Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus. / 人脐带间å 质干细胞通过IGF1R-CHK2-p53信号轴减轻2åž‹ç³–å°¿ç— é›„æ€§å¤§é¼ ç³–å°¿ç— è‚¾ç— .

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

A Genome-Wide Analysis of the Jasmonic Acid Biosynthesis Gene Families in Peanut Reveals Their Crucial Roles in Growth and Abiotic Stresses.

Abiotic stress is a limiting factor in peanut production. Peanut is an important oil crop and cash crop in China. Peanut yield is vulnerable to abiotic stress due to its seeds grown underground. Jasmonic acid (JA) is essential for plant growth and defense against adversity stresses. However, the regulation and mechanism of the jasmonic acid biosynthesis pathway on peanut defense against abiotic stresses are still limitedly understood. In this study, a total of 64 genes encoding key enzymes of JA biosynthesis were identified and classified into lipoxygenases (AhLOXs), alleno oxide synthases (AhAOSs), allene oxide cyclases (AhAOCs), and 12-oxo-phytodienoic acid reductases (AhOPRs) according to gene structure, conserved motif, and phylogenetic feature. A cis-regulatory element analysis indicated that some of the genes contained stress responsive and hormone responsive elements. In addition to proteins involved in JA biosynthesis and signaling, they also interacted with proteins involved in lipid biosynthesis and stress response. Sixteen putative Ah-miRNAs were identified from four families targeting 35 key genes of JA biosynthesis. A tissue expression pattern analysis revealed that AhLOX2 was the highest expressed in leaf tissues, and AhLOX32 was the highest expressed in shoot, root, and nodule tissues. AhLOX16, AhOPR1, and AhOPR3 were up-regulated under drought stress. AhLOX16, AhAOS3, AhOPR1, and AhAOC4 had elevated transcript levels in response to cold stress. AhLOX5, AhLOX16, AhAOC3, AhOPR1, and AhOPR3 were up-regulated for expression under salt stress. Our study could provide a reference for the study of the abiotic stress resistance mechanism in peanut.

The association between urinary sodium and the risk of dementia: Evidence from a population-based cohort study.

BACKGROUND: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear. METHODS: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources. RESULTS: The mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g-5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer's disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11-1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11-1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07-1.24) for all-cause dementia and 1.21 (95 % CI 1.04-1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g. LIMITATIONS: One of the major limitations is the estimation of 24-hour urinary sodium with spot urine samples. CONCLUSIONS: An E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings.

Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus. / 人脐带间å 质干细胞通过IGF1R-CHK2-p53信号轴减轻2åž‹ç³–å°¿ç— é›„æ€§å¤§é¼ ç³–å°¿ç— è‚¾ç— .

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Effectiveness and Influencing Factors of Home-Center-Based Cardiac Rehabilitation as a Transitional Strategy for Acute Myocardial Infarction Patients.

Currently, providing patients, particularly those with acute myocardial infarction (AMI), with comprehensive cardiac rehabilitation (CR) has been challenging because of the inadequate availability of medical resources in developing countries. To ensure balance between disease instability and early rehabilitation, strategies for facilitating professional and comprehensive CR opportunities for patients with AMI must be explored.A prospective cohort study was carried out on 1,533 patients with AMI who were admitted to a tertiary hospital between July 2018 and October 2019. Following the principle of voluntarism, 286 patients with AMI participated in home-center-based CR (HCB group), whereas 1,247 patients received usual care (UC group). The primary endpoint of this study was the occurrence of cardiovascular events at 30 months after AMI. Moreover, the study analyzed factors that influence participation rate and effectiveness of the CR model.After analysis, a significant difference in the occurrence of cardiovascular endpoints between the HCB group and the UC group was observed (harzard ratio, 0.68 [95%CI, 0.51-0.91], P = 0.008), with participation in home-center-based CR being an independent influencing factor. Multivariate regression analysis revealed age, gender, smoking history, triglyceride levels, and ejection fraction as independent factors that influence participation rate. Female gender, peak oxygen uptake per kilogram body weight, and ventilation/carbon dioxide production slope were identified as factors that affect the effectiveness of the CR model.In the context of developing countries, this study demonstrates that the home-center-based CR model is efficient and analyzes factors that influence participation rate and effectiveness of the model. These findings provide practical insights for further development of CR programs.

Suppression of P53 Pathway is an Important Factor Inducing Acute Graft-versus-Host Disease Through T Cell Activation Based on Bioinformatics Analysis.

Purpose: Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The tumour suppressor p53 plays a pivotal role in preventing aGVHD development. However, whether P53 pathway which contains p53 family members and other related genes participates in aGVHD development remains an unsolved question. Patients and Methods: Transcriptomic data was obtained from Gene Expression Omnibus (GEO) database. Gene set enrichment analysis was applied to determine the enrichment degree of signaling pathways. CIBERSORT and ssGSVA were used to evaluate immune cell compositions. Univariate and multivariate logistic regression analysis were performed to examine the independent diagnostic variables. qRT-PCR was utilized to validate the genes expression levels in our cohort. Results: A total number of 102 patients (42 aGVHD patients vs 60 non-aGVHD patients) were obtained after integrating two datasets in GEO database (GSE73809 and GSE4624). P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways. A risk model for aGVHD built by four genes (DDIT3, FBXW7, TPRKB and TOB1) in P53 pathway, exhibiting high differentiate and predictive value. DDIT3 and FBXW7 mRNA expression levels significantly decreased in peripheral blood mononuclear cells (PBMCs) from aGVHD patients compared with non-aGVHD group in our patient cohort, consisting with bioinformatics analysis. Conclusion: P53 pathway plays a potential role in impeding T cell activation through suppressing its related signaling pathways, thereby preventing aGVHD development. P53 pathway may emerge as a promising therapeutic target in aGVHD treatment.

Interfacial Push-Pull Dynamics Enable Rapid Had Desorption for Enhanced Formate Electrooxidation.

The electrocatalytic conversion of formate in alkaline solutions is of paramount significance in the realm of fuel cell applications. Nonetheless, the adsorptive affinity of adsorbed hydrogen (Had) on the catalyst surface has traditionally impeded the catalytic efficiency of formate in such alkaline environments. To circumvent this challenge, our approach introduces an interfacial push-pull effect on the catalyst surface. This mechanism involves two primary actions: First, the anchoring of palladium (Pd) nanoparticles on a phosphorus-doped TiO2 substrate (Pd/TiO2-P) promotes the formation of electron-rich Pd with a downshifted d band center, thereby "pushing" the desorption of Had from the Pd active sites. Second, the TiO2-P support diminishes the energy barrier for Had transfer from the Pd sites to the support itself, "pulling" Had to effectively relocate from the Pd active sites to the support. The resultant Pd/TiO2-P catalyst showcases a remarkable mass activity of 4.38 A mgPd-1 and outperforms the Pd/TiO2 catalyst (2.39 A mgPd-1) by a factor of 1.83. This advancement not only surmounts a critical barrier in catalysis but also delineates a scalable pathway to bolster the efficacy of Pd-based catalysts in alkaline media.

The influence of drug-induced metabolic enzyme activity inhibition and CYP3A4 gene polymorphism on aumolertinib metabolism.

The purpose of this study is to clarify the drug interaction profile of aumolertinib, and the influence of CYP3A4 genetic polymorphism on aumolertinib metabolic characteristics. Through microsomal enzyme reactions, we screened 153 drugs and identified 15 that significantly inhibited the metabolism of aumolertinib. Among them, telmisartan and carvedilol exhibited potent inhibitory activities in rat liver microsomes (RLM) and human liver microsomes (HLM). In vivo, the pharmacokinetic parameters of aumolertinib, including AUC and Cmax, were significantly altered when co-administered with carvedilol, with a notable decrease in the clearance rate CLz/F. Interestingly, the pharmacokinetic parameters of the metabolite HAS-719 exhibited a similar trend as aumolertinib when co-administered. Mechanistically, both telmisartan and carvedilol exhibited a mixed-type inhibition on the metabolism of aumolertinib. Additionally, we used a baculovirus-insect cell expression system to prepare 24 recombinant CYP3A4 microsomes and obtained enzymatic kinetic parameters using aumolertinib as a substrate. Enzyme kinetic studies obtained the kinetic parameters of various CYP3A4 variant-mediated metabolism of aumolertinib. Based on the relative clearance rates, CYP3A4.4, 5, 7, 8, 9, 12, 13, 14, 17, 18, 19, 23, 24, 33, and 34 showed significantly lower clearance rates compared to the wild-type. Among the different CYP3A4 variants, the inhibitory potency of telmisartan and carvedilol on the metabolism of aumolertinib also varied. The IC50 values of telmisartan and carvedilol in CYP3A4.1 were 6.68 ± 1.76 µM and 0.60 ± 0.25 µM, respectively, whereas in CYP3A4.12, the IC50 exceeded 100 µM. Finally, we utilized adeno-associated virus to achieve liver-specific high expression of CYP3A4*1 and CYP3A4*12. In the group with high expression of the less active CYP3A4*12, the magnitude of the drug-drug interaction was significantly attenuated. In conclusion, CYP3A4 genetic polymorphism not only influences the pharmacokinetic characteristics of aumolertinib, but also the inhibitory potency of telmisartan and carvedilol on it.

Portable dual-mode paper chips for highly sensitive and rapid determination of aflatoxin B1 via an aptamer-gated MOFs.

Paper chip as a representative microfluidic device has been mushroomed for rapid identification of contaminants in agro-food. However, the sensitivity and accuracy have still been challenged by inevitable background noise or interference in food matrix. Herein, we designed and fabricated a dual-mode paper chip (DPC) by assembling a patterned paper electrode with a platinum nanoparticles-treated colorimetric region through a flow channel. Dual-mode outputs were guided by an aptamer-gated UiO-66-NH2 metal-organic frameworks (MOFs). UiO-66-NH2 loaded with 3, 3', 5, 5'-tetramethylbenzidine (TMB) was controlled by a switch comprised of CdS quantum dots-aptamer. Aflatoxin B1 (AFB1, a kind of carcinogenic mycotoxin) target came and induced TMB release, triggering colorimetric and ECL signals on DPC, ultra-high sensitivity with a detection limit of 7.8 fg/mL was realized. The practicability of the DPC was also confirmed by spiking AFB1 in real corn samples. This portable paper-based device provides an ideal rapid detection platform tailored for diverse food contaminants analysis.

Exploring Factors Affecting Acceptance of Fecal Microbiota Transplantation for Patients with Recurrent Urinary Tract Infections: a Descriptive Qualitative Study.

Purpose: Patients with recurrent urinary tract infections face complex management challenges. Fecal microbiota transplantation is a superior treatment for chronic infectious diseases, but limited patient knowledge affects treatment decisions. This study aims to identify factors associated with hesitancy towards fecal microbiota transplantation among patients with recurrent urinary tract infections, to help physicians and nurses in providing accurate and useful information to patients. Patients and Methods: A descriptive qualitative approach was employed, utilizing semi-structured interviews conducted with patients experiencing recurrent urinary tract infections who expressed hesitancy towards fecal microbiota transplantation. The interviews took place between September 2021 and December 2022. Thematic analysis was conducted on the semi-structured interviews to identify perceived facilitators and barriers associated with fecal microbiota transplantation. Results: The analysis included interviews with thirty adult female patients with recurrent urinary tract infections. Four facilitators influencing patients' decision-making regarding fecal microbiota transplantation were identified: (1) the motivating role of hope and expectations for active patient participation; (2) the influence of healthcare providers, as well as family members and friends on patients' decisions to pursue fecal microbiota transplantation; (3) the patients' perception of fecal microbiota transplantation as a low-risk treatment option; and (4) the dedication to the advancement of medical treatments. In contrast, two primary barriers to accepting fecal microbiota transplantation were identified: (1) that conventional treatment controls disease activity, while fecal microbiota transplantation effects remain uncertain; and (2) that safety concerns surrounding fecal microbiota transplantation. Conclusion: Comprehensive information about fecal microbiota transplantation, including donor selection, sample processing, the procedure, and potential discomfort, is essential for patients and families to make informed treatment decisions. Registration: CHiCTR2100048970.

Psychological Responses of Chinese Medical Students to the COVID-19 Pandemic: Empirical Research Qualitative.

Aim: This study aims to explore the psychological reactions of medical students during the pandemic. Design: A qualitative study. Methods: A purposive sampling technique was employed, and a qualitative approach was adopted. Semi-structured questionnaires were utilized, and online interviews were conducted. Forty medical students were selected as participants for the interviews. The interview data were analyzed using Colaizzi's seven-step analysis method. Results: The study identified five themes related to the psychological reactions of medical students during the pandemic. Firstly, COVID-19's influence on medical careers was characterized by increased interest and determination in pursuing medical professions, heightened admiration for frontline workers, reinforced commitment to a medical career due to the pandemic, and recognition of the significance of medical education. Secondly, challenges and concerns in medical career pursuit were identified, including negative sentiments towards medical careers during COVID-19 and hesitations and concerns about entering the medical field amidst the pandemic. Thirdly, the impact on mental well-being encompassed diverse anxieties expressed by participants regarding control, transmission, treatment, and intentional spreading of the virus. Participants experienced an emotional progression from calmness to fear and anxiety, with heightened anxiety when relatives or acquaintances contracted COVID-19. Academic delays also contributed to anxiety among medical students. Fourthly, changes in behaviors and mindset were observed, including altered behaviors and mindset in response to the pandemic, as well as increased attention to personal hygiene and disease prevention measures. Lastly, expectations of medical students from government, public, and parents were explored. Conclusion: Understanding the psychological reactions of medical students during public health emergencies is crucial for their well-being and professional development. The findings have implications for medical education and the development of strategies to enhance the psychological well-being of medical students during similar crises.

A flexible, stretchable and wearable strain sensor based on physical eutectogels for deep learning-assisted motion identification.

Physical eutectogels as a newly emerging type of conductive gel have gained extensive interest for the next generation multifunctional electronic devices. Nevertheless, some obstacles, including weak mechanical performance, low self-adhesive strength, lack of self-healing capacity, and low conductivity, hinder their practical use in wearable strain sensors. Herein, lignin as a green filler and a multifunctional hydrogen bond donor was directly dissolved in a deep eutectic solvent (DES) composed of acrylic acid (AA) and choline chloride, and lignin-reinforced physical eutectogels (DESL) were obtained by the polymerization of AA. Due to the unique features of lignin and DES, the prepared DESL eutectogels exhibit good transparency, UV shielding capacity, excellent mechanical performance, outstanding self-adhesiveness, superior self-healing properties, and high conductivity. Based on the aforementioned integrated functions, a wearable strain sensor displaying a wide working range (0-1500%), high sensitivity (GF = 18.15), rapid responsiveness, and excellent stability and durability (1000 cycles) and capable of detecting diverse human motions was fabricated. Additionally, by combining DESL sensors with a deep learning technique, a gesture recognition system with accuracy as high as 98.8% was achieved. Overall, this work provides an innovative idea for constructing multifunction-integrated physical eutectogels for application in wearable electronics.

Virtual Screening, Molecular Dynamics Simulation, and Bioactivity Assessment Validate T13074 as a Dual-Target EGFR/c-Met Inhibitor.

OBJECTIVES: The objective of this study is to identify dual-target inhibitors against EGFR/c-Met through virtual screening, dynamic simulation, and biological activity evaluation. This endeavor is aimed at overcoming the challenge of drug resistance induced by L858R/T790M mutants. METHODS: Active structures were gathered to construct sets of drug molecules. Next, property filtering was applied to the drug structures within the compound library. Active compounds were then identified through virtual screening and cluster analysis. Subsequently, we conducted MTT antitumor activity evaluation and kinase inhibition assays for the active compounds to identify the most promising candidates. Furthermore, AO staining and JC-1 assays were performed on the selected compounds. Ultimately, the preferred compounds underwent molecular docking and molecular dynamics simulation with the EGFR and c-Met proteins, respectively. RESULT: The IC50 of T13074 was determined as 2.446 µM for EGFRL858R/T790M kinase and 7.401 nM for c-Met kinase, underscoring its potential in overcoming EGFRL858R/T790M resistance. Additionally, T13074 exhibited an IC50 of 1.93 µM on the H1975 cell. Results from AO staining and JC-1 assays indicated that T13074 induced tumor cell apoptosis in a concentration-dependent manner. Notably, the binding energy between T13074 and EGFR protein was found to be -90.329 ± 16.680 kJ/mol, while the binding energy with c-Met protein was -139.935 ± 17.414 kJ/mol. CONCLUSION: T13074 exhibited outstanding antitumor activity both in vivo and in vitro, indicating its potential utility as a dual-target EGFR/c-Met inhibitor. This suggests its promising role in overcoming EGFR resistance induced by the L858R/T790M mutation.

CWF19L2 is Essential for Male Fertility and Spermatogenesis by Regulating Alternative Splicing.

The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation of pre-mRNA alternative splicing (AS) at the post-transcriptional level. However, the fundamental mechanism of AS in spermatogenesis remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role in spermatogenesis and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting male sterility, impaired spermatogenesis characterized by increased apoptosis and decreased differentiated spermatogonia and spermatocytes is observed. That CWF19L2 interacted with several spliceosome proteins to participate in the proper assembly and stability of the spliceosome is discovered. By integrating RNA-seq and LACE-seq data, it is further confirmed CWF19L2 directly bound and regulated the splicing of genes related to spermatogenesis (Znhit1, Btrc, and Fbxw7) and RNA splicing (Rbfox1, Celf1, and Rbm10). Additionally, CWF19L2 can indirectly amplify its effect on splicing regulation through modulating RBFOX1. Collectively, this research establishes that CWF19L2 orchestrates a splicing factor network to ensure accurate pre-mRNA splicing during the early steps of spermatogenesis.

New Insight into Bulk Structural Degradation of High-Voltage LiCoO2 at 4.55 V.

The aggravated mechanical and structural degradation of layered oxide cathode materials upon high-voltage charging invariably causes fast capacity fading, but the underlying degradation mechanisms remain elusive. Here we report a new type of mechanical degradation through the formation of a kink band in a Mg and Ti co-doped LiCoO2 cathode charged to 4.55 V (vs Li/Li+). The local stress accommodated by the kink band can impede crack propagation, improving the structural integrity in a highly delithiated state. Additionally, machine-learning-aided atomic-resolution imaging reveals that the formation of kink bands is often accompanied by the transformation from the O3 to O1 phase, which is energetically favorable as demonstrated by first-principles calculations. Our results provide new insights into the mechanical degradation mechanism of high-voltage LiCoO2 and the coupling between electrochemically triggered mechanical failures and structural transition, which may provide valuable guidance for enhancing the electrochemical performance of high-voltage layered oxide cathode materials for lithium-ion batteries.

Spin Symmetry Breaking-induced Hubbard Gap Near-Closure in N-coordinated MnO2 for Enhanced Aqueous Zinc-Ion Battery Performance.

Transition metal oxides (TMOs) are promising cathode materials for aqueous zinc ion batteries (ZIBs), however, their performance is hindered by a substantial Hubbard gap, which limits electron transfer and battery cyclability. Addressing this, we introduce a heteroatom coordination approach, using triethanolamine to induce axial N coordination on Mn centers in MnO2, yielding N-coordinated MnO2 (TEAMO). This approach leverages the change of electronegativity disparity between Mn and ligands (O and N) to disrupt spin symmetry and augment spin polarization. This enhancement leads to the closure of the Hubbard gap, primarily driven by the intensified occupancy of the Mn eg orbitals. The resultant TEAMO exhibit a significant increase in storage capacity, reaching 351 mAh g-1 at 0.1 A g-1. Our findings suggest a viable strategy for optimizing the electronic structure of TMO cathodes, enhancing the potential of ZIBs in energy storage technology.

l-arginine promotes angio-osteogenesis to enhance oxidative stress-inhibited bone formation by ameliorating mitophagy.

Background: Osteoporosis is one of the most common bone diseases in middle-aged and elderly populations worldwide. The development of new drugs to treat the disease is a key focus of research. Current treatments for osteoporosis are mainly directed at promoting osteoblasts and inhibiting osteoclasts. However, there is currently no ideal approach for osteoporosis treatment. l-arginine is a semi-essential amino acid involved in a number of cellular processes, including nitric production, protein biosynthesis, and immune responses. We previously reported that l-arginine-derived compounds can play a regulatory role in bone homeostasis. Purpose: To investigate the specific effect of l-arginine on bone homeostasis. Methods: Mildly aged and ovariectomized mouse models were used to study the effects of l-arginine on osteogenesis and angiogenesis, assessed by micro-computed tomography and immunostaining of bone tissue. The effect of l-arginine on osteogenesis, angiogenesis, and adipogenesis was further studied in vitro using osteoblasts obtained from cranial cap bone, endothelial cells, and an adipogenic cell line. Specific methods to assess these processes included lipid staining, cell migration, tube-forming, and wound-healing assays. Protein and mRNA expression was determined for select biomarkers. Results: We found that l-arginine attenuated bone loss and promoted osteogenesis and angiogenesis. l-arginine increased the activity of vascular endothelial cells, whereas it inhibited adipogenesis in vitro. In addition, we found that l-arginine altered the expression of PINK1/Parkin and Bnip3 in the mitochondria of osteoblast-lineage and endothelial cells, thereby promoting mitophagy and protecting cells from ROS. Similarly, l-arginine treatment effectively ameliorated osteoporosis in an ovariectomized mouse model. Conclusion: l-arginine promotes angio-osteogenesis, and inhibits adipogenesis, effects mediated by the PINK1/Parkin- and Bnip3-mediated mitophagy. The Translational Potential of this Article: L-arginine supplementation may be an effective adjunct therapy in the treatment of osteoporosis.

Effect of Mineral Admixtures on Physical, Mechanical, and Microstructural Properties of Flue Gas Desulfurization Gypsum-Based Self-Leveling Mortar.

The production of flue gas desulfurization gypsum poses a serious threat to the environment. Thus, utilizing gypsum-based self-leveling mortar (GSLM) stands out as a promising and effective approach to address the issue. ß-hemihydrate gypsum, cement, polycarboxylate superplasticizer, hydroxypropyl methyl cellulose ether (HPMC), retarder, and defoamer were used to prepare GSLM. The impact of mineral admixtures (steel slag (SS), silica fume (SF), and fly ash (FA)) on the physical, mechanical, and microstructural properties of GSLM was examined through hydration heat, X-ray diffractometry (XRD), Raman spectroscopy, and scanning electron microscopy (SEM) analyses. The GSLM benchmark mix ratio was determined as follows: 94% of desulfurization building gypsum, 6% of cement, 0.638% each of water reducer and retarder, 0.085% each of HPMC and defoamer (calculated additive ratio relative to gypsum), and 0.54 water-to-cement ratio. Although the initial fluidity decreased in the GSLM slurry with silica fume, there was minimal change in 30 min fluidity. Notably, at an SS content of 16%, the GSLM exhibited optimal flexural strength (6.6 MPa) and compressive strength (20.4 MPa). Hydration heat, XRD, and Raman analyses revealed that a small portion of SS actively participated in the hydration reaction, while the remaining SS served as a filler.

Impact of Cardiovascular and Cerebrovascular Diseases Mortality on Life Expectancy in Tianjin, 2004 and 2020.

This study aims to analyze the impact of cardiovascular and cerebrovascular diseases (CCVDs) mortality on Tianjin's life expectancy (LE) in 2004 compared with 2020 using Arriaga's decomposition method. The LE increment for Tianjin residents due to the decrease in CCVDs mortality was 1.54 years (38.7%). Males, females, urban residents, and rural residents contributed 1.29 years (36.83%), 1.76 years (40.25%), 2.11 years (44.41%), and 0.71 years (25.06%), respectively. A total of 38.2% of the LE increment was attributed to deaths from CCVDs in people aged ≥65 years. Cerebral infarction, intracerebral hemorrhage, acute myocardial infarction, and other heart diseases contributed positively to the increase in LE (24.8%, 22.68%, 16.66%, and 11.3%). Sequelae of cerebrovascular disease and other coronary heart diseases contributed negatively to the increase in LE (-25.2% and -17.92%). Therefore, we need to control the risk factors of the elderly, males, rural residents, sequelae of cerebrovascular disease, and other coronary heart diseases.