Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies.

Background: Metabolic imbalance is the common basis of many diseases. As natural isoquinoline alkaloid, berberine (BBR) has shown great promise in regulating glucose and lipids metabolism and treating metabolic disorders. However, the related mechanism still lacks systematic research. Aim: To discuss the role of BBR in the whole body's systemic metabolic regulation and further explore its therapeutic potential and targets. Method: Based on animal and cell experiments, the mechanism of BBR regulating systemic metabolic processes is reviewed. Potential metabolism-related targets were summarized using Therapeutic Target Database (TTD), DrugBank, GeneCards, and cutting-edge literature. Molecular modeling was applied to explore BBR binding to the potential targets. Results: BBR regulates the whole-body metabolic response including digestive, circulatory, immune, endocrine, and motor systems through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), sirtuin (SIRT)1/forkhead box O (FOXO)1/sterol regulatory element-binding protein (SREBP)2, nuclear factor erythroid 2-related factor (Nrf) 2/heme oxygenase (HO)-1, and other signaling pathways. Through these reactions, BBR exerts hypoglycemic, lipid-regulating, anti-inflammatory, anti-oxidation, and immune regulation. Molecular docking results showed that BBR could regulate metabolism targeting FOXO3, Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (Gpx) 4 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Evaluating the target clinical effects, we found that BBR has the therapeutic potential of anti-aging, anti-cancer, relieving kidney disease, regulating the nervous system, and alleviating other chronic diseases. Conclusion: This review elucidates the interaction between potential targets and small molecular metabolites by exploring the mechanism of BBR regulating metabolism. That will help pharmacologists to identify new promising metabolites interacting with these targets.

AQP5 promotes epithelial-mesenchymal transition and tumor growth through activating the Wnt/ß-catenin pathway in triple-negative breast cancer.

BACKGROUND: Emerging data identifies aquaporin 5 (AQP5) as a vital player in many kinds of cancers. Over expression of AQP5 was associated with increased metastasis and poor prognosis, suggesting that AQP5 may facilitate cancer cell proliferation and migration. Our previous studies also showed that AQP3 and AQP5 were highly expressed in triple-negative breast cancer (TNBC) and the expression of AQP3 and AQP5 in TNBC tissue was positive correlated with advanced clinical stage. OBJECTIVE: We aim to investigate the role of AQP5 in TNBC oncogenesis and development. METHODS: MDA-MB-231 cells were transfected with siRNA-AQP5 and AQP5 overexpression vector to establish a differential expression system for AQP5. Cell proliferation and apoptosis of MDA-MB-231 cells were detected by CCK-8 (Cell Counting Kit-8) and FCM (flow cytometry), respectively. Cell migration and invasion abilities were evaluated by wound healing assay and transwell assay. The qRT-PCR and western blot assays were used to study the effect of AQP5 expression level on the expression of epithelial-to-mesenchymal transition (EMT) related molecules. The effects of ICG-001, a Wnt/ß-catenin signaling pathway inhibitor, on the invasive and migratory capabilities of overexpressed AQP5 cells and downstream molecules were measured. RESULTS: 1. The expression of AQP5 in the MDA-MB-231 cells was significantly higher than that in the MCF-10A cells. 2. Up-regulation of AQP5 significantly promoted the proliferation, migration and invasion of TNBC cells, while inhibited the cell apoptosis; in addition, up-regulation of AQP5 increased the expression of Bcl-2 and decreased the expression of Caspase-3. However, knockdown of AQP5 presented the adverse effects of AQP5 overexpression. 3. Overexpressed AQP5 induced the overexpression of EMT-related factors, which further promoted the migration and invasion of cells. 4. Overexpression of AQP5 could up-regulate the expression of ß-catenin in the nucleus followed by increasing the expression levels of downstream genes in Wnt/ß-catenin signaling pathway. Moreover, ICG-001, the inhibitor of Wnt/ß-catenin signaling pathway, could significantly attenuate the effect of overexpression of AQP5 on cells, further confirming that AQP5 may promote the proliferation, migration and invasion of TNBC cells by activating Wnt/ß-catenin signaling pathway. CONCLUSIONS: In the TNBC cells, AQP5 modulates the expression levels of EMT-related proteins through activation of Wnt/ß-catenin signaling pathway, thus enhancing the cell proliferation, migration and invasion while inhibiting the cell apoptosis.

Factors influencing the continuance intention of the women's health WeChat public account: an integrated model of UTAUT2 and HBM.

Background: Women's health WeChat public accounts play a crucial role in enhancing health literacy and fostering the development of healthy behaviors among women by disseminating women's health knowledge. Improving users' continuous usage behavior and retention rates for the women's health WeChat public account is vital for influencing the overall effectiveness of health communication on WeChat. Objective: This study aimed to construct a comprehensive model, delving into the key factors influencing women's continuance intention of the women's health public accounts from the perspectives of perceived health threats, individual abilities, and technological perceptions. The goal is to provide valuable insights for enhancing user stickiness and the effectiveness of health communication on WeChat public accounts. Method: An online survey was conducted among women receiving gynecological care at a certain hospital to gage their willingness for sustained use of the women's health WeChat public accounts. Through structural equation modeling, the study investigated the influencing factors on women's sustained intention to use the women's health WeChat public accounts. Results: The study included a total of 853 adult women. Among them, 241 (28.3%) women had followed women's health official accounts in the past but do not currently follow them, 240 (28.1%) women had followed women's health official accounts in the past and are still following them, and 372 (43.6%) women had never followed women's health official accounts. Currently, 240 women are still browsing women's health public accounts, 52 of whom read women's health public accounts every day, and most of them read women's health public accounts for 10-20 min at a time (100, 11.7%). The results of the structural equation model revealed that performance expectancy, social influence, hedonic motivation, habit, and e-health literacy had significantly positive effects on women's sustained intention to use public accounts (performance expectancy: ß = 0.341, p < 0.001; social influence: ß = 0.087, p = 0.047; hedonic motivation: ß = 0.119, p = 0.048; habit: ß = 0.102, p < 0.001; e-health literacy: ß = 0.158, p < 0.001). E-health literacy and self-efficacy indirectly influence sustained intention by affecting performance expectancy, effort expectancy, social influence, facilitating conditions, hedonic motivation, and habit. The effect sizes of e-health literacy on performance expectancy, effort expectancy, social influence, facilitating conditions, hedonic motivation, and habit were 0.244 (p < 0.001), 0.316 (p < 0.001), 0.188 (p < 0.001), 0.226(p < 0.001), 0.154 (p < 0.001), and 0.073 (p = 0.046). The effect sizes of self-efficacy on performance expectancy, effort expectancy, social influence, facilitating conditions, hedonic motivation, and habit were 0.502 (p < 0.001), 0.559 (p < 0.001), 0.454 (p < 0.001), 0.662 (p < 0.001), 0.707 (p < 0.001), and 0.682 (p < 0.001). Additionally, perceived severity and perceived susceptibility indirectly affected sustained intention by influencing performance expectancy and social influence. The effect sizes of perceived severity on performance expectancy and social influence were 0.223 (p < 0.001) and 0.146 (p < 0.001). The effect size of perceived susceptibility to social influence was 0.069 (p = 0.042). Conclusion: Users' e-health literacy, self-efficacy, perception of disease threat, and users' technological perceptions of the WeChat public accounts are critical factors influencing women's continuance intention of using the WeChat public accounts. Therefore, for female users, attention should be given to improving user experience and enhancing the professionalism and credibility of health information in public account design and promotion. Simultaneously, efforts should be made to strengthen users' health awareness and cultivate e-health literacy, ultimately promoting sustained attention and usage behavior among women toward health-focused public accounts.

Enhanced rotation sensing with high-order exceptional points in a multi-mode coupled-ring gyroscope.

Exceptional points (EPs) of non-Hermitian systems are sensitive to perturbations and facilitate the development of highly sensitive gyroscopes. We propose a compact multi-mode optical gyroscope protocol that incorporates two coupled rings and exhibits a fourth-order EP, achieving higher sensitivity compared to gyroscopes based on second-order EPs. We show that the gyroscope sensitivity can be further improved by deviating from the fourth-order EP due to the gain dependence on the cavity intensity. Furthermore, our protocol exhibits resilience against backscattering from counter-propagating modes, which leads to a reduced angular random walk (ARW) factor and increased sensitivity. These features make our protocol highly promising for advancing high-performance optical gyroscopes and enhancing angular velocity sensing technologies.

Development and validation of a nomogram predictive model for cognitive impairment in cerebral small vessel disease: a comprehensive retrospective analysis.

Background: Cerebral small vessel disease (CSVD) is a common neurodegenerative condition in the elderly, closely associated with cognitive impairment. Early identification of individuals with CSVD who are at a higher risk of developing cognitive impairment is crucial for timely intervention and improving patient outcomes. Objective: The aim of this study is to construct a predictive model utilizing LASSO regression and binary logistic regression, with the objective of precisely forecasting the risk of cognitive impairment in patients with CSVD. Methods: The study utilized LASSO regression for feature selection and logistic regression for model construction in a cohort of CSVD patients. The model's validity was assessed through calibration curves and decision curve analysis (DCA). Results: A nomogram was developed to predict cognitive impairment, incorporating hypertension, CSVD burden, apolipoprotein A1 (ApoA1) levels, and age. The model exhibited high accuracy with AUC values of 0.866 and 0.852 for the training and validation sets, respectively. Calibration curves confirmed the model's reliability, and DCA highlighted its clinical utility. The model's sensitivity and specificity were 75.3 and 79.7% for the training set, and 76.9 and 74.0% for the validation set. Conclusion: This study successfully demonstrates the application of machine learning in developing a reliable predictive model for cognitive impairment in CSVD. The model's high accuracy and robust predictive capability provide a crucial tool for the early detection and intervention of cognitive impairment in patients with CSVD, potentially improving outcomes for this specific condition.

Expression levels of KATP channel subunits and morphological changes in the mouse liver after exposure to radiation.

BACKGROUND: ATP sensitive K+ (KATP) channels are ubiquitously distributed in various of cells and tissues, including the liver. They play a role in the pathogenesis of myocardial and liver ischemia. AIM: To evaluate the radiation-induced changes in the expression of KATP channel subunits in the mouse liver to understand the potential role of KATP channels in radiation injury. METHODS: Adult C57BL/6 mice were randomly exposed to γ-rays at 0 Gy (control, n = 2), 0.2 Gy (n = 6), 1 Gy (n = 6), or 5 Gy (n = 6). The livers were removed 3 and 24 h after radiation exposure. Hematoxylin and eosin staining was used for morphological observation; immunohistochemical staining was applied to determine the expression of KATP channel subunits in the liver tissue. RESULTS: Compared with the control group, the livers exposed to 0.2 Gy γ-ray showed an initial increase in the expression of Kir6.1 at 3 h, followed by recovery at 24 h after exposure. Exposure to a high dose of 5.0 Gy resulted in decreased expression of Kir6.1 and increased expression of SUR2B at 24 h. However, the expression of Kir6.2, SUR1, or SUR2A had no remarkable changes at 3 and 24 h after exposure to any of these doses. CONCLUSION: The expression levels of Kir6.1 and SUR2B in mouse liver changed differently in response to different radiation doses, suggesting a potential role for them in radiation-induced liver injury.

Prior to ABOi liver transplant with PD-1 inhibitor in patients with hepatocellular carcinoma: A case report.

BACKGROUND: Liver transplantation (LT) is a unique and effective method for treating end-stage liver diseases and acute liver failure, bringing hope to many patients with liver cancer. LT is currently widely used in the treatment of liver diseases. However, there have been no patients with liver cancer who have undergone ABO-incompatible (ABOi) LT after treatment with the programmed cell death protein 1 (PD-1) inhibitor reported in the literature. CASE PRESENTATION: A patient with liver cancer who received sintilimab injection, an anti-PD1 therapy, before LT was admitted in the transplantation centre. This patient underwent ABOi LT. The perioperative treatment strategy of this patient was reported. A desensitisation protocol was conducted urgently for the patient before operation, and the immunosuppression programme of LT was adjusted. After operation, isoagglutinin titer and liver function indicators were strictly monitored. The patient recovered well after operation, and no sign of rejection reaction was observed. CONCLUSION: We reported a patient with hepatocellular carcinoma (HCC) who received PD-1 inhibitor treatment before operation and successfully underwent ABOi LT. The present case report provides novel insights into the perioperative management of utilizing PD-1 inhibitors prior to ABOi LT in patients diagnosed with hepatocellular carcinoma (HCC).

Mapping and analysis of protein and gene profiles identify the important role of TGF-ß in synovial invasion in pigmented villonodular synovitis.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare benign proliferative disease affecting the soft tissue lining the synovial joints and tendons. Its etiology is poorly understood, largely limiting the availability of current therapeutic options. Here, we mapped the synovial gene and protein profiles of patients with PVNS, revealed a link between synovial inflammation and invasion, and elucidated the potential molecular mechanism involved. METHODS: The expression of synovial genes from six control individuals, seven OA patients, and nineteen PVNS patients was analyzed via RNA sequencing. Protein profiles from five control individuals, ten OA patients, and thirty-two PVNS patients were analyzed using label-free proteomics. Microarray and RT-PCR analyses and immunohistochemical staining were used to evaluate inflammatory cytokine and target gene expression levels in synovial tissue, epithelial cells, and synovial fibroblasts (FLSs) derived from PVNS tissue. Various signaling pathway inhibitors, siRNAs, and western blots were used for molecular mechanism studies. Transwell migration and invasion assays were subsequently performed. RESULTS: In total, 522 differentially expressed proteins were identified in the PVNS tissues. By integrating RNA sequencing and microarray analyses, significant changes in the expression of EMT-related genes, including TGFBI, N-cadherin, E-cadherin, SNAIL, and TWIST, were confirmed in the PVNS tissue compared to the control tissue. In vitro, TGF-ß induced EMT and increased epithelial cell migration and invasion. Moreover, TGF-ß not only promoted interactions between epithelial cells and FLSs but also directly increased the migration and invasion abilities of FLSs by activating the classical Smad2/3 and nonclassical JNK/AKT signaling pathways. CONCLUSION: This study provides overall protein and gene profiles of PVNS and identifies the crucial role of TGF-ß in synovial invasion pathology. Exploring the related molecular mechanism may also reveal a new strategy or target for PVNS therapy.

Tianhe Zhuifeng Gao reverses inflammatory response and attenuates bone/cartilage destruction in rheumatoid arthritis via PSMC2-RUNX2-COL1A1 axis based on transcriptional regulatory network analysis and experimental validation.

BACKGROUND: Tianhe Zhuifeng Gao (TZG) is an authorized Chinese patent drug with satisfying clinical efficacy, especially for RA patients with cold-dampness syndrome. However, its underlying pharmacological mechanisms remain unclear. METHOD: Anti-arthritic effects of TZG were evaluated using an adjuvant-induced arthritis (AIA) rat model. Transcriptional regulatory network analysis based on synovial tissues obtained from AIA rats, combining with our previous analysis based on whole blood samples from RA patients with cold-dampness syndrome and co-immunoprecipitation were performed to identify involved dominant pathways, which were experimentally verified using AIA-wind-cold-dampness stimulation modified (AIA-M) animal model. RESULTS: TZG treatment dramatically attenuated joint injury and inflammatory response in AIA rats, and PSMC2-RUNX2-COL1A1 axis, which was closely associated with bone/cartilage damage, was inferred to be one of therapeutic targets of TZG against RA. Experimentally, TZG displayed obvious pharmacological effects for alleviating the joint inflammation and destruction through reinstating the body weight, reducing the arthritis score, the limbs diameters, the levels of RF and CRP, and the inflammatory cytokines, recovering the thymus and spleen indexes, diminishing bone and cartilage destruction, as well elevating the pain thresholds of AIA-M rats. In addition, TZG markedly reversed the abnormal energy metabolism in AIA-M rats through enhancing articular temperature, daily water consumption, and regulating expression levels of energy metabolism parameters and hormones. Moreover, TZG also significantly modulated the abnormal expression levels of PSMC2, RUNX2 and COL1A1 proteins in the ankle tissues of AIA-M rats. CONCLUSION: TZG may exert the bone protective effects in RA therapy via regulating bone and cartilage damage-associated PSMC2-RUNX2-COL1A1 axis.

Prognostic significance of serum Chemerin and neutrophils levels in patients with oral squamous cell carcinoma.

Objectives: Chemerin, as a novel multifunctional adipokine, is proposed to be involved in high cancer risk and mortality. The present study was aimed to evaluate the prognostic value of serum Chemerin and neutrophils in patients with oral squamous cell carcinoma (OSCC). Materials and methods: 120 patients with OSCC were included in this prospective cohort study. The levels of serum Chemerin were measured by enzyme-linked immunosorbent assay (ELISA). We also explored the possible effects of Chemerin on neutrophils' chemokines in OSCC using a real-time PCR, western blotting. Results: Levels of serum Chemerin, neutrophils and NLR were significantly higher among non-survivors compared to survivors of OSCC (both P < 0.05). Higher serum Chemerin levels were associated with advanced TNM stage, lymph node metastasis, differentiation and tumor recurrence (both P < 0.05). Serum Chemerin levels correlated with neutrophils and NLR levels (r = 0.708, r = 0.578, both P < 0.05). Based on ROC analysis, Chemerin + NLR predicted OSCC patient mortality with 81.54 % sensitivity and 87.27 % specificity, with an AUC of 0.8898. In a Kaplan-Meier analysis, high serum Chemerin levels, high neutrophil levels and high NLR levels were associated with shorter overall and disease-free survival (both P < 0.05). A univariate and multivariate Cox regression analysis showed that serum Chemerin and neutrophils were independent risk factors for OSCC. (both P < 0.05). QRT-PCR and western blotting results showed that Chemerin upregulated the expression of chemokines IL-17 and CXCL-5 in neutrophils (both P < 0.05). Conclusions: Our study suggests that measurement of serum Chemerin and neutrophils might be a useful diagnostic and prognostic biomarker for OSCC patients. Chemerin may promote neutrophils infiltration in OSCC through upregulation of chemokines IL17 and CXCL-5.

Analysis of Raffinose Metabolism-Related Sugar Components in Seeds.

Raffinose family oligosaccharides (RFOs) are synthesized from sucrose and subsequent addition of galactose moieties which was provided by galactinol. Galactinol is synthesized from UDP-galactose and myo-inositol. RFOs accumulate at late stage of seed development and play important roles in seed longevity. RFOs are major components in seeds of many plant species. Here, we document a methodology for extraction and quantitative analysis of raffinose metabolism-related soluble sugars or the derivative alcohols in plant seeds. This protocol, based on high-performance liquid chromatography (HPLC), achieves the efficient separation and accurate quantification of sucrose, myo-inositol, galactinol, and raffinose within 25 min of retention time.

Volitional modulation of neuronal activity in the external globus pallidus by engagement of the cortical-basal ganglia circuit.

Volitional modulation of neural activity is not confined to the cortex but extends to various brain regions. Yet, it remains unclear whether neurons in the basal ganglia structure, the external globus pallidus (GPe), can be volitionally controlled. Here, we employed a volitional conditioning task to compare the volitional modulation of GPe and primary motor cortex (M1) neurons as well as the underlying circuits and control mechanisms. The results revealed that the volitional modulation of GPe neuronal activity engaged both M1 and substantia nigra pars reticulata (SNr) neurons, indicating the involvement of the cortex-GPe-SNr loop. In contrast, the volitional modulation of M1 neurons primarily occurred through the engagement of M1 local circuitry. Furthermore, lesioning M1 neurons did not affect the volitional learning or volitional control signal in GPe, whereas lesioning of GPe neurons impaired the learning process for the volitional modulation of M1 neuronal activity at the intermediate stage. Additionally, lesion of GPe neurons enhanced M1 neuronal activity when performing the volitional control task without reward delivery and a random reward test. Taken together, our findings demonstrated that GPe neurons could be volitionally controlled by engagement of the cortical-basal ganglia circuit and inhibit learning process for the volitional modulation of M1 neuronal activity by regulating M1 neuronal activity. Thus, GPe neurons can be effectively harnessed for independent volitional modulation for neurorehabilitation in patients with cortical damage. KEY POINTS: The cortical-basal ganglia circuit contributes to the volitional modulation of GPe neurons. Volitional modulation of M1 neuronal activity mainly engages M1 local circuitry. Bilateral GPe lesioning impedes volitional learning at the intermediate stages. Lesioning of GPe neurons inhibits volitional learning process by regulating M1 neuronal activity.

Investigation of the causes and mechanisms of hypoxia in the central Bohai Sea in the summer of 2022.

The deep-water area in the central Bohai Sea (BS) serves as a spawning ground and nursery for fish, shrimp, and crabs. Frequent hypoxia will affect the ecological environment in the central BS. Data from an on-site investigation of the central BS in the spring and summer of 2022 were used to analyze the relevant factors generating the occurrence of hypoxia in the central BS through the eutrophication index E, apparent oxygen consumption (AOU), and Spearman correlation. The hypoxia area was largely distributed in the study area's deep water section, and stratification was the main cause of hypoxia at the bottom. Organic matter mineralization, degradation, and biological respiration further exacerbated the hypoxia. In the summer of 2022, temperature stratification was the dominant factor influencing hypoxia.

Manipulation of protein corona for nanomedicines.

Nanomedicines have significantly advanced the development of diagnostic and therapeutic strategies for various diseases, while they still encounter numerous challenges. Upon entry into the human body, nanomedicines interact with biomolecules to form a layer of proteins, which is defined as the protein corona that influences the biological properties of nanomedicines. Traditional approaches have primarily focused on designing stealthy nanomedicines to evade biomolecule adsorption; however, due to the intricacies of the biological environment within body, this method cannot completely prevent biomolecule adsorption. As research on the protein corona progresses, manipulating the protein corona to modulate the in vivo behaviors of nanomedicines has become a research focus. In this review, modern strategies focused on influencing the biological efficacy of nanomedicines in vivo by manipulating protein corona, along with their wide-ranging applications across diverse diseases are critically summarized, highlighted and discussed. Finally, future directions for this important yet challenging research area are also briefly discussed. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Structural basis of the human transcriptional Mediator complex modulated by its dissociable Kinase module.

The eukaryotic Mediator, comprising a large Core (cMED) and a dissociable CDK8 kinase module (CKM), regulates RNA Polymerase II (Pol II)-dependent transcription. cMED recruits Pol II and promotes pre-initiation complex (PIC) formation in a manner inhibited by the CKM, which is also implicated in post-initiation control of gene expression. Herein we report cryo-electron microscopy structures of the human complete Mediator and its CKM, which explains the basis for CKM inhibition of cMED-activated transcription. The CKM binds to cMED through an intrinsically disordered region (IDR) in MED13 and HEAT repeats in MED12. The CKM inhibits transcription by allocating its MED13 IDR to occlude binding of Pol II and MED26 to cMED and further obstructing cMED-PIC assembly through steric hindrance with TFIIH and the +1 nucleosome. Notably, MED12 binds to the cMED Hook, positioning CDK8 downstream of the transcription start site, which sheds new light on its stimulatory function in post-initiation events.

Forensic significance of VOCs profiling in decayed ante- and post-mortem injuries by GC×GC-TOF/MS.

Accurately identifying and differentiating the types of injuries in decomposed corpses is a major challenge in forensic identification. Forensic investigations involving decomposed cadavers pose challenges in determining the cause of death. Traditional methods often lack conclusive evidence. However, the implementation of advanced analytical techniques, such as comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOF/MS), shows promise in overcoming these limitations, but the potential in this area remains limited. Therefore, this study aims to bridge this gap by exploring the potential of GC × GC-TOF/MS in the analysis of volatile organic compounds (VOCs) changes within decaying ante- and post-mortem injuries.The research emphasizes the forensic significance of VOCs changes in decomposed cadavers. We used GC × GC-TOF/MS analysis to identify the specific volatile compounds in putrefied corpse tissue samples from mice. The GC × GC-TOF/MS analysis results showed that under winter conditions, PC1 explained 57.16% of the variance, and PC2 explained 25.23% of the variance; while under summer conditions, PC1 explained 71.89% of the variance, and PC2 explained 24.49% of the variance. This demonstrates the potential of GC × GC-TOF/MS in identifying specific VOCs present in tissue samples that can serve as potential biomarkers for distinguishing between antemortem and postmortem injury. GC × GC-TOF/MS analysis revealed distinct VOC patterns in both conditions. Comprehensive use of GC × GC-TOF/MS analysis enhances accuracy in identifying and characterizing ante- and post-mortem injuries in decomposed cadavers. This study can significantly contribute to the field of forensic medicine and improve the accuracy of forensic investigations.

Current Progress of Ferroptosis Study in Hepatocellular Carcinoma.

Ferroptosis, an emerging type of programmed cell death, is initiated by iron-dependent and excessive ROS-mediated lipid peroxidation, which eventually leads to plasma membrane rupture and cell death. Many canonical signalling pathways and biological processes are involved in ferroptosis. Furthermore, cancer cells are more susceptible to ferroptosis due to the high load of ROS and unique metabolic characteristics, including iron requirements. Recent investigations have revealed that ferroptosis plays a crucial role in the progression of tumours, especially HCC. Specifically, the induction of ferroptosis can not only inhibit the growth of hepatoma cells, thereby reversing tumorigenesis, but also improves the efficacy of immunotherapy and enhances the antitumour immune response. Therefore, triggering ferroptosis has become a new therapeutic strategy for cancer therapy. In this review, we summarize the characteristics of ferroptosis based on its underlying mechanism and role in HCC and provide possible therapeutic applications.

Remnant Cholesterol and Carotid Intraplaque Neovascularization Assessed by Contrast-Enhanced Ultrasonography in Patients With Ischemic Stroke.

Background: We investigated the relationship between remnant cholesterol and carotid intraplaque neovascularization (IPN) assessed by contrast-enhanced ultrasonography (CEUS) in patients with ischemic stroke. Methods: This was a single-center study. Remnant cholesterol is calculated as total cholesterol minus low-density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol (HDL-C). All patients underwent CEUS. IPN is graded according to the presence and location of microbubbles within each plaque. Results: The cohort included 110 patients with ischemic stroke. Patients with an IPN grading of 2 had higher triglyceride (TG), non-HDL-C, and remnant cholesterol concentrations than those with an IPN grading of < 2 (TG: 1.45 ± 0.69 vs. 0.96 ± 0.24 mmol/L, P < 0.001; non-HDL-C: 2.63 ± 0.85 vs. 2.31 ± 0.64 mmol/L, P = 0.037; remnant cholesterol: 0.57 ± 0.23 vs. 0.44 ± 0.07 mmol/L, P < 0.001). The multivariate-adjusted odds ratio (95% confidence interval) for remnant cholesterol was 27.728 (2.714 - 283.253) for an IPN grading of 2 in the subset of patients with an optimal LDL-C concentration. Conclusions: The remnant cholesterol concentration is significantly associated with carotid IPN on CEUS in patients with ischemic stroke with an optimal LDL-C concentration. Remnant cholesterol may be an important indicator of risk stratification in patients with ischemic stroke.

Effect of oral glucose tolerance test-based insulin resistance on embryo quality in women with/without polycystic ovary syndrome.

Objective: To explore the effects of insulin resistance (IR) on embryo quality and pregnancy outcomes in women with or without polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Methods: A retrospective cohort study concerning patients with/without PCOS who received gonadotropin-releasing hormone (GnRH)-antagonist protocol for IVF/ICSI from January 2019 to July 2022 was conducted. All the patients included underwent oral glucose tolerance test plus the assessment of insulin release within 6 months before the controlled ovarian stimulation. The Matsuda Index was calculated to diagnose IR. Two populations (PCOS and non-PCOS) were included and each was divided into IR and non-IR groups and analyzed respectively. The primary outcome was the high-quality day 3 embryo rate. Results: A total of 895 patients were included (751 with PCOS and 144 without PCOS). For patients with PCOS, the IR group had a lower high-quality day 3 embryo rate (36.8% vs. 39.7%, p=0.005) and available day 3 embryo rate (67.2% vs. 70.6%, p<0.001). For patients without PCOS, there was no significant difference between the IR and non-IR groups in high-quality day 3 embryo rate (p=0.414) and available day 3 embryo rate (p=0.560). There was no significant difference in blastocyst outcomes and pregnancy outcomes for both populations. Conclusion: Based on the diagnosis by the Matsuda Index, IR may adversely affect the day 3 embryo quality in patients with PCOS but not pregnancy outcomes. In women without PCOS, IR alone seems to have less significant adverse effects on embryo quality than in patients with PCOS. Better-designed studies are still needed to compare the differences statistically between PCOS and non-PCOS populations.