AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: An exploratory study.

BACKGROUND AND AIMS: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH. METHODS: We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. RESULTS: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region. CONCLUSION: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

Metabolomic and transcriptomic analyses of peach leaves and fruits in response to pruning.

BACKGROUND: Pruning is an important cultivation management option that has important effects on peach yield and quality. However, the effects of pruning on the overall genetic and metabolic changes in peach leaves and fruits are poorly understood. RESULTS: The transcriptomic and metabolomic profiles of leaves and fruits from trees subjected to pruning and unpruning treatments were measured. A total of 20,633 genes and 622 metabolites were detected. Compared with those in the control, 1,127 differentially expressed genes (DEGs) and 77 differentially expressed metabolites (DEMs) were identified in leaves from pruned and unpruned trees (pdLvsupdL), whereas 423 DEGs and 29 DEMs were identified in fruits from the pairwise comparison pdFvsupdF. The content of three auxin analogues was upregulated in the leaves of pruned trees, the content of all flavonoids detected in the leaves decreased, and the expression of almost all genes involved in the flavonoid biosynthesis pathway decreased. The phenolic acid and amino acid metabolites detected in fruits from pruned trees were downregulated, and all terpenoids were upregulated. The correlation analysis revealed that DEGs and DEMs in leaves were enriched in tryptophan metabolism, auxin signal transduction, and flavonoid biosynthesis. DEGs and DEMs in fruits were enriched in flavonoid and phenylpropanoid biosynthesis, as well as L-glutamic acid biosynthesis. CONCLUSIONS: Pruning has different effects on the leaves and fruits of peach trees, affecting mainly the secondary metabolism and hormone signalling pathways in leaves and amino acid biosynthesis in fruits.

MGST3 regulates BACE1 protein translation and amyloidogenesis by controlling the RGS4-mediated AKT signaling pathway.

Microsomal glutathione transferase 3 (MGST3) regulates eicosanoid and glutathione metabolism. These processes are associated with oxidative stress and apoptosis, suggesting that MGST3 might play a role in the pathophysiology of Alzheimer's disease (AD). Here, we report that knockdown (KD) of MGST3 in cell lines reduced the protein level of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and the resulting amyloidogenesis. Interestingly, MGST3 KD did not alter intracellular ROS level but selectively reduced the expression of apoptosis indicators which could be associated with the receptor of cysteinyl leukotrienes (cysLTs), the downstream metabolites of MGST3 in arachidonic acid pathway. We then showed that the effect of MGST3 on BACE1 was independent of cysLTs but involved a translational mechanism. Further RNA-seq analysis identified that regulator of G-protein signaling 4 (RGS4) was a target gene of MGST3. Silencing of RGS4 inhibited BACE1 translation and prevented MGST3 KD-mediated reduction of BACE1. The potential mechanism was related to AKT activity, as the protein level of phosphorylated AKT (p-AKT) was significantly reduced by silencing of MGST3 and RGS4, and the AKT inhibitor abolished the effect of MGST3/RGS4 on p-AKT and BACE1. Together, MGST3 regulated amyloidogenesis by controlling BACE1 protein expression, which was mediated by RGS4 and downstream AKT signaling pathway.

Dietary cooking oils and cardiometabolic measurements in an elderly Chinese population.

OBJECTIVE: To investigate three features of dietary cooking oil intake, namely, the consumption, cooking style, and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese population. METHODS: The elderly (≥ 65 years) participants for this study were recruited from two community health centers in the urban area of Shanghai. A questionnaire was administered to collect information on dietary oil consumption (low, medium and high) and cooking styles (fry or stir-fry vs. others) and the composition of fatty acids (poly-unsaturated vs. mono-unsaturated). The cardiometabolic measurements included anthropometry, blood pressure, fasting plasma glucose and serum lipids. RESULTS: The 1186 study participants had a mean age of 70.9 ± 5.4 years. The mean dietary oil consumption was 35.0 g/d, being low (< 25 g/d), medium (25-49 g/d) and high (≥ 50 g/d) in 485,467 and 234 participants, respectively. The proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4% and 27.4%, respectively. Both before and after adjustment for sex, age, current smoking and alcohol intake, dietary oil consumption was significantly (P ≤ 0.02) and positively associated with the prevalence of treated hypertension and fasting plasma glucose concentration. With similar adjustments as above and additional adjustment for dietary oil consumption, the fry or stir-fry cooking style was significantly (P ≤ 0.048) and positively associated with body mass index, but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol, and the dietary intake of oils rich in mono-unsaturated fat acids was significantly (P ≤ 0.02) and positively associated with diastolic blood pressure, serum triglycerides, total cholesterol and low-density lipoprotein cholesterol, and the prevalence of hypertriglyceridemia and hypercholesterolemia. CONCLUSIONS: This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to several cardiometabolic measurements in an elderly Chinese population.

Facile fabrication of chitosan/bone/bamboo biochar beads for simultaneous removal of co-existing Cr(VI) and bisphenol a from water.

Heavy metal Cr(VI) and organic BPA have posed harmful risks to human health, aquatic organisms and the ecosystem. In this work, Chitosan/bone/bamboo biochar beads (CS-AMCM) were synthesized by co-pyrolysis and in situ precipitation method. These microbeads featured a particle size of approximately 1 ± 0.2 mm and were rich in oxygen/nitrogen functional groups. CS-AMCM was characterized using XRD, Zeta potential, FTIR, etc. Experiments showed that adsorption processes of CS-AMCM on Cr(VI) and BPA fitted well to Langmuir model, with theoretical maximum capacities of 343.61 mg/g and 140.30 mg/g, respectively. Pore filling, electrostatic attraction, redox, complexation and ion exchange were the main mechanisms for Cr(VI), whereas for BPA, the intermolecular force (hydrogen bond) and pore filling were involved. CS-AMCM with adsorbed Cr(VI) demonstrated effective activation in producing ·OH and ·O2 from H2O2, which degraded BPA and Cr(VI) with the removal rates of 99.2% and 98.2%, respectively. CS-AMCM offers the advantages of low-cost, large adsorption capacity, high catalytic degradation efficiency, and favorable recycling in treating Cr(VI) and BPA mixed wastewater, which shows great potential in treating heavy metal and organic matter mixed pollution wastewater.

Erratum to 'B4GALNT1 promotes hepatocellular carcinoma stemness and progression via integrin α2ß1-mediated FAK and AKT activation' (JHEP Reports 5 [2023] 100903).

[This corrects the article DOI: 10.1016/j.jhepr.2023.100903.].

Long-Term Remission with Novel Combined Immune-Targeted Treatment for Histiocytic Sarcoma Accompanied by Follicular Lymphoma: Case Report and Literature Review.

Histiocytic sarcoma (HS) is an extremely rare but aggressive hematopoietic malignancy, and the prognosis has been reported to be rather unfavorable with a median overall survival of merely 6 months. We presented a 58-year-old female patient complaining of abdominal pain and fever, who was admitted to our institution in September 2021. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scan showed enlargement of generalized multiple lymph nodes. Subsequently, laparoscopic retroperitoneal lesion biopsy and bone marrow aspiration were performed. The pathological findings indicated the diagnosis of HS concurrent with follicular lymphoma. The immunohistochemistry (IHC) staining of the tumor lesion revealed a high expression of CD38 and PD-L1 proteins. Furthermore, KRAS gene mutation was identified by means of next-generation sequencing. The patient exhibited poor treatment response to both first- and second-line cytotoxic chemotherapies. Therefore, she underwent six cycles of Daratumumab (anti-CD38 monoclonal antibody), Pazopanib (multi-target receptor tyrosine kinases inhibitor) combined with third-line chemotherapy, followed by involved-site radiotherapy and maintenance therapy with the PD-1 inhibitor Tislelizumab. Long-term partial remission was finally achieved after multi-modality treatment. Duration of remission and overall survival reached 22 and 32 months, respectively. Our case indicated that immuno-targeted treatment coupled with chemotherapy and radiotherapy might constitute a potential therapeutic option for HS.

Evidence of synergistic mechanisms of hepatoprotective botanical herbal preparation of Pueraria montana var. lobata and Schisandra sphenanthera.

Background: Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI. Methods: High performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR. Results: Chemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI. Conclusion: Our study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.

Course-based intra-articular injection of medical chitosan mitigates excessive deposition of triacylglycerides in the synovial tissue of the knee osteoarthritis.

BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: 60 patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), VAS, WOMAC scoring, and AKS scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the pre-surgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced a slightly more pronounced decline in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.

Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus.

OBJECTIVE: Alzheimer's disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. METHODS: APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. RESULTS: EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. CONCLUSION: EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.

Prediction models for diagnosis and prognosis of the colonisation or infection of multidrug-resistant organisms in adults: A systematic review, critical appraisal, and meta-analysis.

BACKGROUND: Prediction models help target patients at risk of multidrug-resistant organism (MDRO) colonisation or infection and could serve as tools informing clinical practices to prevent MDRO transmission and inappropriate empiric antibiotic therapy. However, limited evidence identifies which among the available models are of low risk of bias and suitable for clinical application. OBJECTIVES: To identify, describe, appraise, and summarise the performance of all prognostic and diagnostic models developed or validated for predicting MDRO colonisation or infection. DATA SOURCES: Six electronic literature databases and clinical registration databases were searched until April 2022. STUDY ELIGIBILITY CRITERIA: Development and validation studies of any multivariable prognostic and diagnostic models to predict MDRO colonisation or infection in adults. ASSESSMENT OF RISK OF BIAS: The Prediction Model Risk of Bias Assessment Tool was used to assess risk of bias. Evidence certainty was assessed using the GRADE approach. METHODS OF DATA SYNTHESIS: Meta-analyses were conducted to summarise the discrimination and calibration of the models' external validations conducted in at least two non-overlapping datasets. RESULTS: We included 162 models (108 studies) developed for diagnosing (n=135) and predicting (n=27) MDRO colonisation or infection. Models exhibited a high risk of bias, especially in statistical analysis. High-frequency predictors were age, recent invasive procedures, antibiotic usage, and prior hospitalisation. Less than 25% of the models underwent external validations, with only seven by independent teams. Meta-analyses for one diagnostic and two prognostic models only produced very-low to low certainty of evidence. CONCLUSIONS: The review comprehensively described the models for identifying patients at risk of MDRO colonisation or infection. We cannot recommend which models are ready for application due to high risk of bias, limited validations, and low certainty of evidence from meta-analyses, indicating a clear need to improve the conducting and reporting of model development and external validation studies to facilitate clinical application.

Glucose-6-phosphate dehydrogenase alleviates epileptic seizures by repressing reactive oxygen species production to promote signal transducer and activator of transcription 1-mediated N-methyl-d-aspartic acid receptors inhibition.

The pathogenesis of epilepsy remains unclear; however, a prevailing hypothesis suggests that the primary underlying cause is an imbalance between neuronal excitability and inhibition. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, which is primarily involved in deoxynucleic acid synthesis and antioxidant defense mechanisms and exhibits increased expression during the chronic phase of epilepsy, predominantly colocalizing with neurons. G6PD overexpression significantly reduces the frequency and duration of spontaneous recurrent seizures. Furthermore, G6PD overexpression enhances signal transducer and activator of transcription 1 (STAT1) expression, thus influencing N-methyl-d-aspartic acid receptors expression, and subsequently affecting seizure activity. Importantly, the regulation of STAT1 by G6PD appears to be mediated primarily through reactive oxygen species signaling pathways. Collectively, our findings highlight the pivotal role of G6PD in modulating epileptogenesis, and suggest its potential as a therapeutic target for epilepsy.

Comparative Simulative Analysis and Design of Single-Chain Self-Assembled Protein Cages.

Coiled-coil protein origami (CCPO) is a modular strategy for the de novo design of polypeptide nanostructures. It represents a type of modular design based on pairwise-interacting coiled-coil (CC) units with a single-chain protein programmed to fold into a polyhedral cage. However, the mechanisms underlying the self-assembly of the protein tetrahedron are still not fully understood. In the present study, 18 CCPO cages with three different topologies were modeled in silico. Then, molecular dynamics simulations and CC parameters were calculated to characterize the dynamic properties of protein tetrahedral cages at both the local and global levels. Furthermore, a deformed CC unit was redesigned, and the stability of the new cage was significantly improved.

PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Association between driving pressure-guided ventilation and postoperative pulmonary complications in surgical patients: a meta-analysis with trial sequential analysis.

BACKGROUND: Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs. METHODS: We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence. RESULTS: Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56-0.87, P=0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48-0.77, P< 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67-1.10, P=0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies. CONCLUSIONS: Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery. SYSTEMATIC REVIEW PROTOCOL: INPLASY 202410068.

Intravascular Ultrasound vs Angiography-Guided Drug-Coated Balloon Angioplasty: The ULTIMATE â ¢ Trial.

BACKGROUND: Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. OBJECTIVES: This study aimed to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions. METHODS: A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0-4.0 mm, and lesion length ≤15 mm) were randomly assigned to either an IVUS-guided or an angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure at 6 months. RESULTS: A total of 2 patients in the angiography-guided group and 7 patients in the IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance vs -0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm; 95% CI: 0.02-0.26; P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs 1.75 ± 0.63 mm; P < 0.001) and a smaller diameter stenosis (28.15% ± 13.88% vs 35.83% ± 17.69%; P = 0.001) compared with angiography guidance. Five target vessel failures occurred at 6 months, with 4 (3.1%) in the angiography-guided group and 1 (0.8%) in the IVUS-guided group (P = 0.370). CONCLUSIONS: This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance. (Intravascular Ultrasound Versus Angiography Guided Drug-Coated Balloon [ULTIMATE-III]; NCT04255043).

Efficient Ozone Elimination Over MnO2 via Double Moisture-Resistance Protection of Active Carbon and CeO2.

The widespread ozone (O3) pollution is extremely hazardous to human health and ecosystems. Catalytic decomposition into O2 is the most promising method to eliminate ambient O3, while the fast deactivation of catalysts under humid conditions remains the primary challenge for their application. Herein, we elaborately developed a splendidly active and stable Mn-based catalyst with double hydrophobic protection of active carbon (AC) and CeO2 (CeMn@AC), which possessed abundant interfacial oxygen vacancies and excellent desorption of peroxide intermediates (O22-). Under extremely humid (RH = 90%) conditions and a high space velocity of 1200 L h-1 g-1, the optimized CeMn@AC achieved nearly 100% O3 conversion (140 h) at 5 ppm, showing unprecedented catalytic activity and moisture resistance toward O3 decomposition. In situ DRIFTS and theory calculations confirmed that the exceptional moisture resistance of CeMn@AC was ascribed to the double protection effect of AC and CeO2, which cooperatively prevented the competitive adsorption of H2O molecules and their accumulation on the active sites of MnO2. AC provided a hydrophobic reaction environment, and CeO2 further alleviated moisture deterioration of the MnO2 particles exposed on the catalyst surface via the moisture-resistant oxygen vacancies of MnO2-CeO2 crystal boundaries. This work offers a simple and efficient strategy for designing moisture-resistant materials and facilitates the practical application of the O3 decomposition catalysts in various environments.

Bimetal-organic framework-integrated electrochemical sensor for on-chip detection of H2S and H2O2 in cancer tissues.

Studies on the interaction between hydrogen sulfide (H2S) and hydrogen peroxide (H2O2) in redox signaling motivate the development of a sensitive sensing platform for their discriminatory and dynamic detection. Herein, we present a fully integrated microfluidic on-chip electrochemical sensor for the online and simultaneous monitoring of H2S and H2O2 secreted by different biological samples. The sensor utilizes a cicada-wing-like RuCu bimetal-organic framework with uniform nanorods architecture that grows on a flexible carbon fiber microelectrode. Owing to the optimized electronic structural merits and satisfactory electrocatalytic properties, the resultant microelectrode shows remarkable electrochemical sensing performance for sensitive and selective detection of H2S and H2O2 at the same time. The result exhibits low detection limits of 0.5 µM for H2S and 0.1 µM for H2O2, with high sensitivities of 61.93 µA cm-2 mM-1 for H2S, and 75.96 µA cm-2 mM-1 for H2O2. The integration of this biocompatible microelectrode into a custom wireless microfluidic chip enables the construction of a miniature intelligent system for in situ monitoring of H2S and H2O2 released from different living cells to differentiate between cancerous and normal cells. When applied for real-time tracking of H2S and H2O2 secreted by colorectal cancer tissues, it allows the evaluation of their chemotherapeutic efficacy. These findings hold paramount implications for disease diagnosis and therapy.

An ecological dynamics approach to promote physical literacy and well-being of primary school children: a cluster randomised controlled trial study protocol.

BACKGROUND: Little is known about the impact of an ecological dynamics (ED) intervention (EDI) on primary school children's physical literacy and well-being in the Hong Kong context. The aim of this project is to introduce a physical literacy and well-being framework through an EDI that allows primary school children to develop good physical activity (PA) and daily behavioural habits. METHODS AND ANALYSIS: A four-arm (cluster) randomised controlled trial will be conducted to examine the effect of EDI on physical literacy and well-being in primary schools located in each of the 18 administrative districts of Hong Kong. Four classes in senior primary students (grade 4) at each school will be randomly assigned to the four different conditions. These participating schools will be equipped with sit-stand desks, PA recess facility and equipment, and sleep pillows. The research team will adopt both objective measures (aerobic fitness, fundamental movement skills, daily behaviour-physical activity and cognitive function) and self-reported measures (perceived physical literacy, quality of life, sleep quality) covering the elements and domains of physical literacy and well-being to examine the effects of EDIs at four time points, including baseline assessment, 3 months after intervention, postintervention and 3-month follow-up assessment. One-way analyses of variance (ANOVAs) will be used to test for differences in the baseline characteristics of participants between groups. Repeated measure ANOVAs and MANCOVA, with time (baseline, after intervention and follow-up) as within-subjects factor, and intervention group as between-subjects factors, will be used to evaluate the effects of different interventions on the students' physical literacy and well-being. A Bonferonni correction to the p value will be calculated to adjust for multiple tests. ETHICS AND DISSEMINATION: Ethical approval was sought from the Joint CUHK-NTEC Clinical Research Ethics Committee in Hong Kong (CREC Ref.No.:2024.027). The finding of this study will be disseminated via peer-reviewed journals, international conference presentations and academic lectures. For secondary analysis of the data, please contact the corresponding author for permission. TRIAL REGISTRATION NUMBER: ISRCTN84025914.

Randomized Double-Blind Study of the Effect of Injectate Temperature on Intrathecal Bupivacaine Dose Requirement in Spinal Anesthesia for Cesarean Delivery.

BACKGROUND: Increasing the temperature of intrathecal local anesthetics has been shown to increase the speed of onset and block height of spinal anesthesia. However, how this influences dose requirement has not been fully quantified. The aim of this study was to determine and compare the effective dose for anesthesia for cesarean delivery in 50% of patients (ED50) of intrathecal bupivacaine given at temperatures of 37 °C (body temperature) or 24 °C (room temperature). METHODS: Eighty healthy parturients having elective cesarean delivery under combined spinal-epidural anesthesia were randomly assigned to receive intrathecal hyperbaric bupivacaine stored at 37 °C (body temperature group) or 24 °C (room temperature group). The first subject in each group received a bupivacaine dose of 10 mg. The dose for each subsequent subject in each group was varied with an increment or decrement of 1 mg based on the response (effective or noneffective) of the previous subject. Patients for whom the dose was noneffective received epidural supplementation after data collection with lidocaine 2% as required until anesthesia was sufficient for surgery. Values for ED50 were calculated using modified up-down sequential analysis with probit analysis applied as a backup sensitivity analysis. These values were compared and the relative mean potency was calculated. RESULTS: The ED50 (mean [95% confidence interval, CI]) of intrathecal hyperbaric bupivacaine was lower in the body temperature group (6.7 [5.7-7.6] mg) compared with the room temperature group (8.1 [7.7-8.6] mg) (P < .05). The relative potency ratio for intrathecal bupivacaine for the room temperature group versus the body temperature group was 0.84 (95% CI, 0.77-0.93). CONCLUSIONS: Warming hyperbaric bupivacaine to body temperature reduced the dose requirement for spinal anesthesia for cesarean delivery by approximately 16% (95% CI, 7%-23%).