological improvement in patients with spinal MM, with acceptable toxicity profiles. The highly conformal nature of SRS may preserve uninvolved bone marrow and facilitate continuation of systemic therapy. However, the current evidence is limited to small retrospective studies with heterogeneous reporting, and further prospective comparative studies are needed to better define the role of SRS relative to conventional EBRT in spinal MM.

Humans↗

PubMed2026

Systematic modular engineering of genome-integrated Escherichia coli MG1655 for high-level 2'-fucosyllactose production.

2'-Fucosyllactose (2'-FL), the most abundant human milk oligosaccharide (HMO), has attracted considerable interest for its prebiotic and immunomodulatory functions, with broad applications in infant nutrition. In this study, we report the development of a high-yield, genome-integrated 2'-FL-producing strain based on Escherichia coli MG1655 through systematic modular optimization. Starting from a single-copy BKHT strain (MGC06), we first optimized the copy number of the α-1,2-fucosyltransferase (α-1,2-FT) gene BKHT. Subsequently, the GDP-L-fucose supply was enhanced through coordinated genomic integration of the gene clusters cpsG-cpsB and gmd-fcl, while the multidrug efflux transporter gene mdfA was integrated to improve product export and strain robustness. BKHT copy number was then re-evaluated in the optimized background, with four copies yielding the highest production. The final engineered strain, harboring all genetic modifications stably integrated into the chromosome, produced 17.18 g/L 2'-FL in shake-flask culture. In fed-batch fermentation using a 5-L bioreactor, this strain achieved a titer of 154.12 g/L after 60 h, with a productivity of 2.57 g/L/h. Notably, throughout the entire fermentation process, no antibiotics or inducers were supplemented, underscoring the genetic stability and regulatory compliance of this plasmid-free system. To our knowledge, this represents the highest 2'-FL titer reported to date, positioning our engineered strain as a promising candidate for commercial 2'-FL production.

Escherichia coli↗

PubMed2026

Contrasting redox-related physiological responses associated with HaGATA23 and HaGATA36 during Orobanche cumana parasitism in sunflower (Helianthus annuus L.).

Helianthus annuus is an economically important Asteraceae species used for seed oil production and ornamental purposes, but its production is seriously affected by the root-parasitic plant Orobanche cumana. GATA transcription factors are zinc-finger DNA-binding regulators involved in plant development and stress adaptation. However, the molecular characteristics of GATA transcription factors in Helianthus annuus and their contribution to Helianthus annuus -Orobanche cumana interaction remain poorly understood. Here, 36 HaGATA members were retrieved from the Helianthus annuus genome and classified into four phylogenetic clades. Chromosomal placement, collinearity, gene structure, motif composition, and promoter elements varied among the 36 HaGATA members, indicating evolutionary conservation coupled with functional diversification. Expression analysis and RT-qPCR analyses revealed differential expression patterns among HaGATA genes under O. cumana stress, with HaGATA23 markedly downregulated and HaGATA36 strongly upregulated. Overexpression of HaGATA23 was associated with increased malondialdehyde (MDA) accumulation and unfavorable changes in antioxidant enzyme activities, whereas its silencing showed the opposite physiological tendency. In contrast, overexpression of HaGATA36 reduced malondialdehyde accumulation, increased peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activities, while its silencing showed the reverse tendency. These results indicate that HaGATA23 and HaGATA36 are candidate genes associated with contrasting redox-related physiological responses during O. cumana stress. This work provides evidence that GATA transcription factors are associated with redox-related physiological responses in sunflower under O. cumana treatment and identifies HaGATA23 and HaGATA36 as functionally divergent candidate genes for further validation.

Helianthus↗

PubMed2026

Genome-wide identification of the HSP70 superfamily in tropical sea cucumber Stichopus monotuberculatus and their expression analysis under low-salinity stress.

Heat shock proteins (HSPs) are a group of evolutionarily conserved molecular chaperones that serve as indispensable core regulators in preserving cellular homeostasis and orchestrating organismal stress responses. The tropical sea cucumber Stichopus monotuberculatus, a high-value aquaculture species, is sensitive to fluctuations in environmental salinity-a challenge that has emerged as a critical bottleneck limiting its large-scale commercial cultivation. However, no systematic investigation has been conducted to characterize the HSP70 superfamily in S. monotuberculatus and elucidate its functional roles in salinity adaptation. In the present study, we performed a comprehensive genome-wide scan and identified 19 HSP70 superfamily genes in the S. monotuberculatus genome, with the HSP70IV subfamily showing remarkable gene expansion, containing 8 distinct copies. Phylogenetic analysis, conserved motif identification, and gene structure characterization demonstrated high evolutionary conservation within each HSP subfamily. These genes were unevenly distributed across the chromosomes of S. monotuberculatus, and prediction of cis-acting elements revealed that their upstream regulatory regions were enriched with numerous functional elements associated with stress response and immune regulation. Salinity stress experiments revealed that under severe low-salinity conditions (18‰), the expression levels of SmHSPA14L and multiple HSP70IV subfamily members were significantly elevated, while SmHYOU1D was significantly downregulated; in contrast, only subtle changes were detected in the expression of most HSP70 genes under moderate low-salinity stress (24‰). These findings strongly suggest that HSP70 genes, particularly the expanded HSP70IV subfamily, may act as key modulators in the low-salinity stress response. This work provides valuable insight into the molecular mechanisms underlying salinity adaptation in tropical sea cucumbers.

Animals↗

PubMed2026

Oblique Lateral Interbody Fusion With Lateral Vertebral Screw Fixation Versus Transforaminal Lumbar Interbody Fusion for Severe Lumbar Stenosis: Results of a Multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: The benefits of oblique lateral interbody fusion (OLIF) vs transforaminal lumbar interbody fusion (TLIF) in severe lumbar stenosis (Schizas C/D) remain uncertain. This randomized trial compared clinical, radiographic, and safety outcomes of OLIF and TLIF. METHODS: From November 2018 to December 2021, a prospective, multicenter, randomized controlled trial enrolled 260 adults with single-level severe stenosis and instability. In total, 224 patients were randomized to OLIF or TLIF. Prespecified outcomes followed consolidated standards of reporting trials. Primary outcomes were visual analog scale back/leg pain and Oswestry Disability Index (ODI), with minimal clinically important difference thresholds of ODI ≥12-13 points or ≥30% improvement, and visual analog scale ≥1.5-2.0 points. Radiographic measures included disc height, lumbar and segmental lordosis, and canal cross-sectional area (CSA). Complications were recorded. Ethics approval was obtained from the institutional review board, the trial was registered with ISRCTN.com , and all patients provided written informed consent. RESULTS: In total, 224 patients were randomized, 5 were lost to follow-up (TLIF n = 2, OLIF n = 3). Baseline features were comparable. OLIF was associated with shorter operative time, less blood loss, earlier ambulation, and shorter hospital stay (all P < .05). Both groups achieved significant, clinically meaningful improvements. OLIF showed greater back pain reduction at 3-6 months and 2 years ( P < .05) and superior ODI improvement at 3 and 6 months ( P < .001), although long-term ODI scores were similar. Radiographically, OLIF provided greater restoration of disc height and segmental lordosis (all P < .001) and demonstrated progressive CSA increase (dynamic decompression), whereas TLIF achieved immediate, sustained CSA enlargement. Fusion rates were comparable at 1-2 years. Complication rates were low and similar (7.3% TLIF vs 5.5% OLIF), with most OLIF-specific events transient. CONCLUSION: Both OLIF and TLIF yield improvements in severe lumbar stenosis. OLIF offers perioperative advantages, earlier functional recovery, radiographic restoration, and dynamic canal remodeling, supporting its role as an equivalent alternative for lumbar spinal stenosis with some secondary advantages.

Humans↗

PubMed2026

Surgical management of esophageal atresia with tracheoesophageal fistula in extremely low birth weight neonates: A systematic review.

BACKGROUND: Surgical management of esophageal atresia/tracheoesophageal fistula (EA/TEF) in extremely low birth weight (ELBW) neonates remains challenging and controversial. This study systematically reviews surgical strategies and outcomes in this population. METHODS: Following PRISMA guidelines, Cochrane, Embase, MEDLINE, Scopus, and Web of Science (2004-2024) were searched in February 2025 for studies on surgical management of ELBW neonates with EA/TEF (PROSPERO CRD42025636228). Fatal chromosomal abnormalities were excluded. Demographics, comorbidities, surgical techniques, and complications were analyzed descriptively. Risk of bias was assessed. RESULTS: Eleven publications (five case reports and six case series) comprising 30 patients (Gross type B/C = 1/29) met the eligibility criteria. Mean gestational age was 28.1 (23-34) weeks, and mean birth weight was 760.4 (422-995) g. Twelve primary repairs (PR) and 18 delayed primary repairs (DPR) were performed, including staged repair (n = 11), lower esophageal banding (n = 4), and other techniques (n = 3). Postoperatively, four anastomotic leaks were managed conservatively, six strictures and one recurrent TEF required endoscopic intervention, three fundoplications and two aortopexies were reported (follow-up: 1-198 months, n = 19). Overall mortality was 30% (PR: 8.3%; DPR: 44.4%). Mortality was 60% among neonates with major congenital heart defects (CHD) and 40% among those with VACTERL association. EA/TEF-related complications contributed to 33.3% of deaths. CONCLUSIONS: Mortality in this cohort remains high, particularly with major CHD, and is largely unrelated to EA/TEF-specific complications. In selected cases, PR appears feasible as an alternative to DPR, although conclusions are limited by the small sample size and heterogeneous studies.

Humans↗

PubMed2026

Genome-wide characterisation of the myosin light chain gene family in Chinese perch (Siniperca chuatsi) and its expression patterns in muscle fibre types and injury response.

The Class II myosin light chain (myl) genes in Chinese perch (Siniperca chuatsi) have not yet been systematically characterised, and relationships with muscle fibre specification, development, and injury-associated remodelling remain unclear. In this study, fast and slow muscle fibres were initially distinguished using myofibrillar ATPase histochemistry. Subsequently, genome-wide mining identified 16 Class II myl genes, comprising eight essential and eight regulatory light-chain subunits. Their conserved-domain features, chromosomal distribution, phylogenetic relationships and expression profiles were analysed. Transcriptomic profiling showed that summed myl transcript abundance was higher in fast muscle than in slow muscle, accounting for 67.2% of the pooled myl transcript pool across the two muscle types (paired t-test, raw P = 0.036). mylpfa, myl1 and mylz3 were the major fast-muscle-associated genes, whereas myl10, myl2b and myl13 were preferentially expressed in slow muscle at the transcript level. These patterns support these genes as candidate fibre-type-associated expression markers. Developmental profiling identified stage-associated myl expression patterns, including a possible expression shift between mylpfb and mylpfa. In the descriptive injury-repair time course (d0-d7), FPKM profiles indicated that fast-muscle-associated genes (mylpfa, mylz3 and myl1) were lower at d1 and recovered by d3, whereas several slow-muscle-associated genes showed biphasic transcript-level increases. The slow-muscle-associated RLC gene mylpfb showed a delayed expression peak at d7. Notably, the embryonic isoform myl6l showed a modest increase from approximately 2 FPKM at d0 to 4-5 FPKM after injury, suggesting a possible injury-associated expression pattern that requires further validation. Together, these findings provide a genome-wide description of the Chinese perch myl gene family and identify candidate fibre-type-associated genes and descriptive injury-associated isoform expression patterns.

Animals↗

PubMed2026

Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).

BACKGROUNDDespite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.METHODSTo better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).RESULTSOur study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.CONCLUSIONRD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT00861705.FUNDINGNIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.

Humans↗

PubMed2026

The impact of an intact rotator cuff on the outcomes of reverse shoulder arthroplasty: a meta-analysis of 20,924 patients.

BACKGROUND: While reverse shoulder arthroplasty (rTSA) is commonly utilized for rotator cuff tear arthropathy, indications have expanded to include, primary glenohumeral osteoarthritis (GHOA) with intact cuff. The presence of an intact cuff may influence outcomes after rTSA because preserved cuff musculature can contribute to shoulder stability and force which could potentially improve postoperative function and reduce complication rates. However, studies have reported contradictory results on whether or not an intact cuff would provide better outcomes in patients receiving an rTSA. METHODS: This is a systematic review and Meta-analysis performed according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Cochrane, Embase, and Google Scholar (pages 1-20) were queried through December 2025. Inclusion criteria consisted of studies comparing the outcomes of rTSA based on whether patients had a diagnosis of GHOA with intact cuff, or had a deficient rotator cuff (ie had a diagnosis of rotator cuff tears without OA, or cuff tear arthropathy). Extracted data included adverse events, improvement in patient reported outcome measures, and improvement in range of motion. RESULTS: Eleven retrospective articles and 1 prospective article met the inclusion criteria with 4,542 in the GHOA with intact cuff group and 16,382 in the cuff-deficient group (cuff tear arthropathy: 15,423 patients; rotator cuff tear: 959 patients). Patients undergoing rTSA for GHOA and intact cuff had a lower rate of revisions (odds ratio [OR] = 0.53; 95% CI: 0.41- 0.68, P < .001; I2 = 0%), overall complications (OR = 0.57; 95% CI: 0.46-0.71, P < .001; I2 = 0%), acromial stress fracture (OR = 0.22; 95% CI: 0.08- 0.59, P = .003; I2 = 0%), infection (OR = 0.43; 95% CI: 0.26- 0.73, P = .002; I2 = 37%), and instability (OR = 0.60; 95% CI: 0.40- 0.90, P = .01; I2 = 0%). In addition, GHOA patients had a better improvement in both American Shoulder and Elbow Surgeons scores (mean difference = 7.17; 95% CI: 2.13- 12.21, P = .005; I2 = 81%) without exceeding the minimal clinically important difference, and external rotation (mean difference = 12.00°; 95% CI: 9.63- 14.37, P < .001; I2 = 38%). CONCLUSION: Rotator cuff-deficient patients undergoing rTSA have a higher risk of postoperative complications compared to patients undergoing rTSA for GHOA with an intact cuff. They also showed less improvement in American Shoulder and Elbow Surgeons scores and external rotation. However, the clinical significance of these differences should be interpreted with caution, as not all improvements exceeded established thresholds for clinical importance.

Humans↗

PubMed2026

Genetic mutations driving ciprofloxacin resistance in laboratory-evolved Salmonella Typhimurium.

Ciprofloxacin resistance in Salmonella Typhimurium is a significant public health concern, and the mechanisms by which the resistance evolves are poorly defined. Here, by serial passaging under antibiotic selection, we isolated ciprofloxacin-resistant S. Typhimurium mutants and subjected them to whole-genome sequencing to reveal the major mutations associated with resistance. The Low CipR mutant acquired four chromosomal mutations in ramR, icdA, lipB, and gyrA, and the High CipR mutant gained additional mutations in gyrB, yaiC, and corA. Functional characterization determined that mutations in ramR resulted in efflux pump upregulation, while disruptions in the TCA cycle caused by mutations in icdA and lipB led to metabolic alterations. These changes indirectly enhanced resistance by increasing the expression of the global regulator MarA and reducing OmpF-dependent membrane permeability. Despite the observation of the G105A substitution in GyrA, enzymatic assays confirmed the failure to support resistance to ciprofloxacin, possibly because the structural alteration remained minimal. GyrB488-489dup was associated with maintained supercoiling under ciprofloxacin and enhanced fluoroquinolone resistance, suggesting a major role in resistance evolution. Other mutations in yaiC impaired biofilm and, in corA, intracellular accumulation of magnesium, possibly stabilizing the bacterial cell envelope under antibiotic pressure. The findings provide novel explanations for the multifaceted mechanisms leading to ciprofloxacin resistance in Salmonella and suggest targets to combat antimicrobial resistance.IMPORTANCEAntibiotic resistance in Salmonella Typhimurium is an increasing public health concern, yet the genetic changes that allow bacteria to become resistant are not fully understood. In this study, we evolved ciprofloxacin-resistant Salmonella in the laboratory and identified the mutations that arise during resistance development. We found that resistance does not result from a single change but from multiple adaptations affecting drug efflux, metabolism, and the antibiotic target. Some mutations increased the activity of pumps that remove antibiotics from the cell, while others altered bacterial metabolism and reduced membrane permeability, making it harder for the drug to enter. A duplication in the DNA gyrase subunit GyrB played a particularly important role in maintaining DNA function under antibiotic stress. Together, these results reveal how diverse genetic changes cooperate to generate ciprofloxacin resistance and provide insights that may help guide strategies to combat drug-resistant Salmonella infections.

DNA gyrase↗