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Ethnopharmacological Relevance: Simiao Pills, a classical traditional Chinese medicine prescription recorded in Cheng Fang Bian Du, has been traditionally used to treat hyperuricemia due to its heat-clearing and diuretic properties. Studies have shown that Simiao Pills effectively reduce uric acid levels. However, further research is needed to elucidate the precise composition of Simiao Pills for treating hyperuricemia and their potential pharmacological mechanism., Aim of the Study: This study aimed to investigate the therapeutic effects of Simiao Pills on hyperuricemia, with a particular focus on evaluating their protective role against hyperuricemia-induced renal injury and elucidating the underlying mechanism of action., Materials and Methods: UPLC-MS/MS was used to identify the components of Simiao Pills. The hyperuricemia model mice were established by intraperitoneal injecting potassium oxonate (PO) and oral administrating hypoxanthine (HX). Network pharmacology, transcriptome, and metabolomics analyses were integrated to explore the mechanism of Simiao Pills in reducing uric acid and protecting the kidney. Mechanistic and functional studies were conducted to validate the potential mechanisms., Results: Simiao Pills were found to contain 12 characteristic components. Treatment with Simiao Pills significantly reduced serum uric acid levels and ameliorated hyperuricemia-induced renal injury. Simiao Pills inhibited the enzymatic activities of XOD and XDH, and regulated the uric acid transporters in the kidney and ileum. Transcriptome and network pharmacology analyses highlighted quercetin, berberine, kaempferol, and baicalein as the principal active components of Simiao Pills acting on the kidney during hyperuricemia treatment, primarily impacting fibrosis, apoptosis, and inflammation-related signaling pathways. Metabolomic analysis unveiled 21 differential metabolites and 5 metabolic pathways associated with Simiao Pills against renal injury associated with hyperuricemia. Further experimental results validated that Simiao Pills reduced renal fibrosis, apoptotic renal cells, serum inflammation levels, and inhibited the NF-κB/NLRP3/IL-1β signaling pathway., Conclusion: This study demonstrated that Simiao Pills significantly reduced serum uric acid levels and improved renal injury by regulating inflammation, apoptosis, and renal fibrosis. These findings have provided a robust scientific pharmacological basis for the use of Simiao Pills in treating hyperuricemia patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Air quality (AQ) is directly relevant with people's health while implementing effective methods for acquiring pollution details and assessing health impact are very important for public health management. In this paper, we design an end-to-end space-time modelling framework to estimate pixelwise PM 2.5 inhalation volume, called ST-Exposure which goes over the model's practicality and benefits on the following aspects: (1) Use a combination of fixed and mobile AQ sensors, we estimate PM 2.5 inhalation volume based on the inference of PM 2.5 exposure in Beijing (3025 km 2 , 19 Jun - 16 Jul 2018) with the space-time resolution of 1 km × 1 km and 1 h, with <15 % SMAPE (%). (2) Achieve pixelwise PM 2.5 inhalation volume to be inferred with high-resolution (1 km × 1 km, hourly) at city scale, even with sparse space-time coverage. (3) Propose a new calculation mechanism of population distribution which is better than the traditional census-based method, and can achieve more reliable estimation of the total PM 2.5 inhalation volume over the whole region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The self-healing bioconcrete, or bioconcrete as concrete containing microorganisms with self-healing capacities, presents a transformative strategy to extend the service life of concrete structures. This technology harnesses the biological capabilities of specific microorganisms, such as bacteria and fungi, which are integral to the material's capacity to autonomously mend cracks, thereby maintaining structural integrity. This review highlights the complex biochemical pathways these organisms utilize to produce healing compounds like calcium carbonate, and how environmental parameters, such as pH, temperature, oxygen, and moisture critically affect the repair efficacy. A comprehensive analysis of recently published peer-reviewed literature, and contemporary experimental research forms the backbone of this review with a focus on microbiological aspects of the self-healing process. The review assesses the challenges facing self-healing bioconcrete, including the longevity of microbial spores and the cost implications for large-scale implementation. Further, attention is given to potential research directions, such as investigating alternative biological agents and optimizing the concrete environment to support microbial activity. The culmination of this investigation is a call to action for integrating self-healing bioconcrete in construction on a broader scale, thereby realizing its potential to fortify infrastructure resilience and sustainability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

For the first time, combined detection and simulation was performed on microplastic (MP) debris in surface water, sediment, and oyster samples at ten coastal sites of Shing Mun River estuary, Hong Kong at different tidal conditions. The MP debris were extracted and detected using Fourier transform infrared (FT-IR) spectroscopy, and the simulation was conducted using Weather Research & Forecasting Model (WRF) / Regional Ocean Modelling System (ROMS) coupled hydro-dynamic modelling and the subsequent Lagrangian particle tracking. The results demonstrated the majority of polyethylene (with partial chlorine substitution) debris among all the MPs found, and great spatial and tidal variabilities of MP concentrations were observed. The combination of MP observation and simulations referred to the interpretation that a considerable percentage of MPs found in this study originated from South China Sea. Those MPs were probably transported to Tolo Harbour through sea currents and drifted inshore and offshore with tides. This study provided baseline measures of MP concentrations in Shing Mun River estuary and comprehensive understanding for how MPs transport and distribute within a dynamic estuarine system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Shale gas extraction in China often faces inadequate reservoir stimulation after initial fracturing of the wells, leading to production challenges despite abundant residual gas. Refracturing is an effective approach to enhance gas recovery; however, its impact on water consumption remains understudied. This study analyzes two refracturing techniques employed in China's largest shale production field, Fuling: temporary plugging and diverting refracturing (TPD) and wellbore reconstruction refracturing (WR), focusing on fracturing efficiency and water consumption. The results demonstrate that WR refracturing exhibits superior fracturing performance but consumes 1.3 times more water than initial fracturing. Considering 315 wells that required refracturing from 2013 to 2017, this study reveals, for the first time, that the lifecycle water consumption for shale gas production with refracturing is more than twice that without refracturing. The estimated total water consumption for the Fuling shale gas field over the next decade, incorporating refracturing, is approximately 7594.53 × 10 4  m 3 . By including the water consumption of refracturing, this study provides a more comprehensive evaluation of water usage throughout the entire lifecycle of shale gas development. The findings offer new insights for assessing water consumption in global shale gas development and highlight the importance of considering refracturing when evaluating the environmental impacts and resource management strategies associated with shale gas extraction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Handwriting is an outstanding case of a highly complex and efficient fine motor skill. However, little is known about its neural underpinnings during continuous handwriting production. In the present study, we examined the effects of orthographic character complexity (i.e. the stroke number of a Chinese character) on both neural and behavioural activities during an EEG-based naturalistic fluent sentence-handwriting task from 102 adult Chinese native speakers. For each written character, the interval between finishing the preceding character and its onset (inter-character interval) as well as the amplitudes of the onset-synchronized event-related potential (ERP) in pre- and post-onset time windows was defined as dependent variables. The effects of character complexity and other confounding factors were analysed with linear mixed models. Character complexity increased the inter-character interval and significantly affected ERP amplitudes in both pre- and post-onset time windows. The ERP pattern in the pre-event time window exhibited a dipole-like activation in the left motor cortex, and its amplitude increased with character complexity in line with the documented relationship between the lateralized readiness potential and motor complexity. This study demonstrates the feasibility of studying neurocognitive processes in complex naturalistic motor tasks and extends our knowledge about the dynamic pattern of handwriting-related neural activities., (© 2024 The Author(s). British Journal of Psychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Quaternary ammonium compounds (QACs) are widely detected in the aquatic environment due to their extensive use in a wide array of antibacterial products during the pandemic. In the current study, UV/monochloramine (UV/NH 2 Cl) was used to degrade three typical QACs, namely benzalkonium compounds (BACs), dialkyl dimethyl ammonium compounds (DADMACs), and alkyl trimethyl ammonium compounds (ATMACs). This process achieved high efficiency in removing BACs from water samples. The transformation products of QACs treated with UV/NH 2 Cl were identified and characterized using a high-resolution mass spectrometer, and transformation pathways were proposed. The formation of N-nitroso-N-methyl-N-alkylamines (NMAs) and N-nitrosodimethylamine (NDMA) were observed during QAC degradation. The molar formation yield of NDMA from C 12 -BAC was 0.04 %, while yields of NMAs reached 1.05 %. The ecotoxicity of NMAs derived from QACs was predicted using ECOSAR software. The increased toxicity could be attributed to the formation of NMAs with longer alkyl chains; these NMAs, exhibited a one order of magnitude increase in toxicity compared to their parent QACs. This study provides evidence that QACs are the specific and significant precursors of NMAs. Greater attention should be given to NMA formation and its potential threat to the ecosystem, including humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11β-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11β-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11β-HSD1 by using bone-targeted 11β-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11β-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity., (© 2024. The Author(s).)

Background: The actions required to achieve higher-quality and harmonised global surveillance of child and adolescent movement behaviours (physical activity, sedentary behaviour including screen time, sleep) are unclear., Objective: To identify how to improve surveillance of movement behaviours, from the perspective of experts., Methods: This Delphi Study involved 62 experts from the SUNRISE International Study of Movement Behaviours in the Early Years and Active Healthy Kids Global Alliance (AHKGA). Two survey rounds were used, with items categorised under: (1) funding, (2) capacity building, (3) methods, and (4) other issues (e.g., policymaker awareness of relevant WHO Guidelines and Strategies). Expert participants ranked 40 items on a five-point Likert scale from 'extremely' to 'not at all' important. Consensus was defined as > 70% rating of 'extremely' or 'very' important., Results: We received 62 responses to round 1 of the survey and 59 to round 2. There was consensus for most items. The two highest rated round 2 items in each category were the following; for funding (1) it was greater funding for surveillance and public funding of surveillance; for capacity building (2) it was increased human capacity for surveillance (e.g. knowledge, skills) and regional or global partnerships to support national surveillance; for methods (3) it was standard protocols for surveillance measures and improved measurement method for screen time; and for other issues (4) it was greater awareness of physical activity guidelines and strategies from WHO and greater awareness of the importance of surveillance for NCD prevention. We generally found no significant differences in priorities between low-middle-income (n = 29) and high-income countries (n = 30) or between SUNRISE (n = 20), AHKGA (n = 26) or both (n = 13) initiatives. There was a lack of agreement on using private funding for surveillance or surveillance research., Conclusions: This study provides a prioritised and international consensus list of actions required to improve surveillance of movement behaviours in children and adolescents globally., (© 2024. The Author(s).)

Background/objective: Physical activity (PA) self-efficacy plays a crucial role in maintaining and enhancing PA behaviors in children. However, the effectiveness of eHealth interventions in boosting PA self-efficacy among children remains uncertain. Furthermore, which behavior change techniques (BCTs) used in eHealth interventions can positively influence children's PA self-efficacy needs further exploration for designing tailored eHealth interventions. Therefore, this systematic review and meta-analysis aimed to identify the effectiveness of eHealth interventions and BCTs in promoting children's PA self-efficacy., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across six databases (PubMed, Web of Science, EBSCOhost, Ovid, SPORTDiscus, PsycINFO) up to January 8, 2024. Inclusion criteria included randomized controlled trials (RCT), quasi-experimental, and two-group experiments that examined the effect of eHealth interventions on PA self-efficacy among healthy children aged 0-18 years. The Physiotherapy Evidence Database (PEDro) scale was utilized to assess the risk of bias. Random effects meta-analysis was performed to determine the effectiveness of eHealth interventions and BCTs in selected studies., Results: Sixteen studies were screened, including 6020 participants with an average age of 11.58 years (SD = 2.87). The result showed small but significant intervention effects with high heterogeneity (I 2  = 92.34 %) for postintervention PA self-efficacy ( Hedges' g  = 0.315; 95 % CI = 0.069, 0.562, p  = .012). Two BCTs were significantly associated with enhanced PA self-efficacy: instruction on performing the behavior (p = .003) and behavior demonstration ( p  = .036). Additionally, studies that adopted social support (unspecified) a nd prompt/cues were significantly less effective than studies that did not use these BCTs (p = .001)., Conclusions: The findings showed that eHealth interventions positively affect children's PA self-efficacy. This review is the pioneer in focusing on BCTs in eHealth interventions for children. The insights gained provide valuable knowledge about tailored BCTs incorporated into eHealth interventions that promote children's PA self-efficacy., Trial Registration: International Prospective Register of Systematic Review (PROSPERO): CRD42024512058., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Joint pain and osteoarthritis can occur as coronavirus disease 2019 (COVID-19) sequelae after infection. However, little is known about the damage to articular cartilage. Here we illustrate knee joint damage after wild-type, Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vivo. Rapid joint injury with cystic lesions at the osteochondral junction was observed in two patients with post-COVID osteoarthritis and recapitulated in a golden Syrian hamster model. SARS-CoV-2-activated endothelin-1 signalling increased vascular permeability and caused viral spike proteins leakage into the subchondral bone. Osteoclast activation, chondrocyte dropout and cyst formation were confirmed histologically. The US Food and Drug Administration-approved endothelin receptor antagonist, macitentan, mitigated cystic lesions and preserved chondrocyte number in the acute phase of viral infection in hamsters. Delayed macitentan treatment at post-acute infection phase alleviated chondrocyte senescence and restored subchondral bone loss. It is worth noting that it could also attenuate viral spike-induced joint pain. Our work suggests endothelin receptor blockade as a novel therapeutic strategy for post-COVID arthritis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The shortage of food and freshwater sources threatens human health and environmental sustainability. Spirulina grown in seawater-based media as a healthy food is promising and environmentally friendly. This study used three machine learning techniques to identify important cultivation parameters and their hidden interrelationships and optimize the biomass yield of Spirulina grown in seawater-based media. Through optimization of hyperparameters and features, eXtreme Gradient Boosting, along with the recursive feature elimination (RFE) model demonstrated optimal performance and identified 28 important features. Among them, illumination intensity and initial pH value were critical determinants of biomass, which impacted other features. Specifically, high initial pH values (>9.0) mainly increased biomass but also increased nutrient sedimentation and ammonia (NH 3 ) losses. Both batch and continuous additions could decrease nutrient losses by increasing their availability in the seawater-based media. When illumination intensity exceeded 200 μmol photons/m 2 /s, it amplified the growth of Spirulina by mitigating the light attenuation caused by a high initial inoculum level and counteracted the negative effect of low temperature (<25 °C). In large-scale cultivation, production efficiency would be reduced if illumination was not maintained at a high level. High salinity and sodium bicarbonate (NaHCO 3 ) addition promoted carbohydrate accumulation, but suitable dilution could keep the required protein content in Spirulina with relatively low media and production costs. These findings reveal the interactive influence of cultivation parameters on biomass yield and help us determine the optimal cultivation conditions for large-scale cultivation of Spirulina-based seawater system based on a developed graphical user interface website., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The presence of distant metastasis at the time of initial diagnosis is a prevalent issue in non-small cell lung cancer (NSCLC), affecting around 30-40 % of the patients. Acidic tumor microenvironment (TME) provides favorable conditions that increase the invasiveness and aggressiveness of NSCLC. The activity of the glycolytic enzyme lactate dehydrogenase (LDHA) increases intracellular lactate accumulation, which creates an acidic TME. However, it is not yet known whether LDHA is involved in enhancing the metastatic potential of NSCLC and if LDHA is a druggable therapeutic target for NSCLC., Purpose: We aimed to investigate the molecular mechanisms underlying the enhanced NSCLC metastasis in acidic TME, and to explore whether sulforaphane (SFN), an active compound in Raphani Semen, can serve as a LDHA inhibitor to inhibit NSCLC metastasis in the acidic TME., Methods: To mimic the acidic TME, NSCLC cells were cultured in acidic medium (pH 6.6), normal medium (pH 7.4) served as control. Western blotting, bioinformatic analysis, luciferase assay and rescue experiments were used to explore the mechanism and investigate the anti-metastatic effect of SFN both in vitro and in vivo., Results: Acidic environment increases the expression of LDHA which in turn increases the production of lactic acid that contributes to the acidity of TME. Interestingly, elevated LDHA expression results from increased c-Myc expression, which transactivates LDHA. c-Myc expression is directly regulated by miR-7-5p. In vitro study shows that overexpression of miR-7-5p reverses the acidic pH-enhanced c-Myc and LDHA expressions and also abolishes the enhanced NSCLC cell migration. More importantly, SFN significantly inhibits NSCLC growth and metastasis by reducing lactate production via the miR-7-5p/c-Myc/LDHA axis. Besides, it also regulates the expressions of monocarboxylate transporter 1 (MCT1) and MCT4 that transport lactate across cell membrane., Conclusions: The miR-7-5p/c-Myc/LDHA axis is involved in the enhanced NSCLC metastasis in the acidic TME. SFN, a novel LDHA inhibitor, reduces lactate production by targeting the miR-7-5p/c-Myc/LDHA axis, and hence inhibits NSCLC metastasis. Our findings not only delineate a novel mechanism, but also support the clinical translation of SFN as a novel therapeutic agent for treating metastatic NSCLC., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Liver cancer represents a most common and fatal cancer worldwide. Xianglian Pill (XLP) is an herbal formula holding great promise in clearing heat for treating diseases in an integrative and holistic way. However, due to the complex constituents and multiple targets, the exact molecular mechanisms of action of XLP are still unclear., Purpose: This study is focused on hepatocellular carcinoma (HCC), the most common type of liver cancer. The aim of this study is to develop a fast and efficient model to investigate the anti-HCC effects of XLP, and its underlying mechanisms., Materials and Methods: HepG2, Hep3B, Mahlavu, HuH-7, or Li-7 cells were employed in the studies. The ingredients were analyzed using liquid chromatography tandem mass spectrometry (LC-MS). RNA sequencing combined with network pharmacology was used to elucidate the therapeutic mechanism of XLP in HCC via in silico and in vitro studies. An approach was constructed to improve the accuracy of prediction in network pharmacology by combining big data and omics., Results: First, we identified 13 potential ingredients in the serum of XLP-administered rats using LC-MS. Then the network pharmacology was performed to predict that XLP demonstrates anti-HCC effects via targeting 94 genes involving in 13 components. Modifying the database thresholds might impact the accuracy of network pharmacology analysis based on RNA sequencing data. For instance, when the matching rate peak is 0.43, the correctness rate peak is 0.85. Moreover, 9 components of XLP and 6 relevant genes have been verified with CCK-8 and RT-qPCR assay, respectively., Conclusion: Based on the crossing studies of RNA sequencing and network pharmacology, XLP was found to improve HCC through multiple targets and pathways. Additionally, the study provides a way to optimize network pharmacology analysis in herbal medicine research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Triclosan (TCS), triclocarban (TCC), and chlorophenols (CPs) are broad-spectrum antibacterials widely used in dermatological and oral hygiene products, which could induce severe liver and intestine injuries. Hence, it is essential to establish a rapid and sensitive method to monitor TCS, TCC, and CPs in various organisms. In this work, fluorine-functionalized covalent organic framework (COF-F) was prepared by using 4,4',4''-(1,3,5-triazine-2,4,6-triyl)tri-aniline and 2,3,5,6-tetrafluoroterephthalaldehyde as two building units and employed as a solid phase microextraction (SPME) probe for the extraction of TCS, TCC and CPs. The COF-F possessed excellent hydrophobicity, a large specific surface area (1354.3 m 2  g -1 ) and high uniform porosity (3.2 nm), which facilitated high selectivity and adsorption properties towards TCS, TCC, and CPs. Therefore, the as-prepared COF-F-SPME in combination with electrospray ionization mass spectrometry has been developed to provide fast and ultrasensitive detection of TCS, TCC, and CPs in biological samples. The established method demonstrated satisfactory linear ranges (0.01-100.00 μg L -1 ) and low limits of detection (0.003-0.040 μg L -1 ) for TCS, TCC and CPs. The developed method could be successfully applied to detect TCS, TCC and CPs in the liver and kidney tissues of mice, demonstrating the potential for the detection of chlorinated aromatic pollutants in the biological samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR-8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit-8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR-8/SVneo cells, respectively. To assess the expression levels of miR-149-3p and AKT serine/threonine kinase 1 (AKT1), quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were performed. A dual-luciferase reporter assay was used to investigate the potential regulatory relationship between miR-149-3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E-cadherin. Mechanistically, QCT downregulated the expression of miR-149-3p and upregulated the expression of AKT1, and miR-149-3p directly targets AKT1, negatively regulating its expression. Overexpression of miR-149-3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR-8/SVneo cells through the miR-149-3p/AKT1 axis, which may provide a promising therapeutic approach for RSA., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Objective: This study aims to examine the comparative effects of 75 min of volume-matched once-weekly and thrice-weekly high-intensity interval training (HIIT) on body adiposity in adults with central obesity., Methods: This assessor-blinded, three-arm, randomized controlled trial will recruit 315 physically inactive adults with central obesity (aged ≥18 years, body mass index ≥23, waist circumference ≥90 cm for men and ≥80 cm for women). Participants will be randomly allocated to the once-weekly HIIT, thrice-weekly HIIT or usual care control group. Participants in the HIIT groups will receive weekly exercise training sessions for 16 weeks, prescribed either once or three times weekly. Each HIIT session will consist of a supervised program of four 4-min high-intensity intervals at 85%-95% peak heart rate (HR peak ) interspersed with 3-min active recovery intervals at 50%-70% HR peak . Participants in the once-weekly HIIT group will perform the 25-min HIIT bout three times with a break between each 25-min HIIT bout. The usual care control group will receive bi-weekly health education classes. The outcome assessments will be conducted at baseline, 16 weeks (post-intervention) and 32 weeks (follow-up). The primary outcome will be total body adiposity assessed by dual-energy X-ray absorptiometry (DXA). The secondary outcome measures will include markers of cardiovascular and metabolic health (body composition, cardiorespiratory fitness, blood pressure, and blood lipids), mental health, cognitive performance, health-related quality of life, sleep quality, habitual physical activity, diet, medication, adverse events and adherence to the intervention., Impact of the Project: The findings from this study are expected to consolidate the therapeutic efficacy of HIIT for the management of central obesity and inform the comparative compliance, feasibility and suitability of once-weekly and thrice-weekly HIIT as exercise strategies to manage obesity. In particular, the present study is expected to provide a novel perspective on the utility of low-frequency HIIT (i.e., once-weekly) as an effective and sustainable exercise strategy to tackle the obesity pandemic. The anticipated findings will hold substantial translational value by informing public health policies and enhancing exercise compliance in the physically inactive obese population., Trial Registration: ClinicalTrials.gov (NCT04887454)., Competing Interests: The authors declared no competing interests., (© 2024 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Introduction: Type 2 diabetes (T2D) is a heterogeneous metabolic disease with large variations in the relative contributions of insulin resistance and β-cell dysfunction across different glucose tolerance subgroups and ethnicities. A more precise yet feasible approach to categorize risk preceding T2D onset is urgently needed. This study aimed to identify potential metabolic biomarkers that could contribute to the development of T2D and investigate whether their impact on T2D is mediated through insulin resistance and β-cell dysfunction., Methods: A non-targeted metabolomic analysis was performed in plasma samples of 196 incident T2D cases and 196 age- and sex-matched non-T2D controls recruited from a long-term prospective Chinese community-based cohort with a follow-up period of ∼ 16 years., Results: Metabolic profiles revealed profound perturbation of metabolomes before T2D onset. Overall metabolic shifts were strongly associated with insulin resistance rather than β-cell dysfunction. In addition, 188 out of the 578 annotated metabolites were associated with insulin resistance. Bi-directional mediation analysis revealed putative causal relationships among the metabolites, insulin resistance and T2D risk. We built a machine-learning based prediction model, integrating the conventional clinical risk factors (age, BMI, TyG index and 2hG) and 10 metabolites (acetyl-tryptophan, kynurenine, γ-glutamyl-phenylalanine, DG(18:2/22:6), DG(38:7), LPI(18:2), LPC(P-16:0), LPC(P-18:1), LPC(P-20:0) and LPE(P-20:0)) (AUROC = 0.894, 5.6% improvement comparing to the conventional clinical risk model), that successfully predicts the development of T2D., Conclusions: Our findings support the notion that the metabolic changes resulting from insulin resistance, rather than β-cell dysfunction, are the primary drivers of T2D in Chinese adults. Metabolomes as a valuable phenotype hold potential clinical utility in the prediction of T2D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Acetyl-coenzyme A carboxylase (ACC) and diacylglycerol acyltransferase 2 (DGAT2) are recognized as potential therapeutic targets for nonalcoholic fatty liver disease (NAFLD). Inhibitors targeting ACC and DGAT2 have exhibited the capacity to reduce hepatic fat in individuals afflicted with NAFLD. However, there are no reports of dual inhibitors targeting ACC and DGAT2 for the treatment of NAFLD. Here, we aimed to identify potential dual inhibitors of ACC and DGAT2 using an integrated in silico approach. Machine learning-based virtual screening of commercial molecule databases yielded 395,729 hits, which were subsequently subjected to molecular docking aimed at both the ACC and DGAT2 binding sites. Based on the docking scores, nine compounds exhibited robust interactions with critical residues of both ACC and DGAT2, displaying favorable drug-like features. Molecular dynamics simulations (MDs) unveiled the substantial impact of these compounds on the conformational dynamics of the proteins. Furthermore, binding free energy assessments highlighted the notable binding affinities of specific compounds (V003-8107, G340-0503, Y200-1700, E999-1199, V003-6429, V025-4981, V006-1474, V025-0499, and V021-8916) to ACC and DGAT2. The compounds proposed in this study, identified using a multifaceted computational strategy, warrant experimental validation as potential dual inhibitors of ACC and DGAT2, with implications for the future development of novel drugs targeting NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction., Purpose: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms., Methods: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions., Results: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction., Conclusion: PA activates AMPK and ameliorates endothelial dysfunction during hypertension., Competing Interests: Declaration of competing interest All the authors have declared that no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Deaf and hard-of-hearing (DHH) patients often encounter difficulties in effective communication with healthcare professionals and are less likely to receive quality medical care. However, DHH populations are understudied in health communication research. This study examined how offline healthcare obstacles and online health consultation impact DHH patients' health, and the mediating roles of patient-centered care (PCC) and patient activation. Data from 323 DHH patients were analyzed using structural equation modeling to test the hypothesized mediation pathway model. Results indicate that offline healthcare obstacles negatively affect DHH patients' perception of patient-centeredness, which reduces their ability and confidence in self-care (conceptualized as patient activation in this study). This reduced patient activation may jeopardize DHH patients' physical and psychological health. Meanwhile, online health consultation is positively associated with PCC, and higher levels of PCC can increase patient activation, contributing to better physical and psychological health. Testing the same model with hearing-abled participants ( n  = 3542) revealed significant differences in these intervening relationships. Overall, this study provides valuable insights into the relationship between DHH patients' healthcare experience and their health outcomes. The findings support interventions that focus on enhancing PCC and patient activation to improve the physical and psychological health outcomes of DHH patients.

Introduction: Twenty-four-hour movement behaviors: moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep are crucial factors affecting older adults' health. Using a compositional data analysis approach, this study examined the associations of time spent in these four movement behaviors with cardiometabolic health, physical fitness, and mental health among older adults. Furthermore, this study identified the estimated changes in aforementioned health outcomes by reallocating SB time to other movement behaviors., Methods: A population-based cross-sectional study of 4562 participants (67.68 ± 5.03 yr; 55.8% female) were implemented in Hubei China between July 25 and November 19, 2020. Measures included demographics, movement behaviors, cardiometabolic indicators (body mass index, waist circumference, waist-hip ratio, percentage body fat, systolic and diastolic blood pressure), physical fitness, and mental health outcomes (depressive symptoms and loneliness). Compositional data analyses were implemented in R., Results: MVPA and sleep time were associated with greater health outcomes (all P < 0.001), except blood pressure ( P = 0.13-0.83). LPA time was associated with waist circumference ( B = 0.313, P = 0.009), waist-hip ratio ( B = 0.003, P = 0.003), physical fitness ( B = 0.36, P < 0.001), and mental health indicators (both P < 0.001). Reallocating 30-min SB to MVPA and sleep was associated with predicated improvements in all health outcomes, except blood pressure, whereas reallocating 30-min SB to LPA resulted in predicted improvements in physical fitness (0.187 units), depressive symptoms (-0.264 units), and loneliness (-0.395 units). For dose-effect relationships, reallocating 5-60 min of SB to MVPA showed greatest benefits for all health outcomes., Conclusions: This study provides timely empirical evidence for future interventions and policymaking on promoting healthy aging during the post-COVID-19 era. The findings underline the importance of including 24-h movement behaviors in future health promotion among older adults., (Copyright © 2024 by the American College of Sports Medicine.)