Rickettsia symbionts spread via mixed mode transmission, increasing female fecundity and sex ratio shift by host hormone modulating.

Heritable symbionts are common among animals in nature, but the molecular mechanisms underpinning symbiont invasions of host populations have been elusive. In this study, we demonstrate the spread of Rickettsia in an invasive agricultural pest, the whitefly Bemisia tabaci Mediterranean (MED), across northeastern China from 2018 to 2023. Here, we show that the beneficial symbiont Rickettsia spreads by manipulating host hormone signals. Our analyses suggest that Rickettsia have been horizontally acquired by B. tabaci MED from another invasive whitefly B. tabaci Middle East-Asia Minor 1 during periods of coexistence. Rickettsia is transmitted maternally and horizontally from female B. tabaci MED individuals. Rickettsia infection enhances fecundity and results in female bias among whiteflies. Our findings reveal that Rickettsia infection stimulates juvenile hormone (JH) synthesis, in turn enhancing fecundity, copulation events, and the female ratio of the offspring. Consequently, Rickettsia infection results in increased whitefly fecundity and female bias by modulating the JH pathway. More female progeny facilitates the transmission of Rickettsia. This study illustrates that the spread of Rickettsia among invasive whiteflies in northeastern China is propelled by host hormone regulation. Such symbiont invasions lead to rapid physiological and molecular evolution in the host, influencing the biology and ecology of an invasive species.

circNEIL3 inhibits tumor metastasis through recruiting the E3 ubiquitin ligase Nedd4L to degrade YBX1.

Distant metastasis is a major contributor to cancer-related mortality. However, the role of circRNAs in this process remains unclear. Herein, we profiled the circRNA expression in a cohort of 68 colorectal carcinoma (CRC) primary tumors and their paired liver metastatic lesions. By overlapping with the TGFß-responsive circRNAs, circNEIL3 (hsa_circ_0001460) was identified as a TGFß-repressive and metastasis-related circRNA. Functionally, circNEIL3 effectively inhibited tumor metastasis in both and in vivo and in vivo models of various cancer types. Mechanistically, circNEIL3 exerts its metastasis-repressive function through its direct interaction with oncogenic protein, Y-box-binding protein 1 (YBX1), which consequently promotes the Nedd4L-mediated proteasomal degradation of YBX1. Importantly, circNEIL3 expression was negatively correlated to YBX1 protein level and metastatic tendency in CRC patient samples. Collectively, our findings indicate the YBX1-dependent antimetastatic function of circNEIL3 and highlight the potential of circNEIL3 as a biomarker and therapeutic option in cancer treatment.

Air-ventilated normothermic mechanical perfusion improves susceptibility to donation after circulatory death and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis.

End-ischemic normothermic mechanical perfusion (NMP) could provide a curative treatment to reduce cholestatic liver injury from donation after circulatory death (DCD) in donors. However, the underlying mechanism remains elusive. Our previous study demonstrated that air-ventilated NMP could improve functional recovery of DCD in a preclinical NMP rat model. Here, metabolomics analysis revealed that air-ventilated NMP alleviated DCD- and cold preservation-induced cholestatic liver injury, as shown by the elevated release of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and γ-glutamyl transferase (GGT) in the perfusate (p < .05) and the reduction in the levels of bile acid metabolites, including ω-muricholic acid, glycohyodeoxycholic acid, glycocholic acid, and glycochenodeoxycholate (GCDC) in the perfused livers (p < .05). In addition, the expression of the key bile acid metabolism enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is predominantly expressed in hepatocytes, was substantially elevated in the DCD rat liver, followed by air-ventilated NMP (p < .05), and in vitro, this increase was induced by decreased GCDC and hypoxia-reoxygenation in the hepatic cells HepG2 and L02 (p < .05). Knockdown of UGT1A1 in hepatic cells by siRNA aggravated hepatic injury caused by GCDC and hypoxia-reoxygenation, as indicated by the ALT and AST levels in the supernatant. Mechanistically, UGT1A1 is transcriptionally regulated by peroxisome proliferator-activator receptor-γ (PPAR-γ) under hypoxia-physoxia. Taken together, our data revealed that air-ventilated NMP could alleviate DCD- and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis. Based on the results from this study, air-ventilated NMP confers a promising approach for predicting and alleviating cholestatic liver injury through PPAR-γ/UGT1A1 axis.

A high-cholesterol zebrafish diet promotes hypercholesterolemia and fasting-associated liver steatosis.

Zebrafish are an ideal model organism to study lipid metabolism and to elucidate the molecular underpinnings of human lipid-associated disorders. Unlike murine models, to which various standardized high lipid diets such as a high-cholesterol diet (HCD) are available, there has yet to be a uniformly adopted zebrasfish HCD protocol. In this study, we have developed an improved HCD protocol and thoroughly tested its impact on zebrafish lipid deposition and lipoprotein regulation in a dose- and time- dependent manner. The diet stability, reproducibility, and fish palatability were also validated. Fish fed HCD developed hypercholesterolemia as indicated by significantly elevated ApoB-containing lipoproteins (ApoB-LP) and increased plasma levels of cholesterol and cholesterol esters. Feeding of the HCD to larvae for 8 days produced hepatic steatosis that become more stable and severer after 1 day of fasting and was associated with an opaque liver phenotype (dark under transmitted light). Unlike larvae, adult fish fed HCD for 14 days followed by a 3 day fast did not develop a stable fatty liver phenotype, though the fish had higher ApoB-LP levels in plasma and an up-regulated lipogenesis gene fasn in adipose tissue. In conclusion, our HCD zebrafish protocol represents an effective and reliable approach for studying the temporal characteristics of the physiological and biochemical responses to high levels of dietary cholesterol and provides insights into the mechanisms that may underlie fatty liver disease.

Advances in spatial transcriptomics and its applications in cancer research.

Malignant tumors have increasing morbidity and high mortality, and their occurrence and development is a complicate process. The development of sequencing technologies enabled us to gain a better understanding of the underlying genetic and molecular mechanisms in tumors. In recent years, the spatial transcriptomics sequencing technologies have been developed rapidly and allow the quantification and illustration of gene expression in the spatial context of tissues. Compared with the traditional transcriptomics technologies, spatial transcriptomics technologies not only detect gene expression levels in cells, but also inform the spatial location of genes within tissues, cell composition of biological tissues, and interaction between cells. Here we summarize the development of spatial transcriptomics technologies, spatial transcriptomics tools and its application in cancer research. We also discuss the limitations and challenges of current spatial transcriptomics approaches, as well as future development and prospects.

Foxm1-Mediated Transcriptional Inactivation of NLRP3 Inflammasome Promotes Immunosuppression in Cervical Cancer.

Foxm1 functions as an oncogene in multiple human malignancies, including cervical cancer. However, the potential of Foxm1 in the tumor microenvironment (TME) is still unknown. The purpose of the present study is to investigate the role of Foxm1 in CD8+ T cell anti-tumor immunity. RT-qPCR is conducted to calculate mRNA levels. JASPAR is used to predict the binding sites between Foxm1 and NLRP3. ChIP assay is performed to verify the occupancy of Foxm1 on the promoter of NLRP3. Modulatory relationship between Foxm1 and NLRP3 is verified by luciferase assay. In vivo assays are conducted to further verify the role of Foxm1/NLRP3 axis in cervical cancer. HE staining assay is applied for histological analysis. Flow cytometry is conducted to determine the functions of immune cells. We found that Foxm1 knockdown decreases tumor burden and suppresses tumor growth of cervical cancer. Foxm1 knock-down promotes the infiltration of CD8+ T cells. Foxm1 deficiency inhibits the exhaustion of CD8+ T cells and facilitates the maintenance of CD8+ effector and stem-like T cells. Moreover, Foxm1 transcriptionally inactivates NLRP3 and suppresses the expression of innate cytokines IL-1ß and IL-18. However, inhibition of NLRP3 inflammasome or neutralizing IL-1ß and IL-18 inhibits anti-tumor immunity and promoted tumor growth in Foxm1 deficiency in CD8+ T cells. In summary, targeting Foxm1 mediates the activation of NLRP3 inflammasome and stimulates CD8+ T cell anti-tumor immunity in cervical cancer.

Inorganic Oxide-Based "Hydrophobic-Hydrophilic-Hydrophobic" Separators Systems for Long-Life Zinc-Ion Batteries.

Hydrogen reduction reaction (HER) and corrosion limit the long-life cycle of zinc-ion batteries. However, hydrophilic separators are unable to prevent direct contact between water and electrodes, and hydrophobic separators have difficulty in transporting electrolytes. In this work, an inorganic oxide-based "hydrophobic-hydrophilic-hydrophobic" self-assembled separator system is proposed. The hydrophobic layer consists of a porous structure, which can isolate a large amount of free water to avoid HER and corrosion reactions, and can transport electrolyte by binding water. The middle hydrophilic layer acts as a storage layer consisting of the GF separator, storing large amounts of electrolyte for proper circulation. By using this structure separator, Zn||Zn symmetric cell achieve 2200 h stable cycle life at 5 mA cm-2 and 1mAh cm-2 and still shows a long life of 1800 h at 10 mA cm-2 and 1mAh cm-2. The assembled Zn||VO2 full cell displays high specific capacity and excellent long-term durability of 60.4% capacity retention after 1000 cycles at 2C. The assembled Zn||VO2 pouch full cell displays high specific capacity of 172.5mAh g-1 after 40 cycles at 0.5C. Changing the inorganic oxide materials, the hydrophobic-hydrophilic-hydrophobic structure of the separators still has excellent performance. This work provides a new idea for the engineering of water-based battery separators.

Progressive Ataxia due to de novo Missense Variants in the CACNA1A Gene.

The CACNA1A gene encodes the alpha-1A subunit of P/Q type voltage-gated calcium channel Cav2.1, which is associated with a broad clinical spectrum and variable symptomatology. While few patients with progressive ataxia caused by CACNA1A missense variants have been reported, here we report three unrelated Chinese patients with progressive ataxia due to de novo missense variants in the CACNA1A gene, including a novel pathogenic variant (c.4999C > G) and a previously reported pathogenic variant (c.4037G > A). Our findings and a systematic literature review show the unique phenotype of progressive ataxia caused by missense variants and enlarge the genetic and clinical spectrum of CACNA1A. This suggests that in addition to routine screening for dynamic mutations, screening for CACNA1A variants is important for clinicians facing patients with progressive ataxia.

The dynamic role of nucleoprotein SHCBP1 in the cancer cell cycle and its potential as a synergistic target for DNA-damaging agents in cancer therapy.

BACKGROUND: Malignant tumours seriously threaten human life and health, and effective treatments for cancer are still being explored. The ability of SHC SH2 domain-binding protein 1 (SHCBP1) to induce cell cycle disturbance and inhibit tumour growth has been increasingly studied, but its dynamic role in the tumour cell cycle and corresponding effects leading to mitotic catastrophe and DNA damage have rarely been studied. RESULTS: In this paper, we found that the nucleoprotein SHCBP1 exhibits dynamic spatiotemporal expression during the tumour cell cycle, and SHCBP1 knockdown slowed cell cycle progression by inducing spindle disorder, as reflected by premature mitotic entry and multipolar spindle formation. This dysfunction was caused by G2/M checkpoint impairment mediated by downregulated WEE1 kinase and NEK7 (a member of the mammalian NIMA-related kinase family) expression and upregulated centromere/kinetochore protein Zeste White 10 (ZW10) expression. Moreover, both in vivo and in vitro experiments confirmed the significant inhibitory effects of SHCBP1 knockdown on tumour growth. Based on these findings, SHCBP1 knockdown in combination with low-dose DNA-damaging agents had synergistic tumouricidal effects on tumour cells. In response to this treatment, tumour cells were forced into the mitotic phase with considerable unrepaired DNA lesions, inducing mitotic catastrophe. These synergistic effects were attributed not only to the abrogation of the G2/M checkpoint and disrupted spindle function but also to the impairment of the DNA damage repair system, as demonstrated by mass spectrometry-based proteomic and western blotting analyses. Consistently, patients with low SHCBP1 expression in tumour tissue were more sensitive to radiotherapy. However, SHCBP1 knockdown combined with tubulin-toxic drugs weakened the killing effect of the drugs on tumour cells, which may guide the choice of chemotherapeutic agents in clinical practice. CONCLUSION: In summary, we elucidated the role of the nucleoprotein SHCBP1 in tumour cell cycle progression and described a novel mechanism by which SHCBP1 regulates tumour progression and through which targeting SHCBP1 increases sensitivity to DNA-damaging agent therapy, indicating its potential as a cancer treatment.

Urinary exosomal mRNA as a biomarker for the diagnosis of bladder cancer.

OBJECTIVE: To study the diagnostic value of mRNA expression in urinary exocrine body in bladder cancer. METHODS: From February 2022 to December 2022, 60 patients diagnosed with bladder cancer by pathology in the Department of Urology, Affiliated Hospital of Chengde Medical University were selected as the case group. In total, 40 healthy subjects receiving physical examinations were selected as the control group. 100 mL of morning urine samples were collected from the subjects in both groups based on the same standard. Three subjects were randomly selected from each group. Urinary exosomes were extracted by differential ultracentrifugation. High-throughput sequencing (RNA-seq) was used to detect mRNA expression profiles in urinary exosomes and identify differentially expressed genes. Bioinformatic analysis was performed to predict major biological functions of differentially expressed genes and related signaling pathways. RT-PCR validated expression levels of differentially expressed genes in urinary exosomes between the two groups. ROC curves evaluated the diagnostic value of differential genes for bladder cancer. Spearman's correlation analysis determined correlations between differentially expressed genes and the occurrence of bladder cancer. ROC curves speculated the diagnostic value of using combined differentially expressed genes. RESULTS: Compared with normal subjects, there were 189 significantly differentially expressed genes in urinary exosomes of bladder cancer patients, including 33 up-regulated and 156 down-regulated. According to go and kyoto encyclopedia of genes and genomes (KEGG) analysis, the above differentially expressed genes may participate in the occurrence and development of bladder cancer through the MAPK pathway, PPAP signaling pathway, PI3K Akt signaling pathway and Hippo signaling pathway, affect protein and lipid metabolism, RNase activity, polysaccharide synthesis, signal transduction and other biological processes, and participate in cell proliferation, death, movement and adhesion, as well as cell differentiation and signal transduction. RT-PCR verified that the expression of tmeff1, SDPR, ACBD7, SCG2 and COL6A2 in the two groups of samples was statistically significant ( P  < 0.05). The ROC curve showed that the area under curve area under the curve of the five differential genes were 0.6934, 0.7746, 0.7239, 0.6396 and 0.6610, respectively. The sensitivity was 42.11%, 64.86%, 47.37%, 73.53% and 76.47%, and the specificity was 90%, 81.36%, 96.36%, 61.02% and 58.18%, respectively. Spearman correlation analysis showed that tmeff1, SDPR and acbd7 were associated with the occurrence of bladder cancer. The ROC curve of the combined diagnosis of the three and the two combined diagnoses suggested that the area under the curve of the combined diagnosis of SDPR and acbd7 was 0.7945, the sensitivity was 89.09%, and the specificity was 60.53%. CONCLUSION: The gene expression profile in urinary exosomes of bladder cancer patients has changed significantly, and the differential genes may play an important biological role in the occurrence and development of bladder cancer. The combined detection of urinary exosome SDPR and ACBD7 has a certain diagnostic value for bladder cancer.

Arachidonic acid metabolism CYP450 pathway is deregulated in hepatocellular carcinoma and associated with microvascular invasion.

Arachidonic acid metabolism plays a crucial role in the development and progression of inflammatory and metabolic liver diseases. However, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression of key genes involved in the arachidonic acid metabolism pathway in HCC using a combination of bioinformatics, proteomics and immunohistochemistry analyses. Through a comprehensive analysis of publicly available datasets, clinical HCC tissues, and tissue microarrays, we compared the expression of hepatic arachidonic acid metabolic genes. We observed significant downregulation of cytochrome P450 (CYP450) pathway genes at both the messenger RNA and protein levels in HCC tissues compared to normal liver tissues. Furthermore, we observed a strong correlation between the deregulation of the arachidonic acid metabolism CYP450 pathway and the pathological features and prognosis of HCC. Specifically, the expression of CYP2C8/9/18/19 was significantly correlated with pathological grade (r = -.484, p < .0001), vascular invasion (r = -.402, p < .0001), aspartate transaminase (r = -.246, p = .025), gamma-glutamyl transpeptidase (r = -.252, p = .022), alkaline phosphatase (r = -.342, p = .002), alpha-fetoprotein (r = -.311, p = .004) and carbohydrate antigen 19-9 (r = -.227, p = .047). Moreover, we discovered a significant association between CYP450 pathway activity and vascular invasion in HCC. Collectively, these data indicate that arachidonic acid CYP450 metabolic pathway deregulation is implicated in HCC progression and may be a potential predictive factor for early recurrence in patients with HCC.

Rechargeable Batteries for Grid Scale Energy Storage.

Ever-increasing global energy consumption has driven the development of renewable energy technologies to reduce greenhouse gas emissions and air pollution. Battery energy storage systems (BESS) with high electrochemical performance are critical for enabling renewable yet intermittent sources of energy such as solar and wind. In recent years, numerous new battery technologies have been achieved and showed great potential for grid scale energy storage (GSES) applications. However, their practical applications have been greatly impeded due to the gap between the breakthroughs achieved in research laboratories and the industrial applications. In addition, various complex applications call for different battery performances. Matching of diverse batteries to various applications is required to promote practical energy storage research achievement. This review provides in-depth discussion and comprehensive consideration in the battery research field for GSES. The overall requirements of battery technologies for practical applications with key parameters are systematically analyzed by generating standards and measures for GSES. We also discuss recent progress and existing challenges for some representative battery technologies with great promise for GSES, including metal-ion batteries, lead-acid batteries, molten-salt batteries, alkaline batteries, redox-flow batteries, metal-air batteries, and hydrogen-gas batteries. Moreover, we emphasize the importance of bringing emerging battery technologies from academia to industry. Our perspectives on the future development of batteries for GSES applications are provided.

Global, regional, and national burden of inflammatory bowel disease, 1990-2021: Insights from the global burden of disease 2021.

PURPOSE: The prevalence of inflammatory bowel disease (IBD) is on the rise worldwide. We utilizes data from the Global Burden of Diseases (GBD) 2021 to analyze the national-level burden of IBD, trends in disease incidence, and epidemiological characteristics. METHODS: Detailed information on IBD was gathered from 204 countries and territories spanning 1990 to 2021, sourced from the GBD 2021. Calculations were performed for incidence rates, mortality rates, disease-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs). These trends were analyzed based on region, nationality, age, gender, and World Bank income level stratifications. RESULTS: The global age-standardised incident rate (ASIR) of IBD increased from 4.22 per 100000 in 1990 to 4.45 per 100000 in 2021. However, the age-standardised mortality rate (ASMR) decreased from 0.60 per 100000 in 1990 to 0.52 per 100000 in 2021. Similarly, the age-standardised DALYs rate decreased from 21.55 per 100000 in 1990 to 18.07 per 100000 in 2021. Gender comparisons showed negligible differences in disease burden. The greatest increase in IBD-associated ASIR and ASMR occurred in World Bank upper-middle income region (EAPCs, 1.25) and World Bank high-income region (EAPCs, 1.00), respectively. Regionally, East Asia experienced the largest increase in ASIR (EAPCs, 2.89). Among 204 countries, China had the greatest increases in ASIR (EAPCs, 2.93), Netherlands had the highest ASMR in 2021 (2.21 per 100000). CONCLUSIONS: Global incidence rate of IBD have been increasing from 1990 to 2021, while the DALYs and mortality have been decreasing. The escalating incident rates in select Asian regions deserves further attention.

Efficacy and safety of agomelatine in epilepsy patients with sleep and mood disorders: An observational, retrospective cohort study.

OBJECTIVE: To evaluate the therapeutic efficacy and safety of agomelatine for treating the sleep and mood disorders in epilepsy patients. METHODS: Retrospective data were derived from 113 epilepsy patients for at least 8 weeks. All the subjects were divided into two groups, one was treated with agomelatine, the other was treated with escitalopram. Their depression and anxiety states were assessed by Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Scales. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The HAMA, HAMD and PSQI scores in both groups significantly declined after the treatments with agomelatine and escitalopram. However, the agomelatine group exhibited greater improvement in terms of HAMA and PSQI scores compared to the escitalopram group. No severe adverse events were observed in agomelatine group. SIGNIFICANCE: Agomelatine performed better in HAMA and PSQI scores compared to escitalopram, where no significant increase in seizure frequency or side effects were observed. Possibly, agomelatine presents a promising therapeutic option for treating the sleep or mood disorders in epilepsy patients.

Two-dimensional quadratic Weyl points, nodal loops, and spin-orbit Dirac points in PtS, PtSe, and PtTe monolayers.

Topological quasiparticles have garnered significant research attention in condensed matter physics. However, they are exceedingly rare in two-dimensional systems, particularly those hosting unconventional topological quasiparticles. In this work, employing first-principles calculations and symmetry analysis, we demonstrate that PtS, PtSe, and PtTe monolayers serve as high-quality two-dimensional topological semimetal materials. These materials exhibit multiple types of topological quasiparticles around the Fermi level in the absence of spin-orbit coupling, such as conventional linear Weyl points and unconventional quadratic Weyl points in the PtS monolayer, as well as nodal loops in PtSe and PtTe monolayers. When spin-orbit coupling (SOC) is introduced, a tiny gap opens, transforming the systems into quantum spin hall insulators. Simultaneously, three spin-orbit Dirac points, robust against SOC, appear at the X, Y, and M points. We illustrate the symmetry protection, low-energy effective model, and edge states of these topological states. Our work provides an excellent material platform for studying novel two-dimensional topological quasiparticles and topological insulators.

A nanozyme-functionalized bilayer hydrogel scaffold for modulating the inflammatory microenvironment to promote osteochondral regeneration.

BACKGROUND: The incidence of osteochondral defects caused by trauma, arthritis or tumours is increasing annually, but progress has not been made in terms of treatment methods. Due to the heterogeneous structure and biological characteristics of cartilage and subchondral bone, the integration of osteochondral repair is still a challenge. RESULTS: In the present study, a novel bilayer hydrogel scaffold was designed based on anatomical characteristics to imitate superficial cartilage and subchondral bone. The scaffold showed favourable biocompatibility, and the addition of an antioxidant nanozyme (LiMn2O4) promoted reactive oxygen species (ROS) scavenging by upregulating antioxidant proteins. The cartilage layer effectively protects against chondrocyte degradation in the inflammatory microenvironment. Subchondral bionic hydrogel scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) by regulating the AMPK pathway in vitro. Finally, an in vivo rat preclinical osteochondral defect model confirmed that the bilayer hydrogel scaffold efficiently promoted cartilage and subchondral bone regeneration. CONCLUSIONS: In general, our biomimetic hydrogel scaffold with the ability to regulate the inflammatory microenvironment can effectively repair osteochondral defects. This strategy provides a promising method for regenerating tissues with heterogeneous structures and biological characteristics.

Impact of human serum albumin level on symptomatic cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To investigate the impact of human serum albumin (HSA) levels on symptomatic cerebral vasospasm (SCVS) in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We retrospectively reviewed the medical records. SCVS was defined as the development of a new neurological deterioration when the cause was considered to be ischemia attributable to vasospasm after other possible causes of worsening had been excluded. The aSAH patients were divided into two groups: those with SCVS (group 1) and those without SCVS (group 2). The HSA level data on the 1st, 2nd, and 3rd day after admission was collected. Multivariate logistical regression and receiver operating characteristic (ROC) analysis were performed to evaluate the ability of HSA level to predict the development of SCVS. RESULTS: A total of 270 patients were included in our study, of which 74 (27.4%) developed SCVS. The average and lowest HSA levels were lower in group 1 (P < 0.001). In univariate logistic regression, white blood cell count, neutrophil count, and average and lowest HSA levels were associated with SCVS. After adjustment for age, CT Fisher grade, Hunt-Hess grade, and WFNS grade, both the average and lowest HSA levels remained independent predictors of SCVS (P < 0.001). The CT Fisher grade was confirmed to be an independent predictor of SCVS across each model. ROC analysis revealed that the lowest HSA level was a better predictor for SCVS than average HSA level and CT Fisher grade. CONCLUSION: Clinicians are encouraged to measure HSA levels for the first 3 days after admission to predict the occurrence of SCVS after aSAH.

Identification and Characterization of Chemical Constituents from Ammopiptanthus nanus Stem and Their Metabolites in Rats by UHPLC-Q-TOF-MS/MS.

Ammopiptanthus nanus as a Kirgiz medicine is widely used for the treatment of frostbite and chronic rheumatoid arthritis. However, due to a lack of systematic research on the chemical components of A. nanus and their metabolites, the bioactive components in it remain unclear. Herein, a reliable strategy based on UHPLC-Q-TOF-MS/MS was established to comprehensively analyze the chemical components and their metabolites in vivo. In total, 59 compounds were identified from A. nanus stem extract, among which 14 isoflavones, 10 isoprenylated isoflavones, 4 polyhydroxy flavonoids, 9 alkaloids and 1 polyol were characterized for the first time. After oral administration of A. nanus stem extract, 30 prototype constituents and 28 metabolites (12 phase I and 16 phase II metabolites) were speculated on and identified in rat serum, urine and feces. Furthermore, the metabolic pathways of the chemical components were systematically analyzed and proposed. In conclusion, the chemical components from A. nanus stem and their metabolites in vivo were first studied, which may provide useful chemical information for further study on the effective material basis and pharmacological mechanism of A. nanus.

Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function.

BACKGROUND: Endometrial fibrosis, a significant characteristic of intrauterine adhesion (IUA), is caused by the excessive differentiation and activation of endometrial stromal cells (ESCs). Glutaminolysis is the metabolic process of glutamine (Gln), which has been implicated in multiple types of organ fibrosis. So far, little is known about whether glutaminolysis plays a role in endometrial fibrosis. METHODS: The activation model of ESCs was constructed by TGF-ß1, followed by RNA-sequencing analysis. Changes in glutaminase1 (GLS1) expression at RNA and protein levels in activated ESCs were verified experimentally. Human IUA samples were collected to verify GLS1 expression in endometrial fibrosis. GLS1 inhibitor and glutamine deprivation were applied to ESCs models to investigate the biological functions and mechanisms of glutaminolysis in ESCs activation. The IUA mice model was established to explore the effect of glutaminolysis inhibition on endometrial fibrosis. RESULTS: We found that GLS1 expression was significantly increased in activated ESCs models and fibrotic endometrium. Glutaminolysis inhibition by GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES or glutamine deprivation treatment suppressed the expression of two fibrotic markers, α-SMA and collagen I, as well as the mitochondrial function and mTORC1 signaling in ESCs. Furthermore, inhibition of the mTORC1 signaling pathway by rapamycin suppressed ESCs activation. In IUA mice models, BPTES treatment significantly ameliorated endometrial fibrosis and improved pregnancy outcomes. CONCLUSION: Glutaminolysis and glutaminolysis-associated mTOR signaling play a role in the activation of ESCs and the pathogenesis of endometrial fibrosis through regulating mitochondrial function. Glutaminolysis inhibition suppresses the activation of ESCs, which might be a novel therapeutic strategy for IUA.

A novel pencil graphite electrode modified with an iron-based conductive metal-organic framework exhibited good ability in simultaneous sensing bisphenol A and bisphenol S.

Bisphenol A (BPA) and its substitute bisphenol S (BPS) are desirable materials widely used in manufacturing plastic products but can pose carcinogenic risks to humans. A new conductive iron-based metal-organic framework (Fe-HHTP)-modified pencil graphite electrode (PGE) for electrochemically sensing BPA and BPS was prepared and fully characterized by SEM, TEM, FT-IR, XRD, and XPS. Results showed that the optimal conditions for preparing Fe-HHTP/PGE were a pH of 6.5, a Fe-HHTP concentration of 2 mg·mL-1, a deposition potential of 0 V, and a deposition time of 100 s. The Fe-HHTP/PGE prepared under such conditions harbored a significant electrocatalytic activity with a detection limit of 0.8 nM for BPA and 1.7 nM for BPS (S/N = 3). Correspondingly, the electrochemical response current was linearly correlated to BPA and BPS, ranging from 0.01 to 100 µM. Fe-HHTP/PGE also obtained satisfactory recoveries by 93.8-102.1% and 96.0-101.3% for detecting BPA and BPS in plastic food packaging samples. Our work has provided a novel electrochemical tool to simultaneously detect BPA and BPS in food packaging samples and environmental matrixes.