N6-methyladenosine-mediated LINC01087 promotes lung adenocarcinoma progression by regulating miR-514a-3p to upregulate centrosome protein 55.

Long noncoding RNAs are key players in the development of lung adenocarcinoma (LUAD). The present study elucidated the role of LINC01087 in LUAD development. Cell vitality and apoptosis were assessed by the CCK-8 assay and flow cytometry, respectively. The transwell assay was adopted to evaluate cell migration and invasion. Levels of m6A modification of LINC01087 were determined using the methylated RNA binding protein immunoprecipitation assay. The interactions among LINC01087, miR-514a-3p, and centrosome protein 55 (CEP55) were evaluated using dual-luciferase reporter, RNA immunoprecipitation, and RNA-RNA pull-down assays. LINC01087 was highly expressed in LUAD, and its downregulation restrained cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro as well as tumor growth in a xenograft tumor model. Overexpression of miR-514a-3p inhibited malignant phenotypes in LUAD cells by inactivating RhoA/ROCK1 signaling via the suppression of CEP55 expression. Mechanistically, RBM15 increased the expression and mRNA stability of LINC01087 by mediating its m6A modification and LINC01087 induced CEP55 expression by sponging miR-514a-3p. RBM15-induced LINC01087 upregulation accelerated LUAD progression by regulating the miR-514a-3p/CEP55/RhoA/ROCK1 axis, illustrating the potential of LINC01087 as a novel target for LUAD therapy.

Exploring the immune characteristions of CRKP pneumonia at single-cell level.

The immune dysregulation associated with carbapenem-resistant Klebsiella pneumoniae (CRKP) severity was investigated through single-cell RNA sequencing (scRNA-seq) of 5 peripheral blood samples from 3 patients with moderate and severe CRKP pneumonia. Additionally, scRNA-seq datasets from two individuals with COVID-19 were included for comparative analysis. The dynamic characterization and functional properties of each immune cell type were examined by delineating the transcriptional profiles of immune cells throughout the transition from moderate to severe conditions. Overall, most immune cells in CRKP patients exhibited a robust interferon-α response and inflammatory reaction compared to healthy controls, mirroring observations in COVID-19 patients. Furthermore, cell signatures associated with NK cells, macrophages, and monocytes were identified in CRKP progression including PTPRCAP for NK cells, C1QB for macrophages, and S100A12 for both macrophages and monocytes. In summary, this study offers a comprehensive scRNA-seq resource for illustrating the dynamic immune response patterns during CRKP progression, thereby shedding light on the associations between CRKP and COVID-19.

Dual Defect Passivation at the Buried Interface for Printable Mesoscopic Perovskite Solar Cells with Reduced Open-Circuit Voltage Loss.

Numerous defects exist at the buried interface between the perovskite and adjacent electron transport layers in perovskite solar cells, resulting in severe non-radiative recombination and excessive open-circuit voltage (VOC) loss. Herein, a dual defect passivation strategy utilizing guanidine sulfate (GUA2SO4) as an interface modifier is first reported. On the one hand, the SO4 2- preferentially interacts with Pb-related defects, generating water-insoluble lead oxysalts complexes. Additionally, GUA+ diffuses into the perovskite and induces the formation of low-dimensional perovskite. These reactions effectively suppress trap states at the buried interface and perovskite boundaries in printable mesoscopic perovskite solar cells (p-MPSCs), thus increasing the carrier lifetime. Meanwhile, GUA2SO4 optimizes the interface energy band alignment, thus accelerating the charge extraction and transfer at the buried interface. This synergistic effect of trap passivation and interface energy band alignment modulation is strongly demonstrated by an increase in average VOC of 70 mV and the power conversion efficiency improvement from 17.51% to 18.70%. This work provides a novel approach to efficiently improve the performance of p-MPSCs through dual-targeted defect passivation at the buried interface.

Comprehensive mapping of saliva by multiomics in children with idiopathic nephrotic syndrome.

AIM: Saliva can reflect an individual's physiological status or susceptibility to systemic disease. However, little attention has been given to salivary analysis in children with idiopathic nephrotic syndrome (INS). We aimed to perform a comprehensive analysis of saliva from INS children. METHODS: A total of 18 children (9 children with INS and 9 normal controls) were recruited. Saliva was collected from each INS patient in the acute and remission phases. 16S rRNA gene sequencing, widely targeted metabolomics, and 4D-DIA proteomics were performed. RESULTS: Actinobacteria and Firmicutes were significantly enriched in the pretreatment group compared with the normal control group, while Bacteroidota and Proteobacteria were significantly decreased. A total of 146 metabolites were identified as significantly different between INS children before treatment and normal controls, which covers 17 of 23 categories. KEGG enrichment analysis revealed three significantly enriched pathways, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and terpenoid backbone biosynthesis (P < 0.05). A total of 389 differentially expressed proteins were selected between INS children before treatment and normal controls. According to the KEGG and GO enrichment analyses of the KOGs, abnormal ribosome structure and function and humoral immune disorders were the most prominent differences between INS patients and normal controls in the proteomic analysis. CONCLUSION: Oral microbiota dysbiosis may modulate the metabolic profile of saliva in children with INS. It is hypothesized that children with INS might have "abnormal ribosome structure and function" and "humoral immune disorders".

Dark under the Lamp: Neglected Biological Pollutants in the Environment Are Closely Linked to Lung Cancer.

Environmental pollutants are closely linked to lung cancer. The different types of environmental pollutants can be classified as chemical, physical, and biological. The roles of common chemical and physical pollutants such as PM2.5, smoking, radon, asbestos, and formaldehyde in lung cancer have been extensively studied. Notably, the worldwide COVID-19 pandemic raised awareness of the strong link between biological pollution and human health. Allergens such as house dust mites and pollen, as well as bacteria and viruses, are common biological pollutants. A few biological pollutants have been reported to promote lung cancer via inducing inflammatory cytokines secretion, such as IL-1ß, IL-6, and TGF-ß, as well as suppressing immunosurveillance by upregulating regulatory T (Treg) cells while dampening the function of CD8+ T cells and dendritic cells. However, the correlation between common biological hazards, such as SARS-CoV-2, human immunodeficiency viruses, Helicobacter pylori, and house dust mites, and lung cancer is not fully elucidated, and the underlying mechanisms are still unclear. Moreover, the majority of studies that have been performed in lung cancer and biological carcinogens were not based on the perspective of biological pollutants, which has challenged the systematicity and coherence in the field of biological pollutants in lung cancer. Here, in addition to reviewing the recent progress made in investigating the roles of allergens, viruses, and bacteria in lung cancer, we summarized the potential mechanisms underlying biological pollutants in lung cancer. Our narrative review can shed light on understanding the significance of biological pollutants in lung cancer, as well as inspire and broaden research ideas on lung cancer etiology.

Efficient Ternary Organic Solar Cells with Suppressed Nonradiative Recombination and Fine-Tuned Morphology via IT-4F as Guest Acceptor.

The large open circuit voltage (VOC) loss is currently one of the main obstacles to achieving efficient organic solar cells (OSCs). In this study, the ternary OSCs comprising PM6:BTP-eC9:IT-4F demonstrate a superior efficiency of 18.2 %. Notably, the utilization of the medium bandgap acceptor IT-4F as the third component results in an exceptionally low nonradiative recombination energy loss of 0.28 V. The desirable energy level cascade is formed among PM6, BTP-eC9, and IT-4F due to the low-lying HOMO and LUMO energy levels of IT-4F. More importantly, the VOC of PM6:BTP-eC9:IT-4F OSCs can reach as high as 0.86 V, which is higher than both binary OSCs without sacrificing JSC and FF. Besides, this strategy proved that IT-4F can not only broaden the absorption range but also work as a morphology modifier in PM6:BTP-eC9:IT-4F OSCs, and there also exists efficient energy transfer between BTP-eC9 and IT-4F. This result provides a promising way to suppress the nonradiative recombination energy loss and realize higher VOC than the two binary OSCs in ternary OSCs to obtain high power conversion efficiencies.

Room-Temperature Processed Annealing-Free Printable Carbon-Based Mesoscopic Perovskite Solar Cells with 17.34% Efficiency.

Carbon-based printable mesoscopic perovskite solar cells (MPSCs) have promising commercial development due to the use of easily scalable printing processes and low-cost carbon material electrodes. Simplifying the preparation process of MPSCs will undoubtedly contribute to their practical application. Here, we demonstrate that efficient and stable MPSCs can be prepared at room temperature without annealing by using low boiling point 2-methoxyethanol (2-ME) and strongly coordinated N-methyl-2-pyrrolidone (NMP) as a novel mixed solvent under the synergistic effect of ammonium chloride (NH4Cl). The results show that the 2-ME/NMP mixed solvent can generate an optimized coordination environment so that uniform nucleation and crystallization of perovskites in mesopores can be achieved at room temperature without annealing by forming uniform small-sized colloids in the precursor solution. Moreover, our work for the first time introduces NH4Cl as a crystallization modulator during a room-temperature annealing-free process, effectively regulating the crystallization behavior of perovskite in mesopores and obtaining high-quality perovskites. Finally, MPSCs prepared synergistically by a room-temperature annealing-free process based on a low boiling point 2-ME/NMP mixed solvent and NH4Cl modulator achieved a champion power conversion efficiency of 17.34% while demonstrating excellent long-term air stability for over half a year. This work provides a new approach to simplifying the preparation process of MPSCs and preparing efficient and stable MPSCs through a room-temperature annealing-free process.

Reducing Interfacial Losses in Solution-Processed Integrated Perovskite-Organic Solar Cells.

Low bandgap organic semiconductors have been widely employed to broaden the light response range to utilize much more photons in the inverted perovskite solar cells (PSCs). However, the serious charge recombination at the heterointerface contact between perovskite and organic semiconductors usually leads to large energy loss and limits the device performance. In this work, a titanium chelate, bis(2,4-pentanedionato) titanium(IV) oxide (C10H14O5Ti), was directly used as an interlayer between the perovskite layer and organic bulk heterojunction layer for the first time. Impressively, it was found that C10H14O5Ti can not only increase the surface potential of perovskite films but also show a positive passivation effect toward the perovskite film surface. Drawing from the above function, a smoother perovskite active layer with a higher work function was realized upon the use of C10H14O5Ti. As a result, the C10H14O5Ti-modified integrated devices show lower interfacial loss and obtain the best power conversion efficiency (PCE) of up to 20.91% with a high voltage of 1.15 V. The research offers a promising strategy to minimize the interfacial loss for the preparation of high-performance perovskite solar cells.

Lipopolysaccharide-Educated Cancer-Associated Fibroblasts Facilitate Malignant Progression of Ovarian Cancer Cells via the NF-kB/IL-6/JAK2 Signal Transduction.

Gram-negative bacteria increase in ovarian cancer (OC) tissues, but its association with OC progression remains largely unknown. The present study aimed to investigate whether and how cancer-associated fibroblasts (CAFs) pretreated by the main components of bacterial outer membrane lipopolysaccharide (LPS) influence the malignancy of OC cells. Specifically, the culture medium of LPS-preconditioned CAFs (LPS-CM) further accelerated cell proliferation, colony formation and tumorigenesis of OC cells SKOV3 and HEY A8, compared with culture medium of CAFs. Next, we found that LPS pretreatment activated the nuclear factor-kappa B (NF-kB) pathway in CAFs to secret cytokines, including interleukin 1ß (IL-1ß), interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), etc. Neutralization of IL-6 in LPS-CM abolished the promoting effect of LPS-CM on cell proliferation, survival and epithelial-mesenchymal transition (EMT) in SKOV3 and HEY A8 cells. Mechanistically, LPS-CM activated the Janus kinases 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, while application with JAK2 inhibitor also reversed the promoting effect of LPS-CM on malignancy of OC cells. In summary, LPS-pretreated CAFs IL-6-dependently accelerate OC progression via activating the JAK2/STAT3 signal pathway, which enriches our understanding of the molecular mechanisms underlying ovaries-colonized gram-negative bacteria in OC progression.

Agree to disagree: The contradiction between IL-18 and IL-37 reveals shared targets in cancer.

IL-37 is a newly discovered member of the IL-1 cytokine family which plays an important role in regulating inflammation and maintaining physiological homeostasis. IL-37 showed a close relationship with IL-18, another key cytokine in inflammation regulation and cancer development. IL-37 affects the function of IL-18 either by binding to IL-18Rα, a key subunit of both IL-37 and IL-18 receptor, or by drastically neutralizing the IL-18 protein expression of IL-18 binding protein, an important natural inhibitory molecule of IL-18. Moreover, as another subunit receptor of IL-37, IL-1R8 can suppress IL-18Rα expression, functioning as a surveillance mechanism to prevent overactivation of both IL-18 and IL-37 signaling pathways. While IL-18 and IL-37 share the same receptor subunit, IL-18 would in turn interfere with IL-37 signal transduction by binding to IL-18Rα. It is also reported that IL-18 and IL-37 demonstrated opposing effects in a variety of cancers, such as glioblastoma, lung cancer, leukemia, and hepatocellular cancer. Although the mutual regulation of IL-18 and IL-37 and their diametrically opposed effects in cancers has been reported, IL-18 has not been taken into consideration when interpreting clinical findings and conducting mechanism investigations related to IL-37 in cancer. We aim to review the recent progress in IL-18 and IL-37 research in cancer and summarize the correlation between IL-18 and IL-37 in cancer based on their expression level and underlying mechanisms, which would provide new insights into elucidating the conflicting roles of IL-18 and IL-37 in cancer and bring new ideas for translational research related to IL-18 and IL-37.

Trastuzumab deruxtecan (DS8201) for advanced non-small cell lung cancer with HER2 exon 20 insertion mutation: a case report.

An antibody-drug conjugate (ADC) of human epidermal growth factor receptor-2 (HER2) provides effective treatment for patients with HER2-positive non-small cell lung cancer (NSCLC). Exon 20 insertion mutations are the most common among HER2 mutations. This mutant subtype is highly drug-resistant, and patients receiving conventional treatment often have a poor prognosis. Trastuzumab deruxtecan (T-DXd), a novel anti-HER2 ADC, has emerged as a novel treatment option for HER2-positive (mutated, expressed, amplified, alternated) NSCLC, based on several studies and reported results. Herein, we report a case of stage IV NSCLC with HER2 exon 20 mutation in a 52-year-old male patient whose tumor recurred after radical resection of pulmonary carcinoma, who could not tolerate chemotherapy, and presented with bone metastasis. After treatment with T-DXd, the tumor significantly regressed and bone metastasis improved, maintaining a state of no progression for 21 months. This case report evidences the use of T-DXd in the treatment of NSCLC with HER2 exon 20 insertion mutation.

Age, growth, reproduction and status of resource development of Ptychidio jordani, a critically endangered freshwater fish in the Hongshui River, China.

The age, growth, reproduction and resource development status of Ptychidio jordani, as a critically endangered freshwater fish in the Hongshui River, China, was studied in this work. A total of 525 specimens were collected monthly using the cages and gillnets from October 2021 to September 2022 in the Hongshui River. The scale was used for age determination, and the maximum age for both female and male was estimated to be 5 years and 3 years, respectively. Female and male P. jordani showed different growth patterns, which were expressed as Lt  = 261.3 (1-e-0.4885(t-0.1476) ) and Lt  = 251.2 (1-e-0.4758(t+0.9643) ), respectively. The overall sex ratio was 1:0.47 (female:male). Female attained sex maturity at 2.34 years (192 mm body length). Month variation of the gonad somatic index indicated that the spawning period occurred from April to October. The absolute fecundity was estimated at 9046 ± 3434 eggs per individual, and the relative fecundity was 38.08 ± 15.77 eggs per gram. The exploitation rate of female and male was 0.233 and 0.495, which indicated that P. jordani was not overfishing. This study provided data on the key life-history traits of P. jordani, which has not been known previously and is essential for conservation strategy and policy development.

Effect of dietary koumine on the immune and antioxidant status of carp (Cyprinus carpio) after Aeromonas hydrophila infection.

Koumine (KM) has anxiolytic, anti-inflammatory and growth-promoting effects in pigs and sheep. Based on the growth-promoting and immunological effects of koumine, the present study was conducted on Cyprinus carpio (C. carpio) with four KM concentrations: 0 mg/kg, 0.2 mg/kg, 2 mg/kg, and 20 mg/kg for 10 weeks, followed by a 1-week Aeromonas hydrophila (A. hydrophila) infection experiment. The effect of KM on the immunity of A. hydrophila infected carp was analyzed by histopathology, biochemical assay, and qRT-PCR to assess the feasibility of KM in aquaculture. The results showed that the presence of KM alleviated pathogen damage to carp tissues. At 2 mg/kg and 20 mg/kg concentrations of KM successively and significantly elevated (p < 0.05) the SOD activities in the intestinal tract, hepatopancreas and kidney of carp. The expression levels of hepatopancreatic antioxidant genes Nrf2 and IGF-1 were significantly up-regulated in the same group (p < 0.05), while the expression levels of immune genes IL-8 and IL-10 were down-regulated. In summary, KM at concentrations of 2 mg/kg and 20 mg/kg could regulate the expression of antioxidant and immune genes in various tissues in an orderly and rapid manner, and significantly improve the antioxidant and immune abilities of carp, which is conducive to the improvement of the resilience of carp.

Effects of different combinations of koumine and gelsemine on growth performance, intestinal health, and transcriptome of Cyprinus carpio.

Koumine (KM) and gelsemine (GS) have shown significant benefits in livestock production, but their potential in aquaculture remains largely unexplored. This study examined the impact of different KM and GS combinations as feed additives on C. carpio (90 fish per group, initial weight 1.95 ± 0.08 g). KM and GS were introduced in ratios of 2:2 (mg/kg), 2:1 (mg/kg), and 2:0.67 (mg/kg) over a 10-week aquaculture experiment. The results demonstrate that the 2:1 (mg/kg) group increases the villus length, muscular layer thickness, crude protein, and crude fat content. Regarding fatty acid content, KM and GS enhance the levels of various fatty acids, including the total saturated fatty acid and total monounsaturated fatty acid. Additionally, KM and GS improve the composition and function of the intestinal microbiota. The 2:1 (mg/kg) group significantly elevates the enzymatic activities of SOD, MDA, CAT and upregulates the expression of immune-related genes such as toll-like receptor 2, transforming growth factor ß, and glutathione S-transferase. Transcriptomic analysis suggests that KM and GS may have potential benefits for nutrient utilization and immune regulation in C. carpio. In summary, this study provides valuable insights into the use of KM and GS as feed additives in aquaculture.

Toxic Effects of Koumine on the Early-Life Development Stage of Zebrafish.

Koumine is one of the most abundant alkaloids found in Gelsemium elegans, and it has a wide range of pharmacological effects including antitumor, anti-inflammatory, analgesic treatment effects, and antianxiety. However, its high toxicity and unclear mechanism of action have greatly limited the medicinal development and use of koumine. We investigated the toxic effects of koumine on the developmental toxicity and behavioral neurotoxicity of zebrafish embryos and larvae. Embryos at 6 h postfertilization (hpf) were exposed to 12.5, 25, 50, 75, and 100 mg/L of koumine until 120 hpf. Koumine affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas. To identify the neurotoxicity of koumine, the behavior of the larvae was measured. Koumine at 50 and 100 mg/L affect the escape response. The embryos exhibited uncoordinated muscle contractions along the body axis in response to touch at 36 hpf. More importantly, we found that the neurotoxicity of koumine is mainly caused by influencing the ACh content and the activity of AChE without impairing motor neuron development. A comprehensive analysis shows that a high concentration of koumine has obvious toxic effects on zebrafish, and the safe concentration of koumine for zebrafish should be less than 25 mg/L. These results will be valuable for better understanding the toxicity of koumine and provide new insights into the application of koumine.

Achieved 18.9% Efficiency by Fine-Tuning Non-Fullerene Acceptor Content to Simultaneously Increase the Short-Circuit Current and Fill Factor of Organic Solar Cells.

In this study, using PM6:L8-BO as the main system and non-fullerene acceptor IDIC as the third component, a series of ternary organic solar cells (TOSCs) are fabricated. The results reveal that IDIC plays a significant role in enhancing the performance of TOSCs by optimizing the morphology of blended films and forming interpenetrating nanostructure. The improved film morphology facilitates exciton dissociation and collection in TOSCs, which causes an increase in the short-circuit current density (JSC ) and fill factor (FF). Further, by optimizing the IDIC content, the power conversion efficiency (PCE) of TOSCs reaches 18.9%. Besides, the prepared TOSCs exhibit a JSC of 27.51 mA cm-2 and FF of 76.64%, which are much higher than those of PM6:L8-BO-based organic solar cells (OSCs). Furthermore, the addition of IDIC improves the long-term stability of the OSCs. Meanwhile, TOSCs with a large effective area of 1.00 cm2 have been prepared, which exhibit a PCE of 12.4%. These findings suggest that modifying the amount of the third component can be a useful strategy to construct hight-efficiency TOSCs with practical application potential.

Bioinformatics analysis illustrates the functions of miR-377-5p in cervical cancer.

Cervical cancer (CC) is a frequent disease in women whose development is related with miRNA disorder. MiR-377-5p plays a negative role in the development of some tumors, while few studies have revealed its role in CC. In this study, the functions of miR-377-5p in CC were investigated by bioinformatics. Briefly, the expression and survival curve of miR-377-5p in CC was analyzed with the Cancer Genome Atlas (TCGA) database, and the abundance of miR-377-5p in clinical samples and CC cell lines were measured by qRT-PCR. Moreover, the MicroRNA Data Integration Portal (miRDIP) database was used to predict targets of miR-377-5p, and the Database for Annotation Visualization and Integrated Discovery (David) was used for enrichment analysis of the functions of the miR-377-5p. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to screen the hub targets of miR-377-5p. Moreover, the Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the abundance of the genes in CC. Results showed that decreased miR-377-5p was found in the CC tissues and cell lines, and low miR-377-5p was connected with poor prognosis of patients. Besides, the targets of miR-377-5p were enriched in the PI3K/AKT, MAPK and RAS signaling pathways. Moreover, CDC42, FLT1, TPM3 and CAV1 were screened as hub nodes in the targets of miR-377-5p, and increased CDC42, FLT1, TPM3 and CAV1 also indicated the poor survival rates of the patients in the long term. In conclusion, this study suggests that miR-377-5p downregulation is a biomarker event for CC progression.

Solid Additive Enables Organic Solar Cells with Efficiency up to 18.6.

Additive strategies play a critical role in improving the performance of organic solar cells (OSCs). There are only a few reports on the application of solid additives for OSCs, which leaves a large space for further improvement of solid additives and further study on the relationship between material structure and property. PM6:BTP-eC9-based organic solar cells (OSCs) were prepared by using a small molecule BTA3 as a solid additive, and a high energy conversion efficiency of 18.65% is achieved. BTA3 has good compatibility with the acceptor component (BTP-eC9) and optimizes the morphology of the thin films. Moreover, the introduction of a small amount of BTA3 (5 wt %) effectively promotes exciton dissociation and charge transfer and suppresses charge recombination, and the relationship between the BTA3 content and the device parameter is deeply revealed. The use of BTA3 in the active layers is an attractive and effective strategy for high-performance OSCs.

Upregulation of HTRA1 mediated by the lncRNA NEAT1/miR-141-3p axis contributes to endometriosis development through activating NLRP3 inflammasome-mediated pyroptotic cell death and cellular inflammation.

The present study identified a novel upstream long chain non-coding (lncRNA) NEAT1/miR-141-3p/HTRA1 axis that regulated the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome to modulate endometriosis (EM) development. Specifically, clinical data suggested that the expression of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), the cleavage of caspase-1 and gasdermin D (GSDMD), and the production of inflammatory cytokines (interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-18) were all significantly increased in the ectopic endometrium (EE) tissues, compared to the normal endometrium (NE) tissues. Then, through analyzing the datasets from GEO database (GSE2339, GSE58178, and GSE7305) using the GEO2R bioinformatics tools, we verified that HtrA Serine Peptidase 1 (HTRA1) was especially enriched in the EE tissues compared to the NE tissues. To further confirm the biological functions of HTRA1, HTRA1 was overexpressed or downregulated in primary human endometrial stromal cells (hESCs) isolated from NE tissues or EE tissues, respectively. The results showed that upregulation of HTRA1 activated NLRP3 inflammasome-mediated pyroptotic cell death and cellular inflammation in NE-derived hESCs, whereas silencing of HTRA1 played an opposite role in EE-derived hESCs. In addition, the lncRNA NEAT1/miR-141-3p axis was screened as the upstream regulator of HTRA1. Mechanistically, lncRNA NEAT1 sponged miR-141-3p to positively regulate HTRA1 in a competing endogenous RNA (ceRNA) mechanisms-dependent manner. The recovery experiments in hESCs from NE and EE tissues confirmed that lncRNA NEAT1 overexpression promoted NLRP3 inflammasome-mediated pyroptotic cell death through regulating the miR-141-3p/HTRA1 axis. Taken together, this study firstly uncovered the underlying mechanisms by which a novel lncRNA NEAT1/miR-141-3p/HTRA1-NLRP3 pathway contributed to the development of EM, which provided novel diagnostic and therapeutic biomarkers for this disease.

A spectrum of novel anti-vascular endothelial cells autoantibodies in idiopathic nephrotic syndrome patients.

Idiopathic nephrotic syndrome (INS) is a common renal disease characterized by disruption of the glomerular filtration barrier. In a previous study, we screened and identified podocyte autoantibodies in nephrotic syndrome patients and proposed the concept of autoimmune podocytopathy. However, circulating podocyte autoantibodies cannot reach podocytes unless glomerular endothelial cells have been damaged. Therefore, we speculate that INS patients may also have autoantibodies against vascular endothelial cells. Sera from INS patients were used as primary antibodies to screen and identify endothelial autoantibodies by hybridization with vascular endothelial cell proteins separated by two-dimensional electrophoresis. The clinical application value and pathogenicity of these autoantibodies were further verified by clinical study and in vivo and in vitro experiments. Nine kinds of autoantibodies against vascular endothelial cells were screened in patients with INS, which can cause endothelial cell damage. In addition, 89% of these patients were positive for at least one autoantibody.