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1.
Arch Gerontol Geriatr ; 126: 105550, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38991290

RESUMO

OBJECTIVES: To examine the predictive value of intrinsic capacity decline on functional disability among the elderly. DESIGN: Meta-analysis. METHODS: PubMed, EMBASE, Web of Science, The Cochrane Library, Wanfang Database, China Knowledge Resource Integrated Database (CNKI), Weipu Database (VIP), and Chinese Biomedical Database (CBM) were searched for relevant studies published from the inception until June 1, 2024. Stata 17.0 software was used to perform the meta-analysis. The methodological quality was evaluated using the Newcastle Ottawa Scale. The overall quality of evidence used GRADE guidelines to assess. A study protocol was registered in PROSPERO (CRD42023475461). RESULTS: The meta-analysis included 8 cohort studies including 9744 elderly people. Functional disability including ADL disability (n = 6) and IADL disability (n = 7). The results showed that intrinsic capacity decline could predict ADL disability (HR = 1.08, 95 %CI 1.04-1.12; I2 = 98.2 %, P < 0.001) and IADL disability (HR = 1.11, 95 %CI 1.05-1.17; I2 = 96.4 %, P < 0.001). The overall risk of bias was low. And the grade of evidence that assessed by GRADE guidelines was rated as moderate. CONCLUSIONS: Intrinsic capacity decline is a predictor of functional disability in the elderly. Therefore, screening intrinsic capacity decline has important clinical implications for early identifying the risk of functional disability, which contributes to providing individualized interventions ahead of potential functional disability for the elderly, thereby preventing functional disability, improving the quality of life and promoting healthy aging.

2.
Biochemistry ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985857

RESUMO

The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein-coupled receptor that has emerged as a promising therapeutic target in cancer and autoimmune diseases. In the present study, we solved the cryo-electron microscopy (cryo-EM) structure of the human CCR8-Gi complex in the absence of a ligand at 2.58 Å. Structural analysis and comparison revealed that our apo CCR8 structure undergoes some conformational changes and is similar to that in the CCL1-CCR8 complex structure, indicating an active state. In addition, the key residues of CCR8 involved in the recognition of LMD-009, a potent nonpeptide agonist, were investigated by mutating CCR8 and testing the calcium flux induced by LMD-009-CCR8 interaction. Three mutants of CCR8, Y1133.32A, Y1724.64A, and E2867.39A, showed a dramatically decreased ability in mediating calcium mobilization, indicating their key interaction with LMD-009 and key roles in activation. These structural and biochemical analyses enrich molecular insights into the agonism and activation of CCR8 and will facilitate CCR8-targeted therapy.

3.
Ecotoxicol Environ Saf ; 282: 116696, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38986334

RESUMO

The prevalence of dyslipidemia is increasing, and it has become a significant global public health concern. Some studies have demonstrated contradictory relationships between urinary metals and dyslipidemia, and the combined effects of mixed urinary metal exposure on dyslipidemia remain ambiguous. In this study, we examined how individual and combined urinary metal exposure are associated with the occurrence of dyslipidemia. According to the data from the 2018-2019 baseline survey database of the China Multi-Ethnic Cohort (CMEC) Study, a population of 9348 individuals was studied. Inductively coupled plasmamass spectrometry (ICP-MS) was used to measure 21 urinary metal concentrations in the collected adult urinary samples. The associations between urinary metals and dyslipidemia were analyzed by logistic regression, weighted quantile sum regression (WQS), and quantile-based g-computation (qgcomp), controlled for potential confounders to examine single and combined effects. Dyslipidemia was detected in 3231 individuals, which represented approximately 34.6 % of the total population. According to the single-exposure model, Al and Na were inversely associated with the risk of dyslipidemia (OR = 0.95, 95 % CI: 0.93, 0.98; OR = 0.89, 95 % CI: 0.83, 0.95, respectively), whereas Zn, Ca, and P were positively associated (OR = 1.69, 95 % CI: 1.42, 2.01; OR = 1.12, 95 % CI: 1.06, 1.18; OR = 1.21, 95 % CI: 1.09, 1.34, respectively). Moreover, Zn and P were significantly positively associated even after adjusting for these metals, whereas Al and Cr were negatively associated with the risk of dyslipidemia. The results of the WQS and qgcomp analyses showed that urinary metal mixtures were positively associated with the risk of dyslipidemia (OR = 1.26, 95 % CI: 1.15, 1.38; OR = 1.09, 95 % CI: 1.01, 1.19). This positive association was primarily driven by Zn, P, and Ca. In the sensitivity analyses with collinearity diagnosis, interaction, and stratified analysis, the results remained, confirming the reliability of the study findings. In this study, the individual and combined effects of urinary Zn, P, and Ca on dyslipidemia were determined, which provided novel insights into the link between exposure to metals and dyslipidemia.

4.
Invest New Drugs ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990451

RESUMO

PURPOSE: This phase I trial is to determine the recommended dose of the TAS-102, irinotecan plus bevacizumab regimen and assess its safety and efficacy in patients with metastatic colorectal cancer refractory to fluoropyrimidine and oxaliplatin treatment. METHODS: A 3 + 3 designed dose escalation was performed. Patients were administered TAS-102 (30-35 mg/m2 twice daily on days 1-5) and irinotecan (150-165 mg/m2 on day 1) combined with a fixed dose of bevacizumab (5 mg/kg on day 1) every two weeks. The primary endpoint was the determination of the recommended phase II dose. RESULTS: Eighteen patients were enrolled: 6 at the Level 1 (TAS-102 30 mg/m2 twice daily, irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg), six at the Level 2 (TAS-102 35 mg/m2 twice daily, irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg), and six at the Level 3 (TAS-102 30 mg/m2 twice daily, irinotecan 165 mg/m2 plus bevacizumab 5 mg/kg). Five dose-limiting toxicities occurred: one observed at Level 1 (thrombocytopenia), two at Level 2 (neutropenia and diarrhea), and two at Level 3 (fatigue and neutropenia). The RP2D was established as TAS-102 30 mg/m2 twice daily and irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg. The most frequent grade 3/4 treatment-related adverse events were neutropenia (33.3%), diarrhea (16.7%), and thrombocytopenia (11.1%). No treatment-related death occurred. Two patients (11.1%) experienced partial responses and 14 (77.8%) had stable disease. CONCLUSION: The regimen of TAS-102, irinotecan, and bevacizumab is tolerable with antitumor activity for metastatic colorectal cancer patients refractory to first-line fluoropyrimidines and oxaliplatin treatment.

5.
J Pharm Sci ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38996917

RESUMO

The optimal method for administering meropenem remains controversial. This study was conducted to explore the optimal two-step infusion strategy (TIT), and to investigate whether TIT is superior to intermittent infusion therapy (IIT) and prolonged infusion therapy (PIT). A physiologically based pharmacokinetics model for critically ill patients was established and evaluated. The validated model was utilized to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) target attainment of meropenem. The PK/PD target attainment of different TITs varied greatly, and the total infusion duration and the first-step dose greatly affected these values. The optimal TIT was 0.25 g (30 min) + 0.75 g (150 min) at MICs of ≤2 mg/L, and 0.25 g (45 min) + 0.75 g (255 min) at MICs of 4-8 mg/L. The PK/PD target attainment of optimal TIT, PIT, and IIT were 100% at MICs of ≤1 mg/L. When MIC increased to 2-8 mg/L, the PK/PD target attainment of optimal TIT was similar to that of PIT and higher than IIT. In conclusion, TIT did not significantly improve the PK/PD target attainment of meropenem compared with PIT. IIT is adequate at MICs of ≤1 mg/L, and PIT may be the optimal meropenem infusion method in critically ill patients with MICs of 2-8 mg/L.

6.
Cell Mol Immunol ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044027

RESUMO

Brain tumors such as glioblastomas are resistant to immune checkpoint blockade therapy, largely due to limited T cell infiltration in the tumors. Here, we show that mice bearing intracranial tumors exhibit systemic immunosuppression and T cell sequestration in bone marrow, leading to reduced T cell infiltration in brain tumors. Elevated plasma corticosterone drives the T cell sequestration via glucocorticoid receptors in tumor-bearing mice. Immunosuppression mediated by glucocorticoid-induced T cell dynamics and the subsequent tumor growth promotion can be abrogated by adrenalectomy, the administration of glucocorticoid activation inhibitors or glucocorticoid receptor antagonists, and in mice with T cell-specific deletion of glucocorticoid receptor. CCR8 expression in T cells is increased in tumor-bearing mice in a glucocorticoid receptor-dependent manner. Additionally, chemokines CCL1 and CCL8, the ligands for CCR8, are highly expressed in bone marrow immune cells in tumor-bearing mice to recruit T cells. These findings suggested that brain tumor-induced glucocorticoid surge and CCR8 upregulation in T cells lead to T cell sequestration in bone marrow, impairing the anti-tumor immune response. Targeting the glucocorticoid receptor-CCR8 axis may offer a promising immunotherapeutic approach for the treatment of intracranial tumors.

7.
Heart Lung ; 68: 202-207, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39043085

RESUMO

BACKGROUND: Clinical blood resources are scarce and autologous blood transfusion for extracorporeal membrane oxygenation (ECMO) withdrawal is less studied. OBJECTIVES: To assess the use of staged autotransfusion during ECMO decannulation. METHODS: The study included ECMO withdrawal patients. Patients in the autologous transfusion group underwent staged transfusion during ECMO withdrawal, while those in the control group received 2.0 units of allogeneic packed red blood cells (RBCs) to increase hemoglobin (Hb). Parameters such as Hb, hematocrit (Hct), adverse events, decannulation success rate, volume of allogeneic RBC transfusions, and transfusion costs were compared. RESULTS: A total of 82 Chinese patients were enrolled, with a mean age of 46 years, 27 were female, and the top three primary diagnoses were cardiac arrest, acute myocarditis, and severe pneumonia. There were 41 individuals in the autologous blood transfusion group and 41 in the control group. No significant differences were observed in Hb, Hct, adverse events, and the success rate for decannulation between the two groups (all P > 0.05). Compared with the control group, the volume of allogeneic RBC transfusions [0 (0∼1.50) U vs. 3.5 (1.88∼40) U, P < 0.001] and the total cost [130 (130∼390) Chinese Yuan (CNY) vs. 910 (487.50, 1040) CNY, P = 0.002] were lower in the autologous transfusion group. CONCLUSION: In comparison with allogeneic RBC transfusion, staged autotransfusion during ECMO decannulation not only effectively maintained Hb levels but also reduced the requirement for allogeneic RBC transfusions. In addition, this approach decreased the associated costs and did not increase the risk of clinical adverse events.

8.
Emerg Microbes Infect ; 13(1): 2366354, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38979571

RESUMO

In recent years, polymyxin has been used as a last-resort therapy for carbapenem-resistant bacterial infections. The emergence of heteroresistance (HR) to polymyxin hampers the efficacy of polymyxin treatment by amplifying resistant subpopulation. However, the mechanisms behind polymyxin HR remain unclear. Small noncoding RNAs (sRNAs) play an important role in regulating drug resistance. The purpose of this study was to investigate the effects and mechanisms of sRNA on polymyxin B (PB)-HR in carbapenem-resistant Klebsiella pneumoniae. In this study, a novel sRNA PhaS was identified by transcriptome sequencing. PhaS expression was elevated in the PB heteroresistant subpopulation. Overexpression and deletion of PhaS were constructed in three carbapenem-resistant K. pneumoniae strains. Population analysis profiling, growth curve, and time-killing curve analysis showed that PhaS enhanced PB-HR. In addition, we verified that PhaS directly targeted phoP through the green fluorescent protein reporter system. PhaS promoted the expression of phoP, thereby encouraging the expression of downstream genes pmrD and arnT. This upregulation of arnT promoted the 4-amino-4-deoxyL-arabinosaccharide (L-Ara4N) modification of lipid A in PhaS overexpressing strains, thus enhancing PB-HR. Further, within the promoter region of PhaS, specific PhoP recognition sites were identified. ONPG assays and RT-qPCR analysis confirmed that PhaS expression was positively modulated by PhoP and thus up-regulated by PB stimulation. To sum up, a novel sRNA enhancing PB-HR was identified and a positive feedback regulatory pathway of sRNA-PhoP/Q was demonstrated in the study. This helps to provide a more comprehensive and clear understanding of the underlying mechanisms behind polymyxin HR in carbapenem-resistant K. pneumoniae.


Assuntos
Antibacterianos , Proteínas de Bactérias , Carbapenêmicos , Regulação Bacteriana da Expressão Gênica , Klebsiella pneumoniae , Polimixina B , Pequeno RNA não Traduzido , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Polimixina B/farmacologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , Pequeno RNA não Traduzido/genética , Testes de Sensibilidade Microbiana , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Humanos , RNA Bacteriano/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Farmacorresistência Bacteriana/genética
9.
J Affect Disord ; 362: 485-492, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39009318

RESUMO

BACKGROUND: Major depression (MD) is recurrent and devastating mental disease with a high worldwide prevalence. Mounting evidence suggests neuroinflammation triggers cellular immune dysregulation, characterized by increased proportions of circulating monocytes, and T helper 17 cells and proinflammatory cytokines, thereby increasing susceptibility to MD. However, there is ambiguity in the findings of clinical studies that investigate CD4+ T regulatory (Treg) cells in MD. METHODS: The proportion of CD4+ Treg cell from blood mononuclear cells was examined using flow cytometry in healthy controls (HCs: n = 96) and patients with first (FEMD: n = 62) or recurrent (RMD: n = 41) disease episodes of MD at baseline (T0; hospital admission) and after a two-week antidepressant treatment (T14). All participants underwent comprehensive neuropsychological assessments. RESULTS: The initial scores on emotional assessments in patients with MD significantly differed from those of HCs. Both FEMD and RMD patients exhibited a significant decrease in CD4+ Treg cell proportion at baseline compared to HCs. Treg cell proportion rose significantly from T0 to T14 in FEMD patients, who responded to antidepressant therapy, whereas no significant changes were observed in FEMD patients in non-response as well as RMD patients. The improvement of 24-item Hamilton Depression Scale was correlate with changes of Treg cell proportion from T0 to T14 in FEMD patients in response, and the change in Treg cell proportion over a 14-day period exhibited an AUC curve of 0.710. CONCLUSIONS: A decrease in the proportion of CD4+ Treg cells points towards immune system abnormalities in patients with MD. Furthermore, our finding suggests that the immune activation state varies across different stages of depression.

10.
ACS Nano ; 18(29): 18834-18851, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38995623

RESUMO

Given the pressing depletion of lithium resources, sodium-ion batteries (SIBs) stand out as a cost-effective alternative for energy storage solutions in the near future. Layered transition metal oxides (LTMOs) emerge as the leading cathode materials for SIBs due to their superior specific capacities and abundant raw materials. Nonetheless, achieving long-term stability in LTMOs for SIBs remains a challenge due to the inevitable structural degradation during charge-discharge cycles. The complexity and diversity of cation configurations/superstructures within the transition metal layers (TMO2) further complicate the understanding for newcomers. Therefore, it is critical to summarize and discuss the factors leading to structural degradation and the available strategies for enhancing LTMOs' stability. In this review, the cationic configurations of TMO2 layers are introduced from a crystallographic perspective. It then identifies and examines four key factors responsible for structural decay, alongside the impacts of various modification strategies. Finally, more effective and practical research approaches for investigating LTMOs have been proposed. The work aims to enhance the comprehension of the structural deterioration of LTMOs and facilitate a substantial improvement in their cycle life and energy density.

11.
Int J Biol Macromol ; 276(Pt 1): 133918, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019365

RESUMO

Lung cancer is the deadliest and most aggressive malignancy in the world. Preventing cancer is crucial. Therefore, the new molecular targets have laid the foundation for molecular diagnosis and targeted therapy of lung cancer. PLA2G1B plays a key role in lipid metabolism and inflammation. PLA2G1B has selective substrate specificity. In this paper, the recombinant protein molecular structure of PLA2G1B was studied and novel therapeutic interventions were designed to disrupt PLA2G1B activity and impede tumor growth by targeting specific regions or residues in its structure. Construct protein-protein interaction networks and core genes using R's "STRING" program. LASSO, SVM-RFE and RF algorithms identified important genes associated with lung cancer. 282 deg were identified. Enrichment analysis showed that these genes were mainly related to adhesion and neuroactive ligand-receptor interaction pathways. PLA2G1B was subsequently identified as developing a preventative feature. GSEA showed that PLA2G1B is closely related to α-linolenic acid metabolism. Through the analysis of LASSO, SVM-RFE and RF algorithms, we found that PLA2G1B gene may be a preventive gene for lung cancer.

12.
Sci Total Environ ; 946: 174442, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38964387

RESUMO

The decomposition of macrophytes plays a crucial role in the nutrient cycles of macrophyte-dominated eutrophication lakes. While research on plant decomposition mechanisms and microbial influences has rapid developed, it is curious that plant decomposition models have remained stagnant at the single-stage model from 50 years ago, without endeavor to consider any important factors. Our research conducted in-situ experiments and identified the optimal metrics for decomposition-related microbes, thereby establishing models for microbial impacts on decomposition rates (k_RDR). Using backward elimination in stepwise regression, we found that the optimal subset of independent variables-specifically Gammaproteobacteria-Q-L, Actinobacteriota-Q-L, and Ascomycota-Q-L-increased the adjusted R-squared (Ra2) to 0.93, providing the best modeling for decomposition rate (p = 0.002). Additionally, k_RDR can be modeled by synergic parameters of ACHB-Q-L, LDB-Q-L, and AB-Q-L for bacteria, and SFQ for fungi, albeit with a slightly lower Ra2 of 0.7-0.9 (p < 0.01). The primary contribution of our research lies in two key aspects. Firstly, we introduced optimal metrics for modeling microbes, opting for debris surface microbes over sediment microbes, and prioritizing absolute abundance over relative abundance. Secondly, our model represents a noteworthy advancement in debris modeling. Alongside elucidating the focus and innovative aspects of our work, we also addressed existing limitations and proposed directions for future research. SYNOPSIS: This study explores optimum metrics for decomposition-related microbes, offering precise microbial models for enhanced lake nutrient cycle simulation.


Assuntos
Eutrofização , Lagos , Lagos/microbiologia , Lagos/química , Plantas , Monitoramento Ambiental , Bactérias/metabolismo
13.
J Appl Toxicol ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39030796

RESUMO

Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.

14.
J Alzheimers Dis ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39031354

RESUMO

Background: Previous trials have indicated that multimodal training could improve cognitive functions and moods in individuals with mild cognitive impairment (MCI). However, evidence was mainly obtained from studies in high-income countries. Objective: This trial aims to investigate the efficacy, safety, and potential mechanism of a multimodal intervention on cognitive function in individuals with MCI living in a community. Methods: In this single-blind, randomized controlled trial, 120 participants with MCI were randomly assigned to either the intervention group or the control group. The intervention group received the multimodal intervention, while the control group received regular health education. Neuropsychological tests and magnetic resonance imaging (MRI) were conducted at baseline and after the 12-week intervention. Results: Fifty-nine and fifty-seven participants respectively in the intervention and control groups completed the trial. The intervention group shown improvements in primary outcome, Mini-Mental State Exam (MMSE) total score (mean difference -0.96, 95% CI [-1.58, -0.34], p = 0.003), and secondary outcomes: MMSE recall (-0.39, 95% CI [-0.71, -0.07], p = 0.019), MMSE language (-0.26, 95% CI [-0.44, -0.07], p = 0.007), Auditory Verbal Learning Test instantaneous memory (-3.30, 95% CI [-5.70, -0.89], p = 0.008), Digit Symbol Substitution Test total score (-2.91, 95% CI [-5.67, -0.15], p = 0.039), digit span forwards (-1.25, 95% CI [-1.93, -0.56], p < 0.001), and Digit Span Test (-1.33, 95% CI [-2.33, -0.34], p = 0.009) compared to the control group. Improvements were observed in structural and functional connectivity related to language, concentration, executive function, memory, and recall functioning via MRI in the intervention group. Conclusions: The multimodal intervention improved cognitive function in individuals with MCI in cognitive performance and neuroimaging.

15.
Andrology ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979761

RESUMO

BACKGROUND: Understanding the pathogenesis of unexplained recurrent pregnancy loss is paramount for advancing effective treatments. Various biological processes, including spermatogenesis and embryo development, are tightly regulated by N6-methyladenosine modifications. However, few studies have focused on the impact of sperm N6-methyladenosine modifications on embryonic development. Therefore, we aimed to study altered N6-methyladenosine-mediated messenger RNA methylation modifications in the spermatozoa of male partners from couples experiencing unexplained recurrent pregnancy loss, to identify potential diagnostic markers and explore their potential molecular mechanisms in pregnancy loss and embryogenesis. METHODS: Methylated RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing were conducted on the spermatozoa of men from couples in the 'unexplained recurrent pregnancy loss' group (n = 6), and the fertility control group (n = 6). To identify the role of the detected key genes, zebrafish model embryos were studied, and multi-omics (transcriptomics, proteomics, and metabolomics) analyses helped to explore the molecular mechanism of abnormal embryogenesis. FINDINGS: Comparing unexplained recurrent pregnancy loss with the fertility control group, 217 N6-methyladenosine peaks were significantly upregulated, and 40 were downregulated in the spermatozoa. The combined analyses of spermatozoa-methylated RNA immunoprecipitation sequencing and RNA sequencing indicated that N6-methyladenosine methylation and the expression of SEMA5A, MT-ATP6, ZNF662, and KDM4C were significantly different. In zebrafish embryos, the altered expression of the four genes increased embryonic mortality and malformations by disturbing several key signaling pathways and zygotic genome activation. INTERPRETATION: This study highlights the paternal epigenome, which could be one of the reasons for faulty embryogenesis leading to pregnancy loss. The N6-methyladenosine modification, the most prevalent RNA modification, contributes to the exploration and understanding of the paternal epigenome in the maintenance of pregnancy and fetal growth and development. The four genes identified in this study may serve as potential diagnostic markers and elucidate novel molecular mechanisms of embryogenesis.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38985426

RESUMO

Green finance constitutes a fundamental financial institutional arrangement aimed at achieving the dual-carbon objective during China's agricultural transition toward low-carbon, which aligns with the pragmatic necessity for reducing agricultural carbon emissions. For this purpose, this study investigates the impact of green finance on agricultural carbon reduction and its underlying mechanism by analyzing panel data from 30 regions using a two-way fixed effects model. Results indicate that green finance significantly promotes agricultural carbon reduction. The promotion effect of green finance on agricultural carbon reduction demonstrates an uneven spatial distribution, declining from eastern to western to central regions. Notably, non-Yangtze River Economic Belt provinces exhibit more pronounced effects compared to the Yangtze River Economic Belt region. Industrial structure upgrading and green innovation serve as crucial pathways for green finance to augment agricultural carbon reduction. Our finding reveals policymakers should implement differentiated green finance implementation strategies to accelerate the restructuring of the agricultural industry and encourage the introduction and use of innovative low-carbon technologies.

17.
Artigo em Inglês | MEDLINE | ID: mdl-39012897

RESUMO

Ga-doped Li7La3Zr2O12 garnet solid electrolytes exhibit the highest Li-ion conductivities among the oxide-type garnet-structured solid electrolytes, but instabilities toward Li metal hamper their practical application. The instabilities have been assigned to direct chemical reactions between LiGaO2 coexisting phases and Li metal by several groups previously. Yet, the understanding of the role of LiGaO2 in the electrochemical cell and its electrochemical properties is still lacking. Here, we are investigating the electrochemical properties of LiGaO2 through electrochemical tests in galvanostatic cells versus Li metal and complementary ex situ studies via confocal Raman microscopy, quantitative phase analysis based on powder X-ray diffraction, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and electron energy loss spectroscopy. The results demonstrate considerable and surprising electrochemical activity, with high reversibility. A three-stage reaction mechanism is derived, including reversible electrochemical reactions that lead to the formation of highly electronically conducting products. The results have considerable implications for the use of Ga-doped Li7La3Zr2O12 electrolytes in all-solid-state Li-metal battery applications and raise the need for advanced materials engineering to realize Ga-doped Li7La3Zr2O12for practical use.

18.
Child Abuse Negl ; 154: 106895, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38870710

RESUMO

BACKGROUND: A sizeable literature shows that adverse childhood experiences (ACEs) are associated with poor health outcomes in later life. However, most studies on the prevalence and predictors of ACEs have been carried out in high-income countries using cross-sectional approaches. OBJECTIVE: The present study explores the prevalence and predictors of ACEs in Malawi, a low-income country, using prospective longitudinal data collected on adolescents. PARTICIPANTS: We use data on 1375 adolescents and their biological mothers from the Malawi Longitudinal Study of Families and Health (MLSFH). ACEs were reported by adolescents over two survey waves, in 2017-18 and 2021. Predictors were reported by mothers in 2008 and 2010. METHODS: Multivariate ordinary least square and logistic regression analyses of ACEs exposure reported by adolescents on indicators of family arrangements and resources. RESULTS: Adolescents report having been exposed to nearly seven ACEs on average. Among indicators of family arrangements and resources, the only significant predictors of cumulative ACEs exposure are polygyny (linked to parental absence) and mother's SF-12 mental health score (linked to physical abuse and witnessing domestic violence). CONCLUSIONS: ACEs are much more prevalent in the low-income country under study than in middle- and high-income countries surveyed in prior research. Despite adversity being widespread, most indicators of family arrangements and resources highlighted in prior studies are not associated with adolescents' cumulative ACEs exposure in this context. Mothers' mental health in childhood nevertheless emerges as a significant predictor of adolescents' self-reported ACEs. These findings inform efforts aimed at preventing ACEs in high-adversity contexts.

19.
Front Bioeng Biotechnol ; 12: 1285166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872900

RESUMO

Objectives: The goal of this study was to explore the reliability and clinical value of fast, accurate automatic segmentation of the aortic root based on a deep learning tool compared with computed tomography angiography. Methods: A deep learning tool for automatic 3-dimensional aortic root reconstruction, the CVPILOT system (TAVIMercy Data Technology Ltd., Nanjing, China), was trained and tested using computed tomography angiography scans collected from 183 patients undergoing transcatheter aortic valve replacement from January 2021 to December 2022. The quality of the reconstructed models was assessed using validation data sets and evaluated clinically by experts. Results: The segmentation of the ascending aorta and the left ventricle attained Dice similarity coefficients (DSC) of 0.9806/0.9711 and 0.9603/0.9643 for the training and validation sets, respectively. The leaflets had a DSC of 0.8049/0.7931, and the calcification had a DSC of 0.8814/0.8630. After 6 months of application, the system modeling time was reduced to 19.83 s. Conclusion: For patients undergoing transcatheter aortic valve replacement, the CVPILOT system facilitates clinical workflow. The reliable evaluation quality of the platform indicates broad clinical application prospects in the future.

20.
Adv Sci (Weinh) ; : e2404701, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940403

RESUMO

The development of the electric vehicle industry has spurred demand for secondary batteries capable of rapid-charging and slow-discharging. Among them, sodium-ion batteries (SIBs) with layered oxide as the cathode exhibit competitive advantages due to their comprehensive electrochemical performance. However, to meet the requirements of rapid-charging and slow-discharging scenarios, it is necessary to further enhance the rate performance of the cathode material to achieve symmetrical capacity at different rates. Simultaneously, minimizing lattice strain during asymmetric electrochemical processes is also significant in alleviating strain accumulation. In this study, the ordered distribution of transition metal layers and the diffusion pathway of sodium ions are optimized through targeted K-doping of sodium layers, leading to a reduction of the diffusion barrier and endowment of prominent rate performance. At a 20C rate, the capacity of the cathode can reach 94% of that at a 0.1C rate. Additionally, the rivet effect of the sodium layers resulted in a global volume strain of only 0.03% for the modified cathode during charging at a 10C rate and discharging at a 1C rate. In summary, high-performance SIBs, with promising prospects for rapid-charging and slow-discharging capability, are obtained through the regulation of sodium layers, opening up new avenues for commercial applications.

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