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Objective Recurrent spontaneous abortion (RSA) is a major pregnancy complication with unclear pathogenesis. This study aims to investigate the role of miR-20b-5p and its downstream target HIF-1α in trophoblast function and RSA pathogenesis. Methods Placental villous tissues from uRSA patients and healthy pregnant women were collected to assess trophoblast migration, invasion, apoptosis, and placental angiogenesis. The expression levels of miR-20b-5p and HIF-1α were analyzed using qPCR, Western blot, and immunohistochemistry. HTR-8/SVneo cells were transfected with miR-20b-5p mimics, si-miR-20b-5p, and si-HIF-1α to evaluate their effects on trophoblast function. Luciferase reporter assays were performed to confirm the regulatory relationship between miR-20b-5p and HIF-1α. Results Trophoblast cells isolated from uRSA patients exhibited impaired trophoblast invasion and increased trophoblast apoptosis, accompanied by increased trophoblast apoptosis. miR-20b-5p was significantly upregulated, whereas HIF-1α expression was downregulated in uRSA placental tissues. Overexpression of miR-20b-5p inhibited trophoblast migration, invasion, and endothelial-like differentiation, while its knockdown enhanced these functions. HIF-1α was identified as a direct target of miR-20b-5p, and its knockdown partially reversed the effects of miR-20b-5p inhibition. Conclusion miR-20b-5p negatively regulates trophoblast function by targeting HIF-1α, contributing to trophoblast dysfunction and RSA pathogenesis. The miR-20b-5p/HIF-1α axis may serve as a potential therapeutic target for RSA.

Objective Recurrent spontaneous abortion (RSA) is a major pregnancy complication with unclear pathogenesis. This study aims to investigate the role of miR-20b-5p and its downstream target HIF-1[alpha] in trophoblast function and RSA pathogenesis. Methods Placental villous tissues from uRSA patients and healthy pregnant women were collected to assess trophoblast migration, invasion, apoptosis, and placental angiogenesis. The expression levels of miR-20b-5p and HIF-1[alpha] were analyzed using qPCR, Western blot, and immunohistochemistry. HTR-8/SVneo cells were transfected with miR-20b-5p mimics, si-miR-20b-5p, and si-HIF-1[alpha] to evaluate their effects on trophoblast function. Luciferase reporter assays were performed to confirm the regulatory relationship between miR-20b-5p and HIF-1[alpha]. Results Trophoblast cells isolated from uRSA patients exhibited impaired trophoblast invasion and increased trophoblast apoptosis, accompanied by increased trophoblast apoptosis. miR-20b-5p was significantly upregulated, whereas HIF-1[alpha] expression was downregulated in uRSA placental tissues. Overexpression of miR-20b-5p inhibited trophoblast migration, invasion, and endothelial-like differentiation, while its knockdown enhanced these functions. HIF-1[alpha] was identified as a direct target of miR-20b-5p, and its knockdown partially reversed the effects of miR-20b-5p inhibition. Conclusion miR-20b-5p negatively regulates trophoblast function by targeting HIF-1[alpha], contributing to trophoblast dysfunction and RSA pathogenesis. The miR-20b-5p/HIF-1[alpha] axis may serve as a potential therapeutic target for RSA. Keywords: Recurrent spontaneous abortion, Trophoblast, MiR-20b-5p, HIF-1[alpha]

Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems 1 . However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have not been well characterized. We established a ‘single-cell HCL analysis’ pipeline that helps to define human cell identity. Finally, we performed a single-cell comparative analysis of landscapes from human and mouse to identify conserved genetic networks. We found that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct. Our results provide a useful resource for the study of human biology. Single-cell RNA sequencing is used to generate a dataset covering all major human organs in both adult and fetal stages, enabling comparison with similar datasets for mouse tissues.

Background The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) (NHHR) served as a novel comprehensive lipid indicator. This study aimed to explore the association between NHHR and the incidence of cardiometabolic multimorbidity (CMM). Methods This study included 8191 individuals from the China Health and Retirement Longitudinal Study (CHARLS) database. We used multivariable cox proportional hazards regression, logistic regression, and restricted cubic splines (RCS) analysis to evaluate the association between NHHR and CMM. Subgroup analyses and interaction tests were also performed. Results The incidences of CMM among participants in quartiles (Q) 1–4 of NHHR were 7.03%, 8.3%, 10.06%, and 16.55%, respectively. The NHHR was significantly higher in individuals with CMM compared to those without CMM ( P  < 0.001). When assessed as a continuous variable, NHHR was independently associated with the risk of CMM, as demonstrated by both multivariable cox proportional hazards regression analysis (HR = 1.05, 95% CI = 1.02–1.07, P  < 0.001) and logistic regression analysis (OR = 1.09, 95% CI = 1.04–1.15, P  < 0.001). Compared to individuals in the lowest quartiles of the NHHR (Q1), the risk of CMM in the highest quartiles (Q4) was increased by 1.25-fold according to multivariable cox proportional hazards regression analysis (HR = 2.25, 95% CI = 1.73–2.93, P  < 0.001) and by 1.48-fold according to logistic regression analysis (OR = 2.48, 95% CI = 1.86–3.31, P  < 0.001). This association was consistent across nearly all subgroups. RCS analysis revealed a significant nonlinear association between NHHR and CMM. Additionally, the predictive ability of NHHR for CMM was 0.613, which was superior to that of both HDL-C and non-HDL-C ( P  < 0.05). Furthermore, the composite variable comprising NHHR and other traditional risk factors exhibited the highest predictive value (C statistic = 0.679). Conclusion A higher NHHR was closely associated with an increased risk of CMM. Further studies on NHHR could be beneficial for preventing and treating CMM.

Background It is becoming increasingly clear that cancers can rarely be ascribed to just one or a few genomic variations. Genes generally do not function alone, but in groups that function as “networks”. This study aimed to develop a competing endogenous RNA (ceRNA) network to elucidate the role of long non-coding RNA H19 in colorectal cancer. Methods Large-scale RNA-seq data was obtained from The Cancer Genome Atlas database. Differentially expressed RNAs were identified by bioinformatics analysis, and a competing endogenous RNA network was constructed. Functional enrichment analysis and correlation analysis between competing endogenous RNAs and clinical features were performed to reveal their roles in the tumorigenesis of colorectal cancer. To verify the conclusions derived from bioinformatics analysis, we investigated the effect of lncRNA H19 knockdown in human colorectal cancer cell lines HT-29 and HCT116. Results The present study successfully identify various cancer-specific lncRNAs and pseudogenes in CRC. The lncRNA/pseudogene–miRNA–mRNA ceRNA network was constructed using 10 lncRNAs, 5 pseudogenes, 122 mRNAs and 39 miRNAs. In the ceRNA network of CRC, H19 up-regulates various cancer-related mRNA by competitively sponging various miRNA, and participates in PI3K–Akt signaling pathway in this manner. Cox regression and correlation analysis showed that H19 and some other competing endogenous RNAs in the network are associated with poor prognosis and clinical parameters such as tumor grade and metastasis. Knockdown of H19 reduces the protein level of MET, ZEB1, and COL1A1 in vitro. Conclusions H19 regulates PI3K–Akt signal pathway through a competing endogenous RNA network and predicts poor prognosis in colorectal cancer. The pseudogene RPLP0P2 may be an important oncogene like H19 and needs to be studied further.

Iron–nitrogen co-doped carbon (Fe/N/C) catalysts derived from zinc-based zeolite imidazole frameworks (ZIF-8) have been ideal alternatives to platinum group metals (PGM) and shown great potential to catalyze oxygen reduction reaction (ORR). Unfortunately, the ORR performance is seriously suppressed by the insufficient density and accessibility of the electrochemical active Fe–N sites. The precise regulation of ZIF-8 to the formation of Fe/N/C catalysts with the desired Fe–N sites for ORR is a critical challenge. Herein, a citric acid assisted reconstitution strategy is proposed to design Fe doped ZIF-8 frameworks and construct multi-dimensional Fe/N/C catalysts composed of inner concave and entangled carbon nanotubes outer moieties for efficient acid-resistant ORR reaction. The introduction of citric acid imparts Fe/N/C catalysts with dense accessible active sites and highly opened multi-dimensional mass transfer pathways. Therefore, the optimized Fe/N/C catalysts dominant half-wave potential of 0.785 V and great acid stability were obtained in 0.5 M H 2 SO 4 with a high number of transferred electrons and a low yield of H 2 O 2 ( n ¯  = 3.97 and average yield = 4%). This work provides a novel and feasible approach to design and tailoring of Fe/N/C catalysts with improved distribution density and accessibility of the Fe–N active sites. Graphical Abstract

Conversion of heteroatom-doped sites to carbon defects has been developed recently as an efficient strategy to build advanced metal-free carbon electrocatalysts for oxygen reduction reaction (ORR). However, precise control of the configuration conversion to achieve highly active ORR configurations still remains a great challenge to date. Herein, an edge reconfiguration strategy was proposed for N, P-codoped carbon (NPC) to build heteroatom-doped defective carbon system for ORR. Through the thermally induced edge reconfiguration, the ORR activity, 4e− selectivity and stability of prepared NPC materials were significantly improved. Physical characterizations demonstrated that a half of N sites dominated with edge configurations and most P sites were converted to edge carbon defects. The finally econfigured edge nanostructures, consisting of abundant carbon defects, N-doped sites and graphitization-enhanced bulk carbon skeleton, were largely responsible for the improved ORR performance. This work will make an important contribution to the understanding of the edge configuration conversion mechanism and establishment of reasonable design principles of defective carbon-based nanomaterials for extensive electrocatalytic applications.

Objective To compare mid-term survival and health-related quality of life differences between bone grafting (BG) and total hip arthroplasty (THA) in non-traumatic osteonecrosis of the femoral head (NTONFH) patients under 50 years of age. Methods This single-center retrospective study analyzed 165 consecutive NTONFH patients (2015–2020) undergoing BG ( n  = 55) or THA ( n  = 110). Primary outcomes were 5-year survival (revision endpoint), with secondary outcomes including Harris Hip Score, complications, and patient-reported measures (SF-36, JHEQ, UCLA). Survival analysis employed log-rank tests and Cox proportional hazards model. Results The THA group exhibited significantly higher 5-year survival rates than the BG group (95.5% vs. 81.8%, p = 0.003). The THA group demonstrated superior postoperative HHS total scores (91.3 ± 3.2 vs. 82.1 ± 6.7, p < 0.001), pain scores (42.8 ± 1.6 vs. 40.1 ± 3.2, p < 0.001), and physical activity levels (UCLA: 7.2 ± 1.5 vs. 6.5 ± 1.8, p = 0.018). However, the BG group outperformed in mental health domains: SF-36 mental component score (65.8 ± 13.2 vs. 58.4 ± 14.7, p = 0.021) and JHEQ mental score (24.3 ± 4.9 vs. 20.7 ± 5.6, p = 0.004). Subgroup analysis revealed comparable survival rates between BG and THA in ARCO IIIA-stage patients (87.2% vs. 94.6%, p = 0.672), while BG failure rates reached 44.4% in JIC C2-type patients. ​Conclusion THA offers advantages in functional recovery and survival rates, but rigorously selected ARCO IIIA-stage patients undergoing BG achieve comparable survival outcomes to THA while exhibiting superior mental health benefits. BG is recommended for ARCO II-IIIA/JIC A-C1-type patients to preserve joint function and enhance psychosocial adaptation, whereas THA remains the optimal choice for advanced-stage (IIIB/IV) or JIC C2-type patients to ensure rapid functional restoration. This study provides evidence for personalized treatment strategies based on disease staging, anatomical severity, and patient psychological needs.

We investigated genomic evolution of vancomycin-resistant Enterococcus faecium (VREF) during an outbreak in Shenzhen, China. Whole-genome sequencing revealed 2 sequence type 80 VREF subpopulations diverging through insertion sequence-mediated recombination. One subpopulation acquired more antimicrobial resistance and carbohydrate metabolism genes. Persistent VREF transmission underscores the need for genomic surveillance to curb spread.

The design of a 10 cm2 (3.4 cm by 3.4 cm) and a 100 cm2 (10 cm by 10 cm) anion exchange membrane (AEM) water electrolyser cell for hydrogen production are described. The AEM cells are based on a zero-gap configuration where the AEM is sandwiched between the anode and cathode so as to minimise voltage drop between the electrodes. Nonprecious nickel-based metal alloy and metal oxide catalysts were employed. Various experiments were carried out to understand the effects of operating parameters such as current densities, electrolyte concentrations, and testing regimes on the performance of both 10 cm2 and 100 cm2 AEM electrolyser cells. Increasing electrolyte concentration was seen to result in reductions in overpotentials which were proportional to current applied, whilst the use of catalysts improved performance consistently over the range of current densities tested. Extended galvanostatic and intermittent tests were demonstrated on both 10 cm2 and 100 cm2 cells, with higher voltage efficiencies achieved with the use of electrocatalysts. Stability tests in the 100 cm2 AEM electrolyser cell assembled with catalyst-coated electrodes demonstrated that the cell voltages remained stable at 2.03 V and 2.17 V during 72 h operation in 4 M KOH and 1 M KOH electrolyte, respectively, at a current density of 0.3 A cm−2 at 323 K. The inclusion of cycling load tests in testing protocols is emphasized for rational evaluation of cell performance as this was observed to speed up the rate of degradation mechanisms such as membrane degradation.