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Enhanced fracture detection on radiographs with AI assistance for clinicians: a systematic review and meta-analysis.

BACKGROUND: Emergency radiographic interpretation for fractures is prone to missed or misdiagnoses. Artificial intelligence (AI) is expected to become a powerful tool to assist clinicians in fracture detection. PURPOSE: A systematic review and meta-analysis was performed to assess whether AI improves clinicians' ability to detect fractures on radiographs. MATERIALS AND METHODS: A literature search was conducted in PubMed, Web of Science, and Cochrane Library for studies published between January 1, 2010, and October 10, 2025. A meta-analysis of diagnostic accuracy studies was performed using a Summary Receiver Operating Characteristic (SROC) curve. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Subgroup analysis and meta-regression were conducted to explore potential sources of heterogeneity. RESULTS: A total of 26 studies were included . The pooled sensitivity of clinicians increased from 77% (95% CI: 72-81) to 87% (95% CI: 83-90) with AI assistance, while the pooled specificity improved from 88% (95% CI: 85-90) to 92% (95% CI: 89-94). The corresponding AUC values were 0.90 (95% CI: 0.87-0.92) before and 0.95 (95% CI: 0.93-0.97) after AI assistance. Eight studies were rated as high risk of bias. Subgroup analysis and meta-regression identified potential sources of heterogeneity, including fracture location, AI model type, high risk of bias, and reference standards. CONCLUSION: AI assistance significantly improves clinicians' diagnostic performance in detecting fractures on radiographs for extremity and trunk fractures.

Humans

Effectiveness of Topical Huzhang Sanhuang with Standard Nursing for Chemotherapy-Induced Phlebitis: Randomized Controlled Study.

Chemotherapy-induced phlebitis (CIP) is a common complication of peripheral intravenous chemotherapy that can cause pain, local inflammation, treatment interruption, and diminished quality of life. This randomized controlled trial evaluated the efficacy and safety of the topical Huzhang Sanhuang (HZSH) formula, combined with standard nursing care, in managing CIP. Ninety-four hospitalized patients with CIP (grade I or higher) were randomly assigned in a 1:1 ratio to receive either topical HZSH formula plus standard nursing care (experimental group, n = 47) or 50% magnesium sulfate wet dressing plus standard nursing care (control group, n = 47) for 14 days. Prespecified outcomes included phlebitis grade, visual analog scale (VAS) pain score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), symptom resolution time, and safety indicators. By Day 14, patients in the experimental group demonstrated significantly greater improvement in phlebitis severity than those in the control group (risk ratio for grade &#x2265; II, 0.42; 95% confidence interval, 0.20-0.87; P = 0.012). The experimental group also showed significantly larger reductions in VAS pain scores, hs-CRP levels, and IL-6 concentrations (all P < 0.01). Kaplan-Meier analysis further demonstrated faster resolution of multiple local symptoms in the experimental group. Treatment adherence was high in both groups, and no serious adverse events or major safety concerns were observed. These findings indicate that the topical HZSH formula, combined with standard nursing care, is a safe and effective integrative nursing intervention that accelerates clinical recovery, alleviates local symptoms, and reduces the inflammatory burden in patients with chemotherapy-induced phlebitis.

Humans

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&#x2030;), 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&#x2030;). 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

Left ventricular hypertrophy in hypertension: a systematic review and meta-analysis of echocardiographic studies published from 2011 to 2025.

AIM: An updated meta-analysis targeting the prevalence of left ventricular hypertrophy (LVH), a cardinal marker of hypertensive heart disease (HHD), over the last 15&#x200a;years is lacking. Thus, we analyzed the literature in order to provide a comprehensive information on LVH prevalence, as assessed by echocardiography, in the hypertensive setting. METHODS: The PubMed, OVID-MEDLINE, and Cochrane Library databases were analyzed to search English-language articles published from 1 January 2011 up to 31 December 2025. Studies were identified by using MeSH terms and crossing the following search items: 'left ventricular hypertrophy', 'left ventricular mass', 'hypertensive heart disease', 'echocardiography', 'hypertension', and 'subclinical cardiac damage'. RESULTS: A total of 51 studies including 74&#x200a;632 hypertensive patients were considered. Overall, the prevalence of LVH in the pooled cohort, defined according to criteria recommended by echocardiographic guidelines, was 36.6% (95% CI: 33.4-40%). Data provided by 18 studies ( n &#x200a;=&#x200a;40&#x200a;108 patients) showed that the probability of having LVH was lower in men than in women (OR&#x200a;=&#x200a;0.62, CI: 0.48-0.80, P &#x200a;<&#x200a;0.0001). Among patients with LVH (17 studies), the risk of concentric LVH was almost twice as high as eccentric (OR&#x200a;=&#x200a;1.94, CI: 1.52-2.49, P &#x200a;<&#x200a;0.0001). CONCLUSION: Our meta-analysis suggests that the high contemporary prevalence of LVH reflects the failure of therapeutic strategies worldwide in the prevention and treatment of HHD. From a clinical perspective, these data imply the need for a more aggressive treatment of hypertension and related cardiovascular risk factors leading to LVH, especially in women.

Humans

Integrated single-cell and bulk transcriptomic analysis identifies a novel senescent fibroblast subtype associated with poor prognosis in acral melanoma.

BACKGROUND: Acral melanoma (AM) exhibits significant intratumoral heterogeneity, but its tumor microenvironment (TME) and immune regulation remain unclear. This study aims to dissect TME heterogeneity and establish a prognostic model based on key cell subpopulations. METHODS: We collected AM single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Unsupervised clustering, CellChat, and Scissor analysis were performed to characterize cellular heterogeneity, cell-cell communication, and prognosis-related cell subpopulations. Kaplan-Meier analysis was used to assess the prognostic value of key genes, which were further validated by multiplex immunohistochemistry (mIHC). RESULTS: In AM, Mel_C2, C7, and C9 with high SEMA6A and KIT expression were strongly linked to poor prognosis. We further identified a senescent fibroblast subpopulation (sCAF_CDKN2A) characterized by high fibroblast senescence signature (FSS) scores. Integrating Scissor analysis of fibroblast subtypes with bulk prognostic data, we identified COL3A1, VCAN, and KIT as prognosis-associated genes upregulated in poor-outcome-related fibroblast subsets. Cell-cell communication analysis revealed that sCAF_CDKN2A engages in an immunosuppressive network, interacting with regulatory T cells (Tregs) via MIF signaling and receiving signals from exhausted CD8+ T cells through PPIA-BSG interactions. Using transcription factor expression patterns from these fibroblast subtypes, we constructed a prognostic model that effectively stratified patients into distinct risk groups with significant differences in overall survival (OS). mIHC confirmed significantly higher protein levels of SEMA6A and COL3A1 in tumor tissues compared to matched normal tissues. CONCLUSIONS: We established a novel prognostic model for AM and identified sCAF_CDKN2A as an immunosuppressive senescent fibroblast subpopulation driving poor prognosis.

Acral melanoma

Response-optimised training improves learning of a complex motor task and closely related motor tasks.

Regular physical exercise is essential for promoting healthy aging and longevity. In older adults with varying physical and cognitive decline, optimising exercise interventions is crucial to maximise benefits. A promising approach to achieve this goal is by adjusting task demands to individual abilities in turn preventing over- or underloading their abilities. In the field of motor learning, it is currently unclear whether such an optimised training improves not only performance on the trained task but also transfers to untrained motor and cognitive tasks. We conducted a randomized, single-blinded, 6-week dynamic balance training (DBT) with healthy older adults (n&#xa0;=&#xa0;30). Training was tailored to individual balance ability. Participants were assigned to either suboptimal (high or low difficulty) or optimal (moderate difficulty) training groups. Transfer effects were assessed via cognitive tasks (memory and executive) and motor tasks (untrained DBT variations and other balance tasks) measured pre-, mid- and post-intervention. Multivariate longitudinal statistical analysis showed higher performance gains in the optimal training group in three out of six sessions compared to the suboptimal groups, especially under testing conditions with high task demands. The optimal group also showed greater improvements in near motor transfer tasks mid- and post-intervention, while no significant differences were observed in the cognitive tasks. Within-group DBT learning positively correlated with transfer gains, highlighting the role of training response in achieving transfer. In conclusion, optimised task difficulty in balance training enhances both task-specific performance and related motor skills, supporting the use of personalised interventions to maintain function and independence in older adults.

Humans

Routine methods misidentify Serratia spp.: Limitations of MALDI-TOF MS revealed by whole-genome sequencing.

Accurate species-level identification within the genus Serratia remains challenging due to extensive phenotypic overlap and high genomic relatedness among closely related and recently described taxa. This study presents an evaluation of routine and genome-based identification approaches applied to clinical Serratia isolates, integrating phenotypic assays, MALDI-TOF MS (Bruker Daltonics), 16S rRNA gene sequencing, and Whole-Genome Sequencing (WGS). A total of 103 isolates collected from a teaching hospital were analyzed. WGS was performed on a subset of isolates. Conventional biochemical methods classified all isolates as Serratia marcescens, whereas MALDI-TOF MS identified 60.1% as S. marcescens, 11.6% as S. ureilytica, and 28.1% just at the genus level. Peak analysis from MALDI-TOF MS revealed specific peaks associated with S. marcescens and S. ureilytica, but limited discriminatory power. WGS of six isolates initially identified as S. ureilytica by MALDI-TOF MS revealed reclassification as Serratia sarumanii (n = 5) and Serratia montpellierensis (n = 1), supported by Average Nucleotide Identity (ANI), Average Amino Acid Identity (AAI), and Digital DNA-DNA Hybridization (dDDH) thresholds. In contrast, 16S rRNA analysis showed limited species-level resolution. Phylogenomic and SNP-based analyses confirmed these classifications with strong support. Overall, this study underscores the critical role of high-resolution genomic approaches for precise species identification and highlights the need for continuous expansion and curation of MALDI-TOF MS reference databases to support reliable clinical diagnostics and epidemiological surveillance of emerging Serratia species.

Spectrometry, Mass, Matrix-Assisted Laser Desorpti

Comparative effectiveness and safety of pharmacological interventions for sleep outcomes in chronic non-cancer pain: a systematic review and network meta-analysis.

Sleep disturbances are highly prevalent among individuals with chronic non-cancer pain and are associated with worse pain severity and poorer prognosis. The comparative trade-offs between the effectiveness and safety of available pharmacotherapies for sleep outcomes in this population remain poorly defined. Ninety-eight RCTs involving 28,920 participants (mean age 53.2 years, 71.2% female) were included. Moderate-certainty evidence demonstrated that melatonin significantly improved sleep quality compared with placebo (standardized mean difference [SMD]&#x202f;=&#x202f;-0.60, 95%CI: -0.98, -0.22). Ten agents (e.g., amitriptyline, oxycodone, gabapentin, pregabalin, duloxetine) also showed statistically significant improvements in subjective sleep quality (SMD&#x202f;=&#x202f;-0.24 to -1.07), but most effects were supported by low-certainty evidence and were accompanied by an increased risk of adverse events (odds ratio [OR]&#x202f;=&#x202f;1.90 to 37.00). Conversely, melatonin was not associated with an increased risk (OR&#x202f;=&#x202f;0.88, 95%CI: 0.19, 3.94). Our findings indicate that melatonin shows promise as a safe, adjunctive option for improving sleep quality in this population, but larger, condition-specific trials are warranted to confirm these effects. Other pharmacological agents are limited by lower-certainty and unfavorable safety profiles. These results should be interpreted cautiously given limited direct comparisons, heterogeneous chronic pain populations, the high proportion of trials at high risk of bias, and the predominance of subjective sleep outcomes.

Humans

A novel urease-producing strain effectively induces cadmium biomineralization under low-temperature stress.

Microbially induced carbonate precipitation (MICP) has been widely used to immobilize Cadmium (Cd) in contaminated soils in mining-affected regions. However, its remediation efficacy under low-temperature stress, as well as the nucleation process that regulates Cd biomineralization via carbonate precipitation by psychrophilic bacteria, has yet to be investigated. Here, we isolated Pseudomonas sp. J-6, a novel urease-producing strain from tailings in high-altitude cold regions, exhibiting unparalleled cold adaptability at 5 &#xb0;C and achieving 95.85 % Cd removal efficiency by MICP at 10 &#xb0;C. Furthermore, the coprecipitation process of Ca1-xCdxCO3 was clarified through the continuous observation of the precipitates after the low-temperature MICP reaction. The crystal morphology transitioned from loose vaterite in the early stage to a dense square-block morphology in the middle stage. Cd2+ progressively shifted from a surface-bound state to lattice incorporation, ultimately resulting in the formation of stable Cd-substituted calcite crystals. In this process, low temperatures led to the formation of larger, highly ordered Cd-substituted calcite crystals, thereby strengthening Cd sequestration and its long-term stability. In addition, under low-temperature stress, Pseudomonas sp. J-6 induced MICP reaction decreased the bioavailable Cd in alpine slag soil by 44.85 % and enhanced physical properties. In the freeze-thaw cycles, the remediation efficiency remained stable. This study clarified the biomineralization potential in high-altitude cryogenic environments and the nucleation process of Cd biomineralization by psychrophilic bacteria-induced carbonate precipitation, filling a critical research gap in its application under extreme conditions and highlighting its promise for sustainable remediation of heavy metal pollution under low-temperature stress.

Cadmium

Haemodialysis Nurses' Self-Reported Cultural Competence and Responsiveness: A Cross-Sectional Survey.

BACKGROUND: People receiving in-centre haemodialysis have distinct cultural care needs and preferences, and nurses are expected to respond to these. However, haemodialysis nurses' cultural competence and responsiveness are unknown. OBJECTIVES: To examine nurses' cultural competence and responsiveness when caring for people with diverse cultural characteristics. DESIGN: An online cross-sectional survey. PARTICIPANTS: Haemodialysis nurses from Australia and New Zealand (n&#x2009;=&#x2009;123), recruited through the Renal Society of Australasia and professional networks. MEASUREMENTS: The 25-item Cultural Competence Assessment instrument measured cultural awareness and sensitivity, and culturally responsive behaviours. Demographic characteristics were also collected. RESULTS: Of 123 complete responses, overall cultural competence was high (M&#x2009;=&#x2009;5.09, SD&#x2009;=&#x2009;0.76), particularly awareness and sensitivity (M&#x2009;=&#x2009;5.76, SD&#x2009;=&#x2009;0.53), with significantly higher scores among those who had completed cultural awareness training (p&#x2009;=&#x2009;0.009). In contrast, culturally responsive behaviours were moderate (M&#x2009;=&#x2009;4.53, SD&#x2009;=&#x2009;1.23), highlighting the gap between cultural competence and responsiveness. The lowest scoring areas were documentation of patients' cultural needs (M&#x2009;=&#x2009;3.88, SD&#x2009;=&#x2009;2.02) and access to cultural learning resources (M&#x2009;=&#x2009;3.02, SD&#x2009;=&#x2009;1.75), indicating limited supports. Qualitative findings reflected practices of culture care preservation and accommodation, with themes of cultural awareness and language differences highlighting barriers related to language and resources. CONCLUSIONS: High cultural competence does not necessarily translate into culturally responsive behaviour. Organisational supports, including guidance for documenting cultural needs, cultural assessment tools and accessible learning resources, may help strengthen culturally responsive haemodialysis care.

Humans

Genomic and Molecular Interaction Analysis of NodD1 in a Novel Bradyrhizobium yuanmingense sp. B64 Isolate for Nodulation and Symbiosis of Legume Plants.

Rhizobial bacteria are known for their ability to fix nitrogen for leguminous plants and their essential function for sustainable agriculture. This study characterizes the taxonomic status and functional potential of the Bradyrhizobium B64 isolate using integrated genomic and molecular approaches. The whole genome of the B64 isolate was sequenced via Illumina paired-end technology. Species delimitation was performed using average nucleotide identity (ANI) and digital DNA-DNA Hybridization (dDDH). The NodD1 protein structure was modeled using AlphaFold3 and validated by Ramachandran plot analysis. Molecular docking was then conducted to evaluate interactions between NodD1 and four signaling flavonoids: Apigenin, Daidzein, Genistein, and Naringenin. Genomic analysis revealed a maximum ANI of 94.4% and dDDH values between 51.4 and 62.4%. Since these values fall below the standard prokaryotic thresholds (ANI&#x2009;<&#x2009;95%; dDDH&#x2009;<&#x2009;70%), the B64 isolate is identified as a novel species. Physiological assays confirmed nitrogen fixation (1.97 ppm), IAA production (3.67 ppm), and phosphate solubilization (26.10 ppm). Structural validation showed 100% of NodD1 residues in allowed regions, ensuring high model reliability. Docking simulations demonstrated strong binding affinities across all flavonoids, with binding free energies ranging from -&#x2009;8.8 to -&#x2009;9.0&#xa0;kcal/mol. Daidzein exhibited the highest thermodynamic stability (-&#x2009;9.0&#xa0;kcal/mol), whereas apigenin showed the most extensive residue interaction network. The B64 isolate is a novel Bradyrhizobium species with a high symbiotic capacity. The stable NodD1-flavonoid interactions provide a molecular basis for efficient nodulation, positioning B64 as a promising candidate for developing lipo-chitooligosaccharide (LCO)-based biofertilizers.

Bradyrhizobium

Effectiveness of peer recovery support services for substance use disorders: A systematic review of healthcare utilization, behavioral health, and engagement outcomes.

BACKGROUND: Peer recovery support services (PRS) delivered by individuals with lived experience of substance use, are increasingly incorporated into substance use disorder (SUD) care systems to improve care engagement, reduce acute care use, and support recovery. However, existing systematic reviews have focused on substance use outcomes, with limited attention to healthcare utilization, psychosocial functioning, and outcomes across settings, and populations. METHODS: This systematic review, registered in PROSPERO (CRD42023469279), synthesized peer-reviewed studies from 2003 to 2026 evaluating PRS for individuals with alcohol or drug-related SUD. Using MEDLINE, Embase, PsycINFO, and CINAHL, the review included 53 studies primarily conducted in high-income countries that reported quantitative outcomes across substance use, healthcare utilization, behavioral health, and treatment engagement. Risk of bias was assessed using Cochrane RoB 2, ROBINS-I, and ROBINS-E tools. RESULTS: Overall, evidence was most favorable for selected treatment-linkage and engagement outcomes, whereas findings for substance use, emergency department use, hospitalization, overdose, and mortality were inconsistent. Uncontrolled longitudinal studies frequently reported improvements in depression and anxiety, but no randomized trials evaluated these outcomes, limiting causal inference. Exploratory cross-study patterns suggested that sustained navigation, practical assistance, and repeated peer contact were more often present in programs reporting favorable outcomes; however, these components were not independently evaluated. Substantial heterogeneity, frequent multicomponent interventions, high risk of bias in many nonrandomized studies, and limited long-term and economic data constrain conclusions. CONCLUSIONS: Findings support the promise of PRS while underscoring the need for more rigorous comparative studies, cost-effectiveness data, and further research in low- and middle-income countries.

Humans

Effects of H-coil TMS on suicidality in major depression: A secondary analysis of data from a multisite randomized trial comparing accelerated to once-a-day stimulation.

Suicide is the 10th leading cause of death in US adults. Standard once-daily repetitive transcranial magnetic stimulation (rTMS) can reduce suicidal ideation. Yet, antidepressant and anti-suicidal effects often take several weeks to emerge, while rapid improvement is often required. Accelerated TMS has been proposed as a strategy to hasten therapeutic response. A recent FDA-regulated multicenter trial evaluated accelerated intermittent theta burst Deep TMS with the H1-coil versus standard high-frequency Deep TMS in MDD. Both groups demonstrated high remission and response rates for depression, with the accelerated protocol showing non-inferiority and a shorter time to remission. The goal of this exploratory secondary analysis was to evaluate the impact of these two H-coil TMS dosing paradigms on suicidal ideation. The Scale for Suicide Ideation (SSI), as well as suicidality items of HDRS, MADRS and CUDOS were collected and analyzed. On all scales, both accelerated and standard Deep TMS protocols were associated with meaningful reductions in suicidality. The accelerated protocol achieved a faster onset of improvement. Comparison between the timeline of improvement in suicidality and in overall depressive symptoms found a trend for faster improvement in suicidality, especially with the accelerated protocol. These findings highlight the importance of treatment frequency in determining time to clinical benefit and support the use of scalable accelerated protocols for patients requiring more rapid symptom relief.

Humans

Gloeotrichia echinulata genomes from the United States are nontoxigenic and likely geosmin producers.

Six Gloeotrichia echinulata genomes derived from planktonic harmful algal blooms (HABs) with similar colonial morphology have been sequenced from lakes in the west and northeast regions of USA, four of them to completion. The c. 7 Mbp genomes exhibit a high level of conservation, with 98-99% pairwise genome-wide average nucleotide identity and high levels of synteny, representing a single species cluster. We observed strong conservation of gene clusters responsible for the synthesis of the secondary metabolites and bioactive peptides that are characteristic of HAB-forming cyanobacteria. All six G. echinulata genomes lack genes for the synthesis of classic cyanotoxins, including microcystin, but possess genes responsible for the synthesis of the taste and odor compound geosmin. Interestingly, the geoA geosmin synthase gene in three genomes is homologous to other cyanobacterial geoA genes, while the other three geoA genes are related to actinomyces geoA. Phylogenomic analysis places the G. echinulata genomes within a clade of benthic Nostocales, reflecting an ecological niche featuring extensive growth on the sediment surface before colonies disperse into the epilimnion for planktonic growth. We identify genes conserved in all six genomes that could represent physiological adaptations supporting active growth on sediments and pelagic recruitment independent of wind-driven mixing: phycoerythrin light harvesting complexes for optimal photosynthesis at depth; gliding motility to access patchy nutrient distributions; and gas vesicles with relatively small GvpC proteins that predict resistance to higher hydrostatic pressure. The strong genomic similarity across geographically distant populations suggests that G. echinulata in the United States is a tightly related non-toxigenic species group with predictable properties relevant to public health and drinking water management.

Cyanobacteria

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

The aerobic bacterial-algal granular sludge (ABGS) enhanced with heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria, as a novel symbiotic technology, exhibits fluctuating treatment efficiency and unstable performance primarily due to the unstable symbiotic relationship. This study proposes an innovative approach to strengthening the bacteria-algae symbiosis by introducing exogenous signaling molecules. Concurrently, high-throughput, correlation analysis of environmental factors and metagenomic sequencing techniques are employed to elucidate the enhancement mechanisms of the signaling molecules. The results demonstrate that signaling molecule enhancement boosted total nitrogen (TN) removal efficiency by 24.51 % in the bacteria-algae symbiotic system (X1). Scanning electron microscopy (SEM) characterization revealed that the addition of signaling molecules resulted in more compact aerobic granular sludge (AGS) and markedly improved stability. High-throughput sequencing showed signaling molecules enriched denitrifying bacteria (Hydrogenophaga, Pseudoxanthomonas, Thauera, Zoogloea) and organic-degrading Desulfomicrobium, optimizing microbial diversity and enhancing nitrogen/organic removal. Correlation analysis of environmental factors indicate that the addition of C8-HSL facilitates the enrichment and functional activation of specific genera. Metagenomic analysis revealed that signaling molecules enhanced the system's denitrification performance by modulating gene expression and associated metabolic pathways. Quantitative polymerase chain reaction (qPCR) analysis further confirmed that the signaling molecules upregulated the expression of the napA, nirK, and nirS genes. An increased abundance of the napA gene facilitated aerobic denitrification (NO&#x2083;&#x207b;-N&#x2192;NO&#x2082;&#x207b;-N), while upregulated abundance of the nirK and nirS genes accelerated nitrite reduction (NO&#x2082;&#x207b;-N&#x2192;N&#x2082;). This study aims to provide theoretical and practical foundations for implementing advanced bacteria-algae symbiotic technologies.

Denitrification

A versatile reversed-phase liquid chromatography charged aerosol detection method for streamlined monitoring of QS-21 content and stability in liposomal adjuvant formulations.

Identifying and quantifying an active adjuvant along with its degradants in drug formulations is essential for ensuring the safety and efficacy of the drug product. QS-21 is a potent adjuvant that is being evaluated in several clinical trials and is currently formulated in licensed vaccines that protect against shingles, malaria, and RSV. In aqueous environments, QS-21 is subject to hydrolytic degradation that is influenced by pH and temperature, resulting in the formation of a degradant known as QS-21 Hydrolyzed Product, QS-21 HP, which can occur during manufacturing and/or prolonged storage. The intact QS-21 and QS-21 HP induce distinct immune response profiles, making it critical to monitor the degradation of QS-21 in vaccine adjuvant formulations. To date, there has been a paucity of reliable assays for QS-21, its isomers, and degradant QS-21 HP in liposomal adjuvant formulations available that can be transferred seamlessly in quality control (QC) environments. Herein, we introduce a simple and QC-friendly liquid chromatography coupled to a charged aerosol detector (LC-CAD) enabled by stationary phase screening combined with in silico method development optimization. The method exploits 2.7&#xa0;&#x3bc;m fused-core phenyl hexyl particles, ensuring its versatility in standard and ultra-high pressure LC systems. This approach demonstrates a high correlation between predicted retention time (RT) and experimental outcomes with overall &#x2206;RT&#xa0;<&#xa0;4%. In addition, this assay shows great linearity, precision, specificity, and accuracy to advance process development characterization of new vaccine formulations.

Liposomes

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&#x202f;=&#x202f;8) revealed the presence of 263 mineral-associated genes (>1 FPKM) in high (n&#x202f;=&#x202f;4) and 181 in low motile (n&#x202f;=&#x202f;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&#x202f;&#xd7; 10&#x207b;2; ZNF331, ZNF692, ZNF180, etc.), followed by spermatogenesis (FDR: 2.9&#x202f;&#xd7; 10&#x207b;2; CALR3, ADAM18, ADAM29, etc.), proton transmembrane transport (FDR: 4.0&#x202f;&#xd7; 10&#x207b;2; ATP6V0E1, ATP1A4, ATP6V1B2, etc.) and flagellated sperm motility (FDR: 2.3&#x202f;&#xd7; 10&#x207b;1; CATSPERD, EFCAB6, CABS1, etc.). Additionally, the chromatin remodeling pathway (FDR: 3&#x202f;&#xd7; 10&#x207b;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

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans