Joint trajectories of pain, depression and frailty and associations with adverse outcomes among community-dwelling older adults: A longitudinal study.

This study aimed to examine joint trajectories of pain, depression and frailty and their associations with adverse outcomes. Four waves of national data from the China Health and Retirement Longitudinal Study (CHARLS 2011-2018) were used, involving 4217 participants aged ≥60 years. Joint trajectories were fit using parallel-process latent class growth analysis, and their associations with adverse outcomes were evaluated using modified Poisson regression. Four joint trajectories were identified. Compared with most favorable group, other three joint trajectory groups had higher risk of functional disability and hospitalization. Slowly progressive pain, depression and frailty and persistent combination of pain, depression and frailty were also associated with cognitive decline, while slowly reduced pain and depression but persistent frailty was associated with all-cause mortality. The findings highlight unique characteristics and health impacts of concurrent changes in pain, depression and frailty over time, implicating the integrated physical and psychological care for older adults.

Predicting Provider Workload Using Predicted Patient Risk Score and Social Determinants of Health in Primary Care Setting.

BACKGROUND: Provider burnout due to workload is a significant concern in primary care settings. Workload for primary care providers encompasses both scheduled visit care and non-visit care interactions. These interactions are highly influenced by patients' health conditions or acuity, which can be measured by the Adjusted Clinical Group (ACG) score. However, new patients typically have minimal health information beyond social determinants of health (SDOH) to determine ACG score. OBJECTIVES: This study aims to assess new patient workload by first predicting the ACG score using SDOH, age, and gender and then using this information to estimate the number of appointments (scheduled visit care) and non-visit care interactions. METHODS: Two years of appointment data were collected for patients who had initial appointment requests in the first year and had the ACG score, appointment, and non-visit care counts in the subsequent year. State-of-art machine learning algorithms were employed to predict ACG scores and compared with current baseline estimation. Linear regression models were then used to predict appointments and non-visit care interactions, integrating demographic data, SDOH, and predicted ACG scores. RESULTS: The machine learning methods showed promising results in predicting ACG scores. Besides the decision tree, all other methods performed at least 9% better in accuracy than the baseline approach which had an accuracy of 78%. Incorporating SDOH and predicted ACG scores also significantly improved the prediction for both appointments and non-visit care interactions. The R 2 values increased by 95.2 and 93.8%, respectively. Furthermore, age, smoking tobacco, family history, gender, usage of injection birth control, and ACG were significant factors for determining appointments. SDOH factors such as tobacco usage, physical exercise, education level, and group activities were strongly correlated with non-visit care interactions. CONCLUSION: The study highlights the importance of SDOH and predicted ACG scores in predicting provider workload in primary care settings.

Effects of substrates and suppliers of ingredients on microbial community and metabolites of traditional non-salt Suancai.

Aim: Non-salt Suancai is an acidic fermented vegetable consumed by the Chinese Yi ethnic group. Traditionally, it is produced by fermentation without salt in a cold environment. The present study aimed to investigate the metabolite and microbial characteristics, and the effects of substrates/suppliers ingredients on non-salt Suancai. Methods: A simulated fermentation system of non-salt Suancai was constructed by using different substrates/suppliers' ingredients. The coherence and differential detection of the metabolite and microbial characteristics were done through non-target metabolomic and metagenomic analysis. Results: Lactic acid was the predominant organic acid across all samples. The enumeration of the Lactic acid bacteria showed no discernible differences between study groups, but that of yeast was highest in the mustard leaf stem (Brassica juncea var. latipa). The three major biological metabolic pathways were metabolism, environmental information, and genetic information processing based on the KEGG database. The metabolite diversity varied with the substrate/supplier of ingredients based on the PLS-DA plot. Lactiplantibacillus, Leuconostoc, and Lactococcus were prevalent in all samples but differentially. The microbial diversity and richness varied significantly, with 36~291 species being identified. Among the various substrates collected from the same supplier, 29, 59, and 29 differential species were identified based on LEfSe [linear discriminant analysis (LDA) > 2, P < 0.05]. Leuconostoc citreum, Leuconostoc mesenteroides, Leuconostoc pseudomesenteroides, Lactiplantibacillus plantarum, and Leuconostoc lactis were likely to be used as the species to discriminate samples collected from different suppliers. Conclusions: This research contributed to the exploration of microbial and metabolite characteristics behind the ingredient restriction of non-salt Suancai using traditional technology.

Temperature-driven divergence in molecular distribution and microbial invasion and the associated texture softening during dual-phase fermentation of Paocai.

Temperature is an important driving force that shapes the texture of fermented vegetables through driving the molecular distribution and microbial invasion between the liquid phase (brine) and the solid phase (vegetables) during fermentation. The objective of this study was to investigate the texture softening by investigating firmness, microstructure, physicochemical properties, molecular distribution and microbial community between brine and vegetables of Paocai as affected by fermentation temperatures of 10 °C, 20 °C and 30 °C. Results demonstrated that, compared with 10 °C and 30 °C, 20 °C attenuated softening of Paocai by restraining microbial invasion and suppressing pectinolysis. Moreover, at 20 °C, a balanced molecular distribution and microbial community were achieved between vegetables and brine, thus accomplishing acid-production fermentation. By contrast, 10 °C and 30 °C promoted nonfermentative microbial genera, retarding fermentation. This study provided an understanding of the divergent influence of temperature on quality formation of fermented vegetables during fermentation.

Trends in cardiovascular health metrics and associations with long-term mortality among US adults with coronary heart disease.

BACKGROUND AND AIMS: Our study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US. METHODS AND RESULTS: The cohort study was conducted based on the National Health and Nutrition Examination Survey 1999-2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively. CONCLUSION: Substantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them.

Joint trajectories of loneliness, social isolation and sarcopenia and associations with adverse outcomes: A prospective cohort study.

This study aimed to examine joint trajectories of loneliness, social isolation and sarcopenia and their associations with adverse outcomes. A total of 4701 participants aged ≥60 years who had a baseline and at least one follow-up assessment of loneliness, social isolation and sarcopenia across 2011, 2013 and 2015 waves in China Health and Retirement Longitudinal Study. Adverse outcomes were obtained in 2018 wave. Joint trajectories were fit using the parallel process latent class growth analysis, and their associations with adverse outcomes were evaluated using modified Poisson regression. Joint trajectory patterns for social relationship and sarcopenia did not vary by the assessment for sarcopenia, but did vary by the assessment for social relationship. Older adults exhibit distinct joint trajectories and those with persistent combination of loneliness or social isolation and sarcopenia experience greatest risk of adverse outcomes. These findings implicate integration of health care and social care for community-dwelling older adults.

Joint trajectories of physical frailty and social frailty and associations with adverse outcomes: A prospective cohort study.

BACKGROUND: We examined joint trajectories of physical frailty and social frailty as well as their associations with adverse outcomes. METHODS: We conducted a prospective cohort study by using five waves of national data from China Health and Retirement Longitudinal Study (CHARLS 2011-2020), involving 4531 participants aged ≥60 years. We identified 4-year trajectories at three examinations from 2011 to 2015 using parallel process latent class growth analysis. Adverse outcomes were obtained from 2015 to 2020 across two subsequent waves. We calculated hazard ratios (HR) using Cox proportional hazard models. We also conducted analyses by gender. RESULTS: Three joint trajectories were identified, including persistent absence of physical and social frailty (58.5 %), no physical frailty but social frailty (28.1 %), and persistent combination of physical and social frailty (13.4 %). Compared with persistent absence of physical and social frailty, no physical frailty but social frailty and persistent combination of physical and social frailty were associated with higher risk of instrumental activities of daily living (IADL) disability (HR = 1.182-2.020, 95 % CI: 1.014-2.416) and all-cause mortality (HR = 1.440-2.486, 95 % CI: 1.211-3.009). The persistent combination of physical and social frailty was also associated with ADL disability (HR = 2.412, 95 % CI: 1.999-2.911) and falls (HR = 1.410, 95 % CI: 1.196-1.662). Gender differences were observed in relationships between joint trajectories and adverse outcomes. CONCLUSION: Community-dwelling older adults exhibit distinct joint trajectories and those with persistent combination of physical and social frailty experience greatest risk of incident adverse outcomes. Clinical and public health measures targeting physical or social frailty should account for both and be gender-specific.

Superior Low-Temperature All-Solid-State Battery Enabled by High-Ionic-Conductivity and Low-Energy-Barrier Interface.

All-solid-state batteries (ASSBs) working at room and mild temperature have demonstrated inspiring performances over recent years. However, the kinetic attributes of the interface applicable to the subzero temperatures are still unidentified, restricting the low-temperature interface design and operation. Herein, a host of cathode interfaces are constructed and investigated to unlock the critical interface features required for cryogenic temperatures. The unstable interface between LiNi0.90Co0.05Mn0.05O2 (Ni90) and Li6PS5Cl (LPSC) sulfide solid electrolyte (SE) results in unfavorable cathode-electrolyte interphase (CEI) and sluggish lithium-ion transport across the CEI. After inserting a Li2ZrO3 (LZO) coating layer, the activation energy of the Ni90@LZO/sulfide SE interface can be reduced from 60.19 kJ mol-1 to 41.39 kJ mol-1 owing to the suppressed interfacial reactions. Through replacing the LPSC SE and LZO coating layer by the Li3InCl6 (LIC) halide SE, both a highly stable interface and low activation energy (25.79 kJ mol-1) can be achieved, thus realizing an improved capacity retention (26.9%) at -30 °C for the Ni90/LIC/LPSC/Li-In ASSB. Moreover, theoretical evaluation clarifies that cathode/SE interfaces with high ionic conductivity and low energy barrier are favorable to the Li+ conduction through the interphase and the Li+ transfer across the cathode/interphase interface. These critical understandings may provide guidance for low-temperature interface design in ASSBs.

Phytophthora infestans RXLR effector Pi23014 targets host RNA-binding protein NbRBP3a to suppress plant immunity.

Phytophthora infestans is a destructive oomycete that causes the late blight of potato and tomato worldwide. It secretes numerous small proteins called effectors in order to manipulate host cell components and suppress plant immunity. Identifying the targets of these effectors is crucial for understanding P. infestans pathogenesis and host plant immunity. In this study, we show that the virulence RXLR effector Pi23014 of P. infestans targets the host nucleus and chloroplasts. By using a liquid chromatogrpahy-tandem mass spectrometry assay and co-immunoprecipitation assasys, we show that it interacts with NbRBP3a, a putative glycine-rich RNA-binding protein. We confirmed the co-localization of Pi23014 and NbRBP3a within the nucleus, by using bimolecular fluorescence complementation. Reverse transcription-quantitative PCR assays showed that the expression of NbRBP3a was induced in Nicotiana benthamiana during P. infestans infection and the expression of marker genes for multiple defence pathways were significantly down-regulated in NbRBP3-silenced plants compared with GFP-silenced plants. Agrobacterium tumefaciens-mediated transient overexpression of NbRBP3a significantly enhanced plant resistance to P. infestans. Mutations in the N-terminus RNA recognition motif (RRM) of NbRBP3a abolished its interaction with Pi23014 and eliminated its capability to enhance plant resistance to leaf colonization by P. infestans. We further showed that silencing NbRBP3 reduced photosystem II activity, reduced host photosynthetic efficiency, attenuated Pi23014-mediated suppression of cell death triggered by P. infestans pathogen-associated molecular pattern elicitor INF1, and suppressed plant immunity.

The triglyceride glucose index predicts short-term mortality in non-diabetic patients with acute heart failure.

BACKGROUND: The triglyceride glucose index (TyG) has previously been considered a reliable indicator of insulin resistance (IR) and an independent prognostic predictor in heart failure (HF). OBJECTIVES: To clarify the association between the TyG and short-term death in non-diabetic patients admitted for acute heart failure (AHF). MATERIAL AND METHODS: We examined 886 out of 1620 consecutive AHF patients who were admitted to Shunde Hospital, Southern Medical University, Foshan, China, from June 1, 2014, to June 1, 2022. The median of the patientsf TyG values was used to divide them into 2 groups. The following formula was used to calculate the TyG: ln [fasting triglycerides (mg/dL) ~ fasting glucose (mg/dL)/2]. The data on all-cause mortality of AHF patients during their hospital stay were collected. The 30-day Enhanced Feedback for Effective Cardiac Treatment (EFFECT) death risk score was used to assess the risk of death. RESULTS: The TyG level was positively correlated with a poor AHF prognostic marker (N-terminal B-type natriuretic peptide (NT-proBNP)) (D = 0.207, p < 0.001) and negatively correlated with a protective marker (serum albumin) (D = .0.43, p < 0.001). Higher TyG values were associated with an elevated EFFECT score and hospital mortality (p < 0.001). According to multivariate logistic regression analysis, higher TyG levels raised the risk of death in hospital (odds ratio (OR) = 1.73; 95% confidence interval (95% CI): 1.03.3.27; p = 0.031) after adjusting for multiple variables, including age, EFFECT score and NT-proBNP. The TyG had a greater area under the receiver operating characteristic (ROC) curve (AUC: 0.688) for predicting hospital death compared to NT-proBNP (AUC: 0.506). CONCLUSIONS: Our findings show that the TyG is associated with the short-term mortality rate of non-diabetic patients admitted to the hospital for AHF. The TyG testing could be a useful prognostic indicator for these patients.

Myocardial fibrosis and prognosis in heart failure with preserved ejection fraction: a pooled analysis of 12 cohort studies.

OBJECTIVES: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with significant clinical heterogeneity. Myocardial fibrosis has been considered a common pathological process in the development and progress of HFpEF. This study aimed to consolidate data on the prognostic effect of myocardial fibrosis, evaluated by cardiovascular magnetic resonance (CMR) imaging in patients with HFpEF. METHODS: Three medical databases were searched for potentially related articles up to February 28, 2023. Cohort studies reporting associations between myocardial fibrosis and risk of all-cause mortality or composite major adverse cardiac outcomes (MACE) were included. Cardiac fibrosis was evaluated by CMR metrics, including late gadolinium enhancement (LGE) or myocardial extracellular volume (ECV). The hazard ratios (HRs) and 95% confidence intervals (CI) of the outcomes for higher myocardial fibrosis were calculated. RESULTS: Twelve studies with 2787 patients with HFpEF were included for analysis. After a median follow-up duration of 31.2 months, a higher level of cardiac fibrosis was associated with a significant increase in the risk of MACE (HR = 1.34, 95% CI = 1.14-1.57) and all-cause mortality (HR = 1.74, 95% CI = 1.27-2.39), respectively. Furthermore, the increased risk of outcomes was both observed when cardiac fibrosis was defined according to LGE or ECV, respectively. CONCLUSIONS: Higher burden of myocardial fibrosis evaluated by CMR can predict a poor prognosis in patients with HFpEF. Evaluation of LGE or ECV based on CMR could be recommended in these patients for risk stratification and guiding further treatment. CLINICAL RELEVANCE STATEMENT: Inclusion of cardiovascular magnetic resonance examination in the diagnostic and risk-evaluation algorithms in patients with heart failure with preserved ejection fraction should be considered in clinical practice and future studies. KEY POINTS: • Myocardial fibrosis is a common pathological process in heart failure with preserved ejection fraction. • A higher myocardial fibrosis burden on cardiac magnetic resonance predicts a poor prognosis in patients with heart failure with preserved ejection fraction. • Evaluation of myocardial fibrosis may be useful in patients with heart failure with preserved ejection fraction for risk stratification and treatment guidance.

Secreted frizzled-related protein 2 ameliorates diabetic cardiomyopathy by activating mitophagy.

OBJECTIVES: Secreted frizzled-related protein 2 (SFRP2), a novel adipokine that used to be considered an inhibitor of the canonical Wnt pathway, may play a protective role in metabolic disorders. However, its effect on diabetic cardiomyopathy was still unclear. Accumulating evidence indicates that mitophagy can protect cardiac function in the diabetic heart. The present study aimed to explore the roles of SFRP2 on diabetic cardiomyopathy, focusing on the effects and mechanisms for regulating mitophagy. METHODS: Wild-type H9c2 cells, Sfrp2 overexpression and knockdown H9c2 cells were exposed to a glucolipotoxic milieu. Reactive oxygen species (ROS) production, cell viability, apoptosis, mitophagy and lysosomal activity were detected. The interaction of SFRP2 with frizzled 5 (FZD5), and its effect on expression and intracellular localization of transcription factor EB (TFEB) and ß-catenin were also explored. Diabetic rats and Sfrp2 overexpression diabetic rats were constructed to further document the findings from the in vitro study. RESULTS: The expression of SFRP2 was low and mitophagy was inhibited in H9c2 cells in a glucolipotoxic milieu. Sfrp2 overexpression activated mitophagy and reduced H9c2 cells injury, whereas Sfrp2 deficiency inhibited mitophagy and worsened this injury. Consistent with the in vitro findings, Sfrp2 overexpression ameliorated the impairment in cardiac function of diabetic rats by activating mitophagy. Sfrp2 overexpression upregulated the expression of calcineurin and TFEB, but did not affect ß-catenin in vitro and in vivo. The calcineurin inhibitor tacrolimus can inhibit mitophagy and worsen cell injury in Sfrp2 overexpression H9c2 cells. Furthermore, we found that FZD5 is required for the SFRP2-induced activation of the calcineurin/TFEB pathway and interacts with SFRP2 in H9c2 cells. Transfection with small interfering RNA targeting FZD5 opposed the effects of Sfrp2 overexpression on mitophagy and cell survival in a glucolipotoxic environment. CONCLUSIONS: SFRP2 can protect the diabetic heart by interacting with FZD5 and activating the calcineurin/TFEB pathway to upregulate mitophagy in H9c2 cells.

The effects of 5-aminolevulinic acid photodynamic therapy on the local immune response of women with cervical intraepithelial neoplasia grade 2.

Objective: To evaluate and elucidate the effects and mechanism of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the local immune response of women with cervical intraepithelial neoplasia grade 2 (CIN2). Materials and methods: Immunofluorescence staining was used to compare immune cells infiltration before and after ALA-PDT in 23 patients with CIN2. The infiltration of immune cells into the cervical tissues of patients with different outcomes was also compared at the 6-month follow-up period. Immune cell counts in samples collected before and after treatment were compared. Results: We found an increased number of CD8+ T cell infiltration, an increased proportion of CD8+ T cells expressing Granzyme B (GrB), Chemokine receptor 3 (CXCR3), and CD8+ tissue-resident memory T (TRM) cells, and a decreased proportion of CD8+ T cells expressing PD-1 in patients with CIN2 compared to that before ALA-PDT. Moreover, at the 6-month follow-up, there was higher infiltration of CD8+ T and CD8+ TRM cells, higher expression of GrB and CXCR3, and lower expression of PD-1 on CD8+ T cells in the HPV clearance and CIN2 disappearance groups than in the HPV-positive and CIN2 regression groups. However, no significant difference was observed in the number of CD8+ TSCM following ALA-PDT. Conclusion: ALA-PDT could activate CD8+ T cell responses by modulating the expression of CXCR3 and PD-1 in CD8+ T cells and increasing the infiltration of CD8+ TRM cells. And the infiltration of CD8+ T cells is correlated with the prognosis of CIN2.

Associations of Unhealthy Lifestyle and Nonalcoholic Fatty Liver Disease With Cardiovascular Healthy Outcomes.

BACKGROUND: The role of nonalcoholic fatty liver disease (NAFLD) as a mediator in the association between various unhealthy lifestyles and major adverse cardiovascular events and all-cause death remains unclear. METHODS AND RESULTS: This study used data from the UK Biobank, with follow-up until the end of 2021. It involved the calculation of unweighted and weighted lifestyle scores using the Cox model to classify participants on the basis of these scores. Additionally, the research assessed the mediation effect proportion of NAFLD using the difference method and examined the interaction and joint effects of lifestyle and NAFLD on health outcomes. Among the 134 616 enrolled participants, 4024 had records of major adverse cardiovascular events, while among the 130 144 participants included in the analysis of all-cause death, 6697 deaths occurred. The proportions of the association between overall lifestyle and major adverse cardiovascular events mediated by NAFLD were 19.4% and 21.7% (95% CI, 16.2-22.6 and 17.8-25.7) for scores 1 and 2, respectively, and those for all-cause death were 14.1% and 10.1% (95% CI, 11.3-17.1 and 7.9-12.2). After fully adjusting for traditional cardiovascular risk factors, the mediating effects declined across both outcomes. The associations between overall lifestyle and outcomes were stronger among those of the non-NAFLD group, and significant interactions were observed between overall lifestyle and NAFLD status. The joint analysis revealed that patients with NAFLD with unhealthy lifestyle had the highest risk of major adverse cardiovascular events and all-cause death. CONCLUSIONS: Improving lifestyle and addressing metabolic risk factors are essential for cardiovascular risk management in patients with NAFLD.

Characterizing the impact of species/strain-specific Lactiplantibacillus plantarum with community assembly and metabolic regulation in pickled Suancai.

To investigate the colonization and impact of the specific Lactiplantibacillus plantarum strains, four isolated strains were applied in pickled Suancai which is a traditional pickled mustard (Brassica juncea). Results showed that strain-8 with the highest lactic acid bacteria (LAB) counts and acetic acid (p < 0.05). There were 11.42 % ∼ 32.35 % differential volatile compounds detected, although nitriles, esters, and acids were predominant. L. plantarum disturbed the microbial community, in which the microbial composition of strain-11 was most similar to the naturally fermented sample. Amino acids, carbohydrate metabolism, and metabolism of cofactors and vitamins were the main functional classes because of the similar dominant microbes (Lactiplantibacillus and Levilactobacillus). The functional units were separated based on NMDS analysis, in which bacterial chemotaxis, amino acid-related units, biotin metabolism, fatty acid biosynthesis, and citrate cycle were significantly different calculated by metagenomeSeq and Benjamin-Hochberg methods (p < 0.05). The contents of most flavor compounds were consistent with their corresponding enzymes. In particular, glucosinolates metabolites were different and significantly related to the myrosinase and metabolic preference of LAB. Therefore, this study revealed the impact mechanism of the specific L. plantarum strains and provided a perspective for developing microbial resources to improve the flavor diversity of fermented vegetables.

[mRNA Expression Profile Changes in Angiotensin-â ¡-Induced Atrial Myocardial Fibrosis in Rats].

Objective: To study the differences between the mRNA expression profile in angiotensin Ⅱ (Ang Ⅱ)-induced fibrotic cardiomyocytes and that of normal cardiomyocytes and the relevant signaling pathways. Methods: Six 8-week-old male Sprague-Dawley (SD) rats were randomly assigned to a control group and an Ang Ⅱ group, with 3 rats in each group. Rats in the control group were injected via caudal vein with 0.9% normal saline at 2 mg/kg per day, while rats in the Ang Ⅱ group were injected with Ang Ⅱ via caudal vein at 2 mg/kg per day. The medications were continuously administered in the two groups for 14 days. The degree of myocardial fibrosis was determined by Masson's Trichrome staining and the content of collagen Ⅰ was determined by immunohistochemistry. High throughput sequencing was performed to measure the mRNA expression of rat cardiomyocytes in the two groups and to screen for differentially-expressed mRNAs. The differentially-expressed mRNAs were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: Compared with those of the control group, the degree of myocardial fibrosis and the content of collagen Ⅰ in Ang Ⅱ group were significantly higher ( P<0.05). Through sequencing, 313 differentially-expressed mRNAs were identified, with 201 being up-regulated and 112 being down-regulated. Go and KEGG analyses showed that these differentially-expressed mRNA were involved in a variety of biological regulatory functions and pathways of myocardial fibrosis. Conclusion: Ang Ⅱ can cause myocardial fibrosis in rats. There are significant differences in mRNA expression between fibrotic cardiomyocytes and normal cardiomyocytes. The differentially expressed mRNAs may play an important role in biological processes, including immune response, cell remodeling, and extracellular matrix deposition.

Facile Solid-State Synthesis to In Situ Generate a Composite Coating Layer Composed of Spinel-Structural Compounds and Li3PO4 for Stable Cycling of LiCoO2 at 4.6 V.

Due to its high energy density, high-voltage LiCoO2 is the preferred cathode material for consumer electronic products. However, its commercial viability is hindered by rapid capacity decay resulting from structural degradation and surface passivation during cycling at 4.6 V. The key to achieving stable cycling of LiCoO2 at high voltages lies in constructing a highly stable interface to mitigate surface side reactions. In this study, we present a facile in situ coating strategy that is amenable to mass production through a simple wet-mixing process, followed by high-temperature calcination. By capitalizing on the facile dispersion characteristics of nano-TiO2 in ethanol and the ethanol dissolubility of LiPO2F2, we construct a uniform precoating layer on LiCoO2 with nano-TiO2 and LiPO2F2. The subsequent thermal treatment triggers an in situ reaction between the coating reagents and LiCoO2, yielding a uniform composite coating layer. This composite layer comprises spinel-structured compounds (e.g., LiCoTiO4) and Li3PO4, which exhibit excellent chemical and structural stability under high-voltage conditions. The uniform and stable coating layer effectively prevents direct contact between LiCoO2 and the electrolyte, thereby reducing side reactions and suppressing the surface passivation of LiCoO2 particles. As a result, coated LiCoO2 maintains favorable electronic and ionic conductivity even after prolonged cycling. The synergistic effects of spinel-structured compounds and Li3PO4 contribute to the superior performance of LiCoO2, demonstrating a high capacity of 202.1 mA h g-1 (3.0-4.6 V, 0.5 C, 1 C = 274 mA g-1), with a capacity retention rate of 96.7% after 100 cycles.

Transcription factor EB: A potential integrated network regulator in metabolic-associated cardiac injury.

With the worldwide pandemic of metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD), cardiometabolic disease (CMD) has become a significant cause of death in humans. However, the pathophysiology of metabolic-associated cardiac injury is complex and not completely clear, and it is important to explore new strategies and targets for the treatment of CMD. A series of pathophysiological disturbances caused by metabolic disorders, such as insulin resistance (IR), hyperglycemia, hyperlipidemia, mitochondrial dysfunction, oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy dysfunction, calcium homeostasis imbalance, and endothelial dysfunction, may be related to the incidence and development of CMD. Transcription Factor EB (TFEB), as a transcription factor, has been extensively studied for its role in regulating lysosomal biogenesis and autophagy. Recently, the regulatory role of TFEB in other biological processes, including the regulation of glucose homeostasis, lipid metabolism, etc. has been gradually revealed. In this review, we will focus on the relationship between TFEB and IR, lipid metabolism, endothelial dysfunction, oxidative stress, inflammation, ERS, calcium homeostasis, autophagy, and mitochondrial quality control (MQC) and the potential regulatory mechanisms among them, to provide a comprehensive summary for TFEB as a potential new therapeutic target for CMD.

Prediction of gestational diabetes mellitus at the first trimester: machine-learning algorithms.

PURPOSE: Short- and long-term complications of gestational diabetes mellitus (GDM) involving pregnancies and offspring warrant the development of an effective individualized risk prediction model to reduce and prevent GDM together with its associated co-morbidities. The aim is to use machine learning (ML) algorithms to study data gathered throughout the first trimester in order to predict GDM. METHODS: Two independent cohorts with forty-five features gathered through first trimester were included. We constructed prediction models based on three different algorithms and traditional logistic regression, and deployed additional two ensemble algorithms to identify the importance of individual features. RESULTS: 4799 and 2795 pregnancies were included in the Xinhua Hospital Chongming branch (XHCM) and the Shanghai Pudong New Area People's Hospital (SPNPH) cohorts, respectively. Extreme gradient boosting (XGBoost) predicted GDM with moderate performance (the area under the receiver operating curve (AUC) = 0.75) at pregnancy initiation and good-to-excellent performance (AUC = 0.99) at the end of the first trimester in the XHCM cohort. The trained XGBoost showed moderate performance in the SPNPH cohort (AUC = 0.83). The top predictive features for GDM diagnosis were pre-pregnancy BMI and maternal abdominal circumference at pregnancy initiation, and FPG and HbA1c at the end of the first trimester. CONCLUSION: Our work demonstrated that ML models based on the data gathered throughout the first trimester achieved moderate performance in the external validation cohort.