TNFSF14+ natural killer cells prevent spontaneous abortion by restricting leucine-mediated decidual stromal cell senescence.

In preparation for a potential pregnancy, the endometrium of the uterus changes into a temporary structure called the decidua. Senescent decidual stromal cells (DSCs) are enriched in the decidua during decidualization, but the underlying mechanisms of this process remain unclear. Here, we performed single-cell RNA transcriptomics on ESCs and DSCs and found that cell senescence during decidualization is accompanied by increased levels of the branched-chain amino acid (BCAA) transporter SLC3A2. Depletion of leucine, one of the branched-chain amino acids, from cultured media decreased senescence, while high leucine diet resulted in increased senescence and high rates of embryo loss in mice. BCAAs induced senescence in DSCs via the p38 MAPK pathway. In contrast, TNFSF14+ decidual natural killer (dNK) cells were found to inhibit DSC senescence by interacting with its ligand TNFRSF14. As in mice fed high-leucine diets, both mice with NK cell depletion and Tnfrsf14-deficient mice with excessive uterine senescence experienced adverse pregnancy outcomes. Further, we found excessive uterine senescence, SLC3A2-mediated BCAA intake, and insufficient TNFRSF14 expression in the decidua of patients with recurrent spontaneous abortion. In summary, this study suggests that dNK cells maintain senescence homeostasis of DSCs via TNFSF14/TNFRSF14, providing a potential therapeutic strategy to prevent DSC senescence-associated spontaneous abortion.

Novel Fabrication of Bio-polymeric Nanogel Loaded with Nalidixic Acid Formulations for the Effective Prevention of Bacterial Pathogens Leading Urinary Tract Infection and Its Biosafety Evaluation.

Management of urinary tract infections (UTI) is a highly challenging process due to the biofilm-forming ability of human-pathogenic bacteria. Here, we designed to fabricate an effective nanogel with a combination of chitosan bio-polymer and nalidixic acid to prevent biofilm-forming bacterial pathogens. Chitosan-coated nalidixic acid nanogel (NA@CS) exhibits outstanding inhibition potential against bacterial strains. In vitro, anti-bacterial analysis methods (well diffusion, colony-forming assay, and anti-biofilm assay) were performed to study the bacterial inhibition potential of prepared nanogel, which reveals that NA@CS nanogel have greater inhibition potential against selected pathogens. The combination of nalidixic acid with chitosan biopolymer decreases the virulence and pathogenicity of biofilm-forming pathogens due to their ability to membrane phospholipids penetration. Furthermore, the fabricated NA@CS nanogel showed reliable in vitro bio-compatibility on L929 fibroblast cells and in vivo compatibility with Artemia salina animal model. Overall, the results demonstrate that NA@CS nanogel could be an effective therapeutic for treating urinary tract infections and urine bladder wound healing.

Lactoferrin/CD133 antibody conjugated nanostructured lipid carriers for dual targeting of blood-brain-barrier and glioblastoma stem cells.

The main reasons for the difficulty in curing and high recurrence rate of glioblastoma multiforme (GBM) include: 1. The difficulty of chemotherapy drugs in penetrating the blood-brain barrier (BBB) to target tumor cells; 2. The presence of glioma stem cells (GSCs) leading to chemotherapy resistance. Therefore, breaking through the limitations of the BBB and overcoming the drug resistance caused by GSCs are the main strategies to address this problem. This study presents our results on the development of lactoferrin (Lf)/CD133 antibody conjugated nanostructured lipid carriers (Lf/CD133-NLCS) for simultaneously targeting BBB and GSCs. Temozolomide (TMZ) loaded Lf/CD133-NLCS (Lf/CD133-NLCS-TMZ) exhibited high-efficiencyin vitroanti-tumor effects toward malignant glioma cells (U87-MG) and GSCs, while demonstrating no significant toxicity to normal cells at concentrations lower than 200 µg ml-1. The results of thein vitrotargeting GBM study revealed a notably higher cellular uptake of Lf/CD133-NLCS-TMZ in U87-MG cells and GSCs in comparison to Lf/CD133 unconjugated counterpart (NLCS-TMZ). In addition, increased BBB permeability were confirmed for Lf/CD133-NLCS-TMZ compared to NLCS-TMZ bothin vitroandin vivo. Taking together, Lf/CD133-NLCS-TMZ show great potential for dual targeting of BBB and GSCs, as well as GBM therapy based on this strategy.

PVA-assisted spray deposited porous Li4Ti5O12 thin film as high-rate and long-cycle anode for lithium-ion thin-film batteries.

Spinel Li4Ti5O12 (LTO), a zero-strain material, is a promising anode material for solid-state thin-film lithium-ion batteries (TFB). However, the preparation of high-performance Li4Ti5O12 thin-film electrodes through facile methods remains a significant challenge. Herein, we present a novel approach to prepare a binder- and conductor-free porous Li4Ti5O12 (P-LTO) thin-film. This approach polyvinyl alcohol (PVA)-assisted spray deposition and does not require the use of complex or expensive methods. Adding PVA to the precursor solution effectively prevents thin-film cracking during high-temperature annealing, enhances adhesion, and forms a highly interconnected porous structure. This unique structure shortens the lithium-ion diffusion pathways and facilitates electron transport. Therefore, P-LTO thin film electrodes demonstrate exceptional rate capacity of 104.1 mAh/g at a current density of 100C. In addition, the electrodes exhibit ultra-long cycle stability, retaining 80.9 % capacity after 10,000 cycles at 10C. This work offers a novel approach for the preparation of high-performance thin-film electrodes for TFBs.

Network Pharmacology and Molecular Docking Integrated with Molecular Dynamics Simulations Investigate the Pharmacological Mechanism of Yinchenhao Decoction in the Treatment of Non-alcoholic Fatty Liver Disease.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) has become a significant health and economic burden globally. Yinchenhao decoction (YCHD) is a traditional Chinese medicine formula that has been validated to exert therapeutic effects on NAFLD. OBJECT: The current study aimed to explore the pharmacological mechanisms of YCHD on NAFLD and further identify the potential active compounds acting on the main targets. METHODS: Compounds in YCHD were screened and collected from TCMSP and published studies, and their corresponding targets were obtained from the SWISS and SEA databases. NAFLD-related targets were searched in the GeneCards and DisGeNet databases. The "compound- intersection target" network was constructed to recognize the key compounds. Moreover, a PPI network was constructed to identify potential targets. GO and KEGG analyses were performed to enrich the functional information of the intersection targets. Then, molecular docking was used to identify the most promising compounds and targets. Finally, molecular dynamics (MD) simulations were performed to verify the binding affinity of the most potential compounds with the key targets. RESULTS: A total of 53 compounds and 556 corresponding drug targets were collected. Moreover, 2684 NAFLD-related targets were obtained, and 201 intersection targets were identified. Biological processes, including the apoptotic process, inflammatory response, xenobiotic metabolic process, and regulation of MAP kinase activity, were closely related to the treatment of NAFLD. Metabolic pathways, non-alcoholic fatty liver disease, the MAPK signaling pathway, and the PI3K-Akt signaling pathway were found to be the key pathways. Molecular docking showed that quercetin and isorhamnetin were the potential active compounds, while AKT1, IL1B, and PPARG were the most promising targets. MD simulations further verified that the binding of PPARG-isorhamnetin (-35.96 ± 1.64 kcal/mol) and AKT1-quercetin (-31.47 ± 1.49 kcal/mol) was due to their lowest binding free energy. CONCLUSION: This study demonstrated that YCHD exerts therapeutic effects for the treatment of NAFLD through multiple targets and pathways, providing a theoretical basis for further pharmacological research on the potential mechanisms of YCHD in NAFLD.

New Late Pleistocene age for the Homo sapiens skeleton from Liujiang southern China.

The emergence of Homo sapiens in Eastern Asia is a topic of significant research interest. However, well-preserved human fossils in secure, dateable contexts in this region are extremely rare, and often the subject of intense debate owing to stratigraphic and geochronological problems. Tongtianyan cave, in Liujiang District of Liuzhou City, southern China is one of the most important fossils finds of H. sapiens, though its age has been debated, with chronometric dates ranging from the late Middle Pleistocene to the early Late Pleistocene. Here we provide new age estimates and revised provenience information for the Liujiang human fossils, which represent one of the most complete fossil skeletons of H. sapiens in China. U-series dating on the human fossils and radiocarbon and optically stimulated luminescence dating on the fossil-bearing sediments provided ages ranging from ~33,000 to 23,000 years ago (ka). The revised age estimates correspond with the dates of other human fossils in northern China, at Tianyuan Cave (~40.8-38.1 ka) and Zhoukoudian Upper Cave (39.0-36.3 ka), indicating the geographically widespread presence of H. sapiens across Eastern Asia in the Late Pleistocene, which is significant for better understanding human dispersals and adaptations in the region.

Environmental protection investment on performance of heavy-polluting enterprises: evidence from China's A-share listed companies.

Heavy-polluting enterprises' investment in environmental protection will have a "crowding out effect" on their other inputs, affecting enterprise performance. However, if the environmental protection investment of enterprises improves their green technology innovation ability, resulting in the "innovation compensation effect," which can offset the "crowding out effect" of environmental protection inputs, it may have a positive impact on enterprise performance. This can offset the "crowding out effect" of environmental investment and may promote the performance of enterprises. At the same time, equity concentration plays the role of "tunneling effect" and "monitoring and incentive effect" in the process of environmental protection investment affecting the performance of heavy-polluting enterprises. The paper selects the data of A-share listed heavy-polluting enterprises in China from 2010 to 2019 and analyzes the impacts of environmental protection investment and green technology innovation on the performance of heavy-polluting enterprises by using a multidimensional panel fixed-effects model. The results show that environmental protection investment will improve the performance of heavy-polluting enterprises by improving their green technology innovation ability; green technology innovation plays a partly intermediary role in the process of environmental protection investment affecting the performance of enterprises, and the magnitude of this intermediary role is regulated by the concentration of corporate equity. Based on the results of the empirical study, it is recommended that heavy-polluting enterprises should accelerate the pace of green technology research and development and results transformation, optimize the proportion of equity allocation, and achieve the dual goals of fulfilling environmental responsibilities and enhancing corporate performance.

Anoikis-related mRNA-lncRNA and DNA methylation profiles for overall survival prediction in breast cancer patients.

As a type of programmed cell death, anoikis resistance plays an essential role in tumor metastasis, allowing cancer cells to survive in the systemic circulation and as a key pathway for regulating critical biological processes. We conducted an exploratory analysis to improve risk stratification and optimize adjuvant treatment choices for patients with breast cancer, and identify multigene features in mRNA and lncRNA transcriptome profiles associated with anoikis. First, the variance selection method filters low information content genes in RNA sequence and then extracts the mRNA and lncRNA expression data base on annotation files. Then, the top ten key mRNAs are screened out through the PPI network. Pearson analysis has been employed to identify lncRNAs related to anoikis, and the prognosis-related lncRNAs are selected using Univariate Cox regression and machine learning. Finally, we identified a group of RNAs (including ten mRNAs and six lncRNAs) and integrated the expression data of 16 genes to construct a risk-scoring system for BRCA prognosis and drug sensitivity analysis. The risk score's validity has been evaluated with the ROC curve, Kaplan-Meier survival curve analysis and decision curve analysis (DCA). For the methylation data, we have obtained 169 anoikis-related prognostic methylation sites, integrated these sites with 16 RNA features and further used the deep learning model to evaluate and predict the survival risk of patients. The developed anoikis feature is demonstrated a consistency index (C-index) of 0.778, indicating its potential to predict the survival probability of breast cancer patients using deep learning methods.

A P-type pentatricopeptide repeat protein ZmRF5 promotes 5' region partial cleavages of atp6c transcripts to restore the fertility of CMS-C maize by recruiting a splicing factor.

A fast evolution within mitochondria genome(s) often generates discords between nuclear and mitochondria, which is manifested as cytoplasmic male sterility (CMS) and fertility restoration (Rf) system. The maize CMS-C trait is regulated by the chimeric mitochondrial gene, atp6c, and can be recovered by the restorer gene ZmRf5. Through positional cloning in this study, we identified the nuclear restorer gene, ZmRf5, which encodes a P-type pentatricopeptide repeat (PPR) family protein. The over-expression of ZmRf5 brought back the fertility to CMS-C plants, whereas its genomic editing by CRISPR/Cas9 induced abortive pollens in the restorer line. ZmRF5 is sorted to mitochondria, and recruited RS31A, a splicing factor, through MORF8 to form a cleaving/restoring complex, which promoted the cleaving of the CMS-associated transcripts atp6c by shifting the major cleavage site from 480th nt to 344 th nt for fast degradation, and preserved just right amount of atp6c RNA for protein translation, providing adequate ATP6C to assembly complex V, thus restoring male fertility. Interestingly, ATP6C in the sterile line CMo17A, with similar cytology and physiology changes to YU87-1A, was accumulated much less than it in NMo17B, exhibiting a contrary trend in the YU87-1 nuclear genome previously reported, and was restored to normal level in the presence of ZmRF5. Collectively these findings unveil a new molecular mechanism underlying fertility restoration by which ZmRF5 cooperates with MORF8 and RS31A to restore CMS-C fertility in maize, complemented and perfected the sterility mechanism, and enrich the perspectives on communications between nucleus and mitochondria.

GRASP reconstruction amplified with view-sharing and KWIC filtering reduces underestimation of peak velocity in highly-accelerated real-time phase-contrast MRI: A preliminary evaluation in pediatric patients with congenital heart disease.

PURPOSE: To develop a highly-accelerated, real-time phase contrast (rtPC) MRI pulse sequence with 40 fps frame rate (25 ms effective temporal resolution). METHODS: Highly-accelerated golden-angle radial sparse parallel (GRASP) with over regularization may result in temporal blurring, which in turn causes underestimation of peak velocity. Thus, we amplified GRASP performance by synergistically combining view-sharing (VS) and k-space weighted image contrast (KWIC) filtering. In 17 pediatric patients with congenital heart disease (CHD), the conventional GRASP and the proposed GRASP amplified by VS and KWIC (or GRASP + VS + KWIC) reconstruction for rtPC MRI were compared with respect to clinical standard PC MRI in measuring hemodynamic parameters (peak velocity, forward volume, backward volume, regurgitant fraction) at four locations (aortic valve, pulmonary valve, left and right pulmonary arteries). RESULTS: The proposed reconstruction method (GRASP + VS + KWIC) achieved better effective spatial resolution (i.e., image sharpness) compared with conventional GRASP, ultimately reducing the underestimation of peak velocity from 17.4% to 6.4%. The hemodynamic metrics (peak velocity, volumes) were not significantly (p > 0.99) different between GRASP + VS + KWIC and clinical PC, whereas peak velocity was significantly (p < 0.007) lower for conventional GRASP. RtPC with GRASP + VS + KWIC also showed the ability to assess beat-to-beat variation and detect the highest peak among peaks. CONCLUSION: The synergistic combination of GRASP, VS, and KWIC achieves 25 ms effective temporal resolution (40 fps frame rate), while minimizing the underestimation of peak velocity compared with conventional GRASP.

Investigation of Stroke Risk Factors and Prognostic Indicators in NVAF Patients with Low CHA2DS2-VASc Scores.

The prognosis of patients with nonvalvular atrial fibrillation (NVAF) with a low CHA2DS2-VASc score (0-1) following a stroke is not well studied. In this investigation, stroke risk factors and prognostic markers in low-risk NVAF patients who are nonetheless at risk for stroke were examined.From January 2012 to January 2022, we retrospectively assessed atrial fibrillation (AF) patients at Xiamen University's Zhongshan Hospital for ischemic stroke. Along with a control group of patients with CHA2DS2-VASc scores of 0-1 who weren't suffering from a stroke, patients with CHA2DS2-VASc scores of 0-1 at the time of stroke were included in the study. Using multivariate logistic regression, independent risk factors were identified. To assess the cumulative occurrences of in-hospital mortality in patients with NVAF-related stroke, the Kaplan-Meier method was used.The study included 156 out of 3.237 inpatients with AF-related stroke who had CHA2DS2-VASc ratings of 0-1. Left atrial diameter (LAD) (odds ratio [OR]: 1.858, 95% confidence interval (CI) 1.136-3.036, P = 0.013), D-dimer (OR: 2.569, 95% CI 1.274-5.179, P = 0.008), and NT-proBNP (OR: 4.558, 95% CI 2.060-10.087, P = 0.000) were found to be independent risk factors for stroke in NVAF patients with a low CHA2DS2-VASc score. During hospitalization, nine patients with NVAF-related stroke died. In patients with NVAF-related stroke, NT-proBNP (hazard ratio: 3.504, 95% CI 1.079-11.379, P = 0.037) was an indicator of mortality risk.Patients with NVAF and CHA2DS2-VASc scores of 0-1 had independent risk factors for stroke in the form of LAD, D-dimer, and NT-proBNP. Notably, in low-risk NVAF patients with stroke, NT-proBNP was discovered to be a potent predictor of in-hospital death.

TiO2-LiF composite coating for improving NCM622 cathode cycling stability: one-step construction.

The Ni-rich NCM622 is a promising cathode material for future high energy lithium ion batteries, but unstable electrochemical performance of NCM622 hinder its large scale commercial application. The cycling peformance of nickel-rich LiNi0.6Co0.2Mn0.2O2 (NCM622) cathode materials can be improved by surface coating. Here, a one-step approach based on TiF4 is used to successfully manufacture modified NCM622 cathode materials with a TiO2-LiF coating. The TiO2-LiF coated NCM622 preserves 79.7% capacity retention which is higher than the pure NCM622 (68.9%) at 1C after 200 cycles within 2.7-4.3 V. This material serves as the cathode for lithium-ion batteries (LIBs). The uniform TiO2-LiF coating layer can alleviate structural degradation brought on by unfavorable side reactions with the electrolyte has been validated. TiO2-LiF coated on NCM622 cathode materials can be modified easily by one-step approach.

Main-Chain Benzoxazines Containing an Erythritol Acetal Structure: Thermal and Degradation Properties.

In this paper, the bio-based raw material erythritol was used to introduce an acetal structure into the benzoxazine resins. The benzoxazine-based resins containing an erythritol acetal structure could be degraded in an acidic solution and were environmentally friendly thermosetting resins. Compounds and resins were characterized by 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared (FT-IR) analyses, and melting points were studied by a differential scanning calorimeter (DSC); the molecular weight was analyzed by gel permeation chromatography (GPC). The dynamic mechanical properties and thermal stability of polybenzoxazine resins were studied by dynamic mechanical thermal analysis (DMTA) and a thermogravimetric analyzer (TGA), respectively. The thermal aging, wet-heat resistance, and degradation properties of polybenzoxazine resins were tested. The results showed that the polybenzoxazine resins synthesized in this paper had good thermal-oxidative aging, and wet-heat resistance and could be completely degraded in an acidic solution (55 °C DMF: water: 1 mol/L hydrochloric acid solution = 5:2:4 (v/v/v)).

Emerging Roles of Lysophosphatidic Acid in Macrophages and Inflammatory Diseases.

Lysophosphatidic acid (LPA) is a bioactive phospholipid that regulates physiological and pathological processes in numerous cell biological functions, including cell migration, apoptosis, and proliferation. Macrophages are found in most human tissues and have multiple physiological and pathological functions. There is growing evidence that LPA signaling plays a significant role in the physiological function of macrophages and accelerates the development of diseases caused by macrophage dysfunction and inflammation, such as inflammation-related diseases, cancer, atherosclerosis, and fibrosis. In this review, we summarize the roles of LPA in macrophages, analyze numerous macrophage- and inflammation-associated diseases triggered by LPA, and discuss LPA-targeting therapeutic strategies.

Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-κB/Bcl-2 pathway.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1G93A-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1G93A-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract).

[Analysis on the Distribution Characteristics and Influence Mechanism of Migration and Transformation of Heavy Metals in Mining Wasteland].

In order to explore the distribution characteristics and the influence mechanism of migration and transformation of heavy metals in mining wasteland, soil and tailings samples were collected from the mining wasteland in the Dabaoshan Mining area, Guangdong Province, and the morphological characteristics of heavy metals were analyzed. At the same time, the pollution sources of the mining area were analyzed using Pb stable isotope analysis, and the characteristics and influencing factors of heavy metal migration and transformation in the mining area were expounded by combining X-ray diffraction analysis, transmission electron microscope-energy spectrum analysis (TEM-EDS), and Raman analysis of typical minerals in the mining area, as well as laboratory-simulated leaching experiments. Morphological analysis showed that the forms of Cd, Pb, and As in the soil and tailings samples in the mining area were mainly the residual phase, accounting for 85%-95% of the total, followed by the iron and manganese oxide-bound form (1%-15%). The main mineral types in the soil and tailings in the Dabaoshan Mining area were pyrite (FeS2), chalcopyrite (CuFeS2), and metal oxides, as well as a small amount of sphalerite (ZnS) and galena (PbS). Acidic conditions (pH=3.0) were beneficial to the release and migration of Cd and Pb from soil, tailings, and minerals (pyrite, chalcopyrite) and from the residual phase to the non-residual phase. Lead isotope analysis showed that the lead in the soil and tailings mainly came from the release of metal minerals in the mining area, and the contribution of diesel in the mining area was less than 30%. Multivariate statistical analysis showed that Pyrite, Chalcopyrite, Sphalerite, and Metal oxide were the main sources of heavy metals in the soil and tailings in the mining area, in which Cd, As, and Pb were mainly contributed by sphalerite and metal oxide. The form change in heavy metals in the mining wasteland was easily affected by environmental factors. The form characteristics and migration and transformation factors of heavy metals should be considered in the source control of heavy metal pollution in mining wasteland.

Identification of Potential TMPRSS2 Inhibitors for COVID-19 Treatment in Chinese Medicine by Computational Approaches and Surface Plasmon Resonance Technology.

BACKGROUND: Coronavirus disease-19 (COVID-19) pneumonia continues to spread in the entire globe with limited medication available. In this study, the active compounds in Chinese medicine (CM) recipes targeting the transmembrane serine protease 2 (TMPRSS2) protein for the treatment of COVID-19 were explored. METHODS: The conformational structure of TMPRSS2 protein (TMPS2) was built through homology modeling. A training set covering TMPS2 inhibitors and decoy molecules was docked to TMPS2, and their docking poses were re-scored with scoring schemes. A receiver operating characteristic (ROC) curve was applied to select the best scoring function. Virtual screening of the candidate compounds (CCDs) in the six highly effective CM recipes against TMPS2 was conducted based on the validated docking protocol. The potential CCDs after docking were subject to molecular dynamics (MD) simulations and surface plasmon resonance (SPR) experiment. RESULTS: A training set of 65 molecules were docked with modeled TMPS2 and LigScore2 with the highest area under the curve, AUC, value (0.886) after ROC analysis selected to best differentiate inhibitors from decoys. A total of 421 CCDs in the six recipes were successfully docked into TMPS2, and the top 16 CCDs with LigScore2 higher than the cutoff (4.995) were screened out. MD simulations revealed a stable binding between these CCDs and TMPS2 due to the negative binding free energy. Lastly, SPR experiments validated the direct combination of narirutin, saikosaponin B1, and rutin with TMPS2. CONCLUSIONS: Specific active compounds including narirutin, saikosaponin B1, and rutin in CM recipes potentially target and inhibit TMPS2, probably exerting a therapeutic effect on COVID-19.

The microalgae-based wastewater treatment system coupled with Cerium: A potential way for energy saving and microalgae boost.

The microalgae-based system attracts more attention in wastewater treatment for high quality effluent, low carbon emission, and resource utilization. Light is the key factor for algae growth, but the light masking in sewage will cause low efficiency of the system. This study designed laboratory scale experiments with Chlorella to investigate the influence of cerium on the nutrient removal by algae wastewater treatment system under different light intensities. The best removal rates of NH4-N, TP, and COD were 72.43%, 88.87%, and 68.08% under 50 µmol/(m 2·s) light intensity and 1 mg/L Ce. Low concentration of Ce could activate protein synthesis, electron transfer, and antioxidase, while excessive Ce might cause toxicity which could be relieved by strong light for energy supply and further activating superoxide dismutase (SOD) and catalase (CAT). Comparing to other similar experiences, this system reached an equal or greater performance on nutrients removal with better efficiency in light utilization. It might provide a new idea for microalgae-based system development.

Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis.

Introduction: Recurrent implantation failure (RIF) is a frustrating challenge because the cause is unknown. The current study aims to identify differentially expressed genes (DEGs) in the endometrium on the basis of immune cell infiltration characteristics between RIF patients and healthy controls, as well as to investigate potential prognostic markers in RIF. Methods: GSE103465, and GSE111974 datasets from the Gene Expression Omnibus database were obtained to screen DEGs between RIF and control groups. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes Pathway analysis, Gene Set Enrichment Analysis, and Protein-protein interactions analysis were performed to investigate potential biological functions and signaling pathways. CIBERSORT was used to describe the level of immune infiltration in RIF, and flow cytometry was used to confirm the top two most abundant immune cells detected. Results: 122 downregulated and 66 upregulated DEGs were obtained between RIF and control groups. Six immune-related hub genes were discovered, which were involved in Wnt/-catenin signaling and Notch signaling as a result of our research. The ROC curves revealed that three of the six identified genes (AKT1, PSMB8, and PSMD10) had potential diagnostic values for RIF. Finally, we used cMap analysis to identify potential therapeutic or induced compounds for RIF, among which fulvestrant (estrogen receptor antagonist), bisindolylmaleimide-ix (CDK and PKC inhibitor), and JNK-9L (JNK inhibitor) were thought to influence the pathogenic process of RIF. Furthermore, our findings revealed the level of immune infiltration in RIF by highlighting three signaling pathways (Wnt/-catenin signaling, Notch signaling, and immune response) and three potential diagnostic DEGs (AKT1, PSMB8, and PSMD10). Conclusion: Importantly, our findings may contribute to the scientific basis for several potential therapeutic agents to improve endometrial receptivity.

An IGF1-expressing endometrial stromal cell population is associated with human decidualization.

BACKGROUND: Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization. RESULTS: We observed a unique IGF1+ stromal cell that may initiate decidualization by single-cell RNA sequencing. We found the IL1B+ stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell-cell communication for decidualization was developed. An aberrant ratio conversion of IGF1+ stromal cells to IGF1R+ stromal cells is observed in unexplained RIF patients. CONCLUSIONS: Overall, a unique subpopulation of IGF1+ stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.