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Tubulointerstitial inflammation is a common characteristic of acute and chronic kidney injury. However, the mechanism by which the initial injury of tubular epithelial cells (TECs) drives interstitial inflammation remains unclear. This paper aims to explore the role of exosomal miRNAs derived from TECs in the development of tubulointerstitial inflammation. Global microRNA(miRNA) expression profiling of renal exosomes was examined in a LPS induced acute kidney injury (AKI) mouse model and miR-19b-3p was identified as the miRNA that was most notably increased in TEC-derived exosomes compared to controls. Similar results were also found in an adriamycin (ADR) induced chronic proteinuric kidney disease model in which exosomal miR-19b-3p was markedly released. Interestingly, once released, TEC-derived exosomal miR-19b-3p was internalized by macrophages, leading to M1 phenotype polarization through targeting NF-κB/SOCS-1. A dual-luciferase reporter assay confirmed that SOCS-1 was the direct target of miR-19b-3p. Importantly, the pathogenic role of exosomal miR-19b-3p in initiating renal inflammation was revealed by the ability of adoptively transferred of purified TEC-derived exosomes to cause tubulointerstitial inflammation in mice, which was reversed by inhibition of miR-19b-3p. Clinically, high levels of miR-19b-3p were found in urinary exosomes and were correlated with the severity of tubulointerstitial inflammation in patients with diabetic nephropathy. Thus, our studies demonstrated that exosomal miR-19b-3p mediated the communication between injured TECs and macrophages, leading to M1 macrophage activation. The exosome/miR-19b-3p/SOCS1 axis played a critical pathologic role in tubulointerstitial inflammation, representing a new therapeutic target for kidney disease.

Solid‐state batteries that employ solid‐state electrolytes (SSEs) to replace routine liquid electrolytes are considered to be one of the most promising solutions for achieving high‐safety lithium metal batteries. SSEs with high mechanical modulus, thermal stability, and non‐flammability can not only inhibit the growth of lithium dendrites but also enhance the safety of lithium metal batteries. However, several internal materials/electrodes‐related thermal hazards demonstrated by recent works show that solid‐state lithium metal batteries (SSLMBs) are not impenetrable. Therefore, understanding the potential thermal hazards of SSLMBs is critical for their more secure and widespread applications. In this contribution, we provide a comprehensive overview of the thermal failure mechanism of SSLMBs from materials to devices. Also, strategies to improve the thermal safety performance of SSLMBs are included from the view of material enhancement, battery design, and external management. Consequently, the future directions are further provided. We hope that this work can shed bright insights into the path of constructing energy storage devices with high energy density and safety. Focusing on the safety hazards of SSLMBs, an in‐depth understanding of the thermal failure mechanisms of SSLMBs is classified and summarized from materials to devices. Beyond that, future directions in improving battery safety are also involved. This work sheds bright insights into the path of constructing energy storage devices with high energy density and safety.

Background In humans and other mammals, the process of oogenesis initiates asynchronously in specific ovarian regions, leading to the localization of dormant and growing follicles in the cortex and medulla, respectively; however, the current understanding of this process remains insufficient. Results Here, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to comprehend spatial–temporal gene expression profiles and explore the spatial organization of ovarian microenvironments during early oogenesis in pigs. Projection of the germ cell clusters at different stages of oogenesis into the spatial atlas unveils a “cortical to medullary (C-M)” distribution of germ cells in the developing porcine ovaries. Cross-species analysis between pigs and humans unveils a conserved C-M distribution pattern of germ cells during oogenesis, highlighting the utility of pigs as valuable models for studying human oogenesis in a spatial context. RNA velocity analysis with ST identifies the molecular characteristics and spatial dynamics of granulosa cell lineages originating from the cortical and medullary regions in pig ovaries. Spatial co-occurrence analysis and intercellular communication analysis unveils a distinct cell–cell communication pattern between germ cells and somatic cells in the cortex and medulla regions. Notably, in vitro culture of ovarian tissues verifies that intercellular NOTCH signaling and extracellular matrix (ECM) proteins played crucial roles in initiating meiotic and oogenic programs, highlighting an underappreciated role of ovarian microenvironments in orchestrating germ cell fates. Conclusions Overall, our work provides insight into the spatial characteristics of early oogenesis and the regulatory role of ovarian microenvironments in germ cell fate within a spatial context.

Background Epithelial–mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown. We aimed to explore the effect and mechanism of IL-24 on EMT and to verify whether IL-37 could alleviate IL-24-induced EMT in chronic asthma. Methods BEAS-2B cells were exposed to IL-24, and cell migration was assessed by wound healing and Transwell assays. The expression of EMT-related biomarkers (E-cadherin, vimentin, and α-SMA) was evaluated after the cells were stimulated with IL-24 with or without IL-37. A murine asthma model was established by intranasal administration of house dust mite (HDM) extracts for 5 weeks, and the effects of IL-24 and IL-37 on EMT and airway remodeling were investigated by intranasal administration of si-IL-24 and rhIL-37. Results We observed that IL-24 significantly enhanced the migration of BEAS-2B cells in vitro. IL-24 promoted the expression of the EMT biomarkers vimentin and α-SMA via the STAT3 and ERK1/2 pathways. In addition, we found that IL-37 partially reversed IL-24-induced EMT in BEAS-2B cells by blocking the ERK1/2 and STAT3 pathways. Similarly, the in vivo results showed that IL-24 was overexpressed in the airway epithelium of an HDM-induced chronic asthma model, and IL-24 silencing or IL-37 treatment could reverse EMT biomarker expression. Conclusions Overall, these findings indicated that IL-37 mitigated HDM-induced airway remodeling by inhibiting IL-24-mediated EMT via the ERK1/2 and STAT3 pathways, thereby providing experimental evidence for IL-24 as a novel therapeutic target and IL-37 as a promising agent for treating severe asthma.

Peri-implantitis (PI) is a common complication of oral implant surgeries. Understanding the role of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and its ligand galectin-9 (Gal-9) in PI is essential for advancing treatment strategies. This study investigated the effect of the TIM-3/Gal-9 signaling pathway on macrophage polarization in PI. We included 31 PI patients and 30 controls with healthy implants. Peripheral blood and peri-implant tissue samples were collected. Serum Gal-9 and cytokine levels were measured using ELISA. CD86, CD206, and TIM-3 expressions were analyzed via immunohistochemistry. Lipopolysaccharide was used to induce a PI environment in cells, which were divided into blank control, control, and Gal-9 groups. Flow cytometry detected M1, M2, TIM-3+M1, and TIM-3+M2 proportions. There were positive expressions of CD86 and CD206 in peri-implant tissues of PI patients, indicating the presence of both macrophage phenotypes, with a notable predominance of M1. The proportions of CD86+M1 macrophages and CD206+M2 macrophages in peripheral blood were significantly elevated in the PI group, resulting in an increased M1/M2 ratio in the PI group. Correlation analyses indicated that both M1 and M1/M2 were positively correlated with the modified plaque index, modified sulcular bleeding index, and probing depth, suggesting that the M1/M2 ratio reflects the clinical severity of PI. In vitro experiments showed that the addition of Gal-9 led to a significant increase in the proportion of TIM-3+M1 and TIM-3+M2 macrophages and a decrease in M1 cell proportions and M1/M2 ratio. The Gal-9 group exhibited significantly reduced levels of pro-inflammatory cytokines IL-1β and TNF-α. A strong negative correlation was found between TNF-α levels and TIM-3+M1 macrophages. However, no significant difference was found in the anti-inflammatory cytokine IL-10 between the control and Gal-9 groups. The TIM-3/Gal-9 signaling pathway plays a crucial role in modulating macrophage polarization in PI. This work may provide evidence for the development of novel therapeutic targets for managing PI.

The pursuit of sustainable energy has a great request for advanced energy storage devices. Lithium metal batteries are regarded as a potential electrochemical storage system because of the extremely high capacity and the most negative electrochemical potential of lithium metal anode. Dead lithium formed in the stripping process significantly contributes to the low efficiency and short lifespan of rechargeable lithium metal batteries. This review displays a critical review on the current research status about the stripping electrochemistry of lithium metal anode. The significance of stripping process to a robust lithium metal anode is emphasized. The stripping models in different electrochemical scenarios are discussed. Specific attention is paid to the understanding for the electrochemical principles of atom diffusion, electrochemical reaction, ion diffusion in solid electrolyte interphase (SEI), and electron transfer with the purpose to strengthen the insights into the behavior of lithium electrode stripping. The factors affecting stripping processes and corresponding solutions are summarized and categorized as follows: surface physics, SEI, operational and external factors. This review affords fresh insights to explore the lithium anode and design robust lithium metal batteries based on the comprehensive understanding of the stripping electrochemistry. Lithium metal batteries with theoretically high energy density are strongly considered as a potential electrochemical storage system. Dead lithium formed in the stripping process of lithium metal anode significantly hinders the practical applications. This review comprehensively summarizes the current research status about the stripping electrochemistry of lithium metal anode. The stripping models in different electrochemical scenarios are discussed. The factors affecting stripping processes and corresponding solutions are outlined. This review affords fresh insights to design robust lithium metal batteries based on the comprehensive understanding of the stripping electrochemistry.

High‐energy‐density lithium metal batteries (LMBs) are widely accepted as promising next‐generation energy storage systems. However, the safety features of practical LMBs are rarely explored quantitatively. Herein, the thermal runaway behaviors of a 3.26 Ah (343 Wh kg−1) Li | LiNi0.5Co0.2Mn0.3O2 pouch cell in the whole life cycle are quantitatively investigated by extended volume‐accelerating rate calorimetry and differential scanning calorimetry. By thermal failure analyses on pristine cell with fresh Li metal, activated cell with once plated dendrites, and 20‐cycled cell with large quantities of dendrites and dead Li, dendrite‐accelerated thermal runaway mechanisms including reaction sequence and heat release contribution are reached. Suppressing dendrite growth and reducing the reactivity between Li metal anode and electrolyte at high temperature are effective strategies to enhance the safety performance of LMBs. These findings can largely enhance the understanding on the thermal runaway behaviors of Li metal pouch cells in practical working conditions. The thermal runaway features of Li | NCM523 pouch cells (343 Wh kg−1) over the whole life cycle are analyzed quantitatively. The formation of large amounts of dendritic Li and SEI is observed as cycling depth increasing, leading to strong exothermic reactions between SEI components and LiPF6, dendritic Li and electrolytes.

Researching the structural characteristics of the spatial correlation network of cultivated land utilization ecological efficiency is of great significance to China’s food security and agricultural green and low-carbon development. Taking 47 cities (autonomous prefectures) in the upper reaches of the Yangtze River as the research object, the ecological efficiency of cultivated land utilization from 2010 to 2020 was measured based on the unexpected output model (Super SBM), and the spatial correlation matrix was constructed using the revised gravity model. The structural characteristics of the spatial correlation network were analyzed using the social network model (SNA), and finally, the factors affecting the spatial correlation network of cultivated land utilization ecological efficiency in the upper reaches of the Yangtze River were analyzed through the quadratic assignment procedure (QAP) model. The results show that: (1) the ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River has been increasing year by year, but the overall level is low, and there is a large gap among provinces. Sichuan Province has the highest average value of 0.605, and Yunnan Province has the lowest average value of 0.359. (2) The ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River has broken through the provincial boundaries and has formed an obvious spatial correlation network, but the overall density is low, and the network is still relatively loose, needing further development and improvement. Chengdu, Yibin, Luzhou, and other cities are located in the center of the network and have formed four cohesive subgroups. (3)The differences in the level of agricultural economic development, the rural per capita disposable income, the differences in agricultural mechanization intensity, the regional population differences, and spatial adjacency have an impact on the spatial network of ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River. The difference in the level of agricultural economic development, the rural per capita disposable income, and the differences in agricultural mechanization intensity are negatively correlated, while the regional population differences are positively correlated with spatial adjacency.

Introduction: Drug-related problems (DRPs) are not only detrimental to patients' physical health and quality of life but also lead to a serious waste of health care resources. The condition of DRPs might be more severe for patients in primary health care institutions. Objective : This systematic review aims to comprehensively review the characteristics of DRPs for patients in primary health care institutions, which might help find effective strategies to identify, prevent, and intervene with DRPs in the future. Methods: We searched three English databases (Embase, The Cochrane Library, and PubMed) and four Chinese databases (CNKI, CBM, VIP, and Wanfang). Two of the researchers independently conducted literature screening, quality evaluation, and data extraction. Qualitative and quantitative methods were combined to analyze the data. Results: From the 3,368 articles screened, 27 met the inclusion criteria and were included in this review. The median (inter-quartile range, IQR) of the incidences of DRPs was 70.04% (59%), and the median (IQR) of the average number of DRPs per patient was 3.4 (2.8). The most common type of DRPs was “treatment safety.” The causes of DRPs were mainly in the prescribing section, including “drug selection” and “dose selection”, while patients' poor adherence in the use section was also an important cause of DRPs. Risk factors such as the number of medicines, age, and disease condition were positively associated with the occurrence of DRPs. In addition, the medians (IQR) of the rate of accepted interventions, implemented interventions, and solved DRPs were 78.8% (22.3%), 64.15% (16.85%), and 76.99% (26.09%), respectively. Conclusion: This systematic review showed that the condition of DRPs in primary health care institutions was serious. In pharmaceutical practice, the patients with risk factors of DRPs should be monitored more closely. Pharmacists could play important roles in the identification and intervention of DRPs, and more effective intervention strategies need to be established in the future.

The rising lithium metal batteries (LMBs) demonstrate a huge potential for improving the utilization duration of energy storage devices due to high theoretical energy density. Benefiting from the designs in the electrolyte, interface, and lithium host, several attempts have been made in the commercial application of LMBs. However, the application of lithium anode introduces additional safety risks and potential catastrophic accidents due to the high activity of lithium metal and dendrite during the electrochemical cycles. A comprehensive understanding of challenges and design issues on the safety hazards of LMBs in life cycle management is imperative for safe and commercial applications of LMBs. This paper first reviews emerging key safety issues and promising corresponding enhancements of LMBs during their production, utilization, and recycling. The wet air instability of lithium metal anode and gas production during activation have undoubtedly become the most intractable problems in LMBs production. It is necessary to use spraying technology to build a good protection layer upon lithium metal anode. Then, the growth of lithium dendrites poses a higher challenge to the utilization of LMBs, which requires the design of better electrolyte, anode skeleton, and other strategies as well as the prediction of LMBs life through big data and other methods. As for LMBs recovery, it is of great significance to choose the solvent to effectively control the consumption rate and temperature of highly reactive lithium metal powder. At last, further appeals and improvements are proposed for inspiring more related research to push forward the commercial use of LMBs. Safety issues of lithium metal batteries (LMBs) during the whole life cycle are of great importance, including the procedures in manufacturing, utilization, and recycling. This perspective summarizes the recent progress in improving the safety of LMBs, and gives prospects toward the future practical application of LMBs in a safe manner.