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The iron (Fe) metabolism plays important role in regulating systemic metabolism and obesity development. The Fe inside cells can form iron-sulfur (Fe-S) clusters, which are usually assembled into target proteins with the help of a conserved cluster assembly machinery. Family with sequence similarity 96A (FAM96A; also designated CIAO2A) is a cytosolic Fe-S assembly protein involved in the regulation of cellular Fe homeostasis. However, the biological function of FAM96A in vivo is still incompletely defined. Here, we tested the role of FAM96A in regulating organismal Fe metabolism, which is relevant to obesity and adipose tissue homeostasis. We found that in mice genetically lacking FAM96A globally, intracellular Fe homeostasis was interrupted in both white and brown adipocytes, but the systemic Fe level was normal. FAM96A deficiency led to adipocyte hypertrophy and organismal energy expenditure reduction even under nonobesogenic normal chow diet-fed conditions. Mechanistically, FAM96A deficiency promoted mechanistic target of rapamycin (mTOR) signaling in adipocytes, leading to an elevation of de novo lipogenesis and, therefore, fat mass accumulation. Furthermore, it also caused mitochondrial defects, including defects in mitochondrial number, ultrastructure, redox activity, and metabolic function in brown adipocytes, which are known to be critical for the control of energy balance. Moreover, adipocyte-selective FAM96A knockout partially phenocopied global FAM96A deficiency with adipocyte hypertrophy and organismal energy expenditure defects but the mice were resistant to high-fat diet-induced weight gain. Thus, FAM96A in adipocytes may autonomously act as a critical gatekeeper of organismal energy balance by coupling Fe metabolism to adipose tissue homeostasis.

Background: Salt-processed product of cuscutae semen (SCS), which is documented in Chinese pharmacopoeia (2020 edition), is one of the processed products of cuscustae semen. SCS possesses hepatoprotective effects. However, Pharmacokinetic/Pharmacodynamic (PK-PD) study of SCS with intervening acute liver injury (ALI) has not been reported yet. Effective constituents are still not well addressed. Objective: This study was performed to study PK-PD properties with the purpose of linking SCS hepatoprotective effects to key therapeutic outlines to guide therapeutic use in clinical settings. Methods: Rats were orally administered SCS after the acute liver injury model was established. Plasma biochemical analysis, antioxidative analysis, and liver histopathology were measured to evaluate the hepatoprotective effects of SCS. Blood samples were collected at different time points (0 h, 0.083 h, 0.25 h, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 8 h, 12 h, 24 h) for PK/PD study after SCS administration. Contents of chlorogenic acid, hyperoside and astragalin were estimated by UHPLC-ESI-MS. The relationship between concentrations of chlorogenic acid, hyperoside, and astragalin and hepatoprotective effects was assessed by PK-PD modeling. Results: The results showed that SCS ameliorated liver repair and decreased the serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST) markedly. Hepatic oxidative stress was inhibited by SCS, as evidenced by a decrease in malondialdehyde (MDA) and an increase in glutathione (GSH) and superoxide dismutase (SOD) in the liver. PK-PD correlation analysis indicated that concentrations of chlorogenic acid, hyperoside, and astragalin were negatively correlated with level of AST and ALT. Conclusion: The encouraging finding indicates that SCS has beneficial effects on CCl4-induced liver damage. Chlorogenic acid, hyperoside, and astragalin are three effective constituents to exert hepatoprotective effects while astragalin may have maximum pharmacological activity. PK-PD study reveals the positive relationship between drug concentration and action intensity of SCS against liver injury. This research provides a robust foundation for future studies.

Polypyrimidine tract binding protein 1 (PTBP1) is a member of heterogeneous nuclear ribonucleoprotein (hnRNP) family and has recently been reported to contribute to development and progression of various tumors. However, the clinicopathological significance and prognostic value of PTBP1 in gastric cancer have not been sufficiently elucidated.Bioinformatic analysis of The Cancer Genome Atlas (TCGA) data were employed to analyze the expression of PTBP1 mRNA and its prognostic value in gastric cancer. The expression type of PTBP1 in gastric cancer cells was further confirmed through reverse transcription polymerase chain reaction (RT-PCR) and western blot assay. Then, the association between PTBP1 protein expression and clinicopathological features was analyzed based on immunohistochemical staining results in gastric cancer tissue microarray including 311 cases. The prognostic value of PTBP1 protein was explored through univariate and multivariate analyses. Additionally, cell count and transwell assay were performed to detect the biological role of PTBP1 in gastric cancer cellsPTBP1 was highly expressed in gastric cancer cells and tissues at mRNA and protein level. High expression of PTBP1 was closely related to several clinicopathological features, including gender, age at surgery, histological type, TNM stage and lymph node metastasis. Moreover, high expression PTBP1 predicts poor prognosis, and may be an independent prognostic factor for overall survival in gastric cancer patients. Knockdown of PTBP1 substantially suppressed the proliferation, migration and invasion of gastric cancer cellsPTBP1 is up-regulated and predicts poor prognosis in gastric cancer. PTBP1 may serve as a biomarker of poor prognosis and a novel target in treating gastric cancer.

Background. Stable angina pectoris (SAP) is one of the main types of coronary heart disease (CHD). To improve treatment outcomes, more effective biomarkers are needed. Currently, studies on the metabolic characteristics of SAP are lacking. Here, we explored the serum metabolomic profile of SAP and identified potential biomarkers and related pathways to assist the clinical diagnosis and treatment of SAP. Method. Thirty patients with SAP patients and 30 healthy controls (CON) without stenosis were selected for this study. All patients underwent coronary angiography. The metabolites of the two groups’ serum samples were investigated using UHPLC-QE-MS. Changes in serum metabolic profile were evaluated using multivariate statistical analysis and pathway analysis. Result. OPLS-DA analysis identified significant differences in the serum metabolic profiles between patients with SAP and CON. Twenty-five differential metabolites were identified between patients from SAP and CON groups, including choline, creatine, L-arginine, beta-guanidinopropionic acid, isopalmitic acid, xanthine, LysoPC (18 : 1), and LysoPC (20 : 3). Pathway analysis found that these differential metabolites were involved in energy metabolism, oxidative stress, purine metabolism, and other metabolic pathways. Conclusion. By comparing the serum metabolic profiles of SAP patients with a control group, we identified 25 potential biomarkers that could improve the clinical diagnosis and treatment of SAP.

A Ag@CuFe2O4@TiO2 nanocomposite film with high performance of photogenerated cathodic protection was prepared by hydrothermal and photoreduction methods. The results showed that when the CuFe2O4 hydrothermal reaction time was 6 h and the AgNO3 concentration was 0.1 M, the Ag@CuFe2O4@TiO2 nanocomposite material performed the best cathodic protection capability for 304 stainless steel (304SS). In this case, the protective potential achieved −930 mV (versus SCE) associated with the photocurrent density of 475 μA/cm2, which was 14.8 times that of pure TiO2 nanowires. In the dark, the nanocomposite provided cathodic protection of up to 485 mV for 304SS. Due to the heterogeneous junctions at the two interfaces among the three kinds of nanocomposite materials, the build-in electric field was fabricated, which promoted the separation efficiency of photogenerated electrons and holes and effectively improved the photochemical cathodic protection of 304SS.

Hexagonal boron nitride (h-BN) fillers are incorporated into poly(vinyl butyral) (PVB) coatings to improve the corrosion protection performance of copper. It has been revealed that the h-BN fillers exhibit an excellent dispersiblility in PVB coating due to the non-covalent interactions between h-BN fillers and the PVB molecules. Electrochemical characterization reveals that the corrosion resistance of the BN-reinforced PVB (BN-P) coating is 5–6 orders of magnitude higher than that of the pristine PVB coating. Photographs and metallography show that the copper substrate beneath the BN-P coating does not suffer from corrosion after immersion for 2 months, indicating that the BN-P coating can provide a long-term protective barrier for the underlying copper substrate. Loading 0~0.25 g h-BN fillers in 2.0 g PVB, the corrosion protection performance increases with increasing the loading of h-BN fillers. The scratch test results suggest that h-BN fillers do not accelerate copper corrosion when the BN-P coating is damaged.

Chunyu Lin,1,2,&ast; Yuan He,3,&ast; Mengnan Liu,1,4 Aihua Wu,1 Jing Zhang,4 Shurong Li,5 Shuqi Li,6 Qinghua Cao,6 Fang Liu1,2 1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Department of Liver Tumor Center, Nanfang Hospital, Southern Medical University, Guangzhou, 51051, People’s Republic of China; 2Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 51051, People’s Republic of China; 3Department of Radiotherapy, The First Affiliated Hospital of University of Science and Technology of China, Hefei, 23000, People’s Republic of China; 4Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, 51051, People’s Republic of China; 5Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 51008, People’s Republic of China; 6Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 51008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinghua Cao, Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 51008, People’s Republic of China, Email caoqhua@mail.sysu.edu.cn Fang Liu, Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 51051, People’s Republic of China, Email liufang7250@163.comBackground: To investigate the correlation between hepatocellular carcinoma (HCC) pathological types and conventional transarterial chemoembolization (cTACE), and to evaluate the predictive value of the pathological types for efficacy of cTACE.Methods: We investigated 186 naive HCC patients from 2 hospitals, including 63 patients with recurrence after surgical resection, and 123 unresectable cases, who underwent at least one cTACE procedure as the first treatment. All patients were histologically diagnosed with HCC by surgical resection and/or liver biopsy. Lipiodol deposition rate, ORR (objective response rate), PFS (progression-free survival), OS (overall survival) were compared among different HCC pathological types.Results: This study evaluated 186 naive HCC patients and 189 tumor nodules. Vessels that encapsulate tumor clusters (VETC), macrotrabecular-massive (MTM), CK19-positive types were identified in 38% (72/189), 40% (76/189), and 28% (53/189) of the whole cohort, respectively. VETC, MTM and CK19-negative HCCs derived significantly better lipiodol deposition rate and ORR. cTACE prolonged the PFS of VETC and CK19-negative HCCs compared with non-VETC and CK19-positive HCCs in the recurrence, liver biopsy and combining whole cohorts, whereas the OSs of different pathological types were not significantly different. Multivariate analysis showed that VETC (OR, 4.671, 95% CI [1.954, 11.166], P< 0.001) and CK19-positive type (OR, 0.127, 95% CI [0.044, 0.362], P< 0.001) were independent predictive factors for the first cTACE response. However, only VETC type was significantly associated with the second cTACE response in multivariate analysis (OR, 3.31, 95% CI [1.24, 8.83], P=0.017), suggesting that VETC might be a more useful predictor of cTACE response.Conclusion: Our study suggests that VETC is an effective predictor of cTACE response in patients with HCC.Keywords: hepatocellular carcinoma, vessels that encapsulate tumor clusters, CK19-positive, conventional transarterial chemoembolization

Background Primary fallopian tube carcinoma (PFTC) is a rare neoplasm. The purpose of this study is to identify which factors and markers contribute to affect the clinical prognosis of patients with PFTC, and to inform treatment and preventive strategies. Methods Patients were selected from those with confirmed PFTC registered in 2010 till 2015 from the Surveillance, Epidemiology and End Results (SEER) database. Independent prognostic factors were identified using univariate and multivariate Cox proportional hazard regression models. These factors were used to construct a nomogram model, a survival prognostication tool for3-and 5-year overall survival (OS) and tumor-specific survival (CSS) among patients with PFTC. Kaplan-Meier curves and log-rank tests were used to assess differences in survival time between groups. Results A total of 1241 patients were randomly assigned to the training group (n = 869) and the test group (n = 372). Kaplan-Meier survival analysis showed a similar 3-year/5-year OS and CSS in patients with PFTC (70.1%/55.4% and 71.7%/57.2%, respectively). In multivariate Cox regression analysis, age (22–56, 57–71 and 72–92), race (white, black and other), International Federation of Gynecology and Obstetrics (FIGO) staging (I, II, III, and IV) and laterality (lateral and bilateral) were independent prognostic factors for patients with PFTC. Finally, a nomogram consisting of age, race, FIGO stage, type of surgery and lymphadenectomy were constructed. The area under the time-dependent receiver operating characteristic (ROC) curve values of 3-/5-year OS were 0.730/0.750 in the training group and 0.726/0.803 in the test group. Conclusions Nomograms constructed using various clinical indicators could help identify patients with high-risk PFTC. We have identified prognostic factors associated with OS and CSS. These factors can be examined and included further in large clinical trials involving this rare carcinoma.

Background Facetectomy, an important procedure in the in–out and out–in techniques of transforaminal endoscopic lumbar discectomy (TELD), is related to the deterioration of the postoperative biomechanical environment and poor prognosis. Facetectomy may be avoided in TELD with large annuloplasty, but iatrogenic injury of the annulus and a high grade of nucleotomy have been reported as risk factors influencing poor prognosis. These risk factors may be alleviated in TELD with limited foraminoplasty, and the grade of facetectomy in this surgery can be reduced by using an endoscopic dynamic drill. Methods An intact lumbo-sacral finite element (FE) model and the corresponding model with adjacent segment degeneration were constructed and validated to evaluate the risk of biomechanical deterioration and related postoperative complications of TELD with large annuloplasty and TELD with limited foraminoplasty. Changes in various biomechanical indicators were then computed to evaluate the risk of postoperative complications in the surgical segment. Results Compared with the intact FE models, the model of TELD with limited foraminoplasty demonstrated slight biomechanical deterioration, whereas the model of TELD with large annuloplasty revealed obvious biomechanical deterioration. Degenerative changes in adjacent segments magnified, rather than altered, the overall trends of biomechanical change. Conclusions TELD with limited foraminoplasty presents potential biomechanical advantages over TELD with large annuloplasty. Iatrogenic injury of the annulus and a high grade of nucleotomy are risk factors for postoperative biomechanical deterioration and complications of the surgical segment.

Heart failure (HF) is considered the clinical endpoint of all cardiovascular diseases (CVDs). Although a large number of HF drugs and therapies have been developed, it is still need to find therapies with better clinical efficacy and fewer side effects. The purpose of this systematic evaluation is to assess the efficacy and safety of Danshen decoction on HF and the improvement of cardiac function (CF).Four databases will be searched to identify any eligible studies, and this protocol does not require ethics committee review as the research is based on published articles. There are no restrictions set for the language, publication date, or status of the study. The clinical effective rate (CER) of HF treatment is considered to be the main result. CF, various serum inflammatory factors, and adverse events were defined as secondary outcomes. When more than 1 article is used to study the changes and results of the same index, we will conduct a meta-analysis. If the heterogeneity is not statistically significant (P .10 or I2 50%), a fixed-effect model will be established to estimate the overall intervention effect. Otherwise, random effect models will be used to provide more conservative results.The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.This study will provide reliable evidence-based basis for the clinical application of Danshen decoction in the treatment of HF.

Background. Hyperlipidemia is a common clinical chronic disease that increases the incidence of cardiovascular disease. However, although oral drug therapy can reduce blood lipids, long-term drug treatment may cause various side effects. Therefore, it is important to find suitable alternatives for the treatment of hyperlipidemia. The classic traditional Chinese medicine (TCM) prescription Danshen decoction (DSD) has been found effective for the treatment of hyperlipidemia. This protocol aims to evaluate the efficacy and safety of DSD in the treatment of hyperlipidemia. Methods and Analysis. We will screen all the randomized controlled trials (RCTs) which research DSD in the treatment of hyperlipidemia from 7 databases from their inception to July 2022; three investigators will independently screen and select RCTs and extract data and assess the risk of bias. The Cochrane scale, Jadad scale, and GRADE scale will be used to assess the risk of bias, literature quality, and outcome quality, respectively. Review Manager V.5.4 will be used for the meta-analysis, and the results will be presented as the risk ratio (RR) for the binary data and the mean difference (MD) or standardized mean difference (SMD) for the continuous data. Ethical approval and Dissemination. This protocol for a systematic review will be submitted to a peer-reviewed journal for publication and ethical approval is not applicable. PROSPERO registration number.CRD42022352467.

The new Shanghai No. 1 Coal Mine is located in arid and semiarid area of northwest China, which is characterized by scarce rainfall, intense evaporation, and limited water resources. High-intensity coal mining has caused severe damage to groundwater resources. The Baotashan sandstone aquifer of the Jurassic system has abundant water resources, and they are stored in the floor strata of mining coal seams. This poses the risk of high-pressure build-up and water inrush hazards during the mining of coal. To avoid these, the Baotashan sandstone aquifer needs to be drained and depressurized, which can result in a huge waste of water resources. Thus, taking the New Shanghai No. 1 Coal Mine as the basis for the case study, the impact of coal mining on the underground water resources was quantified. Large-scale water release tests were performed under the shaft to determine the hydrogeological properties of the Baotashan sandstone aquifer and a three-dimensional numerical model of the groundwater system was established. The dynamic phenomenon of water drainage was simulated and the drained water discharge was predicted under the condition of safe mining.