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Abstract Autophagy is a cellular process that involves the degradation and recycling of cellular components, including damaged proteins and organelles. It is an important mechanism for maintaining cellular homeostasis and has been implicated in various diseases, including cancer. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that do not code for proteins but instead play regulatory roles in gene expression. Emerging evidence suggests that lncRNAs can influence autophagy and contribute to the development and progression of colorectal cancer (CRC). Several lncRNAs have been identified as key players in modulating autophagy in CRC. The dysregulation of autophagy and non-coding RNAs (ncRNAs) in CRC suggests a complex interplay between these two factors in the pathogenesis of the disease. Modulating autophagy may sensitize cancer cells to existing therapies or improve the efficacy of new treatment approaches. Additionally, targeting specific lncRNAs involved in autophagy regulation could potentially be used as a therapeutic intervention to inhibit tumor growth, metastasis, and overcome drug resistance in CRC. In this review, a thorough overview is presented, encompassing the functions and underlying mechanisms of autophagy-related lncRNAs in a range of critical areas within tumor biology. These include cell proliferation, apoptosis, migration, invasion, drug resistance, angiogenesis, and radiation resistance.

Abstract Background Critically ill patients undergoing liberation often encounter various physiological and clinical complexities and challenges. However, whether the combination of hyperbaric oxygen and in-cabin ventilator therapy could offer a comprehensive approach that may simultaneously address respiratory and potentially improve outcomes in this challenging patient population remain unclear. Methods This retrospective study involved 148 patients experiencing difficulty in liberation after tracheotomy. Inclusion criteria comprised ongoing mechanical ventilation need, lung inflammation on computed tomography (CT) scans, and Glasgow Coma Scale (GCS) scores of ≤ 9. Exclusion criteria excluded patients with active bleeding, untreated pneumothorax, cerebrospinal fluid leakage, and a heart rate below 50 beats per minute. Following exclusions, 111 cases were treated with hyperbaric oxygen combined cabin ventilator, of which 72 cases were successfully liberated (SL group) and 28 cases (NSL group) were not successfully liberated. The hyperbaric oxygen chamber group received pressurization to 0.20 MPa (2.0 ATA) for 20 min, followed by 60 min of ventilator oxygen inhalation. Successful liberation was determined by a strict process, including subjective and objective criteria, with a prolonged spontaneous breathing trial. GCS assessments were conducted to evaluate consciousness levels, with scores categorized as normal, mildly impaired, moderately impaired, or severely impaired. Results Patients who underwent treatment exhibited improved GCS, blood gas indicators, and cardiac function indexes. The improvement of GCS, partial pressure of oxygen (PaO2), oxygen saturation of blood (SaO2), oxygenation index (OI) in the SL group was significantly higher than that of the NSL group. However, there was no significant difference in the improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and stroke volume (SV) between the SL group and the NSL group after treatment. Conclusions Hyperbaric oxygen combined with in-cabin ventilator therapy effectively enhances respiratory function, cardiopulmonary function, and various indicators of critically ill patients with liberation difficulty after tracheostomy.

Abstract A great challenge for electrochemical CO2 reduction is to improve energy efficiency, which requires reducing overpotential while increasing product Faraday efficiency. Here, we designedly synthesize a hybrid electrocatalyst consisting of Fe nanoparticles, pyrrole-type Fe-N4 sites and less-oxygenated carbon supports, which exhibits a remarkable CO Faraday efficiency above 99% at an ultralow overpotential of 21 mV, reaching the highest cathode energy efficiency of 97.1% to date. The catalyst also can afford a CO selectivity nearly 100% with a high cathode energy efficiency (>90%) at least 100 h. The combined results of control experiments, in situ characterizations and theoretical calculations demonstrate that introducing Fe nanoparticles can reduce the overpotential by accelerating the proton transfer from CO2 to *COOH and lowering the free energy for *COOH formation, constructing pyrrole-type Fe-N4 sites and limiting oxygen species on carbon supports can increase CO Faraday efficiency through inhibiting the H2 evolution, thus achieving energy-efficient electrochemical CO2 reduction to CO.

Abstract Background Tumor-associated macrophages (TAMs) are the most abundant types of immune cells in the tumor microenvironment (TME) of breast cancer (BC). TAMs usually exhibit an M2 phenotype and promote tumor progression by facilitating immunosuppression. This study aimed to investigate the effect of CAA-derived IL-6 on macrophage polarization in promoting BC progression. Methods Human BC samples and adipocytes co-cultured with 4T1 BC cells were employed to explore the properties of CAAs. The co-implantation of adipocytes and 4T1 cells in mouse tumor-bearing model and tail vein pulmonary metastasis model were constructed to investigate the impact of CAAs on BC malignant progression in vivo. The functional assays, qRT-PCR, western blotting assay and ELISA assay were employed to explore the effect of CAA-derived IL-6 on macrophage polarization and programmed cell death protein ligand 1 (PD-L1) expression. Results CAAs were located at the invasive front of BC and possessed a de-differentiated fibroblast phenotype. CAAs facilitated the malignant behaviors of 4T1 cells in vitro, and promoted 4T1 tumor growth and pulmonary metastasis in vivo. The IHC staining of both human BC specimens and xenograft and the in vitro experiment indicated that CAAs could enhance infiltration of M2 macrophages in the TME of 4T1 BC. Furthermore, CAA-educated macrophages could enhance malignant behaviors of 4T1 cells in vitro. More importantly, CAAs could secret abundant IL-6 and thus induce M2 macrophage polarization by activating STAT3. In addition, CAAs could upregulate PD-L1 expression in macrophages. Conclusions Our study revealed that CAAs and CAA-educated macrophages enhanced the malignant behaviors of BC. Specifically, CAA-derived IL-6 induced migration and M2 polarization of macrophages via activation STAT3 and promoted macrophage PD-L1 expression, thereby leading to BC progression.

Abstract Objective To establish a prediction model for acute gastrointestinal injury (AGI) in patients with prolonged disorder of consciousness (pDOC) and to evaluate and apply the prediction model. Methods The clinical data of 165 patients with pDOC admitted to the hyperbaric oxygen department from January 2021 to December 2021 were retrospectively reviewed, and the patients were divided into an AGI group (n = 91) and an N-AGI group (n = 74) according to whether AGI occurred. A prediction model was built by fitting multiple independent influencing factors through logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the model, the Hosmer–Lemeshow (H–L) test was used to evaluate the goodness-of-fit of the model, and the ROC curve and calibration curve were drawn to evaluate the predictive performance. A nomogram was plotted to visualize the prediction model. Results According to the multivariate logistic regression analysis results, the prediction model was finally constructed with the CRS-R score, DAO, PCT, ALB, and I-FABP, and a nomogram was generated. The area under the ROC curve (AUC) of the prediction model was 0.931, the sensitivity was 83.5%, and the specificity was 93.2%. The data were divided into 5 groups for the H–L test (χ2 = 2.54, P = 0.468 > 0.05) and into 10 groups for the H–L test (χ2 = 9.98, P = 0.267 > 0.05). A calibration curve was drawn based on the test results, indicating that the prediction model has a good goodness-of-fit and good prediction stability. Conclusion The prediction model for AGI in pDOC patients constructed in this study can be used in clinical practice and is helpful to predict the occurrence of AGI in pDOC patients.

Abstract Background Breast cancer is the leading female cancer type and the cause of cancer-related mortality worldwide. Adipocytes possess important functions of energy supply, metabolic regulation, and cytokine release, and are also the matrix cell that supports mammary gland tissue. In breast cancer tumor microenvironment (TME), adipocytes are the prominent stromal cells and are implicated in inflammation, metastatic formation, metabolic remodeling, and cancer susceptibility. Main body It is well-established that adipocyte secretome is a reservoir engaged in the regulation of tumor cell behavior by secreting a large number of cytokines (IL-6, IL-8, and chemokines), adipokines (leptin, adiponectin, autotaxin, and resistin), lipid metabolites (free fatty acids and β-hydroxybutyrate), and other exosome-encapsulated substances. These released factors influence the evolution and clinical outcome of breast cancer through complex mechanisms. The progression of breast cancer tumors revolves around the tumor-adipose stromal network, which may contribute to breast cancer aggressiveness by increasing the pro-malignant potential of TME and tumor cells themselves. Most importantly, the secretome alterations of adipocytes are regarded as distinctly important targets for breast cancer diagnosis, treatment, and drug resistance. Conclusion Therefore, this review will provide a comprehensive description of the specific adipocyte secretome characteristics and interactions within TME cell populations, which will enable us to better tailor strategies for tumor stratification management and treatment.

Chemotherapy is extensively used to treat cancers and is often associated with ovarian damage and leads to premature ovarian insufficiency and infertility, while the role of mitochondria during ovarian damage with chemotherapy remains unknown. This study used a mouse model with oocyte-specific deletion of mitochondrial stress response gene Caseinolytic peptidase P (Clpp) to investigate mitochondrial homeostasis in oocytes from mice receiving a chemotherapeutic drug cyclophosphamide (CTX). We found that oocyte-specific deletion of Clpp reduced fecundity of the mice at advanced age. The deletion led to meiotic defects with elevated abnormal spindle rate and aneuploidy rate with impaired mitochondrial function in the MII oocytes from 8-week-old mice. Upon CTX treatment at 8-week-old, the oocyte competence and folliculogenesis from the oocyte-specific Clpp knockout mice was further deteriorated with dramatic impairment of mitochondrial distribution and function including elevated ROS level, decreased mitochondrial membrane potential, respiratory chain activity and ATP production. Taken together, the results indicate that that ClpP was required for oocyte competence during maturation and early folliculogenesis, and its deficiency deteriorate cyclophosphamide-induced ovarian damage.

Abstract People often find it more difficult to recognize other- than own-race faces. This other-race effect is robust across numerous ethnic groups. Yet, it remains unclear how this effect changes in people who live in a multiracial environment, and in immigrants whose lifetime perceptual experience changes over time. In the present study, we developed a novel face recognition test that approximates face recognition in the real world. We tested five groups of White and East Asian adults (n = 120) living in racially homogeneous versus heterogeneous cities and East Asians who immigrated to a multiracial city between infancy and adulthood. Multiracial cities reduce the other-race effect. The magnitude of the other-race effect changes as a function of experience, mirroring the racial diversity in perceivers’ living environment. Our study highlights the challenge of forming reliable face representations across naturalistic facial variability and suggests a facilitative role of multiracial environments in eliminating the other-race effect.

Abstract Background Nowadays, wound is associated with a complicated repairing process and still represents a significant biomedical burden worldwide. Bone marrow mesenchymal stem cells (BMSCs) possess multidirectional differentiation potential and secretory function, emerging as potential cellular candidates in treating wounds. Ascorbic acid 2-glucoside (AA2G) is a well-known antioxidant and its function in BMSC-promoting wound healing is worth exploring. Methods The in vitro cell proliferation, migration, and angiogenesis of BMSCs and AA2G-treated BMSCs were detected by flow cytometry, EDU staining, scratch assay, transwell assay, and immunofluorescence (IF). Besides, the collagen formation effect of AA2G-treated BMSCs conditioned medium (CM) on NIH-3T3 cells was evaluated by hydroxyproline, qRT-PCR and IF staining detection. Next, in the wound healing mouse model, the histological evaluation of wound tissue in PBS, BMSCs, and AA2G-treated BMSCs group were further investigated. Lastly, western blot and ELISA were used to detect the expression levels of 5-hmc, TET2 and VEGF protein, and PI3K/AKT pathway activation in BMSCs treated with or without AA2G. Results The in vitro results indicated that AA2G-treated BMSCs exhibited stronger proliferation and improved the angiogenesis ability of vascular endothelial cells. In addition, the AA2G-treated BMSCs CM enhanced migration and collagen formation of NIH-3T3 cells. In vivo, the AA2G-treated BMSCs group had a faster wound healing rate and a higher degree of vascularization in the new wound, compared with the PBS and BMSCs group. Moreover, AA2G preconditioning might enhance the demethylation process of BMSCs by regulating TET2 and up-regulating VEGF expression by activating the PI3K/AKT pathway. Conclusions AA2G-treated BMSCs promoted wound healing by promoting angiogenesis and collagen deposition, thereby providing a feasible strategy to reinforce the biofunctionability of BMSCs in treating wounds.

The objective of this study was to determine the antioxidant activities of defatted walnut kernel extract (DWE) and whole walnut kernel extract (WE) in vitro and in vivo. Three spectrophotometric methods, DPPH, ABTS, and FRAP, were used in in vitro experiments, and mice were used in in vivo experiments. In addition, response surface methodology (RSM) was used to optimize reflux-assisted ethanol extraction of DWE for maximum antioxidant activity and total phenolic content. The results of in vitro experiments showed that both extracts showed antioxidant activity; however, the antioxidant activity of DWE was higher than that of WE. Both extracts improved the mice’s oxidative damage status in in vivo studies. An ethanol concentration of 58%, an extraction temperature of 48 °C, and an extraction time of 77 min were the ideal parameters for reflux-assisted ethanol extraction of DWE. The results may provide useful information for further applications of defatted walnut kernels and the development of functional foods.

BackgroundHigh mobility group protein B3 (HMGB3) is abundantly expressed in a number of malignancies, contributing to tumor cell growth and predicting poor outcomes. More research on the connection between HMGB3 and breast cancer is needed. The prognostic significance of HMGB3 in breast cancer was examined and validated in this study.MethodsUsing The Cancer Genome Atlas (TCGA) database RNA sequencing and clinical data, we investigated the associations between HMGB3 expression and tumor mutations, prognosis, and immune infiltration in breast cancer. The Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), breast cancer gene-expression miner (bc-GenExMiner), UALCAN, OncoLnc, cBio Cancer Genomics Portal (cBioPortal), and LinkedOmics databases were applied to examine the levels of expression, mutation, coexpression, and immune correlation of HMGB3 in breast cancer. cBioPortal and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) were used for coexpression and enrichment analyses, respectively. Experimental tests and a separate cohort of breast cancer patients in our center were used for validation. To determine independent risk factors affecting breast carcinoma prognosis, multivariate Cox regression analysis was performed. The Kaplan-Meier method was applied to analyze the connection between HMGB3 expression and overall survival time in breast cancer.ResultsPan-cancer investigation using the GEPIA and UALCAN databases revealed a high level of HMGB3 expression in different malignancies, including breast cancer. HMGB3 might be a potential diagnostic biomarker, according to the receiver operating characteristic (ROC) curve (AUC=0.932). And immunohistochemistry confirmed higher HMGB3 protein expression in breast cancer tissues in clinical samples. Experimental tests also showed that breast cancer cells have higher expression of HMGB3, and knockdown of HMGB3 can promote the proliferation of breast cancer cells and increase sensitivity to chemotherapy. Human epidermal growth factor receptor 2 (HER2), Nottingham Prognostic Index (NPI), basal-like status, nodal status (N+), triple-negative status, and Scarff-Bloom-Richardson (SBR) grade all showed positive correlations with HMGB3 expression. Conversely, HMGB3 expression was negatively associated with the expression of estrogen receptor (ER) and progesterone receptor (PR) in breast cancer. Breast cancer patients with high HMGB3 expression had poor overall survival, which was validated by an analysis of a separate cohort of breast cancer patients in our center. Cox regression analysis identified high HMGB3 expression as an independently associated risk factor for breast carcinoma. The amount of immunological infiltration was substantially linked with the high expression of HMGB3. The chromosome centromeric region, ATPase activity, and the cell cycle are critical areas where HMGB3 is involved, according to enrichment analysis. Therefore, we suspected that HMGB3 might be a potential biomarker for detecting and treating breast carcinoma.ConclusionBreast cancer tissues had higher HMGB3 expression than normal breast tissues. HMGB3 overexpression may serve as an indicator for poor breast cancer outcomes.

Concomitant traumatic brain injury accelerates bone healing, but the mechanism is unclear. Here, the authors show that injured neurons, mainly those in the hippocampus, release osteogenic miRNA-enriched small extracellular vesicles, which targete osteoprogenitors to stimulate bone formation.

Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer (BC) with vicious behaviors. TNBC is usually associated with relatively poor clinical outcomes, earlier recurrence, and high propensity for visceral metastases than other BC types. TNBC has been increasingly recognized to constitute a very molecular heterogeneous subtype, which may offer additional therapeutic opportunities due to newly discovered cancer-causing drivers and targets. At present, there are multiple novel targeted therapeutic drugs in preclinical researches, clinical trial designs, and clinical practices, such as platinum drugs, poly ADP-ribose polymerase (PARP) inhibitors, immunocheckpoint inhibitors, androgen receptor inhibitors as well as PI3K/AKT/mTOR targeted inhibitors. These personalized, single, or combinational therapies based on molecular heterogeneity are currently showing positive results. The scope of this review is to highlight the latest knowledge about these potential TNBC therapeutic drugs, which will provide comprehensive insights into the personalized therapeutic strategies and options for combating TNBC.

Aberrant glycosylation, a post-translational modification of proteins, is regarded to engage in tumorigenesis and malignant progression of breast cancer (BC). The altered expression of glycosyltransferases causes abnormal glycan biosynthesis changes, which can serve as diagnostic hallmarks in BC. This study attempts to establish a predictive signature based on glycosyltransferase-related lncRNAs (GT-lncRNAs) in BC prognosis and response to immune checkpoint inhibitors (ICIs) treatment. We firstly screened out characterized glycosyltransferase-related genes (GTGs) through NMF and WGCNA analysis and identified GT-lncRNAs through co-expression analysis. By using the coefficients of 8 GT-lncRNAs, a risk score was calculated and its median value divided BC patients into high- and low-risk groups. The analyses unraveled that patients in the high-risk group had shorter survival and the risk score was an independent predictor of BC prognosis. Besides, the predictive efficacy of our risk score was higher than other published models. Moreover, ESTIMATE analysis, immunophenoscore (IPS), and SubMAP analysis showed that the risk score could stratify patients with distinct immune infiltration, and patients in the high-risk group might benefit more from ICIs treatment. Finally, the vitro assay showed that MIR4435-2HG might promote the proliferation and migration of BC cells, facilitate the polarization of M1 into M2 macrophages, enhance the migration of macrophages and increase the PD-1/PD-L1/CTLA4 expression. Collectively, our well-constructed prognostic signature with GT-lncRNAs had the ability to identify two subtypes with different survival state and responses to immune therapy, which will provide reliable tools for predicting BC outcomes and making rational follow-up strategies.

Grass carp (Ctenopharyngodon idellus, C.idellus) is one of the most important globally cultured freshwater fish species, and its growth trait can be improved by dietary supplementation of oligopeptides which is transported through the intestinal oligopeptide transporter PepT1. However, many aspects of the molecular regulation mechanism of C.idellus PepT1 still remains elusive. In this study, the regulation mechanism of C.idellus PepT1 by CDX2 was extensively studied. Firstly, the interaction of the C.idellus CDX2 and SP1 was investigated by mammalian two hybrid assays and co-localization; The promoter sequence of PepT1 was cloned and its activity was directly up-regualted by CDX2. In the further study, the effect of CDX2 changes at both mRNA and protein levels on the expression of PepT1 was examined in vivo and in vitro. The mRNA expression of PepT1 was significantly decreased when CDX2 was repressed and its expression change profile was almost consistent with that of CDX2. To understand the regulation of CDX2 on the expression of PepT1 at protein level, the stability regulation mechanism of CDX2 was initially studied. The results showed that CDX2 protein was degraded via the ubiquitin-proteasome pathways, and increasing phosphorylation level of CDX2 protein declined its turnover and elevated its accumulation level in cells. The expression of PepT1 was significantly elevated with increasing CDX2 protein stability, and expressions of both CDX2 and PepT1 were stimulated by the oligopeptide. In conclusion, these observations may shed new light on the molecular regulation mechanism of PepT1 by CDX2 in C.idellus and provide new perceptions and strategies for the efficient transportation of intestinal oligopeptides in teleost fish.

BackgroundNeoadjuvant chemoradiotherapy (neo-CRT) plus surgery has greatly improved the prognosis of locally advanced esophageal cancer (EC) patients. But which factors may influence the pathological tumor response and long-term survival remains unclear. The purpose of this study was to identify the prognostic biomarkers of locally advanced EC patients receiving neo-CRT.MethodsWe reviewed the data of 72 patients with cT2-4N0-3M0 EC who underwent neo-CRT at our hospital. The patients received intensity-modulated radiation therapy with a total radiation dose of 41.4–60.0 Gy. Most patients received platinum + paclitaxel-based combination regimens every three weeks for 2–4 cycles. The recorded data included age, sex, smoking history, alcohol use, histology, tumor location, clinical TNM stage, tumor length, gross tumor volume (GTV), GTV of primary tumor (GTVp), GTV of lymph nodes (GTVn), radiation dose, and number of chemotherapy cycles. Overall survival (OS), progression-free survival (PFS), and pathological complete response (pCR) were analyzed.ResultsThe 3-year OS and PFS rates of these patients who underwent neo-CRT were 51.14% and 43.28%, respectively. In the univariate analyses, smoking history, clinical stage, GTV, GTVp, and GTVn were significantly associated with OS, whereas alcohol use, GTV, GTVp, and GTVn were significantly associated with PFS. Furthermore, in the multivariate analysis, GTV was an independent prognostic predictor of OS (hazard ratio (HR): 14.14, 95% confidence interval (CI): 3.747–53.33, P < 0.0001) and PFS (HR: 6.090, 95% CI: 2.398–15.47, P < 0.0001). In addition, GTV < 60.50 cm3 compared to > 60.50 cm3 was significantly associated with higher pCR rate (59.3% and 27.8%, respectively, P = 0.038). High dose (> 50 Gy) and increased number of chemotherapy cycles (≥ 3) didn’t improve the OS or PFS in patients with GTV > 60.50 cm3.ConclusionGTV was an independent prognostic factor of long-term survival in EC patients, which may be because GTV is associated with histological response to neo-CRT. Additionally, patients with GTV > 60.50 cm3 didn’t benefit from increased radiation dose or increased number of chemotherapy cycles.

BackgroundPregnant women are a common group of people with tuberculosis,especially in patients infected with HIV at the same time. Antituberculosis drug prophylaxis is effective in reducing tuberculosis infection in pregnant women and fetuses after pregnancy, but its safety is still worthy of in-depth discussion. In this study, we conducted a systematic review and meta-analysis of reports on the use of antituberculosis drugs during pregnancy in recent years to provide evidence for clinical diagnosis and treatment.MethodsThe PubMed, Embase, Web of Science databases, Ovid, and clinicaltrials.gov were searched. Search for clinical randomized controlled studies and cohort studies on the use of antituberculosis drugs during pregnancy published in the databases from January 2000 to September 2021 was performed using the Stata 16.0 software after screening qualified bodies of literature.ResultsOn the basis of the initial search of 408 articles, this study included a total of 8 articles and 2,563 patients after screening; meta-analysis results showed that preventive treatment with antituberculosis drugs did not increase the incidence of serious maternal adverse events [RR = 0.99, 95% CI (.88, 1.12), Z = −0.108, P = 0.914], did not increase drug hepatotoxicity [RR = 1.13, 95% CI (.9, 1.43), Z = 1.071, P = 0.284], did not increase the incidence of peripheral nerve disease [RR = 1.52, 95% CI (.85, 2.71), Z = 1.412, P = 0.158], did not increase maternal mortality [RR = 0.67, 95% CI (.27, 1.7), Z = −0.84, P = 0.401], and could significantly reduce adverse pregnancy outcomes [RR = 0.78, 95% CI (0.68, 0.89), Z = −3.581, P < 0.0001].DiscussionThe use of antituberculosis drugs for preventive treatment during pregnancy is safe and can obtain better pregnancy outcomes.

Abstract Background Chronic kidney disease (CKD) is a worldwide public health problem characterized by changes in kidney structure and function, usually leading to a loss of kidney function. The identification of risk factors and management of patients with early-stage CKD may slow or prevent the progression to end-stage renal disease. Methods This study used the population-based cohort database from the China Health and Nutrition Survey (CHNS). Data from 11,978 patients were collected from the 2009 to 2011 wave of the CHNS. After removing patients with missing data, we finally included 8322 participants. A cross-sectional design was used to assess the association between Apolipoprotein B (Apo-B) levels and CKD. We used overlapping covariates to develop 5 models to evaluate the odds ratios. Results Among the study participants, patients with estimated glomerular filtration rates (eGFR) 1.2 mmol/L, 19.41%), likely to be elderly (> 65 years, 61.76%), likely to be female (61.21%), and likely to be less educated ( 6 & ≤12 years, 32.07 and 52.44%, respectively).The significant association between Apo-B and CKD defined by eGFR even after adjusting for confounders including demographic characteristics, nutritional status, comorbidities, biochemical indicators, and lifestyle factors. In addition, stratified analyses showed that young and middle age ( 25 kg/m2), and hyperuricemia were associated with higher risks of CKD stages. Conclusions The results of this Chinese population-based study revealed a strong positive correlation between Apo-B and CKD stages. The current findings were obtained from an epidemiologic study; therefore, these data cannot directly address the mechanisms of disease progression. The underlying mechanisms require analysis in future independent validation and prospective cohort studies.

Energy security and the reduction of greenhouse gases such as carbon dioxide are two major crises facing the world today. Using carbon dioxide to develop unconventional oil and gas resources is a positive way to reduce greenhouse gas emissions, which can significantly alleviate global energy security issues. This study systematically introduces the prerequisites for CO2 to extract crude oil and CO2 to be safely and effectively stored. Under high temperature and high pressure, the rock properties of deep reservoirs are completely different from those of atmospheric conditions in the two-phase porous media environment of crude oil and high salinity formation water. The research progress on the phase behavior, mutual solubility, CO2 storage potential and mechanism between supercritical CO2 and crude oil, formation water and reservoir are reviewed in detail. In addition, CO2 leakage will inevitably occur during long-term geological storage, the proper estimation and evaluation of the risk and establishment of corresponding sealing methods are the way forward for CO2 geological storage. By systematically elaborating the nature, advantages and disadvantages of fluid–fluid, fluid–solid interaction and geological integrity destruction mechanism, the directions in which several key problems should be solved were pointed out.

Kidney-type glutaminase, encoded by the gls1 gene, plays a critical role in glutamate production and improvement of meat flavor. In this study, a gls1 gene encoding 595 amino acids was cloned from triploid crucian carp (Carassius auratus) (TCC) and showed a high similarity with the gls1 gene found in Cyprinus carpio, Sinocyclocheilus rhinocerous and Puntigrus tetrazona. Comparing the abundance of gls1 in different tissues, we found its expression level in the brain and liver were significantly higher than that in heart, gut, kidney, spleen and muscle. gls1 expression in the brain reached the highest value. In addition, the expression levels of gls1 also appeared different in diurnal variation, with the highest expression seen at 9:00, while it was low at 3:00, 6:00, 15:00 and 24:00. Furthermore, dietary regulation of gls1 expression was investigated in our study. In each feeding trial, each diet was randomly assigned to triplicate tanks. Fish were fed one of the tested diets up to satiation twice daily. The results showed that gls1 expression increased in 32% protein group and decreased in 35–41% protein group. The results of different protein source experiments showed that the expression of gls1 gene in the mixed protein group (the control group) was significantly higher than that in the fish meal and soybean meal groups. Glutamate treatment revealed that appropriate concentrations (0.10 mg/mL in vivo and 2.00% in vitro) of glutamate remarkably improved the expression of gls1. Besides, diets supplemented with 0.80–1.60% lysine-glutamate dipeptide exhibited a down regulatory impact on gls1 expression. In conclusion, this study demonstrated that the expression of gls1 in TCC was increased by 32% protein diet, mixed protein source diet and diet with 2.00% glutamate concentration, while decreased by 0.80–1.60% lysine-glutamate dipeptide. The findings of this study provide a reference for the regulation of gls1 and have a potential application in the optimization of dietary formula in aquaculture.

The nutritional functions of tributyrin (TB) have been extensively studied, but questions remain regarding its influence on the growth of juvenile grass carp (Ctenopharyngodon idellus) and the regulation pathway to PepT1 in the intestine of grass carp. To answer the remaining questions, feeding trials, cell trials, and peritoneal injection trials were conducted in this study. The results showed that an appropriate level of TB (0.5 g/kg and 1.0 g/kg) supplementation in feed significantly promoted the growth performance of juvenile grass carp. The expressions of intestine genes (CDX2, SP1 and PepT1) related to oligopeptide transportation increased in the 0.5 g/kg TB group of feeding trials and both the 5 mM and 10 mM TB groups of the intestine cell trials, respectively. Subsequently, the injection trials of inhibitors CDX2 and SP1 demonstrated that the inhibition of CDX2 or SP1 decreased the mRNA expression of PepT1. Finally, the results of independent or combined treatments of TB and the inhibitors suggested that CDX2/SP1 mediated TB regulation on PepT1. These findings may help us to better understand the functions of TB on growth and PepT1 oligopeptide transportation, which could be modulated by dietary TB through the CDX2/SP1-PepT1 pathway in juvenile grass carp.

Glutamine synthetase (GS) is a key enzyme that catalyzes the synthesis of glutamine from glutamate, which plays a role in the promotion of muscle cell growth and in improving the flavor of meats. In this study, a GS gene encoding 371 amino acids was cloned from triploid crucian carp and showed the highest level of similarity with the GS gene found in Cyprinus carpio. Meanwhile, GS was differentially expressed in different tissues, and its day–night expression changes showed obvious oscillation. Additionally, the effects of glutamate and glutamine on GS expression in muscle cells were investigated in vitro and in vivo. We found that its expression was obviously increased due to high levels of glutamate (2 mg/mL) but decreased by glutamine in vitro. However, it was significantly promoted by glutamate and glutamine in vivo, with an optimal concentration of 2%. Furthermore, the use of lysine–glutamate dipeptides as feed additives also had a positive influence on GS expression (the optimal concentration is 0.8%). Finally, we explored the effects of different protein levels and sources on the expression of GS, and the results demonstrated that GS had the highest expression at the 35% protein level, but no significant differences were observed in the different protein sources between the fish meal diet (FM) and the mixed diet comprising soybean meal and rapeseed meal (SM). This study sheds new light on the regulation of GS in teleost fish and provides new perceptions and strategies for the formulation of high-quality feed for triploid crucian carp.

MicroRNA-126 (miR-126) is an endothelial-specific microRNA that has shown beneficial effects on endothelial dysfunction. However, the underlying molecular mechanism is unclear. The present study evaluated the effects of miR-126 on the cell migration and underlying mechanism in HUVECs treated with palmitate. The present results demonstrated that overexpression of miR-126 was found to decrease cell migration in palmitate-treated HUVECs, with decreased MLCK expression and subsequent decreased phosphorylated MLC level. miR-126 also decreased the phosphorylation of MYPT1 in palmitate-treated HUVECs. In addition, it was demonstrated that miR-126 decreases expression of the NADPH oxidase subunits, p67 and Rac family small GTPase 1 with a subsequent decrease in cell apoptosis. Moreover, the phosphorylation of ERK was reduced by miR-126 in palmitate-induced HUVECs. Taken together, the present study showed that the effect of miR-126 on cell migration and cell apoptosis is mediated through downregulation of MLCK via the ERK/MAPK pathway.

Microorganisms play a significant part in detoxifying and immobilizing excessive metals. The present research isolated a strain (HM7) with high Mn(II) tolerance from Mn(II)-contaminated soil samples. The 16S rDNA sequence analysis showed that HM7 had a 99% similarity to Bacillus thuringiensis, which can survive under a high concentration 4,000 mg/L of Mn(II), and the highest removal rate was up to 95.04% at the concentration of 400 mg/L. The highest Mn(II) removal rate was detected at the contact time 72 h, temperature 30 °C, and pH 5.0, while the differences in strain growth and Mn(II) removal rate among different inoculation doses were insignificant. Scanning electron microscopy indicated B. thuringiensis HM7 cells appeared irregular and cracked under Mn(II) stress. Fourier transform infrared exhibited that functional groups like carboxyl, hydroxyl, amino, sulfhydryl groups, and amide bands might take part in the complexation of Mn(II). In addition, HM7 suggested the ability of indoleacetic acid production, siderophore production, and P’ solubilization potential. Therefore, HM7 might have a potential to promote metal absorption by changing the form of heavy metals, and the experiments supported the application of B. thuringiensis HM7 as a biological adsorbent in Mn(II) contaminated environment remediation.

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

Chemotherapy is extensively used to treat cancers and is often associated with ovarian damage and leads to premature ovarian insufficiency and infertility, while the role of mitochondria during ovarian damage with chemotherapy remains unknown. This study used a mouse model with oocyte-specific deletion of mitochondrial stress response gene Caseinolytic peptidase P (Clpp) to investigate mitochondrial homeostasis in oocytes from mice receiving a chemotherapeutic drug cyclophosphamide (CTX). We found that oocyte-specific deletion of Clpp reduced fecundity of the mice at advanced age. The deletion led to meiotic defects with elevated abnormal spindle rate and aneuploidy rate with impaired mitochondrial function in the MII oocytes from 8-week-old mice. Upon CTX treatment at 8-week-old, the oocyte competence and folliculogenesis from the oocyte-specific Clpp knockout mice was further deteriorated with dramatic impairment of mitochondrial distribution and function including elevated ROS level, decreased mitochondrial membrane potential, respiratory chain activity and ATP production. Taken together, the results indicate that that ClpP was required for oocyte competence during maturation and early folliculogenesis, and its deficiency deteriorate cyclophosphamide-induced ovarian damage. [ABSTRACT FROM AUTHOR]