Exploring the Constituents and Mechanisms of Polygonum multiflorum Thunb. in Mitigating Ischemic Stroke: A Network Pharmacology and Molecular Docking Study.

Polygonum multiflorum Thunb. (PMT) has shown promise in exerting cerebrovascular protective effects, and its potential for treating ischemic stroke (IS) has garnered attention. However, the lack of clarity regarding its chemical constituents and mechanisms has significantly hindered its clinical application. In this study, we employed network pharmacology and molecular docking techniques for the first time to elucidate the potential compounds and targets of PMT in treating IS. The databases CTD, DrugBank, DisGeNET, GeneCards, OMIM, TTD, PGKB, NCBI, TCMIP, CNKI, PubMed, ZINC, STITCH, BATMAN, ETCM and Swiss provided information on targets related to IS and components of PMT, along with their associated targets. We constructed "compound-target" and protein-protein interaction (PPI) networks sourced from the STRING database using the Cytoscape software. Gene Ontology (GO) enrichment analysis and KEGG pathway analysis were conducted using the DAVID database. Molecular docking between core targets and active compounds was conducted using Autodock4 software. Experiments were performed in an oxygen-glucose deprivation and reperfusion (OGD/R) model to validate the anti-IS activity of compounds isolated from PMT preliminarily. Network pharmacological analysis revealed 16 core compounds, including resveratrol, polydatin, TSG, ω- hydroxyemodin, emodin anthrone, tricin, moupinamide, and others, along with 11 high-degree targets, such as PTGS1, PTGS2, ADORA1, ADORA2, CA1, EGFR, ESR1, ESR2, SRC, MMP3 and MMP9. GO and KEGG enrichment analyses revealed the involvement of HIF-1, Akt signaling pathway and energy metabolism-related signaling pathways. Molecular docking results emphasized eight key compounds and confirmed their interactions with corresponding targets. In vitro OGD/R model experiments identified TSG and tricin as the primary active substances within PMT for its anti-stroke activity. This study contributes new insights into the potential development of PMT for stroke prevention and treatment.

mmu-miR-374b-5p modulated inflammatory factors via downregulation of C/EBP ß/NF-κB signaling in Kupffer cells during Echinococcus multilocularis infection.

BACKGROUND: Alveolar echinococcosis (AE) is an important infectious disease caused by the metacestode larvae of Echinococcus multilocularis, seriously threatening global public health security. Kupffer cells (KCs) play important roles in liver inflammatory response. However, their role in hepatic alveolar echinococcosis has not yet been fully elucidated. METHODS: In this study, qRT-PCR was used to detect the expression level of miR-374b-5p in KCs. The target gene of miR-374b-5p was identified through luciferase reporter assays and loss of function and gains. Critical genes involved in NFκB signaling pathway were analyzed by qRT-PCR and western blot. RESULTS: This study reported that miR-374b-5p was significantly upregulated in KCs during E. multilocularis infection and further showed that miR-374b-5p was able to bind to the 3'-UTR of the C/EBP ß gene and suppressed its expression. The expression levels of NF-κBp65, p-NF-κBp65 and pro-inflammatory factors including iNOS, TNFα and IL6 were attenuated after overexpression of miR-374b-5p while enhanced after suppression of miR-374b-5p. However, the Arg1 expression level was promoted after overexpression of miR-374b-5p while suppressed after downregulation of miR-374b-5p. Additionally, increased protein levels of NF-κBp65 and p-NF-κBp65 were found in the C/EBP ß-overexpressed KCs. CONCLUSIONS: These results demonstrated that miR-374b-5p probably regulated the expression of inflammatory factors via C/EBP ß/NF-κB signaling. This finding is helpful to explore the mechanism of inflammation regulation during E. multilocularis infection.

High efficient preparation of low molecular weight galactomannan from Leucaena leucocephala galactomannan through the combination of hydrogen peroxide and oxalic acid.

Researchers have always been interested in polysaccharide degradation because of the increased biological activity and usability following degradation. In this work, low molecular weight galactomannan (LMW-GM) was produced through the degradation of galactomannan by H2O2 and oxalic acid (OA). The optimal reaction conditions were found by conducting the response surface optimization experiment based on single-factor experiment and kinetics analysis. Under these conditions, the LMW-GM yield was 69.48 ± 1.02 %. Ultimately, an analysis of the degradation process revealed that OA attacked GM indiscriminately, and H2O2 has a stronger effect on the removal of branched chains while degrading GM. Hence, the degradation steps were rearranged as H2O2 was added 20 min before OA at a constant total time. The LMW-GM yield was successfully increased to 76.49 ± 1.27 %. The goal of this work is hopefully to give a theoretical foundation for the low-cost preparation and industrial production of the degradation of galactomannan.

The deubiquitinase OTUB2 promotes cervical cancer growth through stabilizing FOXM1.

OBJECTIVES: Ovarian tumor (OTU) domain-containing ubiquitin aldehyde-binding protein Otubain2 (OTUB2) is an important cysteine protease with deubiquitinase activity in the OTU family. However, the role of OTUB2 in cervical cancer (CC) has not been investigated. METHODS: OTUB2 expression was analyzed employing the CC data from The Cancer Genome Atlas (TCGA) database. Western blot and qRT-PCR analysis were performed to identify OTUB2 expression in CC. The oncogenic function of OTUB2 was identified through a series of in vitro and in vivo experiments. Tandem Mass Tag™ Quantitative Proteomics examination was used to identify potential targets of OTUB2. RESULTS: OTUB2 was overexpressed in CC and was related to poor prognosis of patients. In our in-house cohort, we also showed that OTUB2 was overexpressed in tumor tissues of CC compared to para-tumor. Knockdown of OTUB2 suppressed CC cell growth whereas OTUB2 upregulation fostered the proliferation of cancer cells. Forkhead box M1 (FOXM1) was found to be a target of OTUB2. FOXM1 can be positively regulated by OTUB2 in CC cells. In human CC tissues, protein level of FOXM1 was positively correlated with OTUB2. FOXM1 was found to play a critical role in OTUB2-mediated CC cell growth. Mechanistically, OTUB2 could bind FOXM1 and deubiquitinate FOXM1 to stabilize it. CONCLUSION: OTUB2 promotes CC progression through deubiquitinating and stabilizing FOXM1.

Practice guideline on ovarian tissue cryopreservation and transplantation in the prevention and treatment of iatrogenic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.

Mediation effect of self-efficacy on the relationship between perceived social support and resilience in caregivers of patients with first-stroke in China: a cross-sectional survey.

BACKGROUND: Self-efficacy, perceived social support, and resilience in caregivers of first-stroke patients are closely related, while the interaction mechanism remains unclear. This research explores the mediation effect of self-efficacy in the relationship between perceived social support and resilience in caregivers of first-stroke patients in China. METHODS: Convenience sampling was designed and used to recruit participants from the General Hospital of Northern Theater in Shenyang, Liaoning Province, China, from February to October 2022, in which 207 self-reported participants completed the Connor-Davidson Resilience Scale (CD-RISC), Multidimensional Scale of Perceived Social Support (MSPSS) and General Self Efficacy Scale (GSES). In addition, the mediation effect of self-efficacy between perceived social support and resilience was determined by the PROCESS macro for SPSS. RESULT: Among the 207 caregivers of patients with first-stroke, the mean CD-RISC, MSPPS and GSES scores were (72.17 ± 11.28), (71.17 ± 8.99), and (29.64 ± 5.03) respectively. Caregivers' self-efficacy was positively correlated with perceived social support (r = 0.439, p < 0.01) and resilience (r = 0.730, p < 0.01). Self-efficacy served a mediation function partially between perceived social support and resilience, whose effect accounted for 52.90% of the total. CONCLUSION: Both simple and mediation roles of perceived social support and self-efficacy are established in the relationship of resilience among caregivers of first-stroke patients. Positive social support and self-efficacy are two important targets for future interventional studies, and interventions on them may synergistically improve resilience. Hence, the nurses and community workers should correctly evaluate social support and self-efficacy, confirm the health education requirements, and implement counseling intervention to protect and improve the health of first-stroke patients and their families.

p-Toluenesulfonic acid enhanced neutral deep eutectic solvent pretreatment of soybean straw for efficient lignin removal and enzymatic hydrolysis.

Deep eutectic solvent (DES) is a newly-emerged green solvent for efficient pretreatment of lignocellulosic feedstock. To improve the component fractionation performance of neutral DES, p-toluenesulfonic acid (p-TsOH) was employed as catalyst to form a novel ternary DES with benzyltriethylammonium chloride (TEBAC) and glycerol (Gly) for pretreatment of soybean straw. Under the optimum reaction conditions (TEBAC:Gly = 1:12, 1.6 wt% p-TsOH and reacted at 90 °C for 160 min), the lignin and hemicellulose removal from soybean straw were amounted to 92.0 % and 88.2 %, respectively. The pretreated substrate showed satisfactory enzymatic hydrolysis performance, as the glucose and reducing sugar concentrations reached 37.3 g/L and 42.3 g/L, respectively, after 72 h saccharification under the action of cellulase with a relatively low enzyme loading of 10 FPU/g cellulose.This method provides an efficient and mild route for utilization of agricultural waste and production of platform monosaccharides.

Nervous necrosis virus induced vacuolization is a Rab5- and actin-dependent process.

Cytoplasmic vacuolization is commonly induced by bacteria and viruses, reflecting the complex interactions between pathogens and the host. However, their characteristics and formation remain unclear. Nervous necrosis virus (NNV) infects more than 100 global fish species, causing enormous economic losses. Vacuolization is a hallmark of NNV infection in host cells, but remains a mystery. In this study, we developed a simple aptamer labelling technique to identify red-spotted grouper NNV (RGNNV) particles in fixed and live cells to explore RGNNV-induced vacuolization. We observed that RGNNV-induced vacuolization was positively associated with the infection time and virus uptake. During infection, most RGNNV particles, as well as viral genes, colocalized with vacuoles, but not giant vacuoles > 3 µm in diameter. Although the capsid protein (CP) is the only structural protein of RGNNV, its overexpression did not induce vacuolization, suggesting that vacuole formation probably requires virus entry and replication. Given that small Rab proteins and the cytoskeleton are key factors in regulating cellular vesicles, we further investigated their roles in RGNNV-induced vacuolization. Using live cell imaging, Rab5, a marker of early endosomes, was continuously located in vacuoles bearing RGNNV during giant vacuole formation. Rab5 is required for vacuole formation and interacts with CP according to siRNA interference and Co-IP analysis. Furthermore, actin formed distinct rings around small vacuoles, while vacuoles were located near microtubules. Actin, but not microtubules, plays an important role in vacuole formation using chemical inhibitors. These results provide valuable insights into the pathogenesis and control of RGNNV infections.

The Effect of Paternal Co-Parenting on Preschool Children's Problem Behaviors: The Chain-Mediating Role of Maternal Parenting Burnout and Psychological Aggression.

Objective: With the social changes, a growing number of women have joined the workforce, leading to a shift in the traditional roles of child-rearing. There has been a growing focus on the significance of fathers' roles in child development, particularly the influence of fathers on children's problematic behaviors, making it an increasingly prominent issue. However, there is limited understanding regarding the potential mechanisms through which fathers may exert influence on children's problem behaviors. To address this gap, this study sought to investigate the link between paternal co-parenting and preschool children's problem behaviors, and the mediating effects of maternal parenting burnout and psychological aggression. Methods: This study used the Personal Information Form and four scales to administer questionnaires to 1164 mothers of preschool children (Mage = 4.26 ± 0.85) in Guangdong Province, China. The collected data underwent processing and analysis using SPSS 22.0. Results: Paternal co-parenting demonstrated a significantly positive correlation with problem behaviors among preschool children. The impact of paternal co-parenting on children's problem behaviors was mediated by maternal parenting burnout, maternal psychological aggression, and the combined effect of maternal parenting burnout and psychological aggression. Conclusion: Maternal parenting burnout and maternal psychological aggression play a sequential mediating role between paternal co-parenting and problem behaviors among preschool children. This study revealed the internal mechanism through which paternal co-parenting influenced problem behaviors exhibited by children. It provides some evidence to support the important role of fathers in child development, and provides a reference for policymakers and educators to develop interventions for children's problem behaviors.

The association between trouble sleeping and obesity among the U.S. elderly from NHANES 2011-2014: A moderated mediation model of depressive symptoms and cognitive function.

BACKGROUND: Studies have shown a close association between trouble sleeping and obesity in older adults. However, no studies have explored the underlying mechanism of this relationship. The present study was designed to evaluate the roles of depressive symptoms and cognitive function in the association between trouble sleeping and obesity in older American adults. METHODS: A cross-sectional study with 2575 participants (≥60 years old) in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 was used for analysis. Obesity, depressive symptoms, and cognitive function (including Established Consortium for Word Learning in Alzheimer's Disease (CERAD-WL) (immediate learning and recall and delayed recall), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST)) were objectively measured, and trouble sleeping was assessed using a self-reported questionnaire. The moderated mediation analysis was conducted by Hayes' PROCESS macro. RESULTS: Trouble sleeping was positively associated with obesity among older adults. Depressive symptoms partially and indirectly mediated this association, and DSST moderated the association between trouble sleeping and depressive symptoms. Trouble sleeping had a lower impact on depressive symptoms in older adults with higher cognitive function. LIMITATIONS: The cross-sectional design prevents making causal inferences, and part of self-reported information was not objective enough. CONCLUSION: Cognitive function moderated the mediation of depressive symptoms on the indirect, positive association between trouble sleeping and obesity; hence, incorporating methods to strengthen cognitive function and alleviate depressive symptoms may help weak the link between trouble sleeping and obesity among older adults.

Dissecting the early and late endosomal pathways of Singapore grouper iridovirus by single-particle tracking in living cells.

Iridoviruses are large DNA viruses that infect a wide range of invertebrates and lower vertebrates, causing serious threats to ecological security and aquaculture industry worldwide. However, the mechanisms underlying intracellular transport of iridovirus remain unknown. In this study, the transport of Singapore grouper iridovirus (SGIV) in early endosomes (EEs) and late endosomes (LEs) was explored by single-particle tracking technology. SGIV employs EEs to move rapidly from the cell membrane to the nucleus, and this long-range transport is divided into "slow-fast-slow" stages. SGIV within LEs mainly underwent oscillatory movements near the nucleus. Furthermore, SGIV entered newly formed EEs and LEs, respectively, possibly based on the interaction between the viral major capsid protein and Rab5/Rab7. Importantly, interruption of EEs and LEs by the dominant negative mutants of Rab5 and Rab7 significantly inhibited the movement of SGIV, suggesting the important roles of Rab5 and Rab7 in virus transport. In addition, it seems that SGIV needs to enter clathrin-coated vesicles to move from actin to microtubules before EEs carry the virus moving along microtubules. Together, our results for the first time provide a model whereby iridovirus transport depending on EEs and LEs, helping to clarify the mechanism underlying iridovirus infection, and provide a convenient tactic to investigate the dynamic infection of large DNA virus.

Natural isoflavone glabridin targets PI3Kγ as an adjuvant to increase the sensitivity of MDA-MB-231 to tamoxifen and DU145 to paclitaxel.

Glabridin is a natural isoflavone with estrogen receptor agonism and significant anti-tumor activity. Additionally, glabridin has a regulation effect on PI3K/AKT/mTOR pathway, but its exact target remains unclear. In this study, we evaluated the antitumor activity of glabridin against breast cancer and prostate cancer cells, and further clarified its targeting to PI3K. We found that glabridin could significantly inhibit the cell viability of human breast cancer and prostate cancer cell lines. It induced caspase activation cascade and cell apoptosis through decreasing the mitochondrial transmembrane potential and increasing the intracellular reactive oxygen species (ROS). Moreover, glabridin could attenuate epithelial-mesenchymal transition (EMT) progression by inhibiting cell migration. PharmMapper calculation showed that PI3Kγ might be the most potential target protein because of the highest Normal Fit score (0.9735) and z'-score (0.9797). Molecular docking and bio-layer interferometry (BLI) analysis further demonstrated the PI3Kγ targeting of glabridin. In vivo experiments showed that glabridin can effectively inhibit the tumor growth of breast cancer xenograft model, and does not show obvious hepatorenal toxicity. Moreover, glabridin could effectively promote the anti-proliferation and pro-apoptotic effects of tamoxifen on MDA-MB-231 cell and taxol on DU145 cell. Elucidating the targeting of glabridin to PI3K may lay a theoretical foundation for the structural derivatization of glabridin, which is expected to greatly promote the application and development of glabridin in the field of cancer therapy.

Targeting progranulin alleviated silica particles-induced pulmonary inflammation and fibrosis via decreasing Il-6 and Tgf-ß1/Smad.

Long term exposure to silica particles leads to various diseases, among which silicosis is of great concern. Silicosis is an interstitial lung disease caused by inhalation of silica particles in production environments. However, the mechanisms underlying silicosis remains unclear. Our previous studies revealed that progranulin (Pgrn) promoted the expression of pro-inflammatory factors in alveolar macrophages treated with silica particles and the secretion of extracellular matrix of pulmonary fibroblasts. Nevertheless, the role of Pgrn in silica particles-induced silicosis in vivo was unknown. This study found that silica particles increased Pgrn expression in silicosis patients. Pgrn deficiency reduced lung inflammation and fibrosis in silica particles-induced silicosis mouse models. Subsequently, based on transcriptional sequencing and interleukin (Il) -6 knockout mouse models, results demonstrated that Pgrn deficiency might decrease silicosis inflammation by reducing the production of Il-6, thereby modulating pulmonary fibrosis in the early stage of silicosis mouse models. Furthermore, another mechanism through which Pgrn deficiency reduced fibrosis in silicosis mouse models was the regulation of the transforming growth factor (Tgf) -ß1/Smad signaling pathway. Conclusively, Pgrn contributed to silicosis inflammation and fibrosis induced by silica particles, indicating that Pgrn could be a promising therapeutic target.

Pomegranate juice-containing serum inhibits migration of hepatocellular carcinoma cells and promotes apoptosis by induction of mitochondrial dysfunction.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with an insidious onset and poor prognosis. Pomegranate is a fruit rich in many natural products with anti-cancer potential; however, its direct biological effects are difficult to evaluate in vitro because of changes in its active components after absorption and metabolism. This study was conducted to prepare pomegranate juice-containing serum (PJ serum) by gavage of pomegranate juice (PJ) in rats and to collect serum. The aim was to investigate the components and the effects of PJ serum on HCC cells by serum pharmacology. 56 compounds were identified in the PJ serum, including 6 prototype components. PJ serum selectively inhibited HCC cells proliferation and migration, and it promoted apoptosis of HCC cells without affecting LO2 cells activity. Furthermore, PJ serum reduced the mitochondrial membrane potential and increased the calcium ion concentration in HCC cells. Mechanistically, PJ serum up-regulated the expression of the Bax family, Caspases and TIMP2/MMP2, and down-regulated the expression of MMP9. This study revealed that PJ serum inhibited HCC cell migration by regulating the TIMP2/MMP2 balance and MMP9 expression and promoted HCC cell apoptosis by inducing mitochondrial dysfunction and causing a Caspase cascade. The polyphenols and flavonoids in PJ may be important components responsible for its anti-HCC activity after metabolism.

Soybean 40S Ribosomal Protein S8 (GmRPS8) Interacts with 6K1 Protein and Contributes to Soybean Susceptibility to Soybean Mosaic Virus.

Soybean mosaic virus (SMV), a member of Potyvirus, is the most destructive and widespread viral disease in soybean production. Our earlier studies identified a soybean 40S ribosomal protein S8 (GmRPS8) using the 6K1 protein of SMV as the bait to screen a soybean cDNA library. The present study aims to identify the interactions between GmRPS8 and SMV and characterize the role of GmRPS8 in SMV infection in soybean. Expression analysis showed higher SMV-induced GmRPS8 expression levels in a susceptible soybean cultivar when compared with a resistant cultivar, suggesting that GmRPS8 was involved in the response to SMV in soybean. Subcellular localization showed that GmRPS8 was localized in the nucleus. Moreover, the yeast two-hybrid (Y2H) experiments showed that GmRPS8 only interacted with 6K1 among the eleven proteins encoded by SMV. The interaction between GmRPS8 and 6K1 was further verified by a bimolecular fluorescence complementation (BiFC) assay, and the interaction was localized in the nucleus. Furthermore, knockdown of GmRPS8 by a virus-induced gene silencing (VIGS) system retarded the growth and development of soybeans and inhibited the accumulation of SMV in soybeans. Together, these results showed that GmRPS8 interacts with 6K1 and contributes to soybean susceptibility to SMV. Our findings provide new insights for understanding the role of GmRPS8 in the SMV infection cycle, which could help reveal potyviral replication mechanisms.

Rab32, a novel Rab small GTPase from orange-spotted grouper, Epinephelus coioides involved in SGIV infection.

Rab32 is a member of the Rab GTPase family that is involved in membrane trafficking and immune response, which are crucial for controlling pathogen infection. However, the role of Rab32 in virus infection is not well understood. In this study, we focused on the regulation of Rab32 on virus infection and the host immunity in orange-spotted grouper, Epinephelus coioides. EcRab32 encoded a 213-amino acid polypeptide, which shared a high sequence identity with other Rab32 proteins from fishes to mammals. In healthy orange-spotted grouper, the mRNA of EcRab32 was expressed in all the detected tissues, with the more expression levels in the head kidney, liver and gill. Upon SGIV infection, the expression of EcRab32 was significantly up-regulated in vitro, indicating its potential role in viral infection. EcRab32 was observed to be distributed in the cytoplasm as punctate and vesicle-like structures. EcRab32 overexpression was found to notably inhibit SGIV infection, while the interruption of EcRab32 significantly promoted SGIV infection. In addition, using single particle imaging analysis, we found that EcRab32 overexpression prominently reduced the attachment and internalization of SGIV particles. Furthermore, the results demonstrated that EcRab32 played a positive role in regulating the interferon immune and inflammatory responses. Taken together, these findings indicated that EcRab32 influenced SGIV infection by regulating the host immune response, providing an overall understanding of the interplay between the Rab32 and innate immunity.

Rosa Roxburghii Tratt Fruit Extract Prevents Dss-Induced Ulcerative Colitis in Mice by Modulating the Gut Microbiota and the IL-17 Signaling Pathway.

Ulcerative colitis (UC) is a non-specific inflammatory bowel illness characterized by intestinal mucosal barrier degradation, inflammation, oxidative damage, and gut microbiota imbalances. Rosa roxburghii Tratt Fruit extract (RRTE) was extracted from Rosa roxburghii Tratt fruit, exhibiting an excellent prevention effect against UC; RRTE could prevent the damage of DSS-induced human normal colonic epithelial (NCM 460) cells, especially in cell viability and morphology, and oxidative damage. Additionally, in UC mice, RRTE could limit the intestinal mucosal barrier by increasing the expression of intestinal tight junction proteins and mucin, reducing inflammation and oxidative damage in colon tissue. More importantly, RRTE can increase the abundance of beneficial bacteria to regulate gut microbiota such as Ruminococcus, Turicibacter, and Parabacteroides, and reduce the abundance of harmful bacteria such as Staphylococcus and Shigella. Furthermore, transcriptomics of colonic mucosal findings point out that the beneficial effect of RRTE on UC could be attributed to the modulation of inflammatory responses such as the IL-17 and TNF signaling pathways. The qPCR results confirm that RRTE did involve the regulation of several genes in the IL-17 signaling pathway. In conclusion, RRTE could prevent DSS-induced damage both in vitro and in vivo.

Flexo-/Piezoelectric Polarization Boosting Exciton Dissociation in Curved Two-Dimensional Carbon Nitride Photocatalyst.

Two-dimensional (2D) carbon nitride (CN) materials have received tremendous attention as photocatalysts for clean energy and environmental treatment. However, the photocatalytic efficiency of CN is constrained by the high exciton binding energy and sluggish charge kinetics due to weak dielectric screening, impeding the overall process. Herein, localized flexo-/piezoelectric polarization is introduced via strain engineering, boosting exciton dissociation and promoting charge separation to enhance the multielectron photocatalytic process. Consequently, the exciton binding energy of polarized CN is reduced from 52 to 34 meV, and the hydrogen evolution yield increased by 2.9 times compared to that of the pristine CN. For other photocatalytic reactions (e.g., H2O2 production), the polarized CN also maintained a 2.1-fold increase compared to the pristine CN. This strategy of inducing localized polarization via strain engineering provides new insights for boosting photocatalytic reactions involving electrons.

Identification of a prognostic model based on immune and hypoxia-related gene expressions in cervical cancer.

BACKGROUND: Tumour immune microenvironment (TIME) has long been a key direction of tumour research. Understanding the occurrence, metastasis and other processes of cervical cancer (CC) is of great significance in the diagnosis and prognosis of tumours. METHODS: Here, this study applied the univariate Cox regression model to determine the prognostic association of immune and hypoxia signature genes in CC, and used Least Absolute Shrinkage and Selection Operator (LASSO) Cox method to build immune and hypoxia related risk score model to uncover the immune signature of the TIME of CC. Moreover, we used in vitro experiment to validate the expression level of signature genes. Notably, we assessed the predictive effect of anti-PD1/PDL1 immunotherapy using risk score model. RESULTS: Through the LASSO Cox regression model, we obtained 12 characteristic genes associated with the prognosis of CC, and also associated with immunity and hypoxia. Interestingly, the high-risk group had the properties of high hypoxia and low immunity, while the low-risk group had the properties of low hypoxia and high immunity. In the low-risk group, patients lived longer and had a significant therapeutic advantage of anti-PD-1 immunotherapy. CONCLUSIONS: Established risk scores model can help predict response to anti-PD-1 immunotherapy of CC.

The survival rate of cervical cancer (CC) is still low. A prognostic model for CC is urgently needed to improve the prognosis and survival. This study constructed a risk scoring models based on 12 characteristic gene related to hypoxia and immunity, including CX3CL1, CXCL3, GHSR, DLL4, FGFR2, PDF, KLRK1, MAP3K14, RETNLB, PRDX2, P4HA1 and PGK1, which can help predict the prognosis of PD-1 immunotherapy in CC patients. The high-risk group may have the properties of high hypoxia and low immunity, while the low-risk group patients live longer and have obvious therapeutic advantages in anti-PD-1 immunotherapy. Our findings suggest a potential link between hypoxia, immunity, prognosis, tumour immune microenvironment and response to immunotherapy in CC patients.