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PubMed2026

Glycaemic burden disrupts innate immunity in TB by modulating CD206 expression and macrophage antimicrobial responses.

Tuberculosis (TB) and diabetes mellitus (DM) represent a growing dual global health burden, with chronic hyperglycaemia recognized as a major modifier of host immunity against Mycobacterium tuberculosis (Mtb). Macrophages, central to pathogen recognition, phagocytosis, antigen presentation, and intracellular killing, may be particularly vulnerable to diabetic metabolic dysregulation. This study evaluated phenotypic and functional macrophage alterations in individuals with pulmonary TB, type 2 DM, TB-DM comorbidity, and healthy controls. Surface receptor expression was analysed by multicolour flow cytometry, while phagocytosis and intracellular bacterial clearance were assessed using FITC-labelled Mtb assays and colony-forming unit enumeration. Hyperglycaemia was associated with reduced CD11b, MARCO, and TLR2 expression alongside upregulation of the mannose receptor CD206, which correlated positively with HbA1c levels, indicating a shift toward a permissive M2-like phenotype. Phagocytic uptake of Mtb was significantly impaired and inversely correlated with HbA1c. Antigen-presenting capacity was selectively compromised, with reduced CD80 and CD86 expression in DM and TB-DM groups, while HLA-DR remained unchanged. Intracellular Mtb killing was markedly diminished in diabetic macrophages. These findings demonstrate that chronic hyperglycaemia profoundly disrupts macrophage innate immunity, contributing to increased TB susceptibility and poor infection control in diabetic populations.

Humans↗

PubMed2026

Immunohistochemical evaluation of Ki-67 and GLI1 in sporadic and nevoid basal cell carcinoma syndrome-associated odontogenic keratocysts.

INTRODUCTION: Odontogenic keratocyst (OKC) is a developmental odontogenic cyst that may occur sporadically (OKCsp) or in association with nevoid basal cell carcinoma syndrome (NBCCS) (OKC-sy). NBCCS is an autosomal dominant disorder characterised by morphological abnormalities and an increased predisposition to several neoplasms, including basal cell carcinomas. Mutations in the tumour suppressor gene PTCH1 have been reported in patients with OKC and NBCCS. PTCH1 participates in a signalling cascade that culminates in the translocation of GLI transcription factors to the nucleus, thereby activating target genes involved in cell proliferation. Aberrant GLI1 expression has been associated with increased proliferation in lung adenocarcinoma and other cancers. OBJECTIVE: To compare GLI1 and Ki-67 protein expression in OKCs associated with NBCCS versus sporadic OKCs. MATERIALS AND METHODS: We included 13 OKCsp and 9 OKCsy from a children's hospital and university ... Immunohistochemistry was performed using anti-GLI1 and anti-Ki-67 to assess GLI1 expression and cell proliferation. RESULTS: No significant differences were observed in GLI1 or Ki-67 expression in the epithelial component of OKCsy versus OKCsp. A positive correlation between GLI1 and Ki-67 expression was detected in the total sample (r = 0.71, p < 0.05). CONCLUSION: The positive correlation between GLI1 and Ki-67 expression in OKCs suggests an association between SHH pathway activity and cell proliferation in both sporadic and syndromic lesions.

GLI1↗

PubMed2026

Genome-wide identification and functional validation of asparagine synthetase genes (NtASNs) in Nicotiana tabacum.

Asparagine (Asn) is pivotal for plant nitrogen (N) metabolism and plays indispensable roles in plant growth, development, and stress tolerance. However, the systematic characteristics and core functions of asparagine synthetase genes (NtASNs) in tobacco remain unclear. Through a comprehensive genome-wide investigation, nine members of the NtASN gene family were identified. Subsequent CRISPR/Cas9-mediated knockout and overexpression assays of these NtASN genes revealed that NtASN1e, NtASN2a, and NtASN2b are the core genes responsible for Asn biosynthesis in tobacco. Their knockout reduced asparagine synthetase activity and Asn content, delayed seed germination by 2-3 days, and displayed elevated oxidative injury when exposed to salinity conditions. In contrast, overexpression of these genes elevated Asn accumulation. Subcellular localization analysis indicated that NtASN1e was localized to both the cytoplasm and chloroplasts, whereas NtASN2a exhibited dual localization in the cytoplasm and endoplasmic reticulum, and NtASN2b was mainly localized in the cytoplasm. This study systematically clarifies the evolutionary characteristics and core functions of the NtASN gene family and provides candidate genes for optimizing nitrogen metabolism and improving salt-stress adaptation in tobacco. These findings hold important practical significance for molecular breeding and product quality improvement in industrial crops.

Nicotiana↗

PubMed2026

Manual, digital, and AI tumour-infiltrating lymphocyte scoring: a secondary analysis of the APHINITY randomised trial.

BACKGROUND: Stromal tumour-infiltrating lymphocytes (sTILs) are prognostic in early-stage HER2-positive breast cancer, but their role in the context of dual HER2 blockade remains undefined. We evaluated manual, digital, and artificial intelligence (AI)-based sTIL quantification, together with AI-derived spatial metrics, for prognostic and treatment-benefit stratification using tumour samples from the phase 3 APHINITY trial. METHODS: In the APHINITY trial, 4805 patients were randomly assigned to receive chemotherapy plus trastuzumab with pertuzumab or chemotherapy plus trastuzumab with placebo. Median follow-up was 74·1 months (IQR 68·3-75·4). We analysed 4262 haematoxylin and eosin-stained images using manual assessment, an automated digital approach, AI-based lymphocyte quantification (AI percentage lymphocytes), and two AI-derived spatial features (AI-TIL and immune hotspot). Interobserver reproducibility was assessed in 262 randomly chosen tumour samples scored independently by five pathologists. Multivariable Cox models were used to assess associations between TIL levels and invasive disease-free survival (primary outcome in APHINITY), distant recurrence-free interval, and overall survival. The heterogeneity of pertuzumab benefit was evaluated using subgroup analyses, subpopulation treatment effect pattern plot analyses, and nested Cox models with treatment-by-biomarker interaction terms. FINDINGS: Manual scoring showed high interobserver reproducibility (intraclass correlation coefficient 0·84 [95% CI 0·79-0·88]). Concordance between manual and automated methods was modest. AI-based scoring (AI percentage lymphocytes) reclassified 120 (11·6%) of 1035 node-positive tumours from immune-low (by manual scoring) to immune-high; this subgroup of patients showed greater separation of 5-year invasive disease-free survival curves between pertuzumab and placebo groups compared with patients whose tumours were concordantly classified as immune-low by both manual and AI-based approaches. Higher levels of TILs were associated with improved invasive disease-free survival for all sTIL measurement approaches and spatial measurements (hazard ratios [HRs] 0·41-0·93). Pertuzumab was associated with improved invasive disease-free survival at higher sTIL levels across all measurement approaches (HRs 0·36-0·48), but was not associated with higher values of spatial measures. The largest 6-year absolute improvements with pertuzumab were observed in patients with node-positive disease whose tumours scored in the highest level of immune infiltration of manual sTIL scoring (≥70·0%; mean absolute improvement 12·1 percentage points [SD 2·8]). In nested prognostic and predictive models, AI-based immune hotspot scores provided the most consistent additional information when combined with any sTIL measurement (all p<0·010). INTERPRETATION: Standardised manual sTIL scoring was reproducible, and digital and AI-based methods showed consistent prognostic stratification and potential for treatment-benefit stratification despite only modest correlation between platforms. AI spatial metrics provided complementary information beyond sTIL density and could support more scalable immune assessment. Future studies are needed to validate these approaches in independent cohorts and to clarify their clinical utility for stratifying contemporary HER2-directed therapies. FUNDING: None.

Humans↗

PubMed2026

HRAS promotes mutant NRAS-driven transformation with codon and allele specificity.

Wild-type RAS family members determine the signaling and therapeutic response in cancers driven by mutant HRAS and KRAS because they activate alternate RAS effector pathways. Here, we found that the requirement for wild-type RAS to support mutant NRAS-driven transformation correlated with codon-specific differences in GTP hydrolysis. NRAS with mutations at either Gly12 (G12X) or Gly13 (G13X), which retained the GDP-GTP cycling function, had modest autonomous transforming potential. In contrast, NRAS with GTP-locking mutations at Gln61 (Q61X mutants) was uncoupled from receptor tyrosine kinase (RTK) input, rendering wild-type RAS an obligate partner for RTK-stimulated signaling and oncogenesis. In RASless cells expressing mutant NRAS, reintroduction of wild-type HRAS was sufficient to restore signaling and transformation. Global dependency mapping in human cancer cells revealed functional partitioning, wherein mutant NRAS promoted MAPK signaling and wild-type HRAS promoted PI3K-AKT survival signaling. Consequently, allele-specific or pan-RAS(ON) inhibitors synergized with inhibitors of proximal RTK signaling or of wild-type HRAS or KRAS to overcome this signaling plasticity. Pan-RAS(ON) and HRAS inhibition was synergistic for all NRAS mutants tested, with Q61X mutants showing greater sensitivity. These findings define the signaling partnership between mutant NRAS and wild-type HRAS as a targetable vulnerability and provide a biochemical blueprint for dual RAS inhibition in NRAS-mutated malignancies.

Humans↗

PubMed2026

Bacteroides cellulosilyticus-derived 2-hydroxyphenylacetic acid rectifies hepatic lipid homeostasis in MASLD by targeting the PPARγ-CD36 axis.

The gut microbiota plays an important role in the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD), but the specific molecular mechanisms involved have not been fully elucidated. In this study, human cohort studies were performed to identify that the relative abundance of Bacteroides cellulosilyticus (B. cellulosilyticus) was significantly decreased in patients with MASLD. Through the integration of metagenomic and metabolomic analyses, it was confirmed that B. cellulosilyticus and its metabolite 2-hydroxyphenylacetic acid (2HPAA) are key factors regulating the occurrence and development of MASLD. Single-cell sequencing and lipidomic analyses revealed that 2HPAA can enter the liver through the enterohepatic circulation to exert regulatory effects. Specifically, 2HPAA inhibits the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway, thereby suppressing the expression of the fatty acid transporter CD36. Meanwhile, 2HPAA regulates lipid metabolism in hepatocytes by significantly enhancing palmitate conversion efficiency and inhibiting CD36 palmitoylation. This dual regulatory effect on CD36 expression and palmitoylation can reduce lipid accumulation in hepatocytes and ultimately alleviate MASLD progression. These findings reveal the mechanism by which B. cellulosilyticus and 2HPAA alleviate MASLD by targeting the PPARγ-CD36 pathway. This work provides a new perspective for the study of gut microbiota-host interactions in regulating liver diseases.

PPAR gamma↗

PubMed2026

Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.

BACKGROUND: Tranexamic acid (TXA) is widely used for pigmentary disorders, but its anti-ageing potential remains unclear. This study aimed to evaluate whether topical 3% TXA improves early periorbital wrinkles in women with facial melasma and to investigate whether TXA protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. METHODS: Fifty women with melasma were randomized to 3% TXA serum plus moisturizer or moisturizer alone for 8 weeks, with follow-up to week 12. Periorbital wrinkles were graded using a modified Fitzpatrick Wrinkle Scale (MFWS). Separately, D-gal-induced senescence in HDFs was assessed via viability, SA-β-gal activity, senescence markers, ROS, antioxidant enzymes, SASP/ECM gene expression, and MAPK activation. GPR30 involvement was examined using antagonist G15, shRNA knockdown, and molecular docking. RESULTS: Topical TXA produced significantly greater MFWS reductions versus moisturizer alone at weeks 4, 8, and 12, with benefit persisting post-treatment. In HDFs, TXA preserved viability, reduced SA-β-gal positivity, attenuated p21/p16, restored Lamin B1, decreased ROS, and rescued antioxidant activities. TXA downregulated IL-6, IL-8, MMP1, and MMP3, and suppressed D-gal-induced ERK, JNK, and p38 phosphorylation. These effects were weakened by G15 or GPR30 knockdown; docking supported a stable TXA-GPR30 interaction. CONCLUSIONS: TXA showed clinical anti-wrinkle activity in melasma patients and protected HDFs from D-gal-induced senescence, partly via GPR30-dependent modulation of oxidative stress, SASP/ECM expression, and MAPK signalling. TXA is a promising candidate for skin ageing intervention.

Humans↗

PubMed2026

Metabolomic and structural signatures of pigmented and non-pigmented Himalayan rice landraces.

BACKGROUND: This study investigated the anti-oxidant properties, starch composition, pasting behavior, structural properties, textural properties and non-targeted metabolomic profiles of pigmented and non-pigmented rice landraces as potential next-generation functional food ingredients. RESULTS: Pigmented rice demonstrated 1.34 times more anti-oxidant activity as compared to non-pigmented rice. Pigmented landraces showcased superior nutritional and functional attributes, including higher total dietary fiber and starch content. Fourier-transform infrared (FTIR) analysis revealed distinct molecular signatures with enhanced peak transmittance, while X-ray diffraction (XRD) indicated greater crystallinity ranging from 36-44.3% in pigmented rice compared with 30-40% in non-pigmented rice, suggesting improved digestibility and processing versatility. Pigmented rice recorded less amylose content hence tended to possess increased adhesiveness values whereas non-pigmented rice revealed greater amylose content hence was coupled with greater hardness values. Field-emission scanning electron microscopy (FE-SEM) images revealed that pigmented rice had densely packed and polygonal starch granules whereas non-pigmented rice had loosely packed starch granules with intergranular voids. Untargeted gas chromatography-mass spectrometry (GC-MS) profiling identified 84 metabolites, including unique compounds such as 3,3-dimethylbutanol and ethanoic acid, along with shared metabolites such as sucrose and linoleic acid, highlighting notable biochemical diversity. Multivariate statistical analyses using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping further differentiated the metabolomic landscapes, with variable importance in the projection (VIP) scores identifying key bioactive contributors. CONCLUSION: Pigmented rice landraces exhibited significant functional and nutritional advantages, making them promising candidates for functional food development and nutritional improvement programs. These findings support their potential role in advancing sustainable and health-oriented food systems. © 2026 Society of Chemical Industry.

Oryza↗

PubMed2026

Measuring economic efficiency in adult intensive care units: A systematic review of methods, metrics, and evidence.

OBJECTIVES: Intensive care units (ICUs) consume substantial hospital resources, yet "efficiency" is inconsistently defined and measured. This study systematically reviewed how economic efficiency has been conceptualised and quantified in adult ICUs and appraised the quality of evidence. METHODS: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD420251107866), we searched MEDLINE, Embase, CINAHL, Cochrane Library and Web of Science (2000-August 2025), plus global grey sources. Eligible studies explicitly defined efficiency and reported an efficiency metric/model linking ICU inputs (e.g., staff, beds/capacity, time, consumables, or costs) to outputs/outcomes (e.g., throughput/discharges, length of stay/resource use, risk-adjusted mortality). Dual independent screening and extraction were performed. Study quality was appraised using MMAT, and findings were synthesised narratively (SWiM), given heterogeneity. RESULTS: 39 studies (2001-2025) from 17 countries were included, all from high-income or upper-middle-income settings. Four methodological families were identified: (1) frontier modelling (predominantly DEA; occasional SFA/RFDH), (2) benchmarking indicators (risk-adjusted mortality and LOS/resource-use ratios; "efficiency matrix" quadrant classification), (3) cost-outcome evaluations, and (4) operational/process metrics. Across families, variation in decision-making units, input/output selection, and risk adjustment limited comparability; long-term and patient-reported outcomes were absent, and equity considerations were uncommon. CONCLUSIONS: ICU efficiency research is feasible but fragmented and often methodologically limited. Standardised definitions, validated risk adjustment, uncertainty quantification, and inclusion of patient-centred and equity-relevant outcomes are needed before efficiency metrics can reliably inform value-based decision making.

Intensive Care Units↗

PubMed2026

A 12-week, double-blind, quasi-randomized, placebo-controlled study to evaluate the efficacy and safety of Coleus forskohlii (Forcslim) on body weight loss.

BACKGROUND: Overweight and obesity have emerged as a global epidemic, significantly impacting human health. Traditional usage and growing scientific evidence suggest that Coleus forskohlii extract (Forcslim) may aid in reducing excess body weight and fat. This study aimed to evaluate the efficacy and safety of Forcslim supplementation in overweight individuals. METHODS: A quasi-randomized, double-blind, placebo-controlled clinical trial was conducted in 60 overweight subjects aged 20-70 years over a period of 12 weeks. The participants were assigned to receive either Forcslim or placebo. The key outcome measures included body weight, body mass index (BMI), body composition, and anthropometric parameters. Additionally, lipid profile parameters and safety markers (including metabolic, hepatic, and cardiovascular indicators) were assessed throughout the study duration. RESULTS: Compared to the placebo group, the Forcslim group showed significant reductions in waist circumference (-1.83 cm; p < 0.01) and body weight (-1.93 kg; p < 0.001). Significant improvements in anthropometric parameters were observed exclusively in the Forcslim group. Furthermore, triglyceride (TG) levels were significantly reduced (p < 0.01), while high-density lipoprotein (HDL) levels showed a significant increase (p = 0.001). No clinically significant changes were observed in metabolic markers, liver and muscle enzyme levels, heart rate, blood pressure, or reported adverse effects, indicating a favorable safety profile. CONCLUSIONS: Forcslim demonstrated significant anti-obesity effects, including reductions in body weight, waist circumference, and improvements in the lipid profile. These findings suggest that C. forskohlii extract supplementation may serve as a safe and effective alternative to synthetic anti-obesity drugs.

Humans↗

PubMed2026

GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.

BACKGROUND: GPR3(G-protein-coupled receptor 3), an orphan G-protein-coupled receptor (GPCR) with constitutive Gs activity, is expressed in the brain, liver, ovary, and other tissues, regulating cell proliferation, differentiation, and apoptosis across the nervous, reproductive, immune, and metabolic systems. This review synthesizes evidence on its integrated signaling and physiological functions to address the lack of a comprehensive multisystem pathophysiology overview. METHODS: A systematic literature search was conducted on PubMed and Web of Science, using keywords such as "GPR3", "GPCR", "neurodegeneration", "metabolism", "immune", "reproduction", "agonist", "inhibitor", and "therapeutic target". This search identified GPR3's roles in neurodegenerative diseases, immune inflammation, reproduction, and energy metabolism. The analysis focused on signaling pathways, ligand regulation, and therapeutic potential. RESULTS: The research indicates that GPR3 is involved in neuronal survival, synaptic plasticity, and microglial activity via the cAMP/PKA, PI3K/Akt, and β - arrestin pathways. It promotes amyloid - β formation in Alzheimer's disease (AD), yet provides neuroprotection in Parkinson's disease (PD) models. It may contribute to anxiety/depression - like states, maintain oocyte meiotic arrest in the ovary, and activate thermogenic genes in adipose tissue. GPR3 modulates immune responses. Using oleic acid (OA) and diphenyleneiodonium (DPI) as activators, and AF64394 and cannabidiol (CBD) as antagonists, it shows potential in disease models. CONCLUSION: GPR3 acts as a central molecular hub integrating neural, metabolic, immune, and reproductive signaling, highlighting its potential as a therapeutic target for chronic multisystem disorders. However, its dual roles in certain pathologies and translation challenges necessitate further research.

Humans↗

PubMed2026

ATF4-histone 2-hydroxyisobutyrylation feedback loop drives sepsis-induced inflammation.

BACKGROUND AND PURPOSE: The role and mechanisms of lysine 2-hydroxyisobutyrylation (Khib) in the acute inflammatory phase of sepsis remain unclear. We investigated the function and underlying mechanisms of histone H4 lysine 5 2-hydroxyisobutyrylation (H4K5-hib) in sepsis-induced inflammation in vivo and in vitro. EXPERIMENTAL APPROACH: Acute sepsis was induced by caecal ligation and puncture (CLP) in mice, and inflammatory responses were modelled in lipopolysaccharide (LPS)-stimulated macrophages. CUT&Tag-seq was used to identify genomic targets associated with H4K5-hib and activating transcription factor 4 (ATF4). Immunofluorescence, Western blotting, qPCR, dual-luciferase assays, and ELISA were performed to investigate the underlying mechanisms. KEY RESULTS: H4K5-hib levels were increased in macrophages during the acute inflammatory phase of sepsis. LPS stimulation enhanced H4K5-hib enrichment at the ATF4 promoter, thereby promoting ATF4 transcription. Inhibition of EP300-mediated 2-hydroxyisobutyrylation or mutation of H4K5 abolished ATF4 activation. Increased H4K5-hib activated the ATF4/NLRP3 signalling axis, promoting inflammasome assembly and amplifying inflammatory responses. ATF4 directly bound to the EP300 promoter and enhanced its transcription, forming a positive feedback loop that further increased H4K5-hib levels. In CLP-induced sepsis, pharmacological inhibition of EP300 or ATF4 reduced H4K5-hib levels and suppressed NLRP3 inflammasome activation. CONCLUSION AND IMPLICATIONS: These findings reveal a previously unrecognized epigenetic mechanism underlying sepsis-induced inflammation and identify the EP300/ATF4/H4K5-hib positive feedback loop as a potential therapeutic target for sepsis.

Animals↗

PubMed2026

EZH1/2 inhibition selectively targets SMARCA4/2 co-deficient lung cancer cells by suppressing stemness and proliferation.

SMARCA4-deficient thoracic malignancies comprise biologically heterogeneous tumors, ranging from conventional non-small cell lung cancer with SMARCA4 alterations to thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT), an aggressive entity frequently associated with concomitant SMARCA2 loss. However, the extent to which SMARCA4-deficient lung cancer cell lines recapitulate SMARCA4-UT-like biology remains incompletely defined. Here, we characterized lung cancer cell lines across distinct SMARCA4 and SMARCA2 states and identified a subgroup with SMARCA4/2 co-deficiency that exhibited reduced expression of epithelial lineage markers and transcriptional similarity to SMARCA4-UT and other SWI/SNF-deficient malignancies. The EZH1/2 inhibitor HM97662 selectively suppressed growth in SMARCA4/2-deficient cells, with limited effects in SMARCA2-proficient cells. EZH1/2 inhibition broadly reduced H3K27me3 and induced derepression of PRC2 targets regardless of drug sensitivity. However, its biological effects were most pronounced in SMARCA4/2-deficient cells, where it promoted apoptosis, reduced stemness marker expression, attenuated the SMARCA4-UT-associated transcriptional signature, and suppressed proliferative and mTORC1-related programs. Chromatin accessibility analysis further revealed cell-line-specific patterns of accessibility loss, with reduced accessibility at stemness-associated transcription factor motif-enriched regions coupled with transcriptional repression of nearby genes in SMARCA4/2-deficient cells. These findings support dual EZH1/2 inhibition as a potential therapeutic vulnerability in SMARCA4/2-deficient, SMARCA4-UT-like lung cancer cells.

Humans↗

PubMed2026

Analyzing the impact of subcutaneous injection needle, device, and administration characteristics on patient pain, anxiety, and safety: a systematic literature review.

The subcutaneous (SC) injection route is a commonly used and important method for therapeutic delivery of a wide range of compounds, and needle characteristics have a significant influence on patient pain, anxiety, safety, and other outcomes. This systematic review evaluates the evidence on how needle-specific characteristics (e.g. gauge, length, tip design, wall thickness, concealment) and administration- or device-related factors can affect patient-reported outcomes and clinical safety indicators during and following SC injections. A comprehensive search was conducted in MEDLINE, PubMed, Embase, and ClinicalTrials.gov in June 2024. Studies were included if they assessed the relationship between needle characteristics and pain, anxiety, safety, or related outcomes in individuals receiving SC injections. A dual-reviewer process was used for study selection, data extraction, and quality assessment. Sixty-two studies met inclusion criteria. Evidence consistently indicated that thinner and shorter needles reduced patient-reported pain and adverse events such as bruising and bleeding. Tapered and lubricated needles, hidden or retractable needle designs, and use of autoinjectors or prefilled syringes also contributed to reduced anxiety and improved user satisfaction. However, results were heterogeneous, and many studies lacked sufficient power or single-variable evaluation of individual needle parameters, limiting definitive conclusions. Needle characteristics significantly influence patient experience and safety with SC delivery. While both clinical evidence and practical experience clearly favor thinner, shorter, and concealed needles, further standardized, high-quality research is needed to isolate and quantify the specific contributions of individual needle characteristics to optimize injection practices and support patient-centered device design.

Humans↗

PubMed2026

Nitrogen sources and concentrations shape algal odor compounds: Key drivers of β-cyclocitral and β-ionone in water bodies of the lower Yangtze River.

Taste and odor (T&O) compounds derived from cyanobacterial blooms pose escalating threats to freshwater security worldwide, yet the drivers of specific T&O metabolites remain poorly constrained. Here, we investigated the dual effects of nitrogen (N) sources and concentrations on the production of β-cyclocitral and β-ionone, two algal-derived T&O compounds, through integrated field surveys (54 sites across lakes and rivers) in the eutrophic lower Yangtze River, China, and laboratory cultivation of typical cyanobacteria (Microcystis aeruginosa and Pseudanabaena cinerea). Our field data revealed that the concentrations of β-cyclocitral and β-ionone in lakes and rivers were not significantly different, but increased with the trophic level index. Redundancy analysis and Mantel analysis showed that Microcystis and Pseudanabaena were potentially dominant contributors to β-cyclocitral and β-ionone in the water column. Structural equation modeling and variation partitioning analysis showed that enhanced nitrate (NO3--N) significantly promoted the production of these compounds. Laboratory experiments demonstrated that inorganic N (NaNO₃) maximized total T&O yields by promoting algal biomass, whereas organic N (urea and glutamic acid) elevated the T&O production per unit biomass by 1.5- to 9.5-fold. Notably, Pseudanabaena exhibited a 2.3-fold higher β-ionone yield than Microcystis, with greater sensitivity to N concentrations. Our study highlights the critical role of nitrogen pollution, both source and concentration, in the production of T&O compounds by phytoplankton and provides reference data for managing T&O issues in rivers and shallow lakes.

Norisoprenoids↗

PubMed2026

Influence of built environment on occupational health of women workers in tea plantations of India: a systematic review.

The built environment, comprising homes, buildings, roads, public spaces, infrastructure, land use, civic design, and amenities, has a considerable influence on occupational health. In India's tea plantations, where women comprise majority of the workforce, the built environment plays a crucial role in determining occupational health. The aforementioned point can be explained by the co-occurrence of living and working conditions, which often coexist in tea plantations, further resulting in vulnerabilities to the health of women workers. Therefore, to understand the influence of built environment on the occupational health of women workers in tea plantations of India, the present paper employs a systematic review using the PRISMA 2020 framework. In the first search, 421 studies were identified, of which 21 studies met all the inclusion criteria. A quality appraisal and risk of bias of the included studies have been undertaken. The results identified that musculoskeletal disorders (MSDs) are the most prevalent occupational health consequence, affecting over 80 % of the women workers in Indian tea plantations, substantiated by a range of estimates in the studies reviewed. Gendered disparities in wage earning, self-autonomy, and dual responsibilities often lead to emotional distress, as delineated in minimal of the reviewed studies, grounded on self-disclosed or qualitative analysis. Further, deprived housing conditions and other facilities across the reviewed studies reflect institutional negligence. Therefore, by conducting a systematic synthesis of occupational health of women workers in the Indian tea plantation sector through the lens of the built environment, prior accounts have been extended. Addressing these issues is essential for safeguarding women workers, which will ensure the longevity of the Indian tea industry.

Female↗

PubMed2026

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult↗

PubMed2026

Antarctic Peninsula soil carbon stock and efflux: A complex interplay of soil properties and heavy metals.

This study establishes a quantitative framework for understanding surface soil carbon dynamics and ecosystem connectivity in Fildes Peninsula and Ardley Island, King George Island, South Shetland Islands, Antarctic Peninsula. The mean soil organic carbon (SOC) stock across all study sites was 1.10 ± 1.93 kg C/m². Restricting net carbon balance analysis to Fildes Peninsula, where soil respiration (Rs) data were available, yielded a site-specific SOC stock of 0.45 ± 0.45 kg C/m². Scaling Rs to a realistic 120-day active season and assuming stable SOC stocks resulted in estimated annual carbon loss of 15 g C/(m2·yr), equivalent to 3.3 % of standing SOC. Comprehensive sensitivity analyses spanning plausible winter respiration (0 %-20 % of summer rates) and annual change in SOC stocks (-1 %-2 %) consistently supported a net carbon sink, with turnover rates constrained to 3.3 %/yr-4.7 %/yr. Principal component analysis showed that ornithogenic processes as the dominant control on SOC, total nitrogen (TN), zinc (Zn), copper (Cu), and cadmium (Cd) provide a clear multivariate signature of marine-derived nutrient, while Pb was decoupled from this gradient and associated instead with fine-particle size controls. These results reveal dual but independent drivers of soil metal enrichment in this region. Despite their limited spatial extent, ornithogenic soils store disproportionately large carbon pools. Overall, this integrated analysis reveals how marine-terrestrial subsidies regulate Antarctic carbon cycling and provides a quantitative and reproducible framework for assessing carbon dynamics under ongoing climate change.

Antarctic Regions↗