Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

Safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma.

PURPOSE: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma. METHODS: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878). CONCLUSION: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious.

Targeted chemical profiling for p-HAP glycosides by using molecular networking and comparative analysis of their contents between Artemisia japonica and Artemisia capillaris.

A total of 65 phenolic acid compounds were annotated or identified by UHPLC-MS/MS method, among them, 17 p-HAP (p-hydroxyacetophenone) glycosides were firstly targeted profiled based on molecular networking. Their characteristic product ions of MS/MS spectra were found and examined on the guideline of targeted isolation. As a result, a new p-HAP glycoside was thus obtained and determined as 2'-O-caffeoyl-p-HAP-4-O-ß-D-glucopyranoside (33) based on 1D and 2D NMR data. Besides, multicomponents quantitative analysis indicated the distinct regional variability in chemicals distribution of A. japonica, and meanwhile, the contents of p-HAP glycosides from A. japonica were higher than those in A. capillaris as a whole, which further suggested the potential medicinal value of A. japonica.

Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Long-Term Results From the PKUFH Randomized Phase 3 Trial.

PURPOSE: In the randomized, single-center, PKUFH phase 3 trial, dose-intensified (72 Gy) radiation therapy was compared with conventional (66 Gy) radiation therapy. In a previous study, we found no significant difference in biochemical progression-free survival (bPFS) between the 2 cohorts at 4 years. In the current analysis, we provide 7-year outcomes. METHODS AND MATERIALS: Patients with stage pT3-4, positive surgical margins, or a prostate-specific antigen increase ≥0.2 ng/mL after radical prostatectomy were randomly assigned 1:1 to receive either 72 Gy in 36 fractions or 66 Gy in 33 fractions. All the patients underwent image guided intensity modulated radiation therapy. The primary endpoint was bPFS. Secondary endpoints were distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) as estimated using the Kaplan-Meier method. RESULTS: Between September 2011 and November 2016, 144 patients were enrolled with 73 and 71 in the 72- and 66-Gy cohorts, respectively. At a median follow-up of 89.5 months (range, 73-97 months), there was no difference in 7-year bPFS between the 72- and 66-Gy cohorts (70.3% vs 61.2%; hazard ratio [HR], 0.73; 95% CI, 0.41-1.29; P = .274). However, in patients with a higher Gleason score (8-10), the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with the 66-Gy cohort (66.5% vs 30.2%; HR, 0.37; 95% CI, 0.17-0.82; P = .012). In addition, in patients with multiple positive surgical margins, the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with single positive surgical margin (82.5% vs 57.5%; HR, 0.36; 95% CI, 0.13-0.99; P = .037). The 7-year DMFS (88.4% vs 84.9%; HR, 0.93; 95% CI, 0.39-2.23; P = .867), CSS (94.1% vs 95.5%; HR, 1.19; 95% CI, 0.42-3.39; P = .745), and OS (92.8% vs 94.1%; HR, 1.29; 95% CI, 0.51-3.24; P = .594) had no statistical differences between the 72- and 66-Gy cohorts. CONCLUSIONS: The current 7-year bPFS results confirmed our previous findings that dose escalation (72 Gy) demonstrated no improvement in 7-year bPFS, DMFS, CSS, or OS compared with the 66-Gy regimen. However, patients with a higher Gleason score (8-10) or multiple positive surgical margins might benefit from the 72-Gy regimen, but this requires further prospective research.

Proteomic characterization of epithelial ovarian cancer delineates molecular signatures and therapeutic targets in distinct histological subtypes.

Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.

3D-Printed MOFs/Polymer Composite as a Separatable Adsorbent for the Removal of Phenylarsenic Acid in the Aqueous Solution.

Metal-organic frameworks (MOFs) are emerging as advanced nanoporous materials to remove phenylarsenic acid, p-arsanilic acid (p-ASA), and roxarsone (ROX) in the aqueous solution, while MOFs are often present as powder state and encounter difficulties in recovery after adsorption, which greatly limit their practical application in the aqueous environments. Herein, MIL-101 (Fe), a typical MOF, was mixed with sodium alginate and gelatin to prepare MIL-101@CAGE by three-dimensional (3D) printing technology, which was then used as a separatable adsorbent to remove phenylarsenic acid in the aqueous solution. The structure of 3D-printed MIL-101@CAGE was first characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and thermogravimetry and differential thermogravimetry (TG-DTG). The octahedral morphology of MIL-101 (Fe) was found unchanged during the 3D printing process. Then, the adsorption process of MIL-101@CAGE on phenylarsenic acids was systematically investigated by adsorption kinetics, adsorption isotherms, adsorption thermodynamics, condition experiments, and cyclic regeneration experiments. Finally, the adsorption mechanism between MIL-101@CAGE and phenylarsenic acid was further investigated. The results showed that the Langmuir, Freundlich, and Temkin isotherms were well fit, and according to the Langmuir fitting results, the maximum adsorption amounts of MIL-101@CAGE on p-ASA and ROX at 25 °C were 106.98 and 120.28 mg/g, respectively. The removal of p-ASA and ROX by MIL-101@CAGE remained stable over a wide pH range and in the presence of various coexisting ions. The regeneration experiments showed that the 3D-printed MIL-101@CAGE could still maintain a more than 90% removal rate after five cycles. The adsorption mechanism of this system might include π-π stacking interactions between the benzene ring on the phenylarsenic acids and the organic ligands in MIL-101@CAGE, hydrogen-bonding, and ligand-bonding interactions (Fe-O-As). This study provides a new idea for the scale preparation of a separatable and recyclable adsorbent based on MOF material for the efficient removal of phenylarsenic acid in the aqueous solution.

Glutamate-pantothenate pathway promotes antibiotic resistance of Edwardsiella tarda.

Although cellular metabolic states have been shown to modulate bacterial susceptibility to antibiotics, the interaction between glutamate (Glu) and chloramphenicol (CAP) resistance remains unclear because of the specificity of antibiotics and bacteria. We found that the level of Glu was upregulated in the CAP-resistant strain of Edwardsiella tarda according to a comparative metabolomics approach based on LC-MS/MS. Furthermore, we verified that exogenous metabolites related to Glu, the tricarboxylic acid (TCA) cycle, and glutathione (GSH) metabolism could promote CAP resistance in survival assays. If GSH metabolism or the TCA cycle is inhibited by L-buthionine sulfoximine or propanedioic acid, the promotion of CAP resistance by Glu in the corresponding pathway disappears. According to metabolomic analysis, exogenous Glu could change pantothenate metabolism, affecting GSH biosynthesis and the TCA cycle. These results showed that the glutamate-pantothenate pathway could promote CAP resistance by being involved in the synthesis of GSH, entering the TCA cycle by direct deamination, or indirectly affecting the metabolism of the two pathways by pantothenate. These results extend our knowledge of the effect of Glu on antibiotic resistance and suggest that the potential effect, which may aggravate antibiotic resistance, should be considered before Glu and GSH administration in the clinic.

Current advances in the detection and removal of organic arsenic by metal-organic frameworks.

Arsenic (As) is a highly toxic heavy metal and has been widely concerned for its hazardous environmental impact. Aromatic organic arsenic (AOCs) has been frequently used as an animal supplement to enhance feed utilization and prevent dysentery. The majority of organic arsenic could be discharged from the body and evolve as highly toxic inorganic arsenic that is hazardous to the environment and human health via biological conversion, photodegradation, and photo-oxidation. Current environmental issues necessitate the development and application of multifunctional porous materials in environmental remediation. Compared to the conventional adsorbent, such as activated carbon and zeolite, metal-organic frameworks (MOFs) exhibit a number of advantages, including simple synthesis, wide variety, simple modulation of pore size, large specific surface area, excellent chemical stability, and easy modification. In recent years, numerous scientists have investigated MOFs related materials involved with organic arsenic. These studies can be divided into three categories: detection of organic arsenic by MOFs, adsorption to remove organic arsenic by MOFs, and catalytic removal of organic arsenic by MOFs. Here, we conduct a critical analysis of current research findings and knowledge pertaining to the structural characteristics, application methods, removal properties, interaction mechanisms, and spectral analysis of MOFs. We summarized the application of MOFs in organic arsenic detection, adsorption, and catalytic degradation. Other arsenic removal technologies and conventional substances are also being investigated. This review will provide relevant scientific researchers with references.

Overexpression of Taetr1-1 promotes enhanced seed dormancy and ethylene insensitivity in wheat.

MAIN CONCLUSION: Taetr1-1 can promote enhanced seed dormancy and ethylene insensitivity in wheat, indicating a conserved function of ETR1 in regulating seed dormancy. Lots of wheat cultivars have weak dormant seed. Weak seed dormancy can cause pre-harvest sprouting (PHS) in grain which significantly reduces grain yield and quality. The mining of causal genes of PHS resistance will serve to enhance breeding selection and cultivar development. In a previous study in Arabidopsis, we identified reduced dormancy 3 as a loss-of-function mutant of the ethylene receptor 1 (ETR1), which can control seed dormancy through the ERF12-TPL-DOG1 pathway. However, it is unknown whether ETR1 also functions in the regulation of wheat seed dormancy. To identify the regulatory role of ETR1 in wheat, we cloned TaETR1 and overexpressed the gain-of-function mutant Taetr1-1. The result indicated that overexpression of Taetr1-1 can promote enhanced seed dormancy and ethylene insensitivity in wheat. This study contributed to our understanding of the molecular basis for the regulation of wheat PHS resistance.

Outcomes of catheter-directed thrombolysis versus systemic thrombolysis in the treatment of pulmonary embolism: a meta-analysis.

OBJECTIVE: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) versus systemic thrombolysis (ST) in the treatment of pulmonary embolism (PE). METHODS: The Cochrane Library, PubMed, and Embase databases were searched to collect the literature on the comparison of the results of CDT and ST in the treatment of PE from the beginning of their records to May 2020, and meta-analysis was performed by STATA software (version 15.1). Using standardized data-collection forms, the authors screened the studies and independently extracted data, and assessed the quality of the studies using the Newcastle-Ottawa Scale for cohort studies. Cohort studies that examined the following results were included in the current study: in-hospital mortality, all-cause bleeding rate, gastrointestinal bleeding rate, intracranial hemorrhage rate, the incidence of shock, and hospital length of stay. RESULTS: A total of eight articles, with 13,242 participants, involving 3962 participants in the CDT group and 9280 participants in the ST group were included. CDT compared with ST in the treatment of PE can significantly affect in-hospital mortality rate [odds ratio (OR) = 0.41, 95% CI: 0.30-0.56, P < 0.05], all-cause bleeding rate (OR = 1.20, 95% CI: 1.04-1.39, P = 0.012), gastrointestinal bleeding rate (OR = 1.43, 95% CI: 1.13-1.81, P = 0.003), the incidence of shock (OR = 0.46, 95% CI: 0.37-0.57, P < 0.05), and hospital length of stay [standard mean difference (SMD) = 0.16, 95% CI: 0.07-0.25, P < 0.05]. However, there was no significant effect on intracranial hemorrhage rate in patients with PE (OR = 0.70, 95% CI: 0.47-1.03, P = 0.070). CONCLUSIONS: CDT is a viable alternative to ST in the treatment of PE, as it can significantly reduce in-hospital mortality rate, all-cause bleeding rate, gastrointestinal bleeding rate, and incidence of shock. However, CDT may prolong hospital length of stay to a certain extent. Further research is needed to evaluate the safety and efficacy of CDT and ST in the treatment of acute PE and other clinical outcomes.

Steatotic hepatocyte-derived extracellular vesicles promote ß-cell apoptosis and diabetes via microRNA-126a-3p.

Extracellular vesicles (EVs) have emerged as a unique mediator of interorgan communications, playing important roles in the pathophysiologic process of various diseases, including diabetes and other metabolic diseases. Here, we reported that the EVs released by steatotic hepatocytes exerted a detrimental effect on pancreatic ß cells, leading to ß-cell apoptosis and dysfunction. The effect was profoundly attributable to an up-regulation of miR-126a-3p in the steatotic hepatocyte-derived EVs. Accordingly, overexpression of miR-126a-3p promoted, whereas inhibition of miR-126a-3p prevented ß-cell apoptosis, through a mechanism related to its target gene, insulin receptor substrate-2. Moreover, inhibition of miR-126a-3p by its specific antagomir was able to partially reverse the loss of ß-cell mass and ameliorate hyperglycaemia in diabetic mice. Thus, the findings reveal a novel pathogenic role of steatotic hepatocyte-derived EVs, which mechanistically links nonalcoholic fatty liver disease to the development of diabetes.

Efficacy and safety of vena cava filters in preventing pulmonary embolism: A systematic review and meta-analysis.

OBJECTIVES: To assess the treatment effectiveness of inferior vena cava filters (IVCF) versus non-IVCF for patients undergoing varies conditions. METHODS: We systematically searched the databases to identify eligible RCTs from their inception up to 9/20/2020. The primary endpoint was pulmonary embolism (PE), while the secondary endpoints included deep-vein thrombosis (DVT), major bleeding, and all-cause mortality. The RRs with 95% CIs were applied as effect estimates for the treatment effectiveness of IVCF versus non-IVCF and calculated by using the random-effects model. RESULTS: 1,137 patients of 5 RCTs were enrolled. There were no significant differences between IVCF and non-IVCF for the risk of PE, major bleeding, and all-cause mortality, while the risk of DVT was significantly increased for patients treated with IVCF. CONCLUSIONS: The use of IVCF did not yield any benefits on PE, major bleeding, and all-cause mortality risk for patients undergoing various conditions, while the risk of DVT was significantly increased for patients treated with IVCF.

Lignin-based composites with enhanced mechanical properties by acetone fractionation and epoxidation modification.

Epoxy resin is widely used in various fields of the national economy due to its excellent chemical and mechanical properties. Lignin is mainly derived from lignocelluloses as one of the most abundant renewable bioresources. Due to the diversity of lignin sources and the complexity as well as heterogeneity of its structure, the value of lignin has not been fully realized. Herein, we report the utilization of industrial alkali lignin for the preparation of low-carbon and environmentally friendly bio-based epoxy thermosetting materials. Specifically, epoxidized lignin with substituted petroleum-based chemical bisphenol A diglycidyl ether (BADGE) in various proportions was cross-linked to fabricate thermosetting epoxies. The cured thermosetting resin revealed enhanced tensile strength (4.6 MPa) and elongation (315.5%) in comparison with the common BADGE polymers. Overall, this work provides a practicable approach for lignin valorization toward tailored sustainable bioplastics in the context of a circular bioeconomy.

Curcumol Exerts Antitumor Effect via Inhibiting EGFR-Akt-Mcl-1 Signaling.

Dysfunction of epidermal growth factor receptor (EGFR) signaling plays a critical role in the tumorigenesis of oral squamous cell carcinoma (OSCC). In the present study, the data analysis results of immunohistochemistry and the TCGA database verified that the expression of EGFR is significantly upregulated in OSCC tumor tissues, and depletion of EGFR inhibits the growth of OSCC cells in vitro and in vivo. Moreover, these results showed that the natural compound, curcumol, exhibited a profound antitumor effect on OSCC cells. Western blotting, MTS, and immunofluorescent staining assays indicated that curcumol inhibited cell proliferation and induced intrinsic apoptosis in OSCC cells via downregulating myeloid cell leukemia 1 (Mcl-1). A mechanistic study revealed that curcumol inhibited the EGFR-Akt signal pathway, which activated GSK-3[Formula: see text]-mediated Mcl-1 phosphorylation. Further research showed that curcumol-induced Mcl-1 Ser159 phosphorylation is required to disrupt the interaction between deubiquitinase JOSD1 and Mcl-1 and eventually induce Mcl-1 ubiquitination and degradation. In addition, curcumol administration can effectively inhibit CAL27 and SCC25 xenograft tumor growth and is well-tolerated in vivo. Finally, we demonstrated that Mcl-1 is upregulated and positively correlates with p-EGFR and p-Akt in OSCC tumor tissues. Collectively, the present results provide new insights into the antitumor mechanism of curcumol, identifying it as an attractive therapeutic agent that reduces Mcl-1 expression and inhibits OSCC growth. Targeting EGFR/Akt/Mcl-1 signaling could be a promising option in the clinical treatment of OSCC.

Strong Cumulative Evidence of Associations of 6 Single Nucleotide Polymorphisms with Ovarian Cancer Risk: An Umbrella Review.

Background: An increasing number of studies have reported associations between single nucleotide polymorphisms (SNPs) and ovarian cancer (OC) risk. However, some of the findings were inconsistent. The objective of this umbrella review was to evaluate the associations comprehensively and quantitatively. Methods: The protocol of this review was registered in PROSPERO (No. CRD42022332222). We searched the PubMed, Web of Science, and Embase databases to identify related systematic reviews and meta-analyses from inception to 15 October 2021. In addition to estimating the summary effect size by using fixed and random effects models and calculating the 95% prediction interval, we evaluated the cumulative evidence for associations with nominally statistical significance based on the Venice criteria and false positive report probability (FPRP). Results: Forty articles were included in this umbrella review, which referred to a total of 54 SNPs. The median number of original studies per meta-analysis was four, while the median number of total subjects was 3455. All included articles had greater than moderate methodological quality. A total of 18 SNPs were nominally statistically associated with OC risk; 6 SNPs (8 genetic models), 5 SNPs (7 genetic models), and 16 SNPs (25 genetic models) were identified as strong, moderate, and weak cumulative evidence, respectively. Conclusion: This umbrella review revealed associations between SNPs and OC risk and suggested strong cumulative evidence of associations of six SNPs (eight genetic models) with OC risk.

Nomogram based on the O-RADS for predicting the malignancy risk of adnexal masses with complex ultrasound morphology.

OBJECTIVE: The accurate preoperative differentiation of benign and malignant adnexal masses, especially those with complex ultrasound morphology, remains a great challenge for junior sonographers. The purpose of this study was to develop and validate a nomogram based on the Ovarian-Adnexal Reporting and Data System (O-RADS) for predicting the malignancy risk of adnexal masses with complex ultrasound morphology. METHODS: A total of 243 patients with data on adnexal masses with complex ultrasound morphology from January 2019 to December 2020 were selected to establish the training cohort, while 106 patients with data from January 2021 to December 2021 served as the validation cohort. Univariate and multivariate analyses were used to determine independent risk factors for malignant tumors in the training cohort. Subsequently, a predictive nomogram model was developed and validated in the validation cohort. The calibration, discrimination, and clinical net benefit of the nomogram model were assessed separately by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Finally, we compared this model to the O-RADS. RESULTS: The O-RADS category, an elevated CA125 level, acoustic shadowing and a papillary projection with color Doppler flow were the independent predictors and were incorporated into the nomogram model. The area under the ROC curve (AUC) of the nomogram model was 0.958 (95% CI, 0.932-0.984) in the training cohort. The specificity and sensitivity were 0.939 and 0.893, respectively. This nomogram also showed good discrimination in the validation cohort (AUC = 0.940, 95% CI, 0.899-0.981), with a sensitivity of 0.915 and specificity of 0.797. In addition, the nomogram model showed good calibration efficiency in both the training and validation cohorts. DCA indicated that the nomogram was clinically useful. Furthermore, the nomogram model had higher AUC and net benefit than the O-RADS. CONCLUSION: The nomogram based on the O-RADS showed a good predictive ability for the malignancy risk of adnexal masses with complex ultrasound morphology and could provide help for junior sonographers.

Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2/HO-1 signaling pathway.

Oxidative stress is an important pathogenic factor in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), further impairing the entire colon. Intestinal epithelial cells (IECs) are crucial components of innate immunity and play an important role in maintaining intestinal barrier function. Recent studies have indicated that microRNA-222-3p (miR-222-3p) is increased in colon of UC and colorectal cancer (CRC) patients, and miR-222-3p is a crucial regulator of oxidative stress. However, whether miR-222-3p influences IEC oxidative stress in UC and CAC remains unknown. This study investigated the effect of miR-222-3p on the regulation of IEC oxidative stress in UC and CAC. An in vitro inflammation model was established in NCM460 colonic cells, mouse UC and CAC models were established in vivo, and IECs were isolated. The biological role and mechanism of miR-222-3p-mediated oxidative stress in UC and CAC were determined. We demonstrated that miR-222-3p expression was notably increased in dextran sulfate sodium (DSS)-induced NCM460 cells and IECs from UC and CAC mice. In vitro, these results showed that the downregulation of miR-222-3p reduced oxidative stress, caspase-3 activity, IL-1ß and TNF-α in DSS-induced NCM460 cells. We further identified BRG1 as the target gene of miR-222-3p, and downregulating miR-222-3p alleviated DSS-induced oxidative injury via promoting BRG1-mediated activation Nrf2/HO-1 signaling in NCM460 cells. The in vivo results demonstrated that inhibiting miR-222-3p in IECs significantly relieved oxidative stress and inflammation in the damaged colons of UC and CAC mice, as evidenced by decreases in ROS, MDA, IL-1ß and TNF-α levels and increases in GSH-Px levels. Our study further demonstrated that inhibiting miR-222-3p in IECs attenuated oxidative damage by targeting BRG1 to activate the Nrf2/HO-1 signaling. In summary, inhibiting miR-222-3p in IECs attenuates oxidative stress by targeting BRG1 to activate the Nrf2/HO-1 signaling, thereby reducing colonic inflammation and tumorigenesis.

[Meta-analysis and GRADE evaluation of Guanxinning Tablets in treatment of angina pectoris of coronary heart disease].

This study aims to evaluate the efficacy and safety of Guanxinning Tablets+conventional western medicine in the treatment of angina pectoris of coronary heart disease, and provide evidence-based references for clinical medication. Retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, randomized controlled trial(RCT) about Guanxinning Tablets for the treatment of angina pectoris of coronary heart disease from the inception to April 2022 were collected. After literature screening and data extraction, the bias risk assessment tool recommended by the Cochrane evaluation manual handbook 5.1.0 was used to evaluate the quality of the included literature, and RevMan 5.3 and Stata 14.0 were used for Meta-analysis. Eighteen RCTs were finally included, involving 2 281 patients. Meta-analysis showed that, compared with conventional western medicine treatment alone, Guanxinning Tablets+conventional western medicine significantly improved angina pectoris efficacy(RR=1.33, 95%CI[1.13, 1.57], P=0.000 8), electrocardiogram efficacy(RR=1.32, 95%CI[1.02, 1.71], P=0.03), and exercise duration(MD=59.53, 95%CI[39.16, 79.90], P<0.000 01) and reduced the incidence of cardiovascular events(MACE)(RR=0.43, 95%CI[0.30, 0.61], P<0.000 01), high sensitivity C-reactive protein(hs-CRP)(MD=-2.75, 95%CI[-3.71,-1.79], P<0.000 01), and endothelin-1(ET-1) levels(MD=-9.34, 95%CI[-11.36,-7.32], P<0.000 01). There was no statistically significant difference in the incidence of adverse reactions between two groups(RR=0.91, 95%CI[0.68, 1.22], P=0.52). Subgroup analysis showed that Guanxinning Tablets may have better short-term efficacy(less than 6 months) in the treatment of heart-blood stasis syndrome. GRADE grading showed that angina pectoris efficacy, electrocardiogram efficacy, MACE, and ET-1 were in the medium grade, hs-CRP and adverse reactions were in the low grade, and exercise duration was in the extremely low grade. In conclusion, the efficacy of Guanxinning Tablets+conventional western medicine is better than conventional western medicine treatment alone, with good safety. Therefore, it is recommended for the short-term treatment of patients with heart-blood stasis syndrome. However, the evidence quality of some results is low, and more rigo-rous RCT is still needed to enhance the reliability of evidence.

Sorbitol induces flower bud formation via the MADS-box transcription factor EjCAL in loquat.

Sorbitol is an important signaling molecule in fruit trees. Here, we observed that sorbitol increased during flower bud differentiation (FBD) in loquat (Eriobotrya japonica Lindl.). Transcriptomic analysis suggested that bud formation was associated with the expression of the MADS-box transcription factor (TF) family gene, EjCAL. RNA fluorescence in situ hybridization showed that EjCAL was enriched in flower primordia but hardly detected in the shoot apical meristem. Heterologous expression of EjCAL in Nicotiana benthamiana plants resulted in early FBD. Yeast-one-hybrid analysis identified the ERF12 TF as a binding partner of the EjCAL promoter. Chromatin immunoprecipitation-PCR confirmed that EjERF12 binds to the EjCAL promoter, and ß-glucuronidase activity assays indicated that EjERF12 regulates EjCAL expression. Spraying loquat trees with sorbitol promoted flower bud formation and was associated with increased expression of EjERF12 and EjCAL. Furthermore, we identified EjUF3GaT1 as a target gene of EjCAL and its expression was activated by EjCAL. Function characterization via overexpression and RNAi reveals that EjUF3GaT1 is a biosynthetic gene of flavonoid hyperoside. The concentration of the flavonoid hyperoside mirrored that of sorbitol during FBD and exogenous hyperoside treatment also promoted loquat bud formation. We identified a mechanism whereby EjCAL might regulate hyperoside biosynthesis and confirmed the involvement of EjCAL in flower bud formation in planta. Together, these results provide insight into bud formation in loquat and may be used in efforts to increase yield.

Overexpressed Histocompatibility Minor 13 was Associated with Liver Hepatocellular Carcinoma Progression and Prognosis.

Among primary liver carcinoma cases, the proportion of liver hepatocellular carcinoma (LIHC) cases is 75%-85%. Current treatments for LIHC include chemotherapy, surgical excision, and liver transplantation, which are effective for early LIHC treatment. Nevertheless, the early symptoms of liver carcinoma are atypical, so a large proportion of LIHC patients are diagnosed at an advanced stage. Histocompatibility minor 13 (HM13), located in the endoplasmic reticulum, is responsible for catalysing the hydrolysis of some signal peptides after cleavage from the precursor protein. Here, we studied the role of HM13 in LIHC development through bioinformatics analysis. Database analysis showed that HM13 was of great significance for LIHC tumorigenesis. Compared to normal liver tissues, HM13 expression was increased to a greater extent in LIHC tissues. After analysis of Kaplan‒Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) datasets, we discovered that highly expressed HM13 exhibited an association with shorter overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to analyse HM13-related genes, and the data indicated that these genes obviously participated in rRNA processing, ribosome biogenesis, spliceosome, Huntington's disease, and ATP-dependent helicase activity. The Cell Counting Kit-8 (CCK-8) assay and Transwell assay showed that reducing HM13 expression hindered LIHC cell proliferation, migration, and invasion. In conclusion, these findings indicate that HM13 is a biomarker and is related to the poor prognosis of LIHC. Our results are conducive to discovering new targets for LIHC treatment.