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Background: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear. Methods: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo. Results: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs. Conclusions: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear. Methods: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo. Results: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs. Conclusions: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background: The study evaluated the performance of the Mindray N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a healthy population in China, focusing on creating a reference range for future clinical applications adjusted according to different demographics. Methods: The study measured NT-proBNP in 2277 healthy individuals. We analyzed age and sex-stratified data, performed precision, accuracy, linearitcvy, and detection limit studies, and evaluated method comparison and consistency between Roche and Mindray assays on 724 serum samples. We used Excel 2010, Medcalc, and GraphPad Prism 9. Results: In males, the 97.5th centile NT-proBNP concentration at age < 45, 45 to 54, 55 to 64, 65 to 74 and ≧ 75 were 89.4 ng/L, 126 ng/L, 206 ng/L, 386 ng/L and 522 ng/L, respectively. In females, the concentration of NT-proBNP at the same age was 132 ng/L, 229 ng/L, 262 ng/L, 297 ng/L and 807 ng/L, respectively. The repeatability precision coefficient of variation (CV%) for NT-proBNP was between 0.86 and 1.65 in analytical performance. In contrast, the reproducibility precision (CV%) for NT-proBNP was between 1.52 and 3.22, respectively. The study found a bias of accuracy of 3.73% in low-value samples (concentration: 148.69) and 7.31% in high-value samples (concentration: 1939.08). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 125 ng/L were 96.6%, 92.3%, 84.2%, and 98.5%, respectively. In contrast, those of 300 ng/L were 94.0%, 98.2%, 95.7% and 97.5%, respectively. Conclusions: The Mindray NT-proBNP assay showed increased levels in both males and females with age, with higher levels in women. It performs well and aligns with manufacturer specifications. We recommend adjusting cutoff values based on demographic factors. [ABSTRACT FROM AUTHOR]

The widespread application of organophosphate flame retardants has led to pervasive exposure to organophosphate esters (OPEs), prompting considerable concerns regarding their potential health risk to humans. Despite hints from previous research about OPEs' association with breast cancer, their specific effects and underlying mechanisms of triple-negative breast cancer (TNBC) remain unclear. In this study, we investigated the effects of four representative OPEs on cell proliferation, cell cycle regulation, migration, and the expression of genes and proteins associated with the epidermal growth factor receptor (EGFR) and Hippo signaling pathways in TNBC (MDA-MB-231) cells. Our findings revealed that treatment with 1–25 μM triphenyl phosphate (TPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) induced TNBC cell proliferation and accelerated cell cycle progression, with upregulation in MYC, CCND1, and BRCA1 mRNA. Moreover, exposure to 1–25 μM TPHP, 10–25 μM TDCIPP, and 1–10 μM tris (2-chloroethyl) phosphate (TCEP) induced MMP2/9 mRNA expression and enhanced migratory capacity, except for 2-ethylhexyl diphenyl phosphate (EHDPP). Mechanistically, four OPEs treatments activated the EGFR-ERK1/2 and EGFR-PI3K/AKT signaling pathways by increasing the transcript of EGFR, ERK1/2, PI3K, and AKT mRNA. OPEs treatment also suppressed the Hippo signaling pathway by inhibiting the expression of MST1 mRNA and phosphorylation of LATS1, leading to the overactivation of YAP1 protein, thereby promoting TNBC cell proliferation and migration. In summary, our study elucidated that activation of the EGFR signaling pathway and suppression of the Hippo signaling pathway contributed to the proliferation, cell cycle dysregulation, and migration of TNBC cells following exposure to OPEs. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence has indicated a link between the gut microbiota and acute lymphoblastic leukaemia (ALL). However, the acute changes in gut microbiota during chemotherapy and the predictive value of baseline gut microbiota in infectious complication remain largely unknown. Methods: Faecal samples (n = 126) from children with ALL (n = 49) undergoing induction chemotherapy were collected at three timepoints, i.e., initiation of chemotherapy (baseline, T0), 7 days (T1) and 33 days (T2) after initiation of chemotherapy. Gut microbiome profile was performed via metagenomic shotgun sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 3 and HUMAnN) was performed to assign taxonomy and functional annotations. Gut microbiome at T0 were used to predict infection during chemotherapy. Results: The microbial diversities and composition changed significantly during chemotherapy, with Escherichia coli, Klebsiella pneumoniae and Bifidobacterium longum being the most prominent species. The microbial metabolic pathways were also significantly altered during chemotherapy, including the pathway of pyruvate fermentation to acetate and lactate, and assimilatory sulfate reduction pathway. The receiver operating characteristic (ROC) models based on Bifidobacterium longum at T0 could predict infectious complications during the first month of chemotherapy with the area under the curve (AUC) of 0.720. Conclusions: Our study provides new insights into the acute changes in microbial and functional characteristics in children with ALL during chemotherapy. The baseline gut microbiota could be potential biomarkers for infections during chemotherapy. Trial registration: The study was approved by the Ethics Committee of Zhujiang Hospital, Southern Medical University (2021-KY-171-01) and registered on http://www.chictr.org.cn (ChiCTR2200065406, Registration Date: November 4, 2022). [ABSTRACT FROM AUTHOR]

Research on the impact of temperature in tropical regions on the risk of cardiovascular and cerebrovascular diseases was limited. The aim of the study was to investigate this topic using Haikou, a tropical city, as the research area. Outpatient data on cardiovascular and cerebrovascular diseases (CVD and CeVD) from Hainan Provincial People's Hospital during 2016–2018 (total of 77,820) and meteorological and air-quality data were used to establish a distributed-lag nonlinear model (DLNM) based on the nested generalized addition model (GAM) of meteorological elements. The results revealed the impact on the risk of CVD and CeVD was mainly due to the cold effect, which significantly lagged behind. The thermal effect had a strong impact on the onset of CVD and CeVD on the day of high temperature. Males were easily affected by low temperatures, while females were the opposite. The lag period of the working-age group affected by low temperatures was longer and greater than that of the elderly group. The high-temperature effect only had an impact on the working-age group. The lag effect of low temperatures on the risk of hypertension was the greatest. These results can provide technical support for carrying out meteorological forecasting, warning, and services for individuals with CVD and CeVD, suggesting attaching importance to health protection for special populations. [ABSTRACT FROM AUTHOR]

Phytoplasmas are insect-transmitted bacterial pathogens associated with diseases in a wide range of host plants, resulting in significant economic and ecological losses. Perennial deciduous trees in the genus Paulownia are widely planted for wood harvesting and ornamental purposes. Paulownia witches' broom (PaWB) disease, associated with a 16SrI-D subgroup phytoplasma, is a destructive disease of paulownia in East Asia. The PaWB phytoplasmas are mainly transmitted by insect vectors in the Pentatomidae (stink bugs), Miridae (mirid bugs) and Cicadellidae (leafhoppers) families. Diseased trees show typical symptoms, such as branch and shoot proliferation, which together are referred to as witches' broom. The phytoplasma presence affects the physiological and anatomical structures of paulownia. Gene expression in paulownia responding to phytoplasma presence have been studied at the transcriptional, post-transcriptional, translational and post-translational levels by high throughput sequencing techniques. A PaWB pathogenic mechanism frame diagram on molecular level is summarized. Studies on the interactions among the phytoplasma, the insect vectors and the plant host, including the mechanisms underlying how paulownia effectors modify processes of gene expression, will lead to a deeper understanding of the pathogenic mechanisms and to the development of efficient control measures. [ABSTRACT FROM AUTHOR]

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine and nanotechnology, artificial nanozymes offer advanced controllability and functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity and biosafety, still exist between nanozymes and their native counterparts. Here we report a non‐metal single‐selenium (Se)‐atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase‐mimetic activity. This novel single atom nanozyme provides a safe alternative to conventional metal‐based catalysts and effectively cuts off the cellular energy and reduction equivalents through its distinctive catalytic function in tumors. In this study, we have demonstrated the substantial efficacy of SeSAE as an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism of the NADPH oxidase‐like activity of the non‐metal SeSAE was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation of the biological functions, cell death pathways, and metabolic remodeling effects of the nanozyme was conducted, aiming to provide valuable insights into the development of single atom nanozymes with clinical translation potential. [ABSTRACT FROM AUTHOR]

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine and nanotechnology, artificial nanozymes offer advanced controllability and functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity and biosafety, still exist between nanozymes and their native counterparts. Here we report a non‐metal single‐selenium (Se)‐atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase‐mimetic activity. This novel single atom nanozyme provides a safe alternative to conventional metal‐based catalysts and effectively cuts off the cellular energy and reduction equivalents through its distinctive catalytic function in tumors. In this study, we have demonstrated the substantial efficacy of SeSAE as an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism of the NADPH oxidase‐like activity of the non‐metal SeSAE was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation of the biological functions, cell death pathways, and metabolic remodeling effects of the nanozyme was conducted, aiming to provide valuable insights into the development of single atom nanozymes with clinical translation potential. [ABSTRACT FROM AUTHOR]

In this work, by capitalizing on the density functional theory (DFT) and the time-dependent density functional theory (TD-DFT) methods, it has been systematically studied that the excited state double intramolecular proton transfer (ESDPT) process and the photophysical properties of 1,8-dihydroxy-2-naphthaldehyde (DHNA) are affected by the distinct external electric fields (EEFs). The obtained intramolecular hydrogen bond (IHB) parameters containing bond lengths and angles, as well as infrared (IR) vibrational spectra demonstrate that IHB strength changes in the distinct EEFs. Moreover, not only do the potential energy surfaces (PESs) indicate that the ESDPT process of DHNA is stepwise, but also increasing the positive EEF results in a decrease in the energy barrier accordingly, while vice versa. The absorption and fluorescence spectra also undergo a corresponding red or blue shift in the EEF; for instance, when the EEF changes from +10 × 10−4 a.u. to +20 × 10−4 a.u., the fluorescence peak undergoes a blue shift from 602 nm to 513 nm in the keto2 form. In a nutshell, the ESDPT process of DHNA can be influenced by the EEF, which will serve as a reference in regulating and controlling proton transfer that causes luminescence. [ABSTRACT FROM AUTHOR]

Studies have demonstrated a significant correlation between the approximate number system (ANS) and early mathematical achievement. However, various explanations exist regarding the underlying cognitive mechanisms that underpin this association. The present study investigated whether the two hypotheses of inhibition control and visual form perception could explain the relationship between kindergarteners' ANS and mathematical achievements. In spring, data were collected from a sample of 180 kindergarteners (Mage = 5.77 years, SD = 0.59). A parallel mediation analysis was conducted to investigate the role of inhibition control and visual form perception in the link between ANS and math achievement. The results indicated an indirect effect of ANS on mathematical achievements through both inhibition control and visual form perception, with both mediators exhibiting a comparable magnitude. These findings highlight the significance of distinct cognitive abilities that can potentially enhance early mathematical advancement. [ABSTRACT FROM AUTHOR]

Background: Research has widely indicated that the psychological distress experienced by infertile patients during fertility treatments may have a negative effect on the results of assisted reproduction. Although numerous studies have shown that psychological resilience and sleep quality are important influencing factors for psychological distress, the mediating mechanisms of psychological resilience in the relationship between sleep quality and psychological distress for Chinese women in particular remain unclear. Therefore, the current study investigates the association between sleep quality, resilience, and psychological distress in Chinese women with infertility and examines the mediating and moderating roles of resilience on the relationship between sleep quality and psychological distress. Methods: In this cross-sectional study, a total of 595 women with infertility who were undergoing IVF-ET were recruited at the Reproductive Medicine, Shandong University, from April to November 2019. Participants were instructed to complete four questionnaires, including a questionnaire about socio-demographic and clinical-related information, the Pittsburgh Sleep Quality Index (PSQI), the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and the Kessler-10 (K10). Pearson's correlation analysis was conducted preliminarily to describe the relationships between sleep quality, resilience, and psychological distress. A mediation model and a moderated model were constructed and analyzed using the PROCESS macro for SPSS. The Johnson-Neyman (J-N) technique was then used to identify the regions of significance across the levels of moderator values. Results: Patients in the sample had a high prevalence of psychological distress (48.6%, K10 scores > 22), and mediation analysis indicated that resilience played a partially mediating role in the relationship between sleep quality and psychological distress (indict effect = 0.072, P < 0.001). Moderation analysis indicated that resilience also moderated the association between sleep quality and psychological distress. Conclusions: Resilience may play a key role in the relationship between sleep quality and psychological distress. Our findings imply that resilience training may therefore be an effective component of psychological distress intervention in women with infertility. [ABSTRACT FROM AUTHOR]

Accurate traffic flow forecasting is a critical component in intelligent transportation systems. However, most of the existing traffic flow prediction algorithms only consider the prediction under normal conditions, but not the influence of weather attributes on the prediction results. This study applies a hybrid deep learning model based on multi feature fusion to predict traffic flow considering weather conditions. A comparison with other representative models validates that the proposed spatial‐temporal fusion graph convolutional network (STFGCN) can achieve better performance. [ABSTRACT FROM AUTHOR]

Meteorological conditions and air quality are important environmental factors in the occurrence and development of cardiovascular diseases (CVDs) such as hypertension. The aim of this study was to take Haikou City, located on the tropical edge, as the research area and to analyze the exposure–response relationship and lag effect between its meteorological conditions, air quality, and the number of hypertensive patients. Using the data from the hypertension outpatient department of Hainan Provincial People's Hospital from 2016 to 2018, together with meteorological data and air quality data, a distributed lag nonlinear model based on the nested generalized addition model of meteorological element base variables was established. The results showed that the impact of temperature on the risk of hypertension was mainly due to the cold effect, which was associated with high risk, with a lag of 1–10 days. When the temperature dropped to 10 °C, the cumulative effect on the risk of hypertension of relative risk (RR) reached its highest value on the day the low temperature occurred (RR was 2.30 and the 95% confidence interval was 1.723~3.061), passing the test with a significance level of 0.05. This result indicated that efforts should be made to strengthen the prevention of hypertension under low-temperature conditions and the prediction and early warning of disease risks. The impact of the air-quality effect (the environmental Air Quality Index was selected as an indicator) on the risk of hypertension was mainly characterized by a low air-quality effect, with a lag effect of 0–8 days. When the risk reached approximately 124, the RR was highest (RR was 1.63 and the 95% confidence interval was 1.104~2.408), passing the test with a significance level of 0.05. The research results can provide technical support for conducting medical meteorological forecasting, early warning, and services for hypertension. A joint work and research mechanism among multiple departments such as meteorology and medical health should be established to improve the level of medical and health care, optimize the allocation of social resources, and develop targeted prevention and control strategies to reduce the health and economic burden of hypertension. [ABSTRACT FROM AUTHOR]

The effects of meteorological conditions on asthma in Haikou, a tropical city in China, are still unclear. This study aimed to determine the relationships between meteorological factors and the number of asthma hospital visits in Haikou. A Poisson generalized additive model combined with a distributed lag nonlinear model is used to model the nonlinear exposure–response relationship between the daily mean temperature and asthma hospital visits. The daily mean pressure and air quality are used as covariates and simultaneously control the mixed effects of holiday effects, weekend effects, and long-term trends. The results indicate that there is a significant statistical relationship between the daily mean temperature and asthma hospital visits, which shows an inverted J-shaped relationship. When the daily mean temperature is below the reference value (29.3 °C), the number of asthma patients increases considerably, and there is a marked lag in the prevalence of asthma. The longest lag is 9 days, and the most pronounced impact of the daily mean temperature on the number of asthma hospital visits can be found when the lag time is 1–4 days. When the daily mean temperature is 10 °C, the cumulative effect of the relative risk of asthma is 2.204, an increase of 120.4% (95% CI 1.294–3.755). If the daily mean temperature is below the 2.5th percentile value (14.8 °C), the relative risk significantly increases by more than 5.3% (95% CI 1.000–1.110), and the longest lasting impact time is 5 days. This indicates that increases in asthma hospital visits in Haikou, China, are significantly correlated with low-temperature weather. We suggest that preventive measures for asthma should take low-temperature weather into account. Additionally, we also found that extremely high temperatures have a certain impact on the increase in asthma hospital visits, but that the correlation is not significant. [ABSTRACT FROM AUTHOR]

As the mainstay of healthcare, the job satisfaction of medical staff deserves attention. This study aimed to explore the correlation between the perception of the high-performance work system (P-HPWS) and job satisfaction of medical staff in public hospitals and to further investigate the mediating effect of self-efficacy. From November 2019 to January 2020, a cross-sectional survey on working doctors and nurses was conducted in five tertiary public hospitals in China. A total of 520 participants were surveyed. The P-HPWS, job satisfaction, and self-efficacy were assessed using the 25-item self-administered scale, six-item job satisfaction questionnaire, and the General Self-Efficacy Scale, respectively. Linear regression and mediation effects models were used to identify the associations between primary variables. The results showed a significant positive correlation between P-HPWS and job satisfaction (P < 0.01), while self-efficacy played a mediating role between P-HPWS and job satisfaction. This finding reveals the benefits of improving employees' P-HPWS and self-efficacy on their job satisfaction, and that hospitals can improve their management systems by implementing and refining HPWS. [ABSTRACT FROM AUTHOR]

The molecular profiles and tumor immune microenvironment (TIME) of multiple primary lung cancers (MPLCs) presenting as concurrent lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) remain unknown. We aimed to clarify these factors. We performed whole-exome sequencing (WES), RNA sequencing (RNA-Seq), and multiplex immunohistochemistry (mIHC) for five patients with concurrent ADC and SQCC. We found the genetic mutations were similar between ADC and SQCC groups. RNA-Seq revealed that the gene expression and pathways enriched in ADC and SQCC groups were quite different. Gene set enrichment analysis (GSVA) showed that nine gene sets were significantly differentially expressed between the ADC and SQCC groups (p < 0.05), with four gene sets relevant to squamous cell features upregulated in the SQCC group and five gene sets upregulated in the ADC group. Reactome enrichment analysis of differentially expressed genes showed that the immune function-related pathways, including programmed cell death, innate immune system, interleukin-12 family signaling, and toll-like receptor 2/4 pathways, etc. were significantly enriched. Transcriptomic TIME analysis, with mIHC in patient specimens and in vivo validation, showed tumor-infiltrating immune cells were significantly more enriched and diverse in ADC, especially CD8 + T cells. Our results revealed that the transcriptomic profiles and TIME features were quite different between ADC and SQCC lesions. ADC lesions exhibited a more active TIME than SQCC lesions in MPLCs. [ABSTRACT FROM AUTHOR]

China has implemented a series of ecological engineering projects to help achieve the 2060 carbon neutrality target. However, the lack of quantitative research on ecological engineering and the contribution of climate change to terrestrial carbon sinks limits this goal. This study uses robust statistical models combined with multiple terrestrial biosphere models to quantify the impact of China's ecological engineering on terrestrial ecosystem carbon sink trends and their differences according to the difference between reality and nonpractice assumptions. The main conclusions include the following: (1) since 1901, 84% of terrestrial ecosystem carbon sinks in China have shown an increasing trend, and approximately 45% of regional carbon sinks have increased by more than 0.1 g C/m2 every 10 years. (2) Considering the impact of human activities and the implementation of ecological engineering in China, approximately 56% of carbon sinks have improved, and approximately 10% of the regions whose carbon sink growth exceeds 50 g C m−2 yr−1 are mainly in the southeast coastal of China. (3) The carbon sequestration potential and effect of the Sanjiangyuan ecological protection and construction project are better than others, at 1.26 g C m−2 yr−1 and 14.13%, respectively. The Beijing–Tianjin sandstorm source comprehensive control project helps alleviate the reduction in carbon sinks, while the southwest karst rocky desertification comprehensive control project may aggravate the reduction in carbon sinks. This study clarifies the potential of China's different ecological engineering to increase carbon sink potential, and distinguishes and quantifies the contribution of climate and human activity factors to it, which is of great significance to the system management optimization scheme of terrestrial ecosystems and can effectively serve the national carbon neutral strategy. Highlights: • Reality and nonpractice assumptions are used to evaluate the impact of ecological engineering on terrestrial ecosystems. • Multiple terrestrial biosphere models show 45% of China's carbon sinks increase by more than 0.1 g C m-2 every 10 years. • SEPCP is more helpful in improving terrestrial carbon sinks compared to the other two ecological projects. [ABSTRACT FROM AUTHOR]

The stability and large-time behavior problem on the magneto-micropolar equations has evoked a considerable interest in recent years. In this paper, we study the stability and exponential decay near magnetic hydrostatic equilibrium to the two-dimensional magneto-micropolar equations with partial dissipation in the domain $ \Omega =\mathbb {T}\times \mathbb {R} $ Ω = T × R . In particular, we takes advantage of the geometry of the domain $ \mathbb {T}\times \mathbb {R} $ T × R to divide u into zeroth mode and the nonzero modes, and obey a strong version of the Poincaré's inequality, which plays a crucial role in controlling the nonlinearity. Moreover, we find that the oscillation part of the solution decays exponentially to zero. Finally, our result mathematically verifies that the stabilization effect of a background magnetic field on magneto-micropolar fluids. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the instability for Rayleigh–Taylor problem of three‐dimensional incompressible non‐Newtonian fluids with Eills‐type. If the density profile in equilibrium‐state is heavier with increasing height, we prove that the equilibrium‐state solution is unstable under H3$$ {H}^3 $$‐norm by exploiting a bootstrap method. [ABSTRACT FROM AUTHOR]

Sorafenib (SOR) is a molecular targeting agent commonly utilized as a primary treatment for advanced and inoperable hepatocellular carcinoma (HCC). Regrettably, the effectiveness of SOR is frequently hindered by the resistance of multiple HCC cases. The current investigation endeavors to examine the potential of the natural product quercetin (QUE) in reversing the acquired resistance of SOR-resistant cells, known as Huh7R, to SOR. Moreover, this study aims to elucidate the underlying molecular mechanism that contributes to this phenomenon. The results demonstrated that QUE significantly impeded proliferation and stimulated apoptosis in Huh7R cells, while also suppressing the growth of transplanted tumors. The impact of QUE enhanced the efficacy of SOR treatment for Huh7R. Additionally, bioinformatic and western blot analyses indicated that the underlying mechanisms may be associated with EGFR tyrosine kinase inhibitor resistance, the PI3K-AKT signaling pathway, and HCC. Furthermore, molecular docking and dynamics simulation assays revealed that QUE exhibited strong affinity and stability towards its hub targets, EGFR and AKT1. It is noteworthy that the activation of EGFR by its ligand, EGF, mitigated the effects of co-treatment with QUE and SOR. These findings suggest that QUE might potentially serve as a therapeutic agent in treating as well as facilitating SOR against Huh7R cells, which has substantial clinical and research implications for the treatment of acquired resistance to SOR in HCC. [ABSTRACT FROM AUTHOR]

The MiniMovers (MM) APP combines motor development theory with creativity expertise and has been designed to provide parents with developmentally appropriate activities to support children's motor skills. This study investigates how MiniMovers activities enabled parents to support their children's physical development. Families participated in an 8-week MM programme of activities from the MM APP (Mini, Mighty and Mega levels), with pre- and post-intervention data collected using multiple tools (e.g., motion capture system, force plate, eye-tracking glasses, and videos). Mixed research methods were applied among children (N = 8; aged 21–79 months) and their parents, providing quantitative analysis on children's performance (running, throwing, jumping, kicking, balancing and catching), as well as qualitative analysis on parents' attitude and behaviour (two-weekly feedback surveys and interviews). Lab-based measures showed significant improvements in run time, underarm throwing distance, and horizontal jump distance. Test of Gross Motor Development-3 showed a significant gain in running, underarm and overarm throwing, horizontal jump and kicking. Further, developmental stages indicated significant improvements in running, kicking and catching. Parents reported increased enjoyment and knowledge, children's enjoyment, independence and confidence. This pilot study provides support for the research and development of the MM App and suggests more research into the use of APPs to support home activities among families with young children. [ABSTRACT FROM AUTHOR]

In order to solve the problem of frequent snow and ice removal in winter, a micro-surfacing pavement with active snow and ice removal and slow-release function is developed. The snow-melting agent with sodium acetate, calcium acetate, and potassium acetate as the main components was prepared, and the optimum proportion was determined. With the help of hygroscopicity and oil absorption tests, the optimum surface modifier and its optimum concentration were determined. The microstructure of the snowmelt agent were characterized by infrared spectroscopy and scanning electron microscopy. The influence of snow-melting agent on the road performance was explored. The results show that the optimum proportion of sodium acetate, calcium acetate and potassium acetate is 37, 15 and 48 % respectiveiy. When the surface modifier: hydrogen silicone oil and KH560 solution concentration was 4.0% and 1.0% respectively, the slow-release effect was the optimum. The wear resistance and high temperature stability of micro-surfacing with the snowmelt agent were increased by 2.5 % and 8.2 %, respectively. It is most reasonable to determine that the optimal replacement amount of mineral powder is 50%. It is necessary to study the distribution of self-made snowmelt agent in the mixture in the future. [ABSTRACT FROM AUTHOR]

Chemotherapy drugs, though effective against cancer, often pose challenges due to their high toxicity and adverse effects. To address these issues and prevent premature drug release, a straightforward yet smart glutathione (GSH)‐responsive drug delivery system (DDS) based on aptamer‐coated mesoporous silica has been developed. Mesoporous silica serves as the drug carrier, with the anticancer drug model doxorubicin (Dox) efficiently loaded in, sealed by coating with aptamer AS1411. The characteristics of the resulting microspheres were investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, thermogravimetric analysis and zeta potential measurements. These analyses confirmed the successful bonding of AS1411 to the surface of the mesoporous silica. Drug‐release tests were conducted under two distinct pH conditions (pH 5.0 and 7.4), both in the presence and in the absence of GSH. The results demonstrate the remarkable ability of this DDS to respond to GSH, facilitating controlled drug release. The single coated layer on the particle serves a dual purpose by blocking pore openings and triggering an endogenous stimulus response, ensuring the precise release of pharmaceuticals during drug delivery. This GSH‐responsive DDS holds the potential to mitigate drug‐induced harm to healthy tissues, offering a new approach for cancer treatment. [ABSTRACT FROM AUTHOR]

Synthetic nano-calcium silicate hydrate (CSH) is widely known for its ability to act as crystal nuclei in ordinary portland cement. Material performance is largely influenced by its microstructure. Here, nano-CSH was prepared by different siliceous raw materials (Na2SiO3 or Na2SiO3·5H2O). It was found that nano-CSH can be obtained from Na2SiO3 or Na2SiO3·5H2O in the presence of Ca(NO3)2·4H2O and NaOH solution and were labeled as CSH-0 and CSH-5, respectively. The average particle size of CSH-0 and CSH-5 was about 80 nm, and the polymerization degrees of silicon and oxygen atoms in CSH-0 and CSH-5 were different. CSH-0 and CSH-5 can increase the rate of hydration and significantly enhance the early strength of portland cement. Further, CSH-0 and CSH-5 can provide nucleation sites for CSH hydration product; however, CSH-0 and CSH-5 can also react with the calcium ions in the cement paste and produce calcium silicate hydrate with a high Ca/Si ratio. Compared with CSH-5, CSH-0 with a lower Ca/Si ratio can consume more calcium ions in the cement paste. CSH-0 promoted cement hydration better, decreased the volume fractions of macropores, and increased compressive strength more significantly due to the synergistic effect of the nanocrystal nucleus and reactivity with calcium ions in solution. [ABSTRACT FROM AUTHOR]

Background: The Qinghai-Tibet Plateau is the "sensitive area" of climate change, and also the "driver" and "amplifier" of global change. The response and feedback of its carbon dynamics to climate change will significantly affect the content of greenhouse gases in the atmosphere. However, due to the unique geographical environment characteristics of the Qinghai-Tibet Plateau, there is still much controversy about its carbon source and sink estimation results. This study designed a new algorithm based on machine learning to improve the accuracy of carbon source and sink estimation by integrating multiple scale carbon input (net primary productivity, NPP) and output (soil heterotrophic respiration, Rh) information from remote sensing and ground observations. Then, we compared spatial patterns of NPP and Rh derived from the fusion of multiple scale data with other widely used products and tried to quantify the differences and uncertainties of carbon sink simulation at a regional scale. Results: Our results indicate that although global warming has potentially increased the Rh of the Qinghai-Tibet Plateau, it will also increase its NPP, and its current performance is a net carbon sink area (carbon sink amount is 22.3 Tg C/year). Comparative analysis with other data products shows that CASA, GLOPEM, and MODIS products based on remote sensing underestimate the carbon input of the Qinghai-Tibet Plateau (30–70%), which is the main reason for the severe underestimation of the carbon sink level of the Qinghai-Tibet Plateau (even considered as a carbon source). Conclusions: The estimation of the carbon sink in the Qinghai-Tibet Plateau is of great significance for ensuring its ecological barrier function. It can deepen the community's understanding of the response to climate change in sensitive areas of the plateau. This study can provide an essential basis for assessing the uncertainty of carbon sources and sinks in the Qinghai-Tibet Plateau, and also provide a scientific reference for helping China achieve "carbon neutrality" by 2060. Highlights: This study designed a carbon sink estimation method for Qinghai-Tibet Plateau by integrating machine learning and multiple scale ground- and remote sensed-based data. The estimated total carbon sink of the Qinghai-Tibet Plateau is 22.3 Tg C/year, accounting for about 10% of China's total carbon sink. The carbon sink of former estimation maybe greatly underestimated due to the underestimation of carbon input in the Qinghai-Tibet Plateau. [ABSTRACT FROM AUTHOR]

Global warming has caused changes in the area and thickness of permafrost on the Qinghai-Tibet Plateau and prompted the transition from permafrost to seasonally frozen soil, which has affected the soil moisture, soil temperature, and distribution of plant roots. This, in turn, affects grassland vegetation productivity and aboveground/belowground biomass. In this study, we took Qinghai Province in the northeastern Qinghai-Tibet Plateau as the research area to model the spatial pattern of grassland biomass and then evaluated the potential influence of frozen soil type information on aboveground and belowground biomass. Our research shows that there are significantly more biomass observations in seasonally frozen soil regions than in permafrost regions. However, when we ignore the type of frozen soil, the model does not show more accurate simulation in seasonally frozen soil regions, mainly because the stronger correlation between permafrost biomass and environmental factors, such as precipitation, compensates for the lack of observational data. In addition, we found that the biomass estimation error can be reduced significantly by building different models for each type of frozen soil, which implies that the type of frozen soil has an important impact on grassland biomass. Therefore, in considering the effects of future climate warming, more attention should be given to the impact of changes in frozen soil type on regional vegetation productivity. In addition, our investigation contributes a benchmark dataset of above- and belowground vegetation carbon storage in different frozen soil types, which provides the research community with useful information for optimizing process-based carbon cycle models. [ABSTRACT FROM AUTHOR]

We, herein, present dynamic behaviors of droplets entering an ultrasonic standing wave field (19 800 Hz) at different angles. In experiments, droplets' motion is recorded by using a high-speed camera, and an in-house Python program is used to obtain droplet positions and morphological characteristics as functions of time. The experimental results indicate that when the sound intensity is lower than the instability intensity and higher than the levitation intensity, the vertically falling droplet will oscillate up and down based on the equilibrium position. Although the oscillation amplitude decays from 0.52Tl to 0.01Tl (Tl = λ/2, λ is the wavelength) under the action of viscous resistance, the oscillation frequency of the droplet remains unchanged. Meanwhile, as the droplet's position oscillates, the acoustic radiation force on the droplet also periodically fluctuates, resulting in the acoustically forced oscillation of the droplet shape. In addition, when the droplet enters the sound field with a horizontal tilt angle θ of 15°, it undergoes a V-shaped translational motion, first descending and then ascending. As the sound pressure amplitude increases, the rebound position of the droplet advances. When the sound pressure amplitude reaches the instability value (7900 Pa), the droplet undergoes right-hand and left-hand disintegration during its descent and ascent, respectively. This instability is due to the acoustic radiation pressure distribution and the droplet's V-shaped trajectory. This work comprehensively discussed the complex motion of moving droplets in the acoustic standing wave field, which may inspire revealing the spray motion in the liquid engine with high-intensity resonance. [ABSTRACT FROM AUTHOR]

HSPA8 (heat shock protein family A (Hsp70) member 8) plays a significant role in the autophagic degradation of proteins, however, its effect on protein stabilization and anti-bacterial autophagy remains unknown. Here, it is discovered that HSPA8, as a binding partner of RHOB and BECN1, induce autophagy for intracellular bacteria clearance. Using its NBD and LID domains, HSPA8 physically binds to RHOB residues 1–42 and 89–118 as well as to BECN1 ECD domain, preventing RHOB and BECN1 degradation. Intriguingly, HSPA8 contains predicted intrinsically disordered regions (IDRs), and drives liquid-liquid phase separation (LLPS) to concentrate RHOB and BECN1 into HSPA8-formed liquid-phase droplets, resulting in improved RHOB and BECN1 interactions. Our study reveals a novel role and mechanism of HSPA8 in modulating anti-bacterial autophagy, and highlights the effect of LLPS-related HSPA8-RHOB-BECN1 complex on enhancing protein interaction and stabilization, which improves the understanding of autophagy-mediated defense against bacteria. [ABSTRACT FROM AUTHOR]

The excitons are generally decomposed into free charges by the heterojunction due to the low dielectric constant of organic materials. Recent research indicates that owing to the low exciton binding energy, the pure Y6 film can directly and spontaneously generate free charge carriers after photoexcitation, even without the assistance of the donor/acceptor interface driving force. However, the serious bimolecular recombination and trap‐assisted recombination also limit the photovoltaic efficiency of single‐component Y6 devices. Herein, efficient exciton separation and charge collection by changing the buffer layer and using mixed solvents to control the active layer morphology of single‐component devices based on Y6 are achieved. It is found that the short‐circuit current is significantly increased by properly adjusting the proportion of face‐on and edge‐on direction of molecules. Eventually, the power conversion efficiency (PCE) of single‐component devices based on Y6 is increased from 0.15% to 1.41%. The corresponding dynamic process is revealed by ultrafast transient absorption spectroscopy and entropy effect on the exciton dissociation. Effective charge separation and collection in single‐component devices is not only critical to improving the PCE, but provides an in‐depth understanding for the further design of high‐performance multicomponent devices. [ABSTRACT FROM AUTHOR]

Background: The Qinghai-Tibet Plateau is the "sensitive area" of climate change, and also the "driver" and "amplifier" of global change. The response and feedback of its carbon dynamics to climate change will significantly affect the content of greenhouse gases in the atmosphere. However, due to the unique geographical environment characteristics of the Qinghai-Tibet Plateau, there is still much controversy about its carbon source and sink estimation results. This study designed a new algorithm based on machine learning to improve the accuracy of carbon source and sink estimation by integrating multiple scale carbon input (net primary productivity, NPP) and output (soil heterotrophic respiration, Rh) information from remote sensing and ground observations. Then, we compared spatial patterns of NPP and Rh derived from the fusion of multiple scale data with other widely used products and tried to quantify the differences and uncertainties of carbon sink simulation at a regional scale. Results: Our results indicate that although global warming has potentially increased the Rh of the Qinghai-Tibet Plateau, it will also increase its NPP, and its current performance is a net carbon sink area (carbon sink amount is 22.3 Tg C/year). Comparative analysis with other data products shows that CASA, GLOPEM, and MODIS products based on remote sensing underestimate the carbon input of the Qinghai-Tibet Plateau (30–70%), which is the main reason for the severe underestimation of the carbon sink level of the Qinghai-Tibet Plateau (even considered as a carbon source). Conclusions: The estimation of the carbon sink in the Qinghai-Tibet Plateau is of great significance for ensuring its ecological barrier function. It can deepen the community's understanding of the response to climate change in sensitive areas of the plateau. This study can provide an essential basis for assessing the uncertainty of carbon sources and sinks in the Qinghai-Tibet Plateau, and also provide a scientific reference for helping China achieve "carbon neutrality" by 2060. Highlights: This study designed a carbon sink estimation method for Qinghai-Tibet Plateau by integrating machine learning and multiple scale ground- and remote sensed-based data. The estimated total carbon sink of the Qinghai-Tibet Plateau is 22.3 Tg C/year, accounting for about 10% of China's total carbon sink. The carbon sink of former estimation maybe greatly underestimated due to the underestimation of carbon input in the Qinghai-Tibet Plateau. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with the initiation and progression of Triple-negative breast cancer (TNBC). The publicly available TCGA database of breast cancer data was used to analyze the OTUD deubiquitinating family members that were correlated with survival of breast cancer and ovarian tumor domain-containing 2 (OTUD-2), or YOD1 was identified. The aim of present study was to assess YOD1 expression and function in human TNBC and then explored the underlying molecular events. Methods: We detected the expression of YOD1 in 32 TNBC and 44 NTNBC samples by qRT-PCR, Western blot and immunohistochemistry. Manipulation of YOD1 expression was assessed in vitro and in vivo for TNBC cell proliferation, migration, invasion, cell-cycle and drug resistance, using colony formation assay, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis and xenograft tumor assay. Next, proteomic analysis, Western blot, proximity ligation assay, Immunoprecipitation, and Immunofluorescence were conducted to assess downstream targets. Results: It was found that YOD1 was significantly upregulated in TNBC tissues compared with non-triple-negative breast cancer (NTNBC), which was positively correlated with poor survival in TNBC patients. Knockdown of YOD1 effectively inhibited TNBC cell migration, proliferation, cell cycle and resistance to cisplatin and paclitaxel. Mechanistically, YOD1 promoted TNBC progression in a manner dependent on its catalytic activity through binding with CDK1, leading to de-polyubiquitylation of CDK1 and upregulation of CDK1 expression. In addition, YOD1 overexpression was found to be correlated with CDK1 overexpression in human TNBC specimens. Finally, in vivo study demonstrated that YOD1 knockdown or YOD1 inhibitor could inhibit CDK1 expression and suppress the growth and metastasis of TNBC tumors. Conclusion: Our study highlights that YOD1 functions as an oncogene in TNBC via binding to CDK1 and mediated its stability and oncogenic activity. Interfering with YOD1 expression or YOD1 inhibitor could suppress TNBC cells in vitro and in vivo, suggesting that YOD1 may prove to be a promising therapeutic target for TNBC. [ABSTRACT FROM AUTHOR]

The human cardiac organoid (hCO) is three-dimensional tissue model that is similar to an in vivo organ and has great potential on heart development biology, disease modeling, drug screening and regenerative medicine. However, the construction of hCO presents a unique challenge compared with other organoids such as the lung, small intestine, pancreas, liver. Since heart disease is the dominant cause of death and the treatment of such disease is one of the most unmet medical needs worldwide, developing technologies for the construction and application of hCO is a critical task for the scientific community. In this review, we discuss the current classification and construction methods of hCO. In addition, we describe its applications in drug screening, disease modeling, and regenerative medicine. Finally, we propose the limitations of the cardiac organoid and future research directions. A detailed understanding of hCO will provide ways to improve its construction and expand its applications. [ABSTRACT FROM AUTHOR]

Air pollution and global temperature change are expected to affect infectious diseases. Air pollution usually causes inflammatory response and disrupts immune defense system, while temperature mainly exacerbates the effect of vectors on humans. Yet to date overview of systematic reviews assessing the exposure risk of air pollutants and temperature on infectious diseases is unavailable. This article aims to fill this research gap. PubMed, Embase, the Cochrane Library, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature were searched. Systematic reviews and meta-analyses investigated the exposure risk of pollutants or temperature on infectious diseases were included. Two investigators screened literature, extracted data and performed the risk of bias assessments independently. A total of 23 articles met the inclusion criteria, which 3 (13%) were "low" quality and 20 (87%) were "critically low" quality. COVID-19 morbidity was associated with long-term exposure PM2.5 (RR = 1.056 per 1 μ g / m 3 , 95% CI: 1.039–1.072) and NO2 (RR = 1.042 per 1 μ g / m 3 , 95% CI: 1.017–1.068). In addition, for each 1 °C increase in temperature, the morbidity risk of dengue increased 13% (RR = 1.130 per 1 °C, 95% CI: 1.120–1.150), infectious diarrhea increased 8% (RR = 1.080 per 1 °C, 95% CI: 1.050–1.200), and hand, foot and mouth disease (HFMD) increased 5% (RR = 1.050 per 1 °C, 95% CI: 1.020–1.080). In conclusion, PM2.5 and NO2 increased the risk of COVID-19 and temperatures were associated with dengue, infectious diarrhoea and HFMD morbidity. Moreover, the exposure risk of temperature on COVID-19 was recommended to be further explored. [ABSTRACT FROM AUTHOR]

In this paper, we analyze a class of nonlocal Poisson model on manifold under Dirichlet boundary condition. To get second order convergence, the geometric information of the manifold has to be incorporated in the nonlocal model. So the manifold is assumed to be given explicitly such that all geometric information can be calculated explicitly. Under this assumption, the well-posedness of nonlocal model is studied. Moreover, the second-order convergence rate of model is attained by combining the stability argument and the truncation error analysis. Such rate is currently optimal among all nonlocal models. Numerical tests are conducted to verify the convergence. [ABSTRACT FROM AUTHOR]

Fabricating an organic–inorganic nanocomposite hydrogel platform with antibacterial, anti-inflammatory, and osteoinductive properties that mimic bone extracellular matrix composition is decisive for guiding bone development in orthopedic practice. Despite significant progress in developing hydrogels for tissue repair, little attention has been paid to replicating the natural bone ECM microenvironments and addressing the importance of anti-inflammatory agents during osteogenesis. Herein, we developed ciprofloxacin and dexamethasone loaded strontium (Sr) and/or iron (Fe) substituted hydroxyapatite (HAp) nanomaterials precipitated in collagen (Col) to construct a multifunctional bioactive nanocomposite hydrogel platform to prevent inflammation and bacterial adhesion, leading to augmenting bone development in the defect site. The fabricated nanocomposite hydrogels (Sr:HAp-Col, Fe:HAp-Col, and Sr/Fe:HAp-Col) were physicochemically characterized and demonstrated high loading and prolonged drug release, and excellent antibacterial activity against Gram-positive and Gram-negative bacteria. In in vitro experiments, the Sr/Fe:HAp-Col sample exhibited enhanced bioactivity against the preosteoblast MC3T3-E1 cell line, with high alkaline phosphatase and bone-like inorganic calcium deposition, as well as increased gene expression of osteogenesis-related differentiation markers, including OPN, OCN, and RUNX2. Furthermore, in vivo experiments revealed that the Sr/Fe:HAp-Col matrix degraded over time by controlling the release of ions into the body, without causing acute inflammation at the implanted site or in the blood serum, or in the internal organs, including the heart, lungs, liver, and kidney of the Sprague–Dawley rat model. The micro-CT scan and histological examination showed high bone mineral density and more mature bone formation at the nanocomposite hydrogel implanted site associated with the ColMA hydrogel in the femur defect of the rat model. The strategy of applying collagen hydrogel supplemented with HAp to bone regeneration is promising due to its ability to mimic the natural bone ECM. Overall, the developed bioactive nanocomposite hydrogel may have great potential not only in bone regeneration but also in repairing nonunion-infected defects of other tissues. [ABSTRACT FROM AUTHOR]

Considering rare researches on wide-bandgap nonfullerene acceptors for ternary organic solar cells (OSCs), we reported a small molecule acceptor ITCN as the second acceptor for constructing PM6/Y6/ITCN ternary devices with better photovoltaic performance in this work. ITCN exhibits a large bandgap of 2.19 eV and a higher LUMO (the lowest unoccupied molecular orbital) than Y6, resulting in complementary optical absorption in the short-wavelength region and increased open-circuit voltage (VOC). As the content of ITCN increases, the hole mobilities increase continuously and the electron mobilities increase to a maximum value. Moreover, the incorporation of ITCN improves the nanoscale morphology and charge transport property to some extent. From PM6/Y6-based binary device to PM6/Y6/ITCN-based ternary device, the power conversion efficiency is increased from 15.01 to 16.04% with simultaneously enhanced VOC, short-circuit current, and fill factor. These results indicate that the design of wide-bandgap acceptors for high-performance ternary OSCs is available. [ABSTRACT FROM AUTHOR]

Reversible transformations between fractals and periodic structures are of fundamental importance for understanding the formation mechanism of fractals. Currently, it is still a challenge to controllably achieve such a transformation. We investigate the effect of CO and CO2 molecules on Sierpiński triangles (STs) assembled from Fe atoms and 4,4″-dicyano-1,1′:3′,1″-terphenyl (C3PC) molecules on Au surfaces. Using scanning tunneling microscopy, we discover that the gas molecules induce a transition from STs into 1D chains. Based on density functional theory modeling, we propose that the atomistic mechanism involves the transformation of a stable 3-fold coordination Fe(C3PC)3 motif to Fe(C3PC)4 with an axially bonded CO molecule. CO2 causes the structural transformation through a molecular catassembly process. [ABSTRACT FROM AUTHOR]