Recent Advances in Sample Preparation and Chromatographic/Mass Spectrometric Techniques for Detecting Polycyclic Aromatic Hydrocarbons in Edible Oils: 2010 to Present.

Polycyclic aromatic hydrocarbons are considered to be potentially genotoxic and carcinogenic to humans. For non-smoking populations, food is the main source of polycyclic aromatic hydrocarbons exposure. Due to their lipophilic nature, oils and fats rank among the food items with the highest polycyclic aromatic hydrocarbon content. Consequently, the detection of polycyclic aromatic hydrocarbons in edible oils is critical for the promotion of human health. This paper reviews sample pretreatment methods, such as liquid-phase-based extraction methods, adsorbent-based extraction methods, and the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method, combined with detection techniques like mass spectrometry and chromatography-based techniques for accurate quantification of polycyclic aromatic hydrocarbons in edible oils since 2010. An overview on the advances of the methods discussed herein, along with a commentary addition of current challenges and prospects, will guide researchers to focus on developing more effective detection methods and control measures to reduce the potential risks and hazards posed by polycyclic aromatic hydrocarbons.

Proteomic and metabolomic profiling of plasma predicts immune-related adverse events in older patients with advanced non-small cell lung cancer.

The clinical success of immune checkpoint inhibitors is compromised by the fact of immune-related adverse events (irAEs), especially for older patients. To identify predictive biomarkers for older patients with irAEs, we used multiplex immunoassay and flow cytometry and liquid chromatography-tandem mass spectrometry to test immune factors and plasma protein and metabolites levels in non-small cell lung cancer (NSCLC) patients. The results showed that older patients with irAEs displayed lower CD28, CD4+ T cell, and B cell and higher interleukin (IL)-10 and CCL2 levels at baseline. Besides, lower aldolase, fructose-bisphosphate B (ALDOB), higher ST6GAL1, and lower lactate/pyruvate ratio at baseline were found in older patients with irAEs. Based on metabolomic markers, predictive models were developed to distinguish patients with grade 2-4 irAEs from grade 0-1 (Area under curve, AUC = 0.831) and to distinguish patients with grade 3-4 irAEs from grade 2 (AUC = 1). Our results confirmed the predictive value of plasma metabolites for irAEs in older patients with NSCLC.

The mannose-binding lectin (MBL) gene cloned from Exopalaemon carinicauda plays a key role in resisting infection by Vibrio parahaemolyticus.

Mannose-binding lectin (MBL) is a vital member of the lectin family, crucial for mediating functions within the complement lectin pathway. In this study, following the cloning of the mannose-binding lectin (MBL) gene in the ridgetail white prawn, Exopalaemon carinicauda, we examined its expression patterns across various tissues and its role in combating challenges posed by Vibrio parahaemolyticus. The results revealed that the MBL gene spans 1342 bp, featuring an open reading frame of 972 bp. It encodes a protein comprising 323 amino acids, with a predicted relative molecular weight of 36 kDa and a theoretical isoelectric point of 6.18. The gene exhibited expression across various tissues including the eyestalk, heart, gill, hepatopancreas, stomach, intestine, ventral nerve cord, muscle, and hemolymph, with the highest expression detected in the hepatopancreas. Upon challenge with V. parahaemolyticus, RT-PCR analysis revealed a trend of MBL expression in hepatopancreatic tissues, characterized by an initial increase followed by a subsequent decrease, peaking at 24 h post-infection. Employing RNA interference to disrupt MBL gene expression resulted in a significant increase in mortality rates among individuals challenged with V. parahaemolyticus. Furthermore, we successfully generated the Pet32a-MBL recombinant protein through the construction of a prokaryotic expression vector for conducting in vitro bacterial inhibition assays, which demonstrated the inhibitory effect of the recombinant protein on V. parahaemolyticus, laying a foundation for further exploration into its immune mechanism in response to V. parahaemolyticus challenges.

Magnetic resonance-guided laser interstitial thermal therapy vs. stereoelectroencephalography-guided radiofrequency thermocoagulation in epilepsy patients with focal cortical dysplasia: a systematic review and meta-analysis.

Background: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) and stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) are two effective, minimally invasive treatments for epilepsy with focal cortical dysplasia (FCD). The purpose of this study is to conduct a meta-analysis to evaluate and compare the efficacy and safety of these two therapies in epilepsy patients with FCD. Methods: We searched PubMed, Embase, Cochrane, and other databases for articles published before March 2023. The primary objective was to compare the effectiveness and complications of MRgLiTT and SEEG-RFTC in epilepsy patients with FCD. The second objective was to determine which method provides a better prognosis for specific subgroup patients. Results: According to the inclusion and exclusion criteria, 18 studies were included, comprising 270 FCD patients including 37 patients from 6 MRgLiTT studies and 233 from 12 SEEG-RFTC studies. There were no significant differences between MRgLiTT and SEEG-RFTC groups in the seizure-freedom rate (59%, 95% CI 44-74%; 52%, 95% CI 47-57%, P = 0.86) and the rate of ≥50% seizure-reduction of FCD (90%, 95% CI 80-100%; 90%, 95% CI 86-94%, P = 0.42). Both methods had low complication rates (17.1%, 28/159) and long-term complication (2.5%, 4/159) rate, with no significant difference between them (P = 0.17). Conclusion: Both MRgLiTT and SEEG-RFTC are safe and minimally invasive treatments for patients with FCD. They have comparable performance in terms of postoperative seizure-freedom rates in patients with FCD, and both can be used as treatment options for patients with FCD. Our study found that SEEG-RFTC had a better therapeutic effect in the FCD2b subgroup.

De novo transcriptional analysis of the response to starvation stress in the white ridgetail prawn, Exopalaemon carinicauda.

To study the mechanism of the biomolecular response in Exopalaemon carinicauda to starvation stress, we subjected muscle tissue RNA samples from four stress points, including 0 d(control group), 10 d, 20 d, and 30 d, to starvation stress on white ridgetail prawn with a body weight of 1.41 + 0.42 g, aquaculture water temperature of 23-25 °C, salinity of 26, dissolved oxygen ≥5 mg/L, and pH 8-8.5, Then performed de novo transcriptome assembly and gene expression analysis using BGISEQ-500 with a tag-based digital gene expression (DGE) system. By de novo assembling at the four times, we obtained 28,167, 21,115, 24,497, and 27,080 reads, respectively. The results showed that the stress at 10 d led to no significant difference in the expressed genes, while the stress at 20 d and 30 d showed a significant increase (or decrease) in the expression of 97 (276) and 143 (410) genes, respectively, which were involved in 8 different metabolic pathways. In addition, we detected 2647 unigene transcription factors. Eleven upregulated and sixteen downregulated genes from the different starvation stress groups were choose to verify the reliability of the transcriptome data, and the results showed that the expression trends of these genes were consistent with the results shown by the transcriptome. The analysis of the experimental data and our discussion of the response mechanism of white ridgetail prawn under starvation stress provides a foundation for further screening of the key genes of starvation stress and may help to elucidate their functions.

Prognostic and predictive impact of molecular tumor burden index in non-small cell lung cancer patients.

BACKGROUND: The biomarkers of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC) patients have limited predictive performance. In this study we aimed to investigate the feasibility of molecular tumor burden index (mTBI) in circulating tumor DNA (ctDNA) as a predictor for immunotherapy in patients with NSCLC. METHODS: From February 2017 to November 2020, pretreatment and on-treatment (3~6 weeks after first cycle of immunotherapy) dynamic plasma ctDNA samples from NSCLC patients receiving immune monotherapy or combination therapy were analyzed by targeted capture sequencing of 1021 genes. PyClone was used to infer the mTBI. The impact of pretreatment mTBI on survival outcomes was verified in the POPLAR/OAK trials. RESULTS: We found that patients without detectable baseline ctDNA had better survival outcomes (median overall survival [OS]: not reached vs. 12.8 months; hazard ratio [HR], 0.15; p = 0.035]). RB1 and SMARCA4 mutations were remarkably associated with worse survival outcomes. Furthermore, lower pretreatment mTBI was associated with superior OS (median: not reached vs. 8.1 months; HR, 0.22; p = 0.024) and PFS (median: 32.9 vs. 5.4 months; HR, 0.35; p = 0.045), but not objective response, which was validated in the POPLAR/OAK cohort, suggesting that baseline mTBI was a prognostic factor for NSCLC immunotherapy. Early dynamic changes of mTBI (ΔmTBI) significantly distinguished responsive patients, and patients with mTBI decrease to more than 68% at the final tumor evaluation had longer OS (median: 38.2 vs. 4.0 months; HR, 0.18; p = 0.017) and PFS (median: not reached vs. 2.3 months; HR, 0.24; p = 0.030). CONCLUSION: ΔmTBI had a good sensitivity to identify potential beneficial patients based on the best effect CT scans, demonstrating that mTBI dynamics were predictive of benefit from immune checkpoint blockade.

Comparison of uniport versus triport thoracoscopic single or combined basal segmentectomy for stage IA lung cancer.

Background: Single or combined basal segmentectomy (CBS), excluding common basal segmentectomy, is the most difficult of all types of segmentectomies. The purpose of this study was to compare the perioperative outcomes and oncological prognosis between uniport thoracoscopic basal segmentectomy (UTBS) and triport thoracoscopic basal segmentectomy (TTBS). Methods: This study retrospectively collected 300 patients who underwent thoracoscopic single or CBS at the West China Hospital of Sichuan University from April 2015 to May 2022, including 67 and 233 patients in the UTBS and TTBS groups, respectively. Propensity score matching (PSM) was used to reduce confounding bias between the two groups. The primary outcome was recurrence-free survival (RFS). The secondary outcomes were overall survival (OS) and perioperative outcomes. Results: After PSM, the UTBS group (n=64) had significantly less intraoperative blood loss than the TTBS group (n=64) (20 vs. 30 mL, P=0.001). Other perioperative outcomes, including the operation time, number of lymph nodes and lymph node stations harvested, duration of chest tube drainage, postoperative hospital stay, and postoperative complications, were comparable. Subgroup analysis demonstrated that the operative time in the group underwent single basal segmentectomy (SBS) was significantly shorter compared to the group underwent CBS (110 vs. 120 min, P=0.002). There were 5 cases of recurrence in the overall cohort and no recurrence in the matched cohort. No deaths were observed in the overall cohort. Therefore, a survival analysis was conducted only for RFS in the overall cohort. The RFS rate and OS rate of the overall cohort were 98.3% and 100%, respectively. The surgical approach (UTBS vs. TTBS) was not an independent risk factor for RFS (HR: 1.120, 95% CI: 0.342-13.051, P=0.879). Conclusions: UTBS provided similar perioperative outcomes and oncological prognoses compared to TTBS.

Predictors of immune checkpoint inhibitor-related adverse events in older patients with lung cancer: a prospective real-world analysis.

PURPOSE: Older patients with cancer are underrepresented in pivotal trials of immune checkpoint inhibitors (ICIs). This study aimed to investigate immune-related adverse events (irAEs) that occur in older patients with lung cancer treated with ICIs, and explore predictors of the occurrence of irAEs. METHODS: A prospective analysis was performed on older patients with lung cancer aged ≥ 65 years who were treated with anti-programmed cell death-1/-ligand 1 (PD-1/PD-L1) inhibitors in Beijing Hospital from January 2018 to December 2022. The incidence and risk factors of irAEs were estimated by the Chi-square test or Wilcoxon rank-sum tests. The predictive power of Geriatric-8 (G-8) for irAEs was tested by receiver operating characteristic (ROC) curve analysis. Lymphocyte counts were measured by flow cytometry. Cytokine levels were tested by Enzyme-linked immunosorbent assay, respectively. Kaplan-Meier method was used to calculated progression-free survival (PFS) curves, and the log-rank test was used to evaluate differences. RESULTS: A total of 201 older patients aged ≥ 65 years with lung cancer were enrolled in this study. The most common irAEs were interstitial pneumonia, dermatological toxicity and hypothyroidism, with rates of 17.2%, 16.1% and 5.6%, respectively. ROC showed that G-8 could predict the occurrence of irAEs in patients aged 65-71 years (≥ G2 irAEs: AUC = 0.757, p < 0.001; ≥ G3 irAEs: AUC = 0.862, p < 0.001), but not for patients aged ≥ 71 years. NLR, LMR, PNI, hypertension and diabetes were associated with irAEs. Lower CD4 + T cells and B cells, and lower levels of IL-10 were associated with the development of irAEs. CONCLUSION: Our study confirmed the accuracy of G-8 for predicting irAEs in older patients. We also identified several predictors of irAEs in older patients with lung cancer.

Tussilagone ameliorates high-fat diet-induced hepatic steatosis by enhancing energy metabolism and antioxidant activity.

Non-alcoholic fatty liver disease (NAFLD) is a major health problem. However, no effective treatments are currently available. Thus, there is a critical need to develop novel drugs that can prevent and treat NAFLD with few side effects. In this study, Tussilagone (TUS), a natural sesquiterpene isolated from Tussilago farfara L, was explored in vitro and in vivo for its potential to treat NAFLD. Our results showed that in vitro TUS reduced oleic acid palmitate acid-induced triglyceride and cholesterol synthesis in HepG2 cells, reduced intracellular lipid droplet accumulation, improved glucose metabolism disorders and increased energy metabolism and reduced oxidative stress levels. In vivo, TUS significantly reduced fat accumulation and improved liver injury in high-fat diet (HFD)-induced mice. TUS treatment significantly increased liver mitochondrial counts and antioxidant levels compared to the HFD group of mice. In addition, TUS was found to reduce the expression of genes involved in lipid synthesis sterol regulatory element binding protein-1 (SREBP1), fatty acid synthase (FASN), and stearoy-CoA desaturase 1 (SCD1) in vitro and in vivo. Our results suggest that TUS may be helpful in the treatment of NAFLD, suggesting that TUS is a promising compound for the treatment of NAFLD. Our findings provided novel insights into the application of TUS in regulating lipid metabolism.

The Roles of Natural Alkaloids and Polyphenols in Lipid Metabolism: Therapeutic Implications and Potential Targets in Metabolic Diseases.

The prevalence of obesity and its associated diseases has increased dramatically, and they are major threats to human health worldwide. A variety of approaches, such as physical training and drug therapy, can be used to reduce weight and reverse associated diseases; however, the efficacy and the prognosis are often unsatisfactory. It has been reported that natural food-based small molecules can prevent obesity and its associated diseases. Among them, alkaloids and polyphenols have been demonstrated to regulate lipid metabolism by enhancing energy metabolism, promoting lipid phagocytosis, inhibiting adipocyte proliferation and differentiation, and enhancing the intestinal microbial community to alleviate obesity. This review summarizes the regulatory mechanisms and metabolic pathways of these natural small molecules and reveals that the binding targets of most of these molecules are still undefined, which limits the study of their regulatory mechanisms and prevents their further application. In this review, we describe the use of Discovery Studio for the reverse docking of related small molecules and provide new insights for target protein prediction, scaffold hopping, and mechanistic studies in the future. These studies will provide a theoretical basis for the modernization of anti-obesity drugs and promote the discovery of novel drugs.

What is an appropriate gestational weight gain for women with gestational diabetes mellitus: based on the adverse pregnancy outcomes of over 12 thousand participants?

BACKGROUND: Evidence showed possible benefits of a less gestational weight gain (GWG) than the US Institute of Medicine (IOM) recommendation in gestational diabetes mellitus (GDM) pregnancy. Here, we aimed to explore an appropriate GWG range in GDM women according to adverse pregnancy outcomes. METHODS: We enrolled all the singleton GDM pregnant women (n = 14,213) from January 2015 to December 2018 in Xi'an, Northwest China. According to the pre-pregnancy body mass index (BMI), they were classified into the Underweight (< 18.5 kg/m2), Normal weight (18.5-24.9 kg/m2), Overweight (25.0-29.9 kg/m2) and Obesity (≥ 30.0 kg/m2) group, respectively. Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI). The appropriate ranges of GWG were determined based on a significant protective association (OR < 1). RESULTS: Totally, 12,712 participants were finally recruited. There were 1180 (9.3%), 9134 (71.9%), 2097 (16.5%), and 301 (2.4%) patients in the Underweight, Normal weight, Overweight, and Obesity groups, respectively. Adverse outcomes increased with the elevation of pre-pregnancy BMI. Among them, the risk of cesarean section was the highest, followed by large for gestational age (LGA), small for gestational age (SGA), preeclampsia, and gestational hypertension. Through the analysis of the risk of adverse outcomes in continuous GWG categories in each group, an ideal GWG range obtained in this study was as follows: 10-15.9 kg, 8-11.9 kg, 6-7.9 kg, and -5-3.9 kg for the Underweight, Normal weight, Overweight and Obesity group, respectively. Furthermore, the ranges in this study were more protective for adverse outcomes than those from IOM. CONCLUSIONS: Based on the adverse pregnancy outcomes of over 12 thousand participants, our findings showed a more stringent GWG range for GDM women than the IOM criteria recommendation.

Dietary supplementation with perillartine ameliorates lipid metabolism disorder induced by a high-fat diet in broiler chickens.

Lipid metabolism disorders affect the growth and jeopardize the health of poultry, thus, decreasing economic benefits. Perillartine, a sweetener derived from Perilla frutescens, has excellent potential in regulating lipid metabolism. In this study, we explored the effects of perillartine on lipid metabolism in broiler chickens by establishing a nonalcoholic fatty liver model induced by a high-fat diet. By using network pharmacology and molecular docking, we analyzed the potential molecular targets and pathways through which perillartine regulates lipid metabolism and alleviates fatty liver. Perillartine was found to regulate the expression of genes associated with lipogenesis, lipolysis, and lipid transport, including FASN, PPARα, CPT-1, ACCα, APOB, and APOA1 in the liver, and to decrease lipid accumulation in the liver and blood in broilers without affecting growth performance. In addition, we discovered 24 candidate targets of perillartine, including SRD5A2 and XDH, through network pharmacology analysis and successfully constructed a compound-target-pathway-disease network. Our results suggested that perillartine may be a promising, long-lasting therapeutic molecule for modulating lipid metabolism disorders in broilers.

Mitoxantrone alleviates hepatic steatosis induced by high-fat diet in broilers.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a common nutritional metabolic disease in poultry that seriously compromises the health of chickens and reduces the economic benefits of the industry. In this study, we investigated the therapeutic effect of mitoxantrone (MTX) on hepatic steatosis in broilers. We constructed a steatosis cell model in vitro by adding oleic acid and palmitic acid to chicken hepatocytes (LMH cells), to examine influence of MTX on fat deposition on LMH cells. To determine the effects of MTX on hepatic steatosis in broiler livers in vivo, broilers were fed a high-fat diet to establish a fatty liver model. Our data show that MTX reduced the triglyceride (TG) levels and total cholesterol levels in LMH cells. In the MAFLD chick model, MTX decreased mRNA abundance of hepatic-lipid-synthesis-related gene such as FASN and increased mRNA abundance of fatty-acid-ß-oxidation-related genes such as CPT1, PPARα, and reduced hepatic TG levels. MTX also reduced serum lipid and the percentage of abdominal fat. These results suggest that MTX improves hepatic steatosis in broilers as well as reduces circulating lipid levels and fat accumulation in broilers. Our work provides a promising therapeutic strategy for MAFLD and excessive fat accumulation in broiler chickens.

Late-Pregnancy Dysglycemia After Negative Testing for Gestational Diabetes and Risk of the Large-for-Gestational-Age Newborns: A Nest Case-Control Study Based on the Xi'an Longitudinal Mother-Child Cohort Study.

Background: The implications of gestational diabetes mellitus (GDM) on the short- and long-term health outcomes of both mother and child have been extensively studied. However, studies related to negative Oral Glucose Tolerance Test (OGTT) results in the second trimester but dysglycemia in late pregnancy on maternal and infant pregnancy outcomes are rare. Methods: We conducted a nest case-control study within the Xi'an Longitudinal Mother-Child Cohort study (XAMC) to investigate the risk of adverse pregnancy outcomes in mothers and children with maternal negative mid-pregnancy OGTT results but high glycated hemoglobin (HbA1c) levels (≥5.7%) in late pregnancy. All target women who delivered from January 1st, 2017 to December 31st, 2018 in Northwest Women's and Children's Hospital in Xi'an were enrolled as the case group (HbA1c ≥ 5.7%). Others with HbA1c < 5.7% but without GDM were selected as the control group (HbA1c < 5.7%) by matching with the same delivery period. The logistic regression models were used to find out the risk factors of adverse pregnancy outcomes in the target population. Results: A total of 2,116 and 1,907 women were finally enrolled in the case and control groups, respectively. Compared to the control group, more newborns with macrosomia (9.2% vs 4.1%, P < 0.001) and large for gestational age (LGA) (23.7% vs. 13.5%, P < 0.001), but less small for gestational age (SGA) (4.4% vs. 6.1%, P = 0.017) were found in the case group. The differences in other outcomes were not statistically significant. The multiple logistic regression analysis showed that gestational age, fetal length, prenatal HbA1c, and total cholesterol (TG) were independent risk factors for newborns with large-for-gestational-age (LGA). The case group had a 2.516-fold (95% CI, 1.692-3.739) risk of delivering LGA newborns compared to the control group. Conclusion: The glycemic management during the late pregnancy of non-GDM women should be given special consideration to reduce the risk of overweight offspring at birth.

Study on TCM Tongue Image Segmentation Model Based on Convolutional Neural Network Fused with Superpixel.

Tongue image segmentation is a base work of TCM tongue processing. Nowadays, deep learning methods are widely used on tongue segmentation, which has better performance than conventional methods. However, when the tongue color is close to the color of the adjoining area, the contour of tongue segmentation by deep learning may be coarse which could influence the subsequent analysis. Here a novel tongue image segmentation model based on a convolutional neural network fused with superpixel was proposed to solve the problem. Methods. On the basis of a convolutional neural network fused with superpixel, the novel tongue image segmentation model SpurNet was proposed in this study. The residual structure of ResNet18 was introduced as the feature extraction layer on the encoding path, to construct the first stage processing module UrNet of SpurNet. The superpixel segmentation was fused with UrNet to form the second stage process of SpurNet. To verify the effect of SpurNet. The models before and after fusion with superpixel, classical image segmentation models FCN and DeepLab were compared with SpurNet on the dataset of 367 manually labeled tongue images. Results. The SpurNet model performance test with 10-fold cross-validation showed PA of 0.9145 ± 0.0043, MPA of 0.9168 ± 0.0048, MIoU of 0.8417 ± 0.0072 and FWIoU of 0.8454 ± 0.0072. Relative to FCN, DeepLab and their superpixel fused models, the SpurNet model was superior in tongue image segmentation and could increase PA by 1.91%-3.17%, MPA by 1.38%-2.61%, MIoU by 3.09%-5.07%, and FWIoU by 3.11%-5.08%. Compared to UrNet, the first stage processing module, the SpurNet model also increased the PA, MPA, MIoU and FWIoU by 0.15%, 0.09%, 0.24% and 0.24%, respectively. Conclusion. The SpurNet model, after fusing with superpixel image segmentation, can better accomplish the task of tongue image segmentation, more accurately process the margins of tongue and resolve the over-segmentation and under-segmentation. The thought of this study is a new exploration in the field of tongue image segmentation, which could provide a reference for the modern research on TCM tongue images.

A New lncRNA, lnc-LLMA, Regulates Lipid Metabolism in Pig Hepatocytes.

A large variety of long noncoding RNAs (lncRNAs) have been discovered through high-throughput sequencing technology and some have been demonstrated to play important roles in lipid metabolism regulation. In our study, we found a highly expressed lncRNA (lnc-LLMA, liver lipid metabolism-associated lncRNA) in the liver of Duroc pigs, which was enriched in the nucleus. It displays potent tissue specificity among different pig breeds. Overexpression of lnc-LLMA can cause a decline in intracellular triglyceride (TG) levels and increases in ATP and mitochondrial DNA levels in pig primary hepatocytes and HepG2 cells. In addition, the expression levels of MTTP, APOB, CPT1α, and other genes were increased by overexpression of lnc-LLMA. It downregulated expression of G6Pase and SREBP1 genes. Chromatin isolation by RNA purification (ChRIP) experiments demonstrated that microsomal triglyceride transfer protein (MTTP) and glycogen synthase 2 (GYS2) were the potential interacting proteins of lnc-LLMA. The overexpression of the GYS2 gene rescued the decreasing intracellular TG levels caused by the increase of lnc-LLMA. Similarly, overexpression of MTTP was also able to save the lnc-LLMA-induced decrease in intracellular TG. Our study demonstrated that this novel lncRNA was closely related to lipid metabolism and affected lipid transport and mitochondrial function through MTTP and GYS2. Our results provided a new direction for further studying the effect of lncRNA on lipid metabolism regulation.

Long-term high-fat diet consumption by mice throughout adulthood induces neurobehavioral alterations and hippocampal neuronal remodeling accompanied by augmented microglial lipid accumulation.

High-fat diet (HFD) consumption is generally associated with an increased risk of cognitive and emotional dysfunctions that constitute a sizeable worldwide health burden with profound social and economic consequences. Middle age is a critical time period that affects one's health later in life; pertinently, the prevalence of HFD consumption is increasing among mature adults. Given the growing health-related economic burden imposed globally by increasing rates of noncommunicable diseases in rapidly aging populations, along with the pervasive but insidious health impairments associated with HFD consumption, it is critically important to understand the effects of long-term HFD consumption on brain function and to gain insights into their potential underlying mechanisms. In the present study, adult male C57BL/6J mice were randomly assigned a control diet (CD, 10 kJ% from fat) or an HFD (60 kJ% from fat) for 6 months (6 M) or 9 months (9 M) followed by behavioral tests, serum biochemical analysis, and histological examinations of both the dorsal and ventral regions of the hippocampus. In both the 6 M and 9 M cohorts, mice that consumed an HFD exhibited poorer memory performance in the Morris water maze test (MWM) and greater depression- and anxiety-like behavior during the open field test (OFT), sucrose preference test (SPT) and forced swim test (FST) than control mice. Compared with age-matched mice in the CD group, mice in the HFD group showed abnormal hippocampal neuronal morphology, which was particularly evident in the ventral hippocampus. Hippocampal microglia in mice in the HFD group generally had a more activated phenotype evidenced by a smaller microglial territory area and increased cluster of differentiation 68 (CD68, a marker of phagocytic activity) immunoreactivity, while the microglial density in the dentate gyrus (DG) was decreased, indicating microglial decline. The engulfment of postsynaptic density 95 (PSD95, a general postsynaptic marker) puncta by microglia was increased in the HFD groups. Histological analysis of neutral lipids using a fluorescent probe (BODIPY) revealed that the total neutral lipid content in regions of interests (ROIs) and the lipid load in microglia were increased in the HFD group relative to the age-matched CD group. In summary, our results demonstrated that chronic HFD consumption from young adulthood to middle age induced anxiety- and depression-like behavior as well as memory impairment. The negative influence of chronic HFD consumption on behavioral and hippocampal neuroplasticity appears to be linked to a change in microglial phenotype that is accompanied by a remarkable increase in cellular lipid accumulation. These observations highlighting the potential to target lipid metabolism deficits to reduce the risk of HFD-associated emotional dysfunctions.

Comprehensive landscape of the renin-angiotensin system in Pan-cancer: a potential downstream mediated mechanism of SARS-CoV-2.

Background: SARS-CoV-2, the cause of the worldwide COVID-19 pandemic, utilizes the mechanism of binding to ACE2 (a crucial component of the renin-angiotensin system [RAS]), subsequently mediating a secondary imbalance of the RAS family and leading to severe injury to the host. However, very few studies have been conducted to reveal the mechanism behind the effect of SARS-CoV-2 on tumors. Methods: Demographic data extracted from 33 cancer types and over 10,000 samples were employed to determine the comprehensive landscape of the RAS. Expression distribution, pretranscriptional and posttranscriptional regulation and posttranslational modifications (PTMs) as well as genomic alterations, DNA methylation and m6A modification were analyzed in both tissue and cell lines. The clinical phenotype, prognostic value and significance of the RAS during immune infiltration were identified. Results: Low expression of AGTR1 was common in tumors compared to normal tissues, while very low expression of AGTR2 and MAS1 was detected in both tissues and cell lines. Differential expression patterns of ACE in ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC) were correlated with ubiquitin modification involving E3 ligases. Genomic alterations of the RAS family were infrequent across TCGA pan-cancer program, and ACE had the highest alteration frequency compared with other members. Low expression of AGTR1 may result from hypermethylation in the promoter. Downregulation of RAS family was linked to higher clinical stage and worse survival (as measured by disease-specific survival [DSS], overall survival [OS] or progression-free interval [PFI]), especially for ACE2 and AGTR1 in KIRC. ACE-AGTR1, a classical axis of the RAS family related to immune infiltration, was positively correlated with M2-type macrophages, cancer-associated fibroblasts (CAFs) and immune checkpoint genes in most cancers. Conclusion: ACE, ACE2, AGT and AGTR1 were differentially expressed in 33 types of cancers. PTM of RAS family was found to rely on ubiquitination. ACE2 and AGTR1 might serve as independent prognostic factors for LGG and KIRC. SARS-CoV-2 might modify the tumor microenvironment by regulating the RAS family, thus affecting the biological processes of cancer.

Effects of Oral Vitamin C Supplementation on Liver Health and Associated Parameters in Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial.

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18-60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, n = 26), medium (1,000 mg/day, n = 30), or high (2,000 mg/day, n = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, -5.00 (-10.25, -1.75) vs. High, -2.50 (-7.75, 0.00), P = 0.02] and alanine aminotransferase [Medium, -8.00 (-18.00, -1.75) vs. High, -3.50 (-13.75, 4.25), P = 0.05; Medium vs. Low, -3.00 (-9.00, 5.50), P = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.