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Machine learning-assisted Mn-N-C nanozyme colorimetric sensor array for trace-level detection of biogenic amines in meat.

Accurate detection of biogenic amines (BAs) in meat remains challenging due to their high structural similarity and co-occurrence. Herein, an Mn-N-C nanozyme was synthesized via a metal-organic framework confined pyrolysis strategy, possessing excellent oxidase (OXD)- and peroxidase (POD)-like activities. The dual enzyme-like activity showed Km values of 0.1584 mM (OXD) and 0.1498 mM (POD), respectively, in detection system. Leveraging these properties, a colorimetric sensor array was constructed, enabling the detection of four representative BAs within a concentration range of 2-10 ppm with 100% classification accuracy. In addition, a concentration independent recognition model based on an artificial neural network was developed to address signal nonlinearity interference in meat. The integrated system achieved accurate trace-level identification of BAs in perishable fish, pork, and chicken, demonstrating its applicability for early-stage BAs monitoring and quality deterioration warning during storage and transportation.

Biogenic Amines

Ifebemtinib plus garsorasib in previously treated metastatic colorectal cancer with KRASG12C mutation: a multicentre, randomised, phase 1b/2 trial.

BACKGROUND: Ifebemtinib is a potent oral focal adhesion kinase inhibitor. Preclinical evidence supports combining ifebemtinib with the KRASG12C inhibitor garsorasib. This study aimed to evaluate this combination in KRASG12C-mutated solid tumours. METHODS: This multicentre, phase 1b/2 study had a phase 1b component to establish the recommended phase 2 dose and a phase 2 multitumour expansion component. In phase 1b, the safety and tolerability of ifebemtinib combined with garsorasib was assessed using a 3 + 3 design in KRASG12C-mutated solid tumours. No dose-limiting toxic effects were observed, and the recommended phase 2 dose was established as ifebemtinib 100 mg orally once daily plus garsorasib 600 mg orally twice daily. Here, we report the results of the cohort of previously treated KRASG12C-mutated metastatic colorectal cancer from phase 2 expansion. Eligible patients (aged ≥18 years) who had histologically confirmed locally advanced or metastatic colorectal cancer harbouring the KRASG12C mutation, an Eastern Cooperative Oncology Group performance-status score of 0 or 1, and had disease progression after previous irinotecan-based or oxaliplatin-based combination therapy, were recruited from seven of nine participating tertiary hospitals in China. On the basis of the recommended phase 2 dose, phase 2 comprised a single-arm study to evaluate the safety and efficacy of ifebemtinib combined with garsorasib and an open-label, randomised study in which patients were randomly assigned (1:1) to receive ifebemtinib plus garsorasib or garsorasib alone, by use of centralised computer-generated block randomisation with no stratification. Investigators were masked to the block size. The primary efficacy endpoint of phase 2 was investigator-assessed objective response rate (Response Evaluation Criteria in Solid Tumours, version 1.1), assessed in the safety analysis set in the single-arm study and in all randomly assigned patients (intention-to-treat population) in the randomised study. At least six objective responses (safety analysis set) were required in the single-arm study to proceed to the randomised study. This study is registered with ClinicalTrials.gov, NCT06166836 and NCT05379946, and is active but not recruiting. FINDINGS: Between April 7, 2023 and Dec 13, 2024, 51 patients were enrolled in phase 2 (15 in the single-arm study and 36 in the randomised study). In the single-arm study, the median age was 53 years (IQR 39 to 63), nine (60%) patients were female, six (40%) were male, and all were Asian. In the randomised study, the median age was 51 years (IQR 42 to 59) in the combination group and 63 years (IQR 54 to 66) in the monotherapy group, 24 (67%) were female, 12 (33%) were male, and all patients were Asian. In the single-arm part, the confirmed objective response rate was 46·7% (95% CI 21·3 to 73·4). Seven patients had partial responses, triggering progression to the randomised study. In the randomised study, the confirmed objective response rate was 38·9% (95% CI 17·3 to 64·3) with the combination therapy versus 16·7% (95% CI 3·6 to 41·4) with garsorasib alone (between-group difference 22·2%, 95% CI -7·7 to 49·1; one-sided p=0·068). In the single-arm study, grade 3 treatment-related adverse events occurred in four (27%) of 15 patients, and in the randomised study, grade 3 treatment-related adverse events occurred in six (33%) of 18 patients in the combination group and five (28%) of 18 in the garsorasib group. Grade 3 treatment-related adverse events occurring in at least two patients were diarrhoea (six [18%]), proteinuria (two [6%]), and intestinal obstruction (two [6%]) in patients treated with combination therapy (combined), and increased alanine aminotransferase and γ-glutamyltransferase (two [11%] each) in patients treated with garsorasib alone. Serious adverse events occurred in ten (30%) patients in the combination group and in four (22%) patients in the monotherapy group. One patient in the garsorasib monotherapy group died due to the underlying malignancy within 30 days after completing study treatment, which was reported as a serious adverse event. The death was assessed by the investigators as not related to garsorasib. No grade 4 treatment-related adverse events or treatment-related deaths were reported across all cohorts. INTERPRETATION: The combination of ifebemtinib and garsorasib showed promising anticancer activity and manageable safety profile in previously treated patients with KRASG12C-mutated metastatic colorectal cancer. Although the improvement in response rate did not reach statistical significance in the randomised study, these findings support further evaluation of ifebemtinib plus garsorasib in this population. FUNDING: InxMed, InventisBio, National Natural Science Foundation of China, the Jian Bing Ling Yan + X Research and Development Program of Zhejiang Province, and the Zhejiang Province Medical and Health Science and Technology Plan Project.

Humans

Transcriptomic insights into the molecular mechanism of antifouling agent-induced settlement inhibition in the Pacific oyster Crassostrea gigas.

Marine biofouling remains a persistent challenge to maritime industries and marine ecosystems worldwide. In this study, we systematically evaluated the acute toxicity, settlement inhibitory efficacy, and underlying molecular mechanisms of an N-oleyl-1,3-propanediamine-based antifouling agent using pediveliger larvae of the Pacific oyster Crassostrea gigas. The 96 h-LC50 of the agent was determined to be 0.81 mg/L, and exposure to 1.68 mg/L achieved complete larval settlement inhibition without inducing significant acute toxicity. Transcriptomic analysis identified 791 differentially expressed genes, dominated by downregulated genes associated with ribosomal function, translation, cell adhesion, and cytoskeletal organization. The agent exerts its inhibitory effect primarily through the global suppression of protein synthesis, disruption of cell-substrate adhesion and cytoskeletal integrity, and induction of proteotoxic stress responses. These findings reveal a multi-pathway molecular mechanism underlying antifouling agent-induced settlement inhibition in oyster larvae and provide key molecular biomarkers to support the development of eco-friendly antifouling technologies.

Animals

Biological mechanisms of atropine in myopia control (Review).

Myopia is now recognized as a progressive, potentially sight‑threatening disease rather than just a refractive error, with its prevalence rising rapidly worldwide due to its high occurrence, major vision losses and huge public health cost. The World Health Organization estimates that 2.6 billion individuals in the world were myopic in 2020 this figure is projected to increase to 3.364 billion by 2030. Although myopia may be better controlled in its early stages, it may not be completely reversed at this time. Of all of the methods for controlling myopia, atropine, a muscarinic receptor antagonist, remains an effective pharmacological option for slowing myopia progression in children. However, the mechanisms of action of atropine remain to be fully elucidated. This review provided a systematic review for myopia epidemiology, pathogenesis, the effects and side effects, as well as up‑to‑date possible mechanisms, in the hope of facilitating that researchers in this field elucidate its underlying mechanisms so that clinical ophthalmologists may be able to better control this disease.

Humans

A review on the environmental distribution, toxic effects, bioaccumulation characteristics and risk assessment of short-chain chlorinated paraffins.

Chlorinated paraffins (CPs) are synthetic chemicals, widely used as flame retardants and plasticizers. As emerging contaminants, short chain chlorinated paraffins (SCCPs) have attracted tremendous attention due to their persistence, chronic toxicity, long-range transport potential and bioaccumulation potential. This review synthesizes global data on SCCPs' environmental occurrence, toxicological impacts, and bioaccumulation characteristics. SCCPs are ubiquitously detected in various environmental media, including water, sediment, air, soil, and biota. Ecotoxicological studies reveal that SCCPs have lethality, carcinogenicity, growth and developmental toxicities, organs toxicities and endocrine-disrupting effects across species, which pose risks to ecological systems and human health. In addition, the bioaccumulation effects of SCCPs in terrestrial and aquatic ecosystems were analyzed, and proposed the key factors affecting the bioaccumulation of SCCPs. Finally, the risk assessment of SCCPs contamination in the surface water and the soil was carried out, and all soil and most water bodies were found to be low risk. The present study could provide scientific basis and reference for environmental management of CPs products.

Paraffin

Longitudinal Repeated Protein Measurements in a Multiethnic Cohort Identify Novel Diabetes Biomarkers That Reveal Unique Disease Pathways.

There is up to a fourfold increase in diabetes biomarkers identified with longitudinal repeated versus single time point proteomic measurements. The increase in biomarkers identified with longitudinal repeated measurements is supported by a similar proportion being nominated as causal for type 2 diabetes with Mendelian randomization. Proteins unique to the longitudinal repeated analyses highlighted biological pathways (e.g., posttranslational protein modification and cellular structure and cycle regulation) that were distinct from pathways enriched among the shared proteins (e.g., small-molecule metabolic and catabolic processes). Longitudinal protein measurements identify additional novel disease biomarkers and disparate biological pathways compared with single measurement analyses.

Journal Article

Effect of Narrative-Based Palliative Care on Psychological Stress, Quality of Life, and End-of-Life Acceptance in Elderly Terminal Cancer Patients and Their Families.

ObjectiveThis study aimed to preliminarily evaluate the impacts of narrative-based palliative care on psychological stress, end-of-life acceptance, and quality of life in elderly terminally ill cancer patients and their family caregivers.MethodsThis single-center, small-sample randomized controlled study enrolled 50 elderly terminal cancer patients. Patients were randomly assigned to either the observation group or the control group (n = 25 each). The observation group received narrative-based palliative care, while the control group received routine standard care. Family psychological stress was assessed using the Relative Stress Scale (RSS), and patients' perceived stress was evaluated with the Perceived Stress Scale-10 (PSS-10). Caregiver satisfaction was measured using a hospital-developed questionnaire. Patients' quality of life was evaluated using the SF-36, Chinese Version of the Death Attitude Profile (DAP-C), and Pittsburgh Sleep Quality Index (PSQI), respectively.ResultsBaseline characteristics did not differ significantly between the two groups (P > .05). Post-intervention, the observation group demonstrated significantly lower psychological stress among family members and higher caregiver satisfaction (P < .05). Patients in the observation group reported better quality of life, improved sleep, and greater acceptance of death than those in the control group (P < .05).ConclusionAs a small-sample, single-center study, these findings offer preliminary evidence that narrative-based palliative care may reduce psychological stress in elderly terminal cancer patients and caregivers while enhancing patients' quality of life, sleep quality, and acceptance of death. However, the limited sample size, single-site design, and narrow inclusion criteria restrict generalizability. Larger multicenter trials are needed to confirm these results.

Humans

A point-of-use SERS assay for rapid detecting difenoconazole and flusilazole residues in fruit juices using Au/COF substrate.

We developed a ready-to-use surface-enhanced Raman scattering (SERS) sensor for rapid, pretreatment-free detection of difenoconazole (DIF) and flusilazole (FLU) in peach and lychee juices. The substrate combines Au nanoparticles (AuNPs) with covalent organic frameworks (COF) and is implemented on a portable 25-well plate, enabling in situ testing. Juices can be directly applied to the SERS-active Au/COF composite, allowing simultaneous adsorption and signal generation. The correlation between SERS intensity and logarithmic concentration yielded R-values between 0.925 and 0.986, meeting the monitoring needs of non-laboratory scenarios. The entire workflow completes within 12&#xa0;min, offering a faster alternative to conventional methods while maintaining high sensitivity and reproducibility. Detection limits reach 0.96-1.22&#xa0;ppb for DIF and FLU, both of which are below the regulatory maximum residue limits. Distinct SERS fingerprints enable reliable discrimination of mixed residues across juice matrices, supporting rapid on-site monitoring and cost-effective pesticide surveillance.

Triazoles

Animal-assisted therapy in pediatric urodynamics.

INTRODUCTION/BACKGROUND: Urodynamics (UDS) is associated with high levels of patient anxiety/discomfort. Children are often unable to complete UDS, with anesthesia needed to place catheters. Animal-assisted therapy (AAT) has been used in a variety of settings, but it has not been studied for UDS before. OBJECTIVE: To determine if AAT can increase success of completing UDS testing without anesthesia in children who were previously unable to perform UDS, along with decreasing distress levels. STUDY DESIGN: We performed a pilot case series of 7 patients (2 female, 5 male) aged 4-16 (mean 9.7) years who previously were unable to complete UDS awake, with AAT prior to and during the UDS procedure. A visual analog scale (VAS) was used to measure patient stress levels before and after AAT. RESULTS: We were able to successfully complete UDS testing with AAT in 6 of the 7 patients (85.7%) without the need for anesthesia. VAS scores decreased from before to after AAT (5.4-3.6, p = 0.020) but with discrepancy when compared to UDS success. DISCUSSION: Our study was the first to describe AAT during UDS. Our preliminary data found AAT to be feasible in UDS. Subjective distress may not correlate with procedural success. AAT in UDS may be more beneficial in certain populations, such as anxious children who previously were unable to tolerate UDS, and not in others such as severe neurodevelopmental conditions. Our study was limited by the small sample size, a single provider, single center, single therapy dog, inclusion of a specific population of patients, and no control group due to this being a pilot study. CONCLUSION: AAT for certain children undergoing UDS testing could help improve the ability to complete the testing without anesthesia. Further studies are needed to fully demonstrate its usefulness in UDS.

Humans

Insights into the regulation of the HOTAIR proximal promoter.

HOTAIR (HOX transcript antisense RNA) is a HOXC-cluster long intervening non-coding RNA (lincRNA) whose cancer relevance is tightly coupled to how its transcription is wired into hormone, hypoxia, inflammatory, and developmental signaling. HOTAIR is known to associate with cancer cell proliferation, motility, tumor invasion, and metastasis. The present mini-review focuses on the regulatory architecture and mechanistic complexity of HOTAIR transcriptional regulation, with emphasis on three organizing principles. First, we consider the impact of promoter choice between a canonical proximal promoter (P1), which supports the 2.2-2.4 kb transcript, and an alternative upstream promoter/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer-promoter communication between HOTAIR distal enhancer and P1/P2. Third, we summarize the recent epigenetic and epi-transcriptomic mechanisms involved in HOTAIR transcript initiation and elongation. A combination of these events determines isoform-specific transcription to govern cell-type-, context-, and cancer specific modulation of HOTAIR expression that promotes tumor formation and cancer progression. Finally, the review proposes how large-scale RNA datasets, long-read sequencing, and isoform-specific studies can refine our understanding of this versatile lincRNA's regulation.

Humans

Heat stress in cereal crops: reproductive development and grain filling.

Increasingly frequent extreme heat events threaten cereal production and food security under a changing climate. The reproductive-to-grain formation continuum of cereals is particularly vulnerable to elevated temperatures, as heat stress disrupts developmental processes from inflorescence formation and fertilization to grain filling and quality establishment. These disruptions reduce reproductive success, impair yield formation, and compromise grain quality. A comprehensive understanding of the developmental, physiological, molecular, and genetic basis of cereal heat tolerance is therefore essential for developing climate-adapted crops. This review summarizes recent advances in understanding heat stress during cereal reproduction and grain filling across major cereal crops. We first discuss how heat stress affects sequential developmental processes, including inflorescence development, gametophyte development, flowering and pollination, fertilization, and grain filling. We then integrate emerging evidence on cross-cutting mechanisms that connect stage-specific heat responses, focusing on hormonal and redox homeostasis, carbohydrate metabolism and source-sink coordination, proteostasis and endomembrane organization, and genome stability and multilayered gene regulation. Finally, we summarize the genetic basis of cereal heat tolerance by highlighting genetic determinants, favorable alleles, and their potential applications in breeding. We further discuss current bottlenecks and future opportunities for breeding heat-tolerant cereals.

Cereals

The hidden threat from food-derived carbon dots: Formation, biodistribution, and potential health risks.

Food-derived carbon dots (CDs) are a new class of carbon-based nanoparticles generated during the thermal processing of food matrices. These nanomaterials have been extensively studied for their unique fluorescence, good biocompatibility, and tunable surface chemistry in food detection, intelligent packaging, and biomedical applications. However, their nanoscale size and high surface activity have raised safety concerns regarding biological interactions, in vivo biodistribution, and potential long-term health hazards. Although CDs have traditionally been regarded as low-toxicity materials due to their favorable biocompatibility, the potential hidden risks of CDs have not received sufficient attention. CDs exhibit dose-dependent toxicity, not only accumulating in various tissues and organs but also potentially inducing oxidative stress and interfering with cellular metabolic functions. Therefore, this review summarizes the advances in sources, synthetic strategies, and core properties of CDs, with a special focus on in vivo biological interactions, fates, and potential safety challenges. In addition, it is proposed that the standardized detection and risk assessment system should be established to further explore the long-term health effects of CDs under real dietary exposure, thereby ensuring their safety and sustainable application.

Carbon Quantum Dots

A Phase I Study Assessing the Safety, Tolerability, and Pharmacokinetics of Yinfenidone: A Novel, Potent Drug for Idiopathic Pulmonary Fibrosis Treatment in Healthy Chinese Subjects.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a median survival of only 2-3 years after diagnosis. Yinfenidone (HEC585) possesses the potential to inhibit the proliferation of pulmonary fibroblasts, making it a promising candidate for the treatment of IPF. This study assessed the safety, tolerability, pharmacokinetics, and metabolic profile of Yinfenidone hydrochloride capsule in healthy Chinese subjects. METHODS: This single-center, randomized, double-blind, placebo-controlled, single ascending-dose trial included seven dose groups(20, 50, 100, 200, 400, 600, and 800 mg). Each group enrolled8 healthy subjects: 6 received Yinfenidone hydrochloride capsules and 2 received matching placebo under fasting conditions. Serial pharmacokinetic (PK) blood samples were collected pre-dose and post-dose, liquid chromatography-tandem mass spectrometry was used to analyze the plasma concentrations of Yinfenidone. Additionally, metabolic biotransformation of Yinfenidone in plasma were conducted in the 100 mg dose group. Safety and tolerability endpoints were monitored via physical examinations, vital signs measurements, clinical laboratory tests, 12-lead electrocardiography (ECG), and adverse events (AEs) documentation throughout the trial. FINDINGS: Yinfenidone was rapidly absorbed, with a median maximum plasma concentration (Tmax) of 1.8-3.0 hours, and had a mean half-life (t1/2) ranging from 31.9 to 62.0 hours. Within the 20-100 mg dose range, systemic drug exposure generally increased with ascending dose, above 100 mg, exposure increased less than proportionally to dose. Metabolite profiling in the 100 mg group revealed that the parentcompound predominated in plasma, with metabolic pathways including mono-oxygenation and N-dealkylation. All reported AEswere mild, classified as Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1. No serious AEs observed; no subject discontinued the trial due to AEs. Single oral doses of 20-800 mg Yinfenidone hydrochloride capsules administered under fasting conditions demonstrated favorable safety and tolerability profiles in healthy Chinese subjects. IMPLICATIONS: Yinfenidone exhibited rapid absorption (median Tmax, 1.8-3.0 hours) and a long terminal t1/2 ranging from 31.9 to 62.0 hours in this single ascending-dose study, indicating that Yinfenidone can be taken once a day in subsequent clinical studies. Yinfenidone mainly exists in human plasma as the original drug and is metabolized through a variety of metabolic pathways. The AEs observed with Yinfenidone in this study, such as diarrhea, nausea, and dizziness, were similar to those reported with pirfenidone. Overall, Yinfenidone demonstrated a favorable safety and tolerability profile in this cohort of healthy subjects.

Adult

Quo vadis, BGA? A collaborative EDNAP exercise on the challenges and progress in forensic biogeographical ancestry inference.

There is a broad consensus that forensic tests for the prediction of externally visible characteristics (EVC) and analysis of biogeographic ancestry (BGA) of an individual are technically reliable. However, interpretation of the results and population-specific genotype distribution patterns remains challenging. EVC and BGA analyses provide valuable information for population genetics studies and as investigative leads for criminal cases, as well as for historical and contemporary identification tests. However, inaccurate or incorrect predictions, for example, from subjective bias in the interpretations made, have the potential to misdirect police investigations. The legal situation regarding EVC and BGA testing varies by country: ranging from countries where it is explicitly prohibited, to those without specific regulations on biogeographic ancestry prediction, and others that have already enacted laws governing its use. The reluctance to utilize these analyses is not only due to legal restrictions and data protection concerns, but also to initial limited sets of sufficiently comprehensive forensic DNA assays. Forensic BGA marker panels typically contain up to &#x223c;300 SNPs. This relatively small number of genetic markers, along with limited reference population data, complicates the interpretation of results from donors of unknown origin. This paper presents the results of a collaborative EDNAP study, which, for the first time, evaluated the approach to reporting EVC and BGA data between international laboratories. For the study, DNA from nine individuals with self-reported ancestry was collected and analysed using various forensic panels differing in the number and composition of ancestry-informative markers genotyped, comprising: the Precision ID mtDNA Whole Genome Panel, the VISAGE Basic Tool and the VISAGE Enhanced Tool for Appearance and Ancestry Prediction, and the Ion AmpliSeq&#x2122; PhenoTrivium Panel. To ensure full data protection, all SNP genotypes and uniparental marker haplotypes obtained were not shared with third parties. Instead, the genetic data were analysed using a range of commonly used population analysis software packages. These analysis outcomes were then distributed to twelve European forensic laboratories (both academic and law enforcement institutions), who were asked to prepare reports based on their interpretation of the phenotypes and ancestry they inferred from the analysis data. A questionnaire sent alongside the genetic information, aimed to evaluate which difficulties were encountered by the participants in processing the BGA analysis data they were given.

Humans

Effects of erector spinae plane block on postoperative pain in patients undergoing implant-based breast reconstruction for breast cancer: a randomized controlled trial.

BACKGROUND: Implant-based breast reconstruction after mastectomy causes acute pain. OBJECTIVE: To determine whether a single-shot T5 erector spinae plane block (ESPB) reduces postoperative pain. DESIGN: Single-center, RCT with allocation concealment; blinded assessors and statisticians. SETTING: Tertiary cancer center in China. PATIENTS: 100 adults scheduled for radical mastectomy with implant reconstruction were randomized (1:1); follow-up complete. INTERVENTION: Before induction, ESPB was given under ultrasound guidance at T5 with 30 mL of 0.375% ropivacaine plus dexmedetomidine 1 &#x3bc;g/kg; controls received no block. Standardized general anesthesia and postoperative PCA for both groups. MAIN OUTCOME MEASURES: Resting NRS at 6 h (MCID=1). Secondary outcomes were opioid consumption, quality of recovery, and PONV. RESULTS: ESPB did not significantly reduce resting pain at 6 h at the median (&#x3c4; =0.50; adjusted difference -0.9; p = 0.08). At the upper tail, pain intensity was lower (&#x3c4; = 0.75; -1.8; p <0.01). Repeated measures provided additional time-point information, improving estimation precision and test sensitivity. ESPB get lower pain scores at 6, 12, and 24 hours (all p <0.01). But, the 95% CI includes the MCID, the clinical benefit remains uncertain. Opioid use decreased at 24 h (-13.5 mg; p <0.01) and 48 h (-6.6 mg; p <0.01). Quality of recovery improved at 24 h (difference 5 points; p <0.01), but not later. No differences were observed in intraoperative hemodynamics or PONV. CONCLUSIONS: Single-shot T5 ESPB with perineural dexmedetomidine may reduce postoperative pain and opioid requirements and improve early recovery. Further large trials are warranted. Clinical relevance remains to be confirmed. TRIAL REGISTRATION: ClinicalTrials.gov NCT06143020.

Humans

Hepatotoxicity of OBS: A review of the emerging PFOS substitute.

As an alternative to perfluorooctanesulfonic acid (PFOS), sodium perfluorononenyl oxobenzene sulfonate (OBS) is widely used due to its cost-effectiveness. Multiple studies have shown that the liver is a classic target organ for OBS. However, there is currently no systematic review on the hepatotoxic effects of OBS. This review systematically summarizes the exposure characteristics of OBS in the environment and human populations, as well as its mechanisms of liver toxicity. In vivo studies consistently demonstrate that OBS induces hepatotoxic effects, such as hepatomegaly, vacuolization, elevated serum transaminases, and lipid dysregulation, though the manifestation of these phenotypes varies across species and exposure routes. In vitro evidence further shows that OBS reduces cell viability and survival, and triggers necrosis accompanied by inflammation. Mechanistically, oxidative stress, inflammatory signaling, and metabolism disorder are implicated. Critically, most existing work addresses subacute or subchronic exposure, leaving a gap in chronic risk assessment for long-term, low-dose OBS exposure. Moreover, mechanistic studies have focused predominantly on downstream transcriptional and signaling changes, with limited exploration of upstream epigenetic controls. Overall, this study aims to provide a comprehensive reference for future toxicological investigations and liver injury risk assessments related to OBS exposure.

Humans

Emphysematous pyelonephritis in children: Lessons from a case report and systematic review.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a rare, life-threatening gas-producing renal infection. Literature on pediatric EPN remains scarce. OBJECTIVE: To describe a case of pediatric EPN and systematically review the data on clinical presentations, diagnostic modalities, management strategies, and prognosis in pediatric emphysematous pyelonephritis. METHODS: A comprehensive search in PubMed, Embase and Web of Science using defined search terms was done, along with the Joanna Briggs Institute (JBI) critical appraisal checklist for quality assessment. RESULTS: Of 100 records, 20 studies (n = 21) were included in the review. The median (IQR) age of presentation was 48 (8-138) months. The major risk factor was reflux/obstructive nephropathy (52.3 %), and E. coli was the common organism. Management included antibiotics (47.6 %), minimally invasive procedures (33.3 %), or nephrectomy (19 %). We additionally report an adolescent girl with Type 1 diabetes mellitus and class 3A right-sided EPN. She improved with antibiotics and percutaneous nephrostomy (PCN) insertion. CONCLUSION: Obstructive or reflux nephropathy is a major risk factor for pediatric EPN. Antibiotics are the mainstay for treatment with supportive management. Refractory cases may require percutaneous drainage or partial/total nephrectomy.

Humans

Multi&#x2011;omics approaches to decipher the molecular mechanisms of exercise&#x2011;mediated bone protection: From mechanistic insights to personalized exercise prescription (Review).

The global burden of bone metabolic disorders necessitates a shift from generic exercise recommendations toward personalized prescription strategies. Exercise confers skeletal protection through mechanotransduction, yet the underlying molecular networks remain incompletely understood. Multi&#x2011;omics technologies, including transcriptomics, proteomics, metabolomics and single&#x2011;cell spatial approaches, have revolutionized the capacity to decode exercise&#x2011;mediated bone adaptation at the systems level. The present review synthesizes current single&#x2011;omics landscapes and integrative multi&#x2011;omics analyses that elucidate the core regulatory networks, mechanobiological coupling mechanisms and multiorgan crosstalk that are implicated in the bone response to mechanical loading. Translational applications across clinical scenarios such as osteoporosis, osteoarthritis and disuse bone loss are evaluated, and the technical, analytical and translational challenges limiting clinical implementation are addressed. Finally, the present review provides a framework for translating multi&#x2011;omics molecular signatures into personalized exercise prescriptions for optimized skeletal health.

Humans