Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

Objective To investigate the role and potential mechanism of glutathione peroxidase 3 (GPX3) in ischemia-reperfusion injury (IRI) during kidney transplantation. Methods C57BL/6 mice were divided into four groups according to different interventions: sham operation group (Sham group), kidney transplantation group (KT group), kidney transplantation + GPX3 overexpression group (KT+GPX3 group) and kidney transplantation + GPX3 overexpression + reactive oxygen species (ROS) agonist group (KT+GPX3+CADD522 group). Twenty-four hours after model establishment, inferior vena cava blood was collected to detect blood urea nitrogen (BUN) and serum creatinine (Scr). Left renal tissues were harvested for immunofluorescence staining to detect ROS and NADPH oxidase 2 (NOX2). Enzyme-linked immunosorbent assay (ELISA) was performed to measure neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF) -α and interleukin (IL)-1β. Western blotting was used to detect myeloperoxidase (MPO) and citrullinated histone H3 (CitH3). Results Compared with the Sham group, the expression level of GPX3 was decreased in the KT group; compared with the KT group, GPX3 expression was increased in the KT+GPX3 group; compared with the KT+GPX3 group, GPX3 expression was reduced in the KT+GPX3+CADD522 group (all P<0.05). Compared with the Sham group, the levels of Scr, BUN, NGAL and KIM-1 were elevated in the KT group; compared with the KT group, the above indicators were decreased in the KT+GPX3 group; compared with the KT+GPX3 group, the levels of Scr, BUN, NGAL and KIM-1 were increased in the KT+GPX3+CADD522 group (all P<0.05). Compared with the Sham group, the expression levels of NOX2 and ROS were increased in the KT group; compared with the KT group, NOX2 and ROS levels were decreased in the KT+GPX3 group; compared with the KT+GPX3 group, NOX2 and ROS levels were upregulated in the KT+GPX3+CADD522 group (all P<0.05). Compared with the Sham group, the expression levels of MPO and CitH3 were increased in the KT group; compared with the KT group, MPO and CitH3 levels were decreased in the KT+GPX3 group; compared with the KT+GPX3 group, MPO and CitH3 levels were increased in the KT+GPX3+CADD522 group (all P<0.05). Compared with the Sham group, the expression levels of TNF-α and IL-1β were increased in the KT group; compared with the KT group, TNF-α and IL-1β levels were decreased in the KT+GPX3 group; compared with the KT+GPX3 group, TNF-α and IL-1β levels were increased in the KT+GPX3+CADD522 group (all P<0.05). Conclusions GPX3 may alleviate renal tissue inflammation by inhibiting ROS-mediated neutrophil extracellular trap (NET) formation, thereby attenuating IRI in renal transplantation.

Background The high work intensity and possible subsequently increased susceptibility to occupational hazards of calcium carbide plants may lead to hypertension in workers, but there are few studies on the relationship between occupational hazard exposure and hypertension in workers involving the production process of calcium carbide. Objective To explore the influence of occupational hazards on the incidence of hypertension in calcium carbide plants. Methods Using historical cohort design, the employees of a calcium carbide factory in the western part of Inner Mongolia Autonomous Region were selected as research subjects. According to the pre-determined inclusion and exclusion criteria, the study population comprised an exposure group of 377 employees (including furnace workers, inspection workers, and maintenance workers) exposed to dust, noise & carbon monoxide, and a control group of 388 employees (including central control workers, electricians, and administrative personnel) without above-mentioned exposure. The total sample size was 765 participants. The follow-up period was from April 2011 to October 2022, and the study endpoint was defined as the conclusion of the follow-up period or diagnosed hypertension in annual occupational health examination. Information on general demographic characteristics, living habits, and work status was collected from all study subjects. Cox proportional hazards regression model was used to analyze the association between occupational hazard exposure and the risk of hypertension among the calcium carbide plant employees. Results The average age, mean systolic and diastolic blood pressure, proportion of males, smoking rate, and alcohol consumption rate in the exposure group were higher than those in the control group (P<0.05). Compared to baseline, both systolic and diastolic blood pressure levels increased in the exposure group and the control group at the end of the follow-up (P<0.05). At the end of the follow-up, the average differences between systolic/ diastolic blood pressure and baseline values in the exposure group were higher than those in the control group (P<0.05). During the follow-up period, a total of 223 cases of hypertension occurred, with a total follow-up of 2785 person-years, resulting in an incidence density of 8007.18 per 100000 person-years, an average age of onset of (35.90±8.22) years, and an average working age of onset of (2.69±1.97) years. The incidence density in the exposure group was 128.71% higher than that in the control group, and the risk of hypertension in the exposure group was 2.115 times that of the control group. The risk of hypertension was 2.199 times higher for men than for women, 1.344 times higher for those aged 30 and above than for those under 30, 1.546 times higher for smokers than for non-smokers, and 1.750 times higher for drinking workers than for non-drinking ones. The results of Cox proportional hazards regression modeling indicated that the hazard ratio (95%CI) of hypertension among the employees exposed to dust, noise, and carbon monoxide was 2.254 (1.703, 2.982), 1.594 (1.107, 2.295), and 1.567 (1.079, 2.274), respectively, when different covariates (gender, age, smoking, and alcohol consumption) were included. The results of Log-rank test showed that there were statistically significant differences in the distribution of disease-free survival between the exposure group and the control group (P<0.05). Conclusion Occupational exposures to dust, noise, and carbon monoxide may increase the risk of hypertension among calcium carbide plant workers.

Objective To investigate the effect of circSKA3 on the malignant behaviors of ovari-an cancer cells and its potential mechanism.Methods Human ovarian cancer SK-OV-3 cells were cultured in vitro and randomly divided into si-NC group,si-circSKA3 group,miR-NC group,miR-532-5p group and si-circSKA3+anti-miR-NC and si-circSKA3+anti-miR-532-5p group.The expres-sion levels of circSKA3 and miR-532-5p were detected by quantitative real-time polymerase chain re-action(qRT-PCR).Cell proliferation,apoptosis and migration were detected by CCK-8 assay,plate clone formation assay,flow cytometry and Transwell assay.The targeting relationship between circS-KA3 and miR-532-5p was evaluated using dual-luciferase reporter assays.Protein expression of Cleaved-caspase3 was measured by Western blotting.Results The expression level of circSKA3 in ovarian cancer tissues was significantly higher than that in adjacent normal ovarian tissues(P＜0.05).The expression of miR-532-5p in the ovarian cancer tissues was significantly lower than that in the adjacent normal ovarian tissues(P＜0.05).Compared with the si-NC group,the si-circSKA3 group showed significantly reduced circSKA3 expression,increased miR-532-5p expression,elevat-ed cell proliferation inhibition rates and apoptosis rates,decreased colony formation numbers and mi-grating cell counts,and significantly higher Cleaved-caspase3 protein expression(P＜0.05).Circ-SKA3 was found to target miR-532-5p.After transfection with miR-532-5p mimictors,cell prolifera-tion and cell migration were inhibited,and the inhibition rate of cell proliferation,the apoptosis rate,and the protein level of Cleaved-caspase3 were significantly increased(P＜0.05).Compared with transfection with circSKA3 small interfering RNA alone,co-transfection with circSKA3 small in-terfering RNA and miR-532-5p inhibitor promoted cell proliferation and migration,inhibited apopto-sis rates,and reduced Cleaved-caspase3 protein expression(P＜0.05).Conclusion Silencing circSKA3 upregulates miR-532-5p expression,thereby inhibiting the malignant development of ovar-ian cancer cells.

Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines. Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies, which are incapable of repairing the pulp-dentin complex defects. Although biomaterial-based strategies show remarkable progress in antibacterial, anti-inflammatory, and pulp regeneration, the important modulatory effects of nerves within pulp cavity have been greatly overlooked, making it challenging to achieve functional pulp-dentin complex regeneration. In this study, we propose an injectable bioceramics-containing composite hydrogel in combination of Li-Ca-Si (LCS) bioceramics and gelatin methacrylate matrix with photo-crosslinking properties. Due to the sustained release of bioactive Li, Ca and Si ions from LCS, the composite hydrogels possess multiple functions of promoting the neurogenic differentiation of Schwann cells, odontogenic differentiation of dental pulp stem cells, and neurogenesis-odontogenesis couples in vitro. In addition, the in vivo results showed that LCS-containing composite hydrogel can significantly promote the pulp-dentin complex repair. More importantly, LCS bioceramics-containing composite hydrogel can induce the growth of nerve fibers, leading to the re-innervation of pulp tissues. Taken together, the study suggests that LCS bioceramics can induce the innervation of pulp-dentin complex repair, offering a referable strategy of designing multifunctional filling materials for functional periodontal tissue regeneration.
Dental Pulp/drug effects* ; Hydrogels/pharmacology* ; Animals ; Ceramics/pharmacology* ; Dentin/drug effects* ; Biocompatible Materials/pharmacology* ; Rats ; Gelatin ; Regeneration/drug effects* ; Cell Differentiation/drug effects* ; Injections ; Humans ; Odontogenesis/drug effects*

Stresses induced by the deficiency or excess of trace mineral elements, such as manganese (Mn), represent a common limiting factor for the production of crops like Brassica napus. To identify key genes involved in Mn allocation in B. napus and elucidate the underlying mechanisms, a member of the metal tolerance protein (MTP) family obtained in the previous screening of cDNA library of B. napus under Mn stress was selected as the research subject. Based on the sequence information and phylogenetic analysis, it was named as BnMTP10. It belongs to the Mn-cation diffusion facilitator (CDF) subfamily. Expression of BnMTP10 in yeast significantly improved the tolerance of transformants to excessive Mn and iron (Fe) and reduced the accumulation of Mn and Fe. However, the yeast transformants exhibited no significant changes in tolerance to excess cadmium, boron, aluminum, zinc, or copper. The qRT-PCR results demonstrated that the flowers of B. napus had the highest expression of BnMTP10, followed by roots and leaves. Subcellular localization studies revealed that BnMTP10 was localized in the endoplasmic reticulum (ER). Compared with wild-type plants, transgenic Arabidopsis overexpressing BnMTP10 exhibited enhanced tolerance to excessive Mn stress but showed no significant difference under Fe stress. Correspondingly, under excessive Mn stress, the Mn content in the roots of transgenic Arabidopsis increased significantly. However, under excessive Fe stress, the Fe content in transgenic Arabidopsis did not alter significantly. According to the results, we hypothesize that BnMTP10 may alleviate excessive Mn stress in plants by mediating Mn transport to the ER. This study facilitated our understanding of efficient mineral nutrients, and provided theoretical foundations and gene resources for breeding B. napus.
Brassica napus/genetics* ; Manganese/metabolism* ; Plants, Genetically Modified/genetics* ; Plant Proteins/physiology* ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Cation Transport Proteins/metabolism* ; Stress, Physiological

Background: Curcumin, the main yellow pigment in turmeric, is a potent anticancer agent. However, its effect on the viability of human prostate cancer (PCa) cells and underlying mechanisms remain unclear. This study aimed to determine the effects of curcumin on the proliferation and glucose metabolism of PCa cells. Methods: Cell viability was measured by MTS assay, and apoptosis was measured by flow cytometry. Glucose metabolism was assessed by measuring glucose intake, lactate production, and adenosine triphosphate content. Western blotting was performed to detect the expression of apoptosis-related proteins. Results: Curcumin treatment significantly reduced the viability of two types of PCa cells. We also found that curcumin increased apoptosis and glycolysis by inhibiting the activities of phosphatidylinositol 3-kinase/protein kinase B and hypoxia-inducible factor-1α. Furthermore, curcumin reduced the expression of ETS-related gene (ERG). However, after the ERG was knocked out, the effects of curcumin treatment were attenuated. Conclusion This study investigated the effects of curcumin on the proliferation and apoptosis of PCa cells, which may be related to the inhibition of glycolysis, and further explored the pathway involved. The subsequent effect on ERG expression indicated that these effects may be related to this oncogene.

This article reported a case of successful delivery in a woman with right atrial angiosarcoma and ovarian metastasis. At 31 weeks of gestation, the pregnant woman experienced dyspnea, osphyalgia, nausea, and vomiting. An echocardiogram performed at a local hospital indicated a hypoechoic mass in the right atrium. On December 12, 2023 (32 weeks of gestation), she was transferred to the Third Affiliated Hospital of Guangzhou Medical University. On admission, cardiac ultrasound suggested an irregular slightly high echo in the right atrium, and MRI indicated a malignant tumor. On the day of admission, the patient underwent cardiac exploratory surgery and cesarean section. An enlarged left ovary was found during the surgery, and postoperative pathology confirmed primary right atrial angiosarcoma with left ovarian metastasis. The patient was transferred to the intensive care unit for further treatment. At the request of her family, she was discharged after her condition improved (11 d after the surgery). A male infant who had shallow breathing but did not cry at birth was delivered via cesarean section. He was transferred to the neonatal department for intubation and positive pressure ventilation with a resuscitation bag and was discharged 25 d after birth. The patient was lost to follow-up after discharge.

Objective The stress variations during the wear process of an artificial knee joint were studied.Then,a signal acquisition system was designed to capture the vibration signals induced by the wear of knee joint prosthesis.The aim was to provide new technical means for online wear monitoring of the artificial knee joint.Methods To effectively collect vibration signals,the optimal installation position of the vibration sensors was determined by analyzing the dynamic model of the knee joint prosthesis during motion and identifying the main distribution areas of the tibial insert contact stress.The dynamic model of the femoral prosthesis was solved using Lagrangian equations.The torque variation curve of the femoral prosthesis was obtained to validate the effectiveness of finite element analysis.The signals collected by the vibration sensors installed at different positions in the friction wear experiments and the surface morphology in different areas were compared to verify the effectiveness of the acquisition system design and finite element analysis results.Results The stress concentration regions of the tibial pad under four degrees of freedom(flexion,internal and external rotation,anterior-posterior displacement,and up-and-down displacement)were obtained based on a dynamic simulation.A stress concentration was evident in the middle and posterior regions of the tibial pad.A vibration signal with a higher amplitude was collected when the vibration sensor was installed at the rear end of the tibial pad.This aided the vibration feature extraction of the knee joint prosthesis.Conclusions The vibration signal acquisition system designed based on the dynamic simulation analysis effectively collected the vibration signals generated by the artificial knee joint during the wear process.This study provides an important means for evaluating the wear mechanisms of artificial knee joints and monitoring their full-life health status.

Liver failure often has rapid progression， multiple complications， and dangerous conditions. Acute pancreatitis is a common comorbidity during the progression of liver failure， and since acute pancreatitis has extremely similar clinical symptoms and signs to liver failure complicated by spontaneous peritonitis， it is often neglected in clinical practice. This article elaborates on the mechanisms of liver failure complicated by acute pancreatitis from the five aspects of inflammatory response， duodenal papillary dysfunction， gut microbiota dysbiosis， oxidative stress， and microcirculatory disturbance and proposes corresponding preventive measures based on these mechanisms.