ERP29 regulates the proliferation of endometrial carcinoma via M6A modification.

AIMS: Endoplasmic reticulum protein 29 (ERP29) is crucial for endoplasmic reticulum stress (ERS). M6A plays an important role in the progression of endometrial cancer (EC). The study investigated the role of ERS-related gene (ERP29) and m6A in EC. MATERIALS AND METHODS: We screened ERS-related genes based on the GEO dataset, GSEA dataset and TCGA-UCEC database using WGCNA and two machine learning algorithms. The m6A-related GEO dataset was employed to identify the ERS-related hub genes with m6A. Expression of hub genes in different cell types were visualize through scRNA-seq data analyzing. Using qPCR, Western blot, and Immunohistochemical assays to detect the expression of ERP29, the effect of ERP29 on cancer cell proliferation was investigated through CCK8, EdU and clone formation experiments. M6A modifications were studied using m6A Dot blot and MeRIP-qPCR. Finally, we conducted rescue experiments. KEY FINDINGS: Ten ERS-related hub genes with m6A were identified. ERP29 is highly expressed in EC. ERP29 knockdown inhibits EC cell proliferation. METTL3 overexpression increases the ERP29 mRNA m6A and decreases the expression of ERP29. Cycloleucine (Cyc), a nucleic acid methylation inhibitor, treatment reduces ERP29 mRNA m6A and increases the expression of ERP29. Cyc rescue the low expression of ERP29 caused by overexpression of METTL3 through m6A. ERP29 knockdown rescued the increased proliferation of EC cells caused by low m6A. SIGNIFICANCE: ERP29 is highly expressed in EC. m6A regulates ERP29 expression and affects the proliferation of endometrial cancer cells. This represents the premise for applying ERP29 and m6A modifications in diagnosing and treating EC.

Enhanced Postoperative Pain Management and Mobility Following Arthroscopic Knee Surgery: A Comparative Study of Adductor Canal Block with and without IPACK Block.

BACKGROUND Arthroscopic knee surgery (AKS) is minimally invasive, reducing hospital stay compared to traditional surgery, but postoperative pain remains a significant issue. This study compared the analgesic and functional outcomes following AKS following anesthesia using adductor canal block (ACB) with and without anesthesia using the interspace between the popliteal artery and posterior capsule of the knee (IPACK) block under spinal anesthesia (SA). MATERIAL AND METHODS We randomly allocated 120 patients into 3 groups: IPACK+ACB+SA for Group A (n=40), ACB+SA for Group B (n=40), and SA for Group C (n=40). The outcome was the visual analog scale (VAS) score evaluated at rest and during activity at 3 h, 6 h, 12 h, 24 h, and 48 h postoperatively, the frequency of administration of postoperative rescue analgesic, and the maximal walking distance at 24 h and 48 h postoperatively. RESULTS Compared with Group C, the VAS scores in Group A were significantly lower at 48 h postoperatively (P<0.05). There was a significant difference in the frequency of postoperative rescue analgesia use among the 3 groups (P=0.001). In a subgroup analysis of meniscus shaping under arthroscopy, the resting VAS score in Group A was lower than that in Group B and Group C at 48 h postoperatively (P<0.05). The maximum walking distance of Group A was longer than that of Group B and Group C at 24 h and 48 h postoperatively (P<0.01). CONCLUSIONS The effect of postoperative analgesia in the group receiving IPACK combined with ACB after AKS was obviously superior. In arthroscopic meniscus repair surgery, the duration of analgesia was longer, and the maximum walking distance at 48 h postoperatively was longer.

EPAS1, a hypoxia- and ferroptosis-related gene, promotes malignant behaviour of cervical cancer by ceRNA and super-enhancer.

Hypoxia and Ferroptosis are associated with the malignant behaviour of cervical cancer. Endothelial PAS domain-containing protein 1 (EPAS1) contributes to the progression of cervical cancer. EPAS1 plays important roles in hypoxia and ferroptosis. Using the GEO dataset, machine-learning algorithms were used to screen for hypoxia- and ferroptosis-related genes (HFRGs) in cervical cancer. EPAS1 was identified as the hub gene. qPCR and WB were used to investigate the expression of EPAS1 in normal and cervical cancer tissues. The proliferation, invasion and migration of EPAS1 cells in HeLa and SiHa cell lines were detected using CCK8, transwell and wound healing assays, respectively. Apoptosis was detected by flow cytometry. A dual-luciferase assay was used to analyse the MALAT1-miR-182-5P-EPAS1 mRNA axis and core promoter elements of the super-enhancer. EPAS1 was significantly overexpressed in cervical cancer tissues. EPAS1 could increase the proliferation, invasion, migration of HeLa and SiHa cells and reduce the apoptosis of HeLa and SiHa cell. According to the double-luciferase assay, EPAS1 expression was regulated by the MALAT1-Mir-182-5p-EPAS1 mRNA axis. EPAS1 is associated with super-enhancers. Double-luciferase assay showed that the core elements of the super-enhancer were E1 and E3. EPAS1, an HFRG, is significantly overexpressed in cervical cancer. EPAS1 promotes malignant behaviour of cervical cancer cells. EPAS1 expression is regulated by super-enhancers and the MALAT1-miR-182-5P- EPAS1 mRNA axis. EPAS1 may be a target for the diagnosis and treatment of cervical cancer.

Development of family resource indicators for people with schizophrenic disorder in community by modified Delphi method in Beijing, China.

INTRODUCTION: Most people with schizophrenia in China are supported by their family members in community. The patient's family is confronted with severe care burden and pressure, which directly affects the caregiver's own health and social life, and indirectly affects the patient's rehabilitation. Adequate family resources can reduce the burden and pressure on families. But there is an absence of systematic family resource indicators for people with schizophrenic disorder in China. OBJECTIVES: This study aimed to develop a set of family resource indicators for people with schizophrenic disorder in China. DESIGN: Preliminary family resource indicators were generated and refined by literature review and an expert consultation meeting. Two rounds of email-based Delphi survey were carried out to identify family resource indicators. SETTING: Two rounds of email-based Delphi survey were performed from July to September 2021 in Beijing, China. PARTICIPANTS: There were 15 mental health doctors from community health service centres and four psychiatrists from tertiary hospitals, and two primary care researchers from universities in the first and second rounds Delphi survey. RESULTS: All the 21 experts participated in both rounds of Delphi survey. A total of 46 indicators achieved consensus for inclusion in the final set of indicators after two rounds of Delphi survey. The final set of indicators was grouped into 10 domains: financial support (three indicators), psychological and spiritual support (eight indicators), medical treatment (three indicators), information and education (three indicators), structural support (two indicators), external family resources included social resources (five indicators), cultural resources (two indicators), economic resources (seven indicators), environmental resources (four indicators) and medical resources (nine indicators). CONCLUSIONS: A set of 46 family resource indicators for people with schizophrenic disorder in community was identified by an iterative Delphi process in Beijing, China. However, the indicators still need to be validated by testing in further studies.

Optimization of Preparation Conditions for Quercetin Nanoliposomes Using Response Surface Methodology and Evaluation of Their Stability.

Quercetin is a flavonol compound with excellent biological activities. However, quercetin exhibits poor stability and solubility in water, which limits its application. In this study, quercetin nanoliposomes (QUE-NL-1) were prepared using an ultrasonic thin-film dispersion method, and the preparation conditions were optimized using response surface methodology. The optimal conditions for preparing QUE-NL-1 were as follows: an evaporation temperature of 35 °C, a drug concentration of 0.20 mg/mL, and a lipid bile ratio of 4:1. The encapsulation rate of QUE-NL-1 is (63.73 ± 2.09)%, the average particle size is 134.11 nm, and the average absolute value of the zeta potential is 37.50 and PDI = 0.24. By analyzing the storage temperature, storage time, and leakage rate of QUE-NL-1 in simulated gastrointestinal fluid, it was found that quercetin exhibits good stability after embedding and can achieve sustained release in intestinal juice. In addition, the cytotoxicity of QUE-NL-1 was not significant, and the survival rate of Caco-2 cells was >90% when the concentration range of QUE-NL-1 was 0.1-0.4 mg/mL. This study provides an efficient method for preparing QUE-NL-1 with small particle sizes, good stability, and high safety, which is of great significance for expanding the application range of quercetin.

Conditional deletion of Zeb1 in Csf1r+ cells reduces inflammatory response of the cornea to alkali burn.

ZEB1 is an essential factor in embryonic development. In adults, it is often highly expressed in malignant tumors with low expression in normal tissues. The major biological function of ZEB1 in developing embryos and progressing cancers is to transdifferentiate cells from an epithelial to mesenchymal phenotype; but what roles ZEB1 plays in normal adult tissues are largely unknown. We previously reported that the reduction of Zeb1 in monoallelic global knockout (Zeb1+/-) mice reduced corneal inflammation-associated neovascularization following alkali burn. To uncover the cellular mechanism underlying the Zeb1 regulation of corneal inflammation, we functionally deleted Zeb1 alleles in Csf1r+ myeloid cells using a conditional knockout (cKO) strategy and found that Zeb1 cKO reduced leukocytes in the cornea after alkali burn. The reduction of immune cells was due to their increased apoptotic rate and linked to a Zeb1-downregulated apoptotic pathway. We conclude that Zeb1 facilitates corneal inflammatory response by maintaining Csf1r+ cell viability.

Caregiving experiences of family caregivers of patients with schizophrenia in a community: a qualitative study in Beijing.

OBJECTIVES: This study aims to understand the caregiving experiences of family caregivers of people with schizophrenia in a community. DESIGN: A qualitative study based on phenomenological analysis was conducted through in-depth interviews. SETTING: This study was carried out from May to June 2023 in two community health service centres in urban Beijing, China. PARTICIPANTS: We selected 16 family caregivers for interviews using purposive sampling method. RESULTS: Four themes and 10 subthemes were identified: (1) psychosocial distress of family caregivers (feeling unprepared and helpless at the beginning, confronting negative emotions in long-term care and straying away from social life); (2) adverse impacts on the whole family (poor cooperation within the family, insufficient family involvement in professional care); (3) coping with family caregiving (accepting the reality of the patients' illness, struggling with family life balance and having realistic expectations); (4) concerns about future care (daily living support, physical health management). CONCLUSION: Family caregivers experienced psychosocial distress and family stress in the process of caregiving. They had to cope with caregiving stress and were concerned about the long-term care of people with schizophrenia. These findings provide implications for intervention programmes to strengthen social support, family involvement, and active coping for caregivers and develop long-term care mechanisms for people with schizophrenia.

Impact of blood lipid levels on venous thromboembolism in acute stroke patients.

BACKGROUND: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication of stroke with a high incidence of underdiagnosis. The relationship between dyslipidemia and VTE remains uncertain. Therefore, this study aimed to explore this connection in acute stroke patients to enhance diagnostic and preventative strategies. METHODS: Retrospective data from 7854 acute stroke patients admitted to Dongyang Hospital, Affiliated with Wenzhou Medical University, between 2010 and 2020 were extracted. Differential tests were compared among various blood lipid parameters and the presence or absence of venous thrombosis. Logistic regression analysis was employed to estimate associations. RESULTS: The prevalences of DVT and PE were 3.9 % and 1.1 %, respectively. Additionally, 43 cases (0.5 %) exhibited combined DVT and PE. A high triglyceride (TG) level was associated with a decreased risk of VTE (adjusted odd ratio [aOR] = 0.69, 95 % confidence interval [CI]: 0.54-0.89, P = 0.004), whereas a high low-density lipoprotein cholesterol (LDL-C) level was associated with an increased risk of VTE (aOR = 1.51, 95 % CI: 1.16-1.97, P = 0.002), after adjusting for confounding factors. No significant associations were observed for high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) levels with VTE risk. Subgroup analyses revealed that these associations were significant in ischemic stroke patients. CONCLUSION: Low TG levels and high LDL-C levels were found to be associated with an increased risk of VTE in acute stroke patients, offering valuable insights for the early identification and management of high-risk individuals.

Prevalence of workplace violence in Chinese obstetric nurses under the new situation and its correlation with violence prevention knowledge-attitude-practice and climate perception: a cross-sectional study.

BACKGROUND: Workplace violence severely impacts individual nurses. With the three-child opening policy of China and the impact of the COVID-19 epidemic in the recently years, obstetric nurses face the double attack of heavy workload and staffing shortage. This study aimed to evaluate the current situation of workplace violence among Chinese obstetric nurses under the new situation, assess the level of violence prevention knowledge-attitude-practice and climate perception in Chinese obstetric nurses and explore the correlation between workplace violence and the level of violence prevention knowledge-attitude-practice and climate perception. METHODS: A cross-sectional survey on the workplace violence for Chinese obstetric nurses was conducted from August to February 2023. All the questionnaires came from 10 provinces and 3 autonomous regions in China. The basic characteristics of obstetric nurse's workplace violence, workplace violence prevention knowledge-attitude-practice scale and workplace violence climate perception scale were collected. RESULTS: Totally, 522 Chinese obstetric nurses were included. 55.0% of obstetric nurses (287) had experienced workplace violence in the past 12 months, including verbal assault (40.4%), physical assault (34.1%), and sexual assault (31.0%). The overall level of obstetric nurses' workplace violence prevention knowledge-attitude-practice and climate perception of workplace violence was low. Multiple linear regression analysis showed that the violence prevention knowledge dimension significantly influenced obstetric nurses' workplace violence (B = -0.278, P < .001), attitude dimension (B = -0.241, P < .001), behavior dimension (B = -0.216, P < .001) and the violence climate perception's organizational management (B = -0.177, P < .001), organizational training (B = -0.175, P < .001), organizational support (B = -0.143, p < .001) and the violence handling (B = -0.165, P < .001). CONCLUSION: The incidence of workplace violence among obstetric nurses in the new situation is high. However, the overall violence prevention knowledge-attitude-practice and climate perception levels are low. Therefore, nursing managers should take targeted measures according to the relevant influencing factors and the characteristics of obstetrics to improve the level of obstetric nurses' violence prevention knowledge-attitude-practice and climate perception to reduce workplace violence among obstetric nurses.

Acidic Environment Induces Pyroptosis of NLRP3 Inflammatory Vesicle-Mediated Nucleus Pulposus Cells Through Up-Regulation of POSTN Expression

SUMMARY: Intervertebral disc degeneration (IVDD) is induced by nucleus pulposus (NP) dysfunction as a result of massive loss of NP cells. It has been reported that the acidic microenvironment of the intervertebral disc (IVD) can induce NP cell pyroptosis, and that up-regulation of periostin (POSTN) expression has a negative effect on NP cell survival. However, the relationship between the acidic environment, POSTN expression level and NP cell pyroptosis is unclear. Therefore, the aim of this study was to explore the relationship between acidic environment and POSTN expression level in NP cells, as well as the effect of POSTN in acidic environment on NP cell pyroptosis. NP cells were obtained from the lumbar vertebrae of Sprague Dawley (SD) male rats. These cells were divided into normal and acidic groups according to whether they were exposed to 6 mM lactic acid solution. And NP cells in the acidic group were additionally divided into three groups: (1) Blank group: no transfection; (2) NC group: cells transfected with empty vector plasmid; (3) sh-POSTN group: cells transfected with sh-POSTN plasmid to knock down the expression level of POSTN. Quantitative real-time PCR (qRT-PCR) and western blot was performed to assess the expression of POSTN at the mRNAand protein levels. CCK8 was used to evaluate cell survival. Western blot, in addition, was performed to examine acid-sensing ion channels (ASIC)-related proteins. And pyroptosis was detected by ELISA and western blot. The expression level of POSTN was significantly increased in NP cells in acidic environment. Knockdown of POSTN expression promoted the survival of NP cells in acidic environment and reduced the protein levels of ASIC3 and ASIC1a in NP cells. Moreover, knockdown of POSTN expression decreased the pyroptosis proportion of NP cells and the levels of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. The levels of pyroptosis-related proteins NLRP3, ASC, cleaved-Caspase-1, and cleaved-GSDMD were also affected by the decreased POSTN expression. The extracellular acidic environment created by lactic acid solution activated NLRP3 inflammatory vesicle-induced caspase-1 to get involved in NP cell pyroptosis by up-regulating POSTN expression.

La degeneración del disco intervertebral (DDIV) es inducida por una disfunción del núcleo pulposo (NP) como resultado de una pérdida masiva de células NP. Se ha informado que el microambiente ácido del disco intervertebral (DIV) puede inducir la piroptosis de las células NP y que la regulación positiva de la expresión de periostina (POSTN) tiene un efecto negativo en la supervivencia de las células NP. Sin embargo, la relación entre el ambiente ácido, el nivel de expresión de POSTN y la piroptosis de las células NP es poco clara. Por lo tanto, el objetivo de este estudio fue explorar la relación entre el ambiente ácido y el nivel de expresión de POSTN en células NP, así como el efecto de POSTN en ambiente ácido sobre la piroptosis de las células NP. Las células NP se obtuvieron de las vertebras lumbares de ratas macho Sprague Dawley (SD). Estas células se dividieron en grupos normales y ácidos según se expusieron a una solución de ácido láctico 6 mM. Las células NP en el grupo ácido se dividieron adicionalmente en tres grupos: (1) Grupo en blanco: sin transfección; (2) grupo NC: células transfectadas con plásmido vector vacío; (3) grupo sh-POSTN: células transfectadas con plásmido sh-POSTN para reducir el nivel de expresión de POSTN. Se realizó una PCR cuantitativa en tiempo real (qRT-PCR) y una transferencia Western para evaluar la expresión de POSTN en los niveles de ARNm y proteína. Se utilizó CCK8 para evaluar la supervivencia celular. Además, se realizó una transferencia Western para examinar las proteínas relacionadas con los canales iónicos sensibles al ácido (ASIC). La piroptosis se detectó mediante ELISA y Western blot. El nivel de expresión de POSTN aumentó significativamente en células NP en ambiente ácido. La eliminación de la expresión de POSTN promovió la supervivencia de las células NP en un ambiente ácido y redujo los niveles de proteína de ASIC3 y ASIC1a en las células NP. Además, la eliminación de la expresión de POSTN disminuyó la proporción de piroptosis de las células NP y los niveles de citocinas proinflamatorias interleucina (IL) - 1β e IL-18. Los niveles de proteínas relacionadas con la piroptosis NLRP3, ASC, Caspasa-1 escindida y GSDMD escindida también se vieron afectados por la disminución de la expresión de POSTN. El ambiente ácido extracelular creado por la solución de ácido láctico activó la caspasa-1 inducida por vesículas inflamatorias NLRP3 para involucrarse en la piroptosis de las células NP mediante la regulación positiva de la expresión de POSTN.

Evaluation of fused multisource data of air temperature based on dropsonde and satellite observation.

Continuous vertical air temperature (AT) from in-situ observation is of crucial importance for understanding the atmospheric environment, but the satellite data that have complete spatial coverage lacked vertical in-situ observation data, and the vertical dropsonde data from in-situ observations only were single-point observations. Therefore, this article introduced machine learning algorithms for fusing in-situ observation and multi-satellite data to achieve spatial continuity of vertical data on a large scale. Specially, random forest (RF), support vector regression (SVR), artificial neural network (ANN) and recurrent neural network (RNN) were employed to capture the non-linear relationships between the variables and estimated AT. The pre-training process and fine-tuning process ensured the prediction of AT spatiotemporal distribution. The four models were implemented for three-dimensional AT estimating across China. Additionally, we used the radiosonde observation data to evaluate the accuracy of estimated AT data under conventional weather and typhoon conditions. Our results revealed that the RF model performed the best with the R of 0.9992, the MAE of 0.70 °C, and the RMSE of 1.04 °C at the national scale, followed by the SVR and ANN models. The RNN model exhibited promising results under typhoon conditions, which will be valuable insights for further research on the applicability of machine learning models under different weather conditions. Besides, having a larger sample size does not necessarily result in reduced errors. For instance, the MAE value for SVR in the pressure height range of 100-200 hPa was larger than that in the pressure height range of 300-400 hPa, but the former sample size was 16,324, which was 7433 higher than the latter.

Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa.

Most mutations in retinitis pigmentosa (RP) arise in rod photoreceptors, but cone photoreceptors, responsible for high-resolution daylight and color vision, are subsequently affected, causing the most debilitating features of the disease. We used mass spectroscopy to follow 13C metabolites delivered to the outer retina and single-cell RNA sequencing to assess photoreceptor transcriptomes. The S cone metabolic transcriptome suggests engagement of the TCA cycle and ongoing response to ROS characteristic of oxidative phosphorylation, which we link to their histone modification transcriptome. Tumor necrosis factor (TNF) and its downstream effector RIP3, which drive ROS generation via mitochondrial dysfunction, are induced and activated as S cones undergo early apoptosis in RP. The long/medium-wavelength (L/M) cone transcriptome shows enhanced glycolytic capacity, which maintains their function as RP progresses. Then, as extracellular glucose eventually diminishes, L/M cones are sustained in long-term dormancy by lactate metabolism.

Effects of exercise on bone mineral density in middle-aged and older men: A comprehensive meta-analysis.

This meta-analysis including 10 randomised controlled trials suggests that exercise is associated with a statistically significant, but relatively mild, improvement effect on bone mineral density in middle-aged and older men, indicating that exercise has the potential to be a safe and effective way toavert bone loss in men. PURPOSE: To determine the effect of exercise on bone mineral density (BMD) in middle-aged and older men. METHODS: We searched three electronic databases up to March 21, 2022. A systematic review of the literature according to the PRISMA statement included (1) randomised controlled trials (RCTs), with (2) at least one exercise group as an intervention versus a control group, (3) men aged ≥ 45 years old, and (4) areal BMD of the lumbar spine (LS) and/or femoral neck (FN) and/or total hip (TH) and/or trochanter region. Mean differences (MD) for BMD changes at the LS, FN, TH, and trochanter were defined as outcome measures. RESULTS: A total of 10 eligible RCTs were included (N = 555 participants). Exercise significantly improved BMD, and the summarised MD was 0.02 (95% CI: 0.00 to 0.05) for LS BMD, 0.01 (95% CI: 0.00 to 0.02) for FN BMD, 0.01 (95% CI: 0.00 to 0.01) for TH BMD, and 0.03 (95% CI: 0.00 to 0.05) for trochanter BMD. Subgoup analyses showed the improvement effect was statistically significant in trials with longer duration and higher intensity in LS (≥ 12 months: MD, 0.01, 95% CI:0.00 to 0.03; higher intensity: MD, 0.01, 95% CI:0.00 to 0.03) and FN (≥ 12 months: MD, 0.02, 95% CI:0.01 to 0.02; higher intensity: MD, 0.01, 95% CI:0.01 to 0.02). CONCLUSION: Our results suggested a relatively mild, improvement effect of exercise on LS and proximal femur BMD. Exercise has the potential to be an effective way to avert bone loss in middle-aged and older men.

Radical Scavenging Capability and Mechanism of Three Isoflavonoids Extracted from Radix Astragali: A Theoretical Study.

As a valuable traditional Chinese herbal medicine, Radix Astragali has attracted much attention due to its extensive pharmacological activities. In this study, density functional theory (DFT) was used thermodynamically and kinetically in detail to predict the antioxidant activity and reaction mechanisms involved in the free radical scavenging reactions of three representative isoflavonoids (formononetin, calycosin, and calycosin-7-glucoside) extracted from Radix Astragali. Three main mechanisms, including hydrogen atom transfer (HAT), proton transfer after electron transfer (SET-PT), and sequential proton loss electron transfer (SPLET) were examined by calculating the thermodynamic parameters. It was found that HAT is the predominant mechanism in the gas phase, while SPLET is supported in the solvent environment. The isoflavonoids' order of antioxidant activity was estimated as: calycosin > calycosin-7-glucoside > formononetin. For the calycosin compound, the result revealed the feasibility of double HAT mechanisms, which involve the formation of stable benzodioxazole with significantly reduced energy in the second H+/e- reaction. In addition, the potential energy profiles and kinetic calculations show that the reaction of •OH into the 3'-OH site of calycosin has a lower energy barrier (7.2 kcal/mol) and higher rate constant (4.55 × 109 M-1 s-1) compared with other reactions in the gas phase.

A review of recent advances on cyanidin-3-glucoside: the biotransformation, absorption, bioactivity and applications of nano-encapsulation.

Anthocyanins are a class of dietary polyphenols that exhibit technological and bioactive-relevant properties. C3G is absorbed in its unmodified molecular form in the upper digestive tract, goes through the extended first-passage metabolism and its metabolites enter the bloodstream. The C3G metabolites possess health benefits such as antioxidant, cardio-protective, anti-inflammatory, neuroprotective, anti-cancer, anti-diabetic, and anti-thrombotic activities. However, the efficacy and distribution of C3G in the human body are restricted due to its low stability and bioaccessibility. Inspiringly, the lipid-, polysaccharide-, protein-, and nanocapsule-associated conjugates have achieved targeted delivery with enhanced bioaccessibility and controlled release. In this review, the absorption and transportation modes, decomposition and metabolism processes, functional activity mechanisms, and improved methods for enhancing the bioavailability of C3G are summarized. Moreover, the aspects of the gut microbiota regulation, C3G-mediated cytoprotection and different biocompatible materials applications are briefly discussed.

[Progress on three-dimensional cell culture technology and their application].

Three-dimensional (3D) cell culture model is a system that co-culture carriers with 3D structural materials and different types of cells in vitro to simulate the microenvironment in vivo. This novel cell culture model has been proved to be close to the natural system in vivo. In the process of cell attachment, migration, mitosis and apoptosis, it could produce biological reactions different from that of monolayer cell culture. Therefore, it can be used as an ideal model to evaluate the dynamic pharmacological effects of active substances and the metastasis process of cancer cells. This paper compared and analyzed the different characteristics of cell growth and development under two-dimensional (2D) and 3D model culture and introduced the establishment method of 3D cell model. The application progress of 3D cell culture technology in tumor model and intestinal absorption model was summarized. Finally, the application prospect of 3D cell model in the evaluation and screening of active substance was revealed. This review is expected to provide reference for the development and application of new 3D cell culture models.

Sc@B28-, Ti@B28, V@B28+, and V@B292-: Spherically Aromatic Endohedral Seashell-like Metallo-Borospherenes.

Transition-metal-doped boron nanoclusters exhibit unique structures and bonding in chemistry. Using the experimentally observed seashell-like borospherenes C2 B28-/0 and Cs B29- as ligands and based on extensive first-principles theory calculations, we predict herein a series of novel transition-metal-centered endohedral seashell-like metallo-borospherenes C2 Sc@B28- (1), C2 Ti@B28 (2), C2 V@B28+ (3), and Cs V@B292- (4) which, as the global minima of the complex systems, turn out to be the boron analogues of dibenzenechromium D6h Cr(C6H6)2 with two B12 ligands on the top and bottom interconnected by four or five corner boron atoms on the waist and one transition-metal "pearl" sandwiched at the center in between. Detailed molecular orbital, adaptive natural density partitioning (AdNDP), and iso-chemical shielding surface (ICSS) analyses indicate that, similar to Cr(C6H6)2, these endohedral seashell-like complexes follow the 18-electron rule in bonding patterns (1S21P61D10), rendering spherical aromaticity and extra stability to the systems.

Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility.

The cornea is the outmost ocular tissue and plays an important role in protecting the eye from environmental insults. Corneal epithelial wounding provokes pain and fear and contributes to the most ocular trauma emergency assessments worldwide. ZEB1 is an essential transcription factor in development; but its roles in adult tissues are not clear. We identify Zeb1 is an intrinsic factor that facilitates corneal epithelial wound healing. In this study, we demonstrate that monoallelic deletion of Zeb1 significantly expedites corneal cell death and inhibits corneal epithelial EMT-related cell migration upon an epithelial debridement. We provide evidence that Zeb1-regulation of corneal epithelial wound healing is through the repression of genes required for Tnfa-induced epithelial cell death and the induction of genes beneficial for epithelial cell migration. We suggest utilizing TNF-α antagonists would reduce TNF/TNFR1-induced cell death in the corneal epithelium and inflammation in the corneal stroma to help corneal wound healing.

Identification of stemness subtypes and features to improve endometrial cancer treatment using machine learning.

Endometrial cancer is one of the most common malignant tumours in women, and cancer stem cells are known to play an important role in its growth, invasion, metastasis, and drug resistance. Immunotherapy for endometrial cancer is still under research. In this study, a total of 547 endometrial cancer cases were randomly divided into training set (351 cases) set and test set (196 cases). The stemness index of patients was calculated using the One-Class Logistic Regression (OCLR) machine learning algorithm to explore the clinicopathological differences between index levels. Stemness subtypes were determined according to the characteristics of cancer stemness and their clinicopathological characteristics, immune features, and therapeutic effects were described. Our study suggests that endometrial cancer is classified into two stemness subtypes. Stemness subtypes, which are associated with its clinical features, may be independent prognostic factors for endometrial cancer. The stemness subtypes differed significantly in immune activity, immune cell infiltration, and the immune microenvironment, including sensitivity to chemotherapeutic drugs and potential therapeutic compounds. Algorithms were utilised to construct a stemness subtype prediction model and predictor. These findings will provide guidance for the clinical diagnosis, treatment, and prognosis of endometrial cancer.

Prognosis, immune microenvironment, and personalized treatment prediction in Rho GTPase-activating protein 4-mutant cervical cancer: Computer strategies for precision oncology.

AIMS: Cervical cancer with different mutations is associated with specific genomic differences. We developed a new mutation prediction model of the ARHGAP4 gene for cervical cancer. MAIN METHODS: We conducted a panoramic analysis of CESC mutations based on The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC) database. We made copy number variation analysis and correlation analysis of somatic mutations and tumor mutation load fraction. Then we established a prediction model of ARHGAP4 mutation, screened related genes based on the risk scores, calculated the correlation between the risk score and immune microenvironment, and analyzed drug sensitivity. KEY FINDINGS: The prediction model of ARHGAP4 mutation based on mRNA expression is closely related to the survival rate of cervical cancer patients and to the effect of immunotherapy. The prediction model is also related to the infiltration of immune cells and human leukocyte antigen family expression in the immune microenvironment. After computational analysis, three drugs (cytarabine, docetaxel, imatinib) were identified as potential agents for the ARHGAP4 mutation high-risk group, and two drugs (erlotinib, methotrexate) were shown to have therapeutic significance for patients in the low-risk group. The expression of ARHGAP4 was higher in cervical cancer tissues. The proliferation ability of HeLa and SiHa cells decreased after ARHGAP4 knockdown. SIGNIFICANCE: This study provides not only a new approach for the prediction of the response of the cervical cancer patients to targeted drug therapy but also a new strategy for combining risk stratification with precision treatment.