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Department of Pharmacology

 

Cardiovascular disease risk reduction interventions for indigenous women: an umbrella review

Tue, 21/04/2026 - 11:00

Health Promot Int. 2026 Mar 2;41(2):daag051. doi: 10.1093/heapro/daag051.

ABSTRACT

Cardiovascular disease (CVD) prevention strategies are predominantly informed by studies conducted in men from the general population, which can disadvantage women-particularly Indigenous women-whose CVD needs differ in terms of symptom presentation, healthcare access, receipt of guideline-recommended care and sociocultural roles. This review aims to summarize the effectiveness of CVD prevention interventions in Indigenous women in the USA, Canada, New Zealand and Australia. Umbrella review of systematic reviews and randomized and non-randomized interventions examines the effectiveness of pharmacological and nonpharmacological interventions in reducing CVD risk in target countries in Indigenous adult studies with ≥50% women. Systematic searches were conducted across six electronic databases between January and February 2024 (update: February 2025). Quality assessment applied standard methods and evidence was synthesized qualitatively. The protocol was PROSPERO registered (CRD42024575310). Six systematic reviews and 16 primary studies (7 randomized and 9 non-randomized; 11,473 participants; 50%-100% women) in Indigenous participants were included. Evidence was limited and generally of low certainty. Four randomized studies were exclusively in Indigenous women (Australia and USA). Only one pharmacological study was identified, investigating vitamin D in reducing blood pressure. Non-pharmacological interventions demonstrated potential to improve CVD risk factors, primarily adiposity, blood pressure, lipids, and glucose. Participant involvement was generally limited and continuation was problematic. This first umbrella review on CVD risk reduction in Indigenous women suggests an urgent need for high-quality evidence to inform and make CVD prevention accessible and equitable for them. Future studies should employ consumer-led, innovative, and context-specific strategies to ensure inclusive recruitment and sustain participant engagement.

PMID:42011628 | DOI:10.1093/heapro/daag051

Machine learned potential for defected single layer hexagonal boron nitride

Thu, 16/04/2026 - 11:00

J Chem Phys. 2026 Apr 21;164(15):154705. doi: 10.1063/5.0314075.

ABSTRACT

The development of machine learned interatomic potentials (MLIPs) is critical for performing reliable simulations of materials at length and time scales that are comparable to those in the laboratory. We present here a MLIP suitable for simulations of the temperature dependent structure and dynamics of single layer hexagonal boron nitride (h-BN) with defects and grain boundaries, developed using a strictly local equivariant deep neural network, Allegro. The training dataset consisted of ∼30 000 images of h-BN with and without point defects generated with ab initio molecular dynamics simulations, based on density functional theory (DFT), at 500, 1000, and 1500 K. The developed MLIP predicts potential energies and forces with a mean absolute error of 4 meV/atom and 60 meV/Å, respectively. It also reproduces phonon dispersion curves and density of vibrational states of pristine bulk h-BN that are comparable with those obtained from DFT calculations. Using this MLIP to study the motion of the 4|8 grain boundary in h-BN we show that the initial motion of the first unit has an activation barrier of ∼2.2 eV. Moving the grain boundary units past the first shows much lower activation barriers of ∼0.42 eV, suggesting a facile motion of the grain boundary once the initial movement is stimulated. Molecular dynamics simulations of the grain boundary yield a scaled mobility of 1.739 × 10-11 m3/Js at 1500 K which, given the different setups without continuous e-beam irradiation, is not too far from the experimental value of 1.36 × 10-9 m3/Js. The ability to predict grain boundary mobility within reasonable agreement with experiment demonstrates the robustness of the MLIP and its suitability for reliable simulations of defect structures and dynamics in single layer h-BN.

PMID:41989120 | DOI:10.1063/5.0314075

Development of a national root cause analysis system for post-endoscopy upper gastrointestinal cancer

Mon, 13/04/2026 - 11:00

Endosc Int Open. 2026 Mar 16;14:a27883285. doi: 10.1055/a-2788-3285. eCollection 2026.

ABSTRACT

BACKGROUND AND STUDY AIMS: Post-endoscopy upper gastrointestinal cancer (PEUGIC) is a key performance indicator for endoscopy. PEUGIC represents a delay in diagnosis: a patient has an endoscopy that did not diagnose cancer, and another investigation, usually endoscopy, 3 to 36 months later that diagnoses upper gastrointestinal (UGI) cancer. We describe a national system to identify PEUGIC and undertake root cause analysis.

METHODS: This retrospective national study was undertaken in the English National Health Service (NHS) and consisted of: 1) identification of PEUGIC; 2) development of an online platform for root cause analysis; and 3) pooled national analysis of PEUGIC. Two national datasets--Hospital Episode Statistics and National Cancer Registration and Analysis Service's cancer registry--enabled identification of people diagnosed with UGI cancer who had endoscopy in the previous 3 to 36 months without a cancer diagnosis (PEUGIC). The online portal informed every endoscopy provider of their PEUGIC and enabled a comprehensive root cause analysis.

RESULTS: This methodology was successful in identifying 3907 PEUGIC from January 1, 2017 to October 30, 2023. Root cause analysis was completed for 2666 PEUGIC during the study period and represents the world's largest cohort of PEUGIC. 664 (17%) PEUGIC were ineligible on local review as they did not meet study criteria.

CONCLUSIONS: A process to identify PEUGIC across a national healthcare system and to perform root cause analysis is described. The methodology is transferable to other healthcare systems with large national datasets, but even without such datasets, the root cause analysis process developed allows identification of learning from PEUGIC for local endoscopy quality improvement.

PMID:41970682 | PMC:PMC13063305 | DOI:10.1055/a-2788-3285

Improving Context-Aware Personalized Nudging: Using Wearable Sensors to Reduce Sedentary Behavior

Tue, 07/04/2026 - 11:00

Dela J Public Health. 2026 Mar 31;12(1):106-112. doi: 10.32481/djph.2026.03.14. eCollection 2026 Mar.

ABSTRACT

OBJECTIVES: To improve nudge outcome classification accuracy in a context-aware personalized nudging framework using wearable sensor data targeted to reduce sedentary behavior using Just- in-Time Adaptive Interventions (JITAIs).

METHODS: Data were collected using a custom smartwatch application in a free-living observational study conducted at the University of Delaware (Newark, Delaware, USA) between Spring 2021 and Fall 2022. A total of 18 participants were enrolled. The system continuously recorded motion, physiological, and contextual data and delivered adaptive behavioral prompts. A decision- tree model was trained using sitting and walking bouts enriched with contextual features such as time, location, physiological state, and prior intervention outcomes. Behavioral responses were automatically evaluated using sensor-derived outcomes.

RESULTS: The proposed model improved classification accuracy for nudge outcomes from 0.42 to 0.78 across 787 sitting bouts. A walking-nudge model achieved an accuracy of 0.70 on 207 walking bouts. Nudged walking bouts were longer in duration, covered greater distances, and exhibited higher average speeds than non-nudged bouts.

CONCLUSIONS: Context-aware adaptive nudging can improve both the timing and behavioral effectiveness of wearable-based interventions. Incorporating contextual and historical features enables personalized and behaviorally meaningful intervention delivery.

POLICY IMPLICATIONS: Wearable-based adaptive interventions offer a scalable and cost-effective strategy to reduce sedentary behavior and support population-level health promotion.

PMID:41943732 | PMC:PMC13048762 | DOI:10.32481/djph.2026.03.14

Prion Protein-Derived Cell-Penetrating Peptide Inhibits Type II Diabetes-Associated Islet Amyloid Polypeptide Aggregation and Cytotoxicity

Thu, 02/04/2026 - 11:00

Biochemistry. 2026 Apr 2. doi: 10.1021/acs.biochem.5c00634. Online ahead of print.

ABSTRACT

Islet amyloid polypeptide (IAPP) is a 37-residue peptide hormone copackaged and cosecreted with insulin by pancreatic β-cells. A pathological hallmark of type II diabetes is the self-assembly of IAPP into β-sheet rich amyloid fibers, which is associated with β-cell impairment. Previously, we showed that a cell-penetrating peptide (CPP) construct, consisting of a hydrophobic signal sequence coupled to a polycationic nuclear localization signal (NLS)-like sequence, exhibited potent antiprion activity and antagonism of Alzheimer's disease-associated amyloid-β (Aβ) peptide aggregation and neurotoxicity. Here, we have extended this approach toward type II diabetes by assessing the efficacy of the CPP construct, designated as neural cell adhesion molecule-1 (NCAM1)-prion protein (PrP), in inhibiting IAPP oligomerization, fiber formation, and associated cytotoxicity. Using complementary in vitro and in silico experiments, we show that NCAM1-PrP effectively modulates IAPP's toxic structures into nontoxic conformations. This study underlines the potential of our designed CPP-based therapeutic approach as a versatile tool in the battle against amyloid-associated pathologies.

PMID:41926749 | DOI:10.1021/acs.biochem.5c00634

Comparative histopathology of climbing perch<em>, Anabas testudineus</em> challenged with <em>Aeromonas veronii</em> via IM and IP routes

Thu, 02/04/2026 - 11:00

J Adv Vet Anim Res. 2025 Dec 25;12(4):1275-1285. doi: 10.5455/javar.2025.l988. eCollection 2025 Dec.

ABSTRACT

OBJECTIVE: The focal purpose of this investigation was to contrast the pathological changes from different histological observations of Anabas testudineus artificially infected with Aeromonas veronii.

MATERIALS AND METHODS: Intramuscular (IM) and intraperitoneal (IP) injection routes were used to challenge fish with three different bacterial concentrations, including 2.1 × 105, 2.1 × 105, and 2.1 × 104cfu ml-1 of bacteria to investigate the effects of various loads of A. veronii on the histopathological alterations in the skin-muscle, liver, and intestine of A. testudineus during 13 days of post challenge test. Two replicates (n = 10) were used for each of the IM and IP groups, corresponding to the three aforementioned bacterial loads, in the challenge test for this study.

RESULTS: The highest bacterial challenge (2.1× 104 cfu ml-1) groups from both IP and IM produced some prominent clinical signs, e.g., red spots, ulcers, and lesions on the body surface, and highest cumulative mortality (IP = 50% and IM = 40%) compared to the control groups having no pathological signs in all organs. Histopathological alterations observed under the light microscope revealed significant pathologies (e.g., vacuolation and necrosis) in all organs studied, particularly at the highest bacterial loads, compared to the other challenges and control groups. It suggests that varied bacterial loads can produce different types of pathology in various fish organs.

CONCLUSION: Aeromonas veronii can cause mortality and remarkable pathological changes in different organs of A. testudineus. Findings from experimental infections can be used as an effective tool to predict the virulence of pathogens and to develop advanced prevention and health management strategies in aquaculture.

PMID:41923832 | PMC:PMC13037601 | DOI:10.5455/javar.2025.l988

Iatrogenic Anteverted Pelvis After Adult Spinal Deformity Surgery: Is It a Risk Factor for Postoperative Mechanical Complications in a Young Adult Population or a Physiological Variant?

Thu, 26/03/2026 - 10:00

Spine (Phila Pa 1976). 2026 Mar 20. doi: 10.1097/BRS.0000000000005693. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective cohort study based on a multicenter prospectively collected database.

OBJECTIVE: To determine whether postoperative anteverted pelvis (AP) in patients with preoperative normo- or retroverted pelvis (NRP) is associated with increased risk of mechanical or clinical complications after adult spinal deformity (ASD) surgery.

SUMMARY OF BACKGROUND DATA: Pelvic anteversion is a rare spinopelvic morphology, typically considered physiological in young patients with low pelvic incidence. However, its occurrence after ASD correction-especially in patients with initially normo- or retroverted pelvic orientation-raises concerns about its potential impact on postoperative outcomes.

METHODS: From a database of 2043 surgically treated ASD patients, 84 patients with postoperative AP were identified. Based on preoperative pelvic version, patients were categorized into two groups: preoperative AP (n=38) and preoperative NRP converted to postoperative AP (n=46). Demographic, surgical, radiographic, and health-related quality of life (HRQoL) parameters were analyzed at baseline and at 2-year follow-up.

RESULTS: There were no significant differences in age, BMI, or baseline HRQoL between groups. Both groups underwent similar surgical procedures, although the NRP group required more frequent decompression and pelvic fixation. At 2 years, both groups showed significant improvement in ODI and SRS-22 scores. Mechanical complication rates were not significantly different (10.5% in AP vs. 23.9% in NRP, P=0.154). Radiographic analysis showed that postoperative AP patients maintained a lumbar lordosis >60°, despite low or normal pelvic incidence. NRP patients exhibited greater changes in spinopelvic parameters postoperatively.

CONCLUSIONS: Postoperative AP does not appear to be associated with increased mechanical complications, even in patients who were normo- or retroverted preoperatively. These findings suggest that iatrogenic AP may represent a physiological adaptation rather than a pathologic outcome, particularly in younger patients without hip or neuromuscular comorbidities. Pelvic fixation is not necessary in cases of isolated AP when global sagittal balance is restored.

PMID:41887717 | DOI:10.1097/BRS.0000000000005693

A multiplicative behavioral model of DNA replication initiation in cells

Thu, 26/03/2026 - 10:00

Open Life Sci. 2025 Dec 30;20(1):20251229. doi: 10.1515/biol-2025-1229. eCollection 2025.

ABSTRACT

DNA replication is a precisely timed cellular decision rather than a continuous biochemical process. Despite extensive mechanistic detail, no unified framework quantitatively explains how structural, metabolic, chromatin, and phase-dependent factors converge to initiate replication. Here, we introduce the ARCH × Φ model, which defines replication onset as a multiplicative threshold event integrating structural, metabolic, chromatin, and phase-control domains. Derived from the recently formalized ARCH behavioral framework, the model expresses replication initiation as R = Φ(A × D × C), where A denotes the origin-licensing architecture, D the metabolic and kinase drives, C the chromatin context, and Φ the phase-control term governing cell-cycle permissiveness. The model predicts (i) all-or-none S-phase entry, (ii) synergistic inhibition when multiple pathways are partially reduced, and (iii) reversible arrest through checkpoint-mediated suppression of Φ. A simple mathematical formulation enables stability analysis and simulation using standard nonlinear control methods. The framework can be falsified by perturbation-matrix experiments measuring whether replication onset scales multiplicatively rather than additively with A, D, and C. By formalizing replication as a threshold-governed system, ARCH × Φ links molecular control of genome duplication with broader principles of biological decision-making, providing a quantitative bridge between cell-cycle dynamics and systems theory.

PMID:41883401 | PMC:PMC13011602 | DOI:10.1515/biol-2025-1229

Genetic Diversity and Historical Divergence of Malays and Indigenous Populations in Peninsular Malaysia and Northern Borneo

Wed, 25/03/2026 - 10:00

Ann Hum Genet. 2026 Mar 24. doi: 10.1111/ahg.70036. Online ahead of print.

ABSTRACT

Previous studies have highlighted significant genetic structure among Southeast Asian populations, with Northern Borneo natives closely related to Austronesians from Taiwan and the Philippines, and Peninsular Malaysia indigenous populations potentially linked to the indigenous Andamanese. In this study, we analyzed 96 genomes from indigenous populations in Peninsular Malaysia, genotyped with approximately 2 million genome-wide autosomal SNPs, alongside datasets from Singapore cosmopolitan Malays and five native populations from Sabah, Northern Borneo. Our findings reveal distinct genetic structures between indigenous populations and Malays, despite their shared habitat. The Malays exhibit substantial admixture with East Asian, Austronesian, and indigenous Peninsular Malaysian ancestral components. Indigenous populations showed lower within-population diversity and longer linkage disequilibrium compared to benchmark populations. Estimated divergence times suggest that the Semang represent an earlier branching population (∼10,000 years ago), followed by Northern Borneo natives (∼7,600-6,H800 years ago), with Malays diverging more recently. These results support a scenario of successive migration waves into Southeast Asia, providing insights into the genetic history and population structure of the region.

PMID:41877419 | DOI:10.1111/ahg.70036

Cromolyn inhibits PGE<sub>2</sub>-mediated sensitisation of TRPV1 in a GPR35-dependent manner in sensory neurons

Fri, 20/03/2026 - 10:00

Neurosci Lett. 2026 Mar 18:138585. doi: 10.1016/j.neulet.2026.138585. Online ahead of print.

ABSTRACT

There is a pressing need for effective alternatives to opioid analgesics, the development of which requires the identification of novel anti-nociceptive drug targets. Here, we have further investigated the anti-nociceptive properties of a GPR35 agonist, cromolyn, in an in vitro model of inflammatory sensitisation. We used ratiometric Ca2+ imaging of cultured sensory neurons to examine the effect of cromolyn on prostaglandin E2 (PGE2)-mediated sensitisation of the pro-nociceptive ion channel, transient receptor potential cation channel, subfamily V, member 1 (TRPV1). The sensitisation of TRPV1 by PGE2 was inhibited by cromolyn in a GPR35-dependent manner. These observations provide further evidence in support of an anti-nociceptive role for GPR35, highlighting the potential use of GPR35 agonists as analgesics.

PMID:41862074 | DOI:10.1016/j.neulet.2026.138585

Publisher Correction: Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome

Thu, 19/03/2026 - 10:00

Nat Commun. 2026 Mar 18;17(1):2537. doi: 10.1038/s41467-026-69133-5.

NO ABSTRACT

PMID:41851079 | DOI:10.1038/s41467-026-69133-5

Identification of new prognostic molecular markers in glioblastoma: a single-center retrospective study

Mon, 16/03/2026 - 10:00

Oncologist. 2026 Mar 16:oyag095. doi: 10.1093/oncolo/oyag095. Online ahead of print.

ABSTRACT

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary CNS tumor in adults and carries a poor prognosis. Although molecular classification has advanced, patient outcomes remain variable. Next-generation sequencing (NGS) can reveal genomic alterations that, while not yet treatment-guiding, offer prognostic and biological insight. The study aimed to investigate the association between molecular alterations in primary GBM tumors and patient survival outcomes.

MATERIALS AND METHODS: This study analyzed medical records of consecutive GBM patients treated between November 1, 2018 and December 31, 2021 at a comprehensive cancer center, for whom NGS data from the tumor was available. Survival analyses were performed according to clinical, radiological, therapeutic, and molecular data.

RESULTS: Of 199 patients, 38 were excluded: 15 for recurrence-only data and 23 for incomplete molecular data after first progression. In the survival analysis of the cohort (n = 161) adjusted on surgical resection, MGMT promoter methylation status, number of alterations, age, tumor localization, MIB1 and performance status, EGFR substitutions were significantly associated with increased overall survival (OS) (HR = 0.43 [0.26; 0.72], p = 0.001), while CDKN2A/B loss and TP53 substitutions were associated with decreased OS (HR = 1.75 [1.08; 2.84], p = 0.023 and HR = 1.69 [1.04; 2.74], p = 0.034 respectively). NOTCH1 substitutions showed a trend towards improved progression-free survival (PFS) (HR = 0.55 [0.30; 1.01], p = 0.054).

CONCLUSION: We identified new prognostic markers in GBM, showing for the first time that EGFR substitutions improve OS. Validation in external cohorts and preclinical studies is needed.

PMID:41838417 | DOI:10.1093/oncolo/oyag095

Visible-light-assisted degradation of crystal violet using CuO- and ZnO-incorporated (Am-<em>co</em>-BA)@PVA hydrogel nanocomposites

Thu, 12/03/2026 - 10:00

RSC Adv. 2026 Mar 10;16(15):13332-13346. doi: 10.1039/d6ra00342g. eCollection 2026 Mar 9.

ABSTRACT

Industrial effluents containing dyes such as crystal violet (CV) have adverse environmental effects due to their chemical inertness, toxicity and nonbiodegradability. Conventional separation techniques used to remove these pollutants are often inefficient; however, photocatalytic degradation using hydrogel photocatalysts is an effective and sustainable approach for wastewater treatment. CuO and ZnO nanoparticles (NPs) were successfully synthesized via a common co-precipitation method. The prepared metal oxide NPs were then incorporated into the hydrogel matrix to form hydrogel nanocomposites. For hydrogel preparation, polyvinyl alcohol (PVA) was used as a polymer, acrylic amide (Am) and butyl acrylate (BA) were used as monomers, and ammonium persulphate (APS) was used as an initiator. The successful fabrication of the hydrogel nanocomposite was verified using FTIR spectroscopy, XRD, SEM, and Brunauer-Emmett-Teller (BET) analysis. From FTIR spectroscopy data, the interaction and cross-linking of monomers and the polymer matrix were confirmed. The average crystallite size and uniform incorporation of metal oxide NPs into the hydrogel network were studied using XRD parameters. SEM images showed that after the integration of spherical-shaped metal oxide NPs into the hydrogel network, the surface of the hydrogel nanocomposite became rough and stratified, and the BET results indicated that the specific surface areas of ZnO- and CuO-doped hydrogel composites were 4.0835 cm2 g-1 and 4.9142 cm2 g-1, respectively. The photocatalytic activity of the synthesized hydrogel nanocomposites was investigated using an initial crystal violet (CV) concentration of 5 ppm to evaluate their degradation efficiency under visible light irradiation. The results showed that within an irradiation time of 110 min, the photocatalytic removal efficiency of CV reached 92.86% for the ZnO-doped hydrogel nanocomposite and 94.21% for the CuO-doped hydrogel nanocomposite at pH 9 using 0.01 g of the photocatalyst under visible light irradiation. The photocatalytic activity followed pseudo-first-order kinetics with rate constants of 0.0154 min-1 and 0.0148 min-1 for CuO- and ZnO-doped hydrogel nanocomposites, respectively. Furthermore, scavenging experiments showed that ˙OH radicals were the prominent species responsible for the degradation of CV. In this study, metal oxide-doped hydrogel nanocomposites were explored as sustainable and efficient photocatalysts for environmental remediation. The synthesized materials exhibited promising efficacy for the treatment of dye-contaminated wastewater.

PMID:41815394 | PMC:PMC12973283 | DOI:10.1039/d6ra00342g

Assessment of Anti-Diarrheal Effect of Schaftoside Through μ-Opioid and Cyclooxygenase Interaction Pathway: In Vivo and In Silico Studies

Tue, 10/03/2026 - 10:00

Neurogastroenterol Motil. 2026 Mar;38(3):e70269. doi: 10.1111/nmo.70269.

ABSTRACT

BACKGROUND: Diarrhea remains a significant global health burden, necessitating the discovery of safer and more effective therapeutic agents. Schaftoside (SCF), a bioactive flavonoid, has demonstrated diverse pharmacological properties, though its anti-diarrheal potential remains underexplored. This study aimed to evaluate the anti-diarrheal activity of SCF and elucidate its underlying mechanisms.

METHODS: The in vivo efficacy of SCF was assessed in a castor oil-induced diarrhea model using 2-day-old chicks. Animals were pretreated orally with SCF (5, 10, 20 mg/kg), loperamide (3 mg/kg), or bismuth subsalicylate (10 mg/kg). Diarrheal parameters, including latency period, stool frequency, and secretion weight, were recorded. Complementary in silico molecular docking was performed to investigate SCF's binding affinity (BA) and interactions with the μ-opioid receptor (PDB ID: 8EFB), cyclooxygenase-1 (COX-1; 6Y3L), and cyclooxygenase-2 (COX-2; 5F19).

RESULTS: SCF administration produced a significant, dose-dependent anti-diarrheal effect. The highest dose (20 mg/kg) markedly reduced diarrheal secretion and stool frequency while prolonging the onset of diarrhea, with efficacy comparable to standard drugs. In silico analysis revealed strong binding affinities of SCF for the μ-opioid receptor (-9.8 kcal/mol) and COX-2 (-9.0 kcal/mol), supported by multiple hydrogen bond and hydrophobic interactions with key active-site residues.

CONCLUSION: These findings demonstrate that SCF possesses substantial anti-diarrheal activity, potentially mediated through dual modulation of the μ-opioid receptor and COX-2 pathways. SCF represents a promising natural candidate for further development as a therapeutic agent for diarrhea management.

PMID:41804700 | DOI:10.1111/nmo.70269

Elucidating the rate-limiting step of CO<sub>2</sub> electroreduction on metal phthalocyanines

Tue, 10/03/2026 - 10:00

Nat Commun. 2026 Mar 10. doi: 10.1038/s41467-026-70445-9. Online ahead of print.

ABSTRACT

Immobilized molecular catalysts, especially metal phthalocyanines, have garnered substantial interest for the electrochemical CO2 reduction reaction (CO2RR) due to their well-defined active sites and promising performance. Yet, the reaction mechanism, particularly the rate-limiting step, remains debated. Here, using electrochemical analysis and kinetic isotope effect measurements, we identify the rate-limiting step of CO2RR to CO on immobilized metal phthalocyanines, with Au as a reference. Notably, cobalt phthalocyanine (CoPc) exhibits dispersion-dependent kinetics: protonation of adsorbed *CO2 is rate-limiting on molecularly dispersed CoPc supported on carbon nanotubes (CoPc/CNTs), whereas CO2 adsorption becomes rate-limiting on aggregated CoPc due to a weakened interfacial electric field at the Co active sites. This mechanistic distinction further elucidates the role of electrolyte anions: HCO3-, largely a spectator on Au, promotes CO2RR on CoPc/CNTs by serving as a proton donor in the rate-limiting protonation step. These findings provide mechanistic insights into CO2RR on metal phthalocyanines and guide the rational design of molecular electrocatalysts.

PMID:41803170 | DOI:10.1038/s41467-026-70445-9

Sex change in clownfish as an ARCH-governed biological decision

Thu, 05/03/2026 - 11:00

Horm Behav. 2026 Mar 4;180:105907. doi: 10.1016/j.yhbeh.2026.105907. Online ahead of print.

ABSTRACT

Single causal factors rarely govern biological transitions that are rapid, discrete, and largely irreversible. Instead, they emerge from the coordinated alignment of multiple regulatory domains that collectively determine whether execution occurs. Here, we apply the ARCH framework-a multiplicative, threshold-based model of biological decision-making-to socially controlled sex change in clownfish (Amphiprion spp.). The ARCH model formalizes execution as requiring convergence across four jointly necessary domains: Archetype (latent structural readiness), Drive (endocrine activation favoring ovarian differentiation), Context (social and environmental permissiveness), and Phase (temporal, developmental, and physiological gating). Using evidence from behavioral, endocrine, molecular, and developmental studies, we show that sex change in clownfish exhibits defining properties of ARCH-governed decisions, including zero-term veto effects, persistence of metastable intermediate states, non-linear interactions among regulatory inputs, and hysteresis following commitment. Removal of the dominant female is necessary but insufficient for transition; endocrine manipulations can veto execution despite social permissiveness, and stress and developmental constraints modulate the timing and probability of commitment. Framing sex change as an ARCH-governed biological decision unifies disparate empirical findings and generates explicit, falsifiable predictions regarding how perturbations across domains interact to control the probability, timing, and stability of sexual transition. More broadly, this work positions sequential hermaphroditism as a model system for studying threshold-governed decision architectures linking social context, endocrine signaling, and irreversible behavioral change.

PMID:41785597 | DOI:10.1016/j.yhbeh.2026.105907

Evaluation of antimicrobial resistance governance across 193 countries to inform the 2026 Global Action Plan update

Tue, 03/03/2026 - 11:00

Nat Med. 2026 Mar 3. doi: 10.1038/s41591-026-04257-1. Online ahead of print.

ABSTRACT

Antimicrobial resistance (AMR) poses a major global health threat, yet the effectiveness of national action plans (NAPs) remains uncertain. Here we developed a multidimensional One Health governance index through a structured Delphi expert consultation to evaluate AMR governance across 193 countries (2017-2022), integrating 269 policy documents, expert-weighted indicators and multinational survey and surveillance datasets. Difference-in-differences and joinpoint regression analyses were used to link governance to antimicrobial use, AMR prevalence and AMR-related mortality. Global governance scores improved from 30.7 to 44.5/100, although implementation and monitoring lagged behind policy design, particularly in animal and environmental sectors. A significant increase in AMR prevalence scores was observed only 5 years after NAP adoption (two-stage difference-in-differences, β = 2.43, 95% confidence interval (CI) 1.02-3.85, P < 0.05), underscoring the delayed impact of policy. Multisector engagement (early-adopting countries, β = 0.05, 95% CI 0.02-0.08, P < 0.01) and antimicrobial use surveillance system (early-adopting countries, β = 0.05, 95% CI 0.03-0.07, P < 0.01) showed the strongest associations with improvement in AMR outcomes. As the 2026 Global Action Plan update approaches, sustained financing and integrated One Health surveillance, with stronger environmental and agricultural engagement, are essential for translating NAPs into sustained reductions in resistance.

PMID:41776078 | DOI:10.1038/s41591-026-04257-1

Diet Quality as an Associated Factor for Liver Function Enzyme Abnormalities Among Women of Reproductive Age

Tue, 03/03/2026 - 11:00

Cureus. 2026 Jan 29;18(1):e102608. doi: 10.7759/cureus.102608. eCollection 2026 Jan.

ABSTRACT

Background Elevated liver enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are early indicators of liver dysfunction in non-alcoholic fatty liver disease (NAFLD). The prevalence of NAFLD is increasing in Bangladesh, with studies indicating a higher prevalence among women. Additionally, rapid dietary transitions toward energy-dense foods rich in fat and sugar have contributed to the rising burden of non-communicable diseases. This study aimed to investigate the association between dietary intake, diet quality indicators, and elevated liver enzymes (ALT and AST) among women of reproductive age in Bangladesh. Methods A cross-sectional study was conducted among 240 women of reproductive age (15-49 years) randomly selected from community households in three selected districts of Bangladesh. Anthropometric and socioeconomic data were collected using standardized tools. Dietary intake was assessed using a single 24-hour dietary recall method and a Food Frequency Questionnaire (FFQ). Three complementary indices were applied to evaluate diet quality: Dietary Diversity (DD), Food Consumption Score (FCS), and the Bangladesh Healthy Eating Index (BD_HEI). The participant's blood was collected after overnight fasting. Serum ALT and AST levels were measured using a biochemical analyzer, and elevations in liver enzymes were defined according to standard clinical cut-off values. Descriptive and inferential statistics were performed using STATA version 15.1 (Stata Corp LLC, College Station, TX, USA). Results Among the 240 participants, 69 (28.7%) exhibited elevated ALT and/or AST levels, while 171 (71.3%) had normal values. Participants with elevated liver enzymes had higher intake of saturated fat (5.89 vs. 4.41 g, IQR: (3.84-9.63 vs. 2.98-7.15), p =0.010), cholesterol (55.21 vs. 30.41 mg, IQR: (15.21-137.92 vs. 0-106.61), p = 0.015). Participants with elevated liver enzymes had significantly lower FCS scores (23.2% vs. 9.4%, p = 0.014) but higher DD (27.5% vs. 15.8%, p = 0.036) as compared to normal liver enzymes. Multivariable logistic regression revealed that low FCS significantly increased the odds of elevated liver enzymes (AOR = 3.64, 95% CI: 1.53-8.62, p = 0.003). Conclusion This study highlights a significant association between poor FCS and liver enzyme abnormalities among Bangladeshi women of reproductive age. Integrating dietary quality interventions into reproductive health and noncommunicable disease (NCD) prevention programs could play a vital role in maintaining liver health and metabolic well-being in this vulnerable population.

PMID:41773114 | PMC:PMC12949846 | DOI:10.7759/cureus.102608

The landscape of the intestinal microbiome among patients with newly diagnosed invasive breast cancer and ductal carcinoma in situ (DCIS)

Fri, 27/02/2026 - 11:00

NPJ Breast Cancer. 2026 Feb 27. doi: 10.1038/s41523-026-00922-3. Online ahead of print.

ABSTRACT

The intestinal microbiome shapes immune responses and is associated with patient outcomes in cancer following immunotherapy. We evaluated differences between the intestinal microbiome profiles of patients with early-stage invasive breast cancer (BC) and ductal carcinoma in situ (DCIS) by subtype using whole genome metagenomic sequencing. There were no significant differences in microbiome composition between DCIS and invasive BC as measured by alpha diversity (p = 0.20, ANOVA) or beta diversity (p = 0.52, PERMANOVA). Within invasive BC, patients with hormone receptor-positive (HR + )/HER2 + BC differed significantly in beta diversity relative to other subtypes (p < 0.05), with differences in six species (q < 0.25). Bacteroides ovatus was significantly more abundant in patients with stage III BC vs. stage I (p = 0.0003). Functional pathway analysis using HUMAnN3 revealed stage-specific enrichment of amino acid biosynthesis and nucleotide-related pathways. Altogether, these findings highlight potential microbial signatures associated with BC subtype and stage.

PMID:41760690 | DOI:10.1038/s41523-026-00922-3

Rank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis

Fri, 27/02/2026 - 11:00

Nat Commun. 2026 Feb 27. doi: 10.1038/s41467-026-70020-2. Online ahead of print.

ABSTRACT

Rank signaling regulates mammary gland development and epithelial differentiation. While Rank is expressed in both basal and luminal cells, its basal-specific role is unclear. Here, using inducible basal-specific Rank expression and lineage tracing, we show that Rank signaling regulates basal cell identity in postnatal mammary glands. Increased basal Rank activity disrupts basal and luminal identities, causing aberrant luminal-like differentiation, lactation defects, and premalignant lesions composed of hybrid basal-derived cells that progress to basal and luminal adenocarcinomas. Conversely, Rank loss reduces tumor formation and also impairs cell identity. Mechanistically, proteomic, transcriptomic, and chromatin analyses reveal that Rank activation drives epigenetic remodeling, leading to basal identity loss and tumor initiation. A basal Rank gene signature correlates with ductal carcinoma in situ recurrence, as well as poor outcomes in luminal breast cancers. Thus, basal Rank-driven lineage infidelity promotes pre-invasive lesions and transition to invasive breast cancer in females.

PMID:41760656 | DOI:10.1038/s41467-026-70020-2