Associations between metabolic dysfunction-associated fatty liver disease and atherosclerotic cardiovascular disease.

Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide has contributed to the rising incidence of NAFLD. It is widely believed that atherosclerotic cardiovascular disease (ASCVD) is associated with NAFLD. In the past decade, the clinical implications of NAFLD have gone beyond liver-related morbidity and mortality, with a majority of patient deaths attributed to malignancy, coronary heart disease (CHD), and other cardiovascular (CVD) complications. To better define fatty liver disease associated with metabolic disorders, experts proposed a new term in 2020 - metabolic dysfunction associated with fatty liver disease (MAFLD). Along with this new designation, updated diagnostic criteria were introduced, resulting in some differentiation between NAFLD and MAFLD patient populations, although there is overlap. The aim of this review is to explore the relationship between MAFLD and ASCVD based on the new definitions and diagnostic criteria, while briefly discussing potential mechanisms underlying cardiovascular disease in patients with MAFLD.

The role of tumor-associated macrophages in the radioresistance of esophageal cancer cells via regulation of the VEGF-mediated angiogenic pathway.

Tumor-associated macrophages (TAMs) are known to promote tumor growth, invasion, metastasis, and protumor angiogenesis, but the role of TAMs in evading radiotherapy in esophagus cancer remains unclear. In this study, we first induced TAMs from human monocytes (THP-1) and identified using immunofluorescence and Western blotting assays. We then co-cultured them with human esophageal cancer cell lines. CCK-8, colony formation, Transwell, scratch test, and TUNEL assays showed that TAMs could promote proliferation, survival rate, invasion, migration, and radioresistance and could inhibit apoptosis of the esophageal squamous carcinoma cell lines KYSE-150 and TE-1 before and after radiotherapy both in vivo and in vitro. Using LV-VEGFA-RNAi lentiviral vectors, we also found that TAMs could increase the expression of VEGFA and that inhibition of VEGFA could inhibit the biological function caused by TAMs. Finally, a Western blotting assay was used to evaluate the expression of various factors underlying the mechanism of TAMs. VEGFA, MAPK, P-MAPK, BCL-2, and Snail proteins were found to be overexpressed in co-cultured groups, whereas after VEGFA inhibition, MAPK, P-MAPK, BCL-2, and Snail proteins were found to be significantly downregulated in the radiotherapy group. These study results offer important information regarding the mechanism of radioresistance in esophageal cancer.

Sesamin ameliorates nonalcoholic hepatic steatosis by inhibiting CD36-mediated hepatocyte lipid accumulation in vitro and in vivo.

Hepatic steatosis is a critical factor in the development of nonalcoholic steatohepatitis (NASH). Sesamin (Ses), a functional lignan isolated from Sesamum indicum, possesses hypolipidemic, liver-protective, anti-hypertensive, and anti-tumor properties. Ses has been found to improve hepatic steatosis, but the exact mechanisms through which Ses achieves this are not well understood. In this study, we observed the anti-hepatic steatosis effects of Ses in palmitate/oleate (PA/OA)-incubated primary mouse hepatocytes, AML12 hepatocytes, and HepG2 cells, as well as in high-fat, high-cholesterol diet-induced NASH mice. RNA sequencing analysis revealed that cluster of differentiation 36 (CD36), a free fatty acid (FA) transport protein, was involved in the Ses-mediated inhibition of hepatic fat accumulation. Moreover, the overexpression of CD36 significantly increased hepatic steatosis in both Ses-treated PA/OA-incubated HepG2 cells and NASH mice. Furthermore, Ses treatment suppressed insulin-induced de novo lipogenesis in HepG2 cells, which was reversed by CD36 overexpression. Mechanistically, we found that Ses ameliorated NASH by inhibiting CD36-mediated FA uptake and upregulation of lipogenic genes, including FA synthase, stearoyl-CoA desaturase 1, and sterol regulatory element-binding protein 1. The findings of our study provide novel insights into the potential therapeutic applications of Ses in the treatment of NASH.

Deep-Learning-Based Analysis Reveals a Social Behavior Deficit in Mice Exposed Prenatally to Nicotine.

Cigarette smoking during pregnancy is known to be associated with the incidence of attention-deficit/hyperactive disorder (ADHD). Recent developments in deep learning algorithms enable us to assess the behavioral phenotypes of animal models without cognitive bias during manual analysis. In this study, we established prenatal nicotine exposure (PNE) mice and evaluated their behavioral phenotypes using DeepLabCut and SimBA. We optimized the training parameters of DeepLabCut for pose estimation and succeeded in labeling a single-mouse or two-mouse model with high fidelity during free-moving behavior. We applied the trained network to analyze the behavior of the mice and found that PNE mice exhibited impulsivity and a lessened working memory, which are characteristics of ADHD. PNE mice also showed elevated anxiety and deficits in social interaction, reminiscent of autism spectrum disorder (ASD). We further examined PNE mice by evaluating adult neurogenesis in the hippocampus, which is a pathological hallmark of ASD, and demonstrated that newborn neurons were decreased, specifically in the ventral part of the hippocampus, which is reported to be related to emotional and social behaviors. These results support the hypothesis that PNE is a risk factor for comorbidity with ADHD and ASD in mice.

Association of LDL-C/HDL-C ratio with coronary heart disease: A meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is a common heart disease and a leading cause of death in developed countries and some developing countries such as China. It is recognized as a multifactorial disease, with dyslipidemia being closely associated with the progression of coronary atherosclerosis. Numerous studies have confirmed the relationship between a single indicator of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) and CHD. However, the association between LDL-C to HDL-C ratio (LHR) and CHD remains unclear. This study aimed to comprehensively explore the association between LHR and CHD. METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched up to June 15, 2023, to find the studies that indicated the connection between LHR and CHD. A total of 12 published studies were selected. The random-effects model was used to pool the data and mean difference (MD), and the 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the study selection. The Review Manager 5.4 and Stata 12 were used to analyze the data. RESULTS: Twelve high-quality clinical studies involving 5544 participants, including 3009 patients with CHD, were enrolled in the meta-analysis. The findings revealed that the LHR was higher by 0.65 in patients with CHD than in those without CHD (MD, 0.65; 95% CI, 0.50-0.80). CONCLUSION: The LHR was found to be positively correlated with CHD, suggesting that it may serve as a potential indicator of CHD.

Mesopic pupil indices as potential risk factors for glare disability after intraocular implantable collamer lens implantation: prospective study.

PURPOSE: To explore the influence of preoperative factors, including varying pupil sizes and refractive attributes, on postoperative glare disability in patients undergoing implantable collamer lens (ICL) implantation. SETTING: Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China. DESIGN: Prospective observational study. METHODS: The preoperative ocular characteristics and 6-month postoperative glare status in eligible patients who underwent EVO-Visian ICL V4c (VICMO) implantation were analyzed. The glare disability criteria encompassed a glare symptom score >6 and glare sensitivity exceeding 1:2.7. Logistic regression analysis was used to explore the relationship between the preoperative ocular parameters and post-ICL glare. RESULTS: The study included 95 patients (mean age, 26.04 ± 6.29 years), comprising 30 men (58 eyes) and 65 women (129 eyes). Multivariate analysis revealed a significant correlation between postoperative glare disability and increased spherical power in preoperative mesopic pupils (ß = -0.124, P = .039), as well as elevated cylinder power in preoperative mesopic (ß = -0.412, P = .009) and photopic pupils (ß = -0.430, P = .007). Moreover, a larger preoperative mesopic pupil diameter (ß = 0.561, P = .005) demonstrated a significant correlation with glare disability. CONCLUSIONS: Preoperative mesopic pupil dimensions and associated refractive parameters, such as sphere and cylinder, were correlated with glare disability, including the cylinder aspect in photopic pupils, which can assist clinicians in optimizing preoperative selection for ICL implantation, aiding in the anticipation of potential glare disability risks.

CoronaVac and BBIBP-CorV vaccines against SARS-CoV-2 during predominant circulation of Omicron BA.5.2 and BF.7 in China, a retrospective cohort study.

Pandemic of COVID-19 hit China at the end of 2022. According to China Center for Disease Control and Prevention, Omicron BA.5.2 and BF.7 were the main circulating variants. Chinese people had a high COVID-19 vaccination rate, and the most widely used vaccines were CoronaVac (Sinovac) and BBIBP-CorV (Sinopharm). An online questionnaire was distributed to survey the vaccination history and infection information of China mainland residents during this pandemic. A total of 4250 subjects were included for propensity score matching, 566 unvaccinated subjects and 1072 vaccinated subjects were finally included to analyze the effects of the two vaccines on BA.5.2 and BF.7. The SARS-CoV-2 infection rate was 84.5% in the vaccinated group and 82.3% in the unvaccinated group (p = 0.255). Vaccinated subjects had significantly higher rates of COVID-19-related symptoms, including fever, cough, nasal obstruction, runny nose, and sore throat. However, vaccinated people had lower risk of pneumonia (odds ratio [OR]: 0.467, 95% confidence interval [CI]: 0.286-0.762) and hospitalization (OR: 0.290, 95% CI: 0.097-0.870) due to COVID-19. In general, the current study did not observe the protective effect of CoronaVac and BBIBP CorV against BA.5.2 and BF.7 infection. However, these vaccines can still reduce the risk of adverse outcomes such as pneumonia and hospitalization.

Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein.

CASK-related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including microcephaly with pontine and cerebellar hypoplasia (MICPCH), epilepsy, congenital nystagmus, and neurodevelopmental disorders. Whole-genome sequencing has identified various mutations, including nonsense and missense mutations, from patients with CASK-related disorders, revealing correlations between specific mutations and clinical phenotypes. Notably, missense mutations associated with epilepsy and intellectual disability were found throughout the whole region of the CASK protein, while missense mutations related to microcephaly and MICPCH were restricted in certain domains. To investigate the pathophysiology of CASK-related disorders, research groups have employed diverse methods, including the generation of CASK knockout mice and the supplementation of CASK to rescue the phenotypes. These approaches have yielded valuable insights into the identification of functional domains of the CASK protein associated with a specific phenotype. Additionally, recent advancements in the AI-based prediction of protein structure, such as AlphaFold2, and the application of genome-editing techniques to generate CASK mutant mice carrying missense mutations from patients with CASK-related disorders, allow us to understand the pathophysiology of CASK-related disorders in more depth and to develop novel therapeutic methods for the fundamental treatment of CASK-related disorders.

Downregulating NHE-1 decreases the apoptosis of hippocampal cells in epileptic model rats based on the NHE-1/calpain1 pathway.

Seizure is associated with pathological changes of hippocampus, but the mechanism by which hippocampal neuronal apoptosis promotes epilepsy is unclear. Our previous study showed that the expression of NHE-1 was increased in epileptic model rats. Therefore, this study further explores the effect of NHE-1 on hippocampal cells apoptosis and seizure in lithium chloride-pilocarpine epileptic model rats. First, we established a lithium chloride-pilocarpine induced epileptic rat model and detected the expression of NHE-1, calpain1 and apoptosis in the hippocampus. Then, we further down-regulated NHE-1 to observe the expression of calpain1 and apoptosis in the hippocampus, as well as its effect on seizures in rats. We found that the expression of NHE-1 and calpain1 and apoptosis in the hippocampus was significant increased in the model group. After down-regulating NHE-1, the expression of calpain1 was decreased, and hippocampal cell apoptosis was alleviated. In addition, down-regulation of NHE-1 reduced the frequency and duration of seizures in epileptic rats. Therefore, hippocampal NHE-1 overexpression is closely related to the development of neuronal apoptosis in a rat model of epilepsy, and downregulating NHE-1 expression can reduce cell apoptosis. Moreover, the NHE-1/calpain1 signaling pathway may be an important mechanism leading to hippocampal cell apoptosis.

Programmable-Modulated Ultrasonic Transducer Array for Contactless Detection of Viral RNAs.

The current polymerase chain reactions-based nucleic acid tests for large-scale infectious disease diagnosis are always lab-dependent and generate large amounts of highly infectious plastic waste. Direct non-linear acoustic driven of microdroplets provide an ideal platform for contactless spatial and temporal manipulation of liquid samples. Here, a strategy to programmable-manipulate microdroplets using potential pressure well for contactless trace detection is conceptualized and designed. On such contactless modulation platform, up to seventy-two piezoelectric transducers are precisely self-focusing single-axis arranged and controlled, which can generate dynamic pressure nodes for effectively contact-free manipulating microdroplets without vessel contamination. In addition, the patterned microdroplet array can act as contactless microreactor and allow multiple trace samples (1-5 µL) biochemical analysis, and the ultrasonic vortex can also accelerate non-equilibrium chemical reactions such as recombinase polymerase amplification (RPA). The results of fluorescence detection indicated that such programmable modulated microdroplet achieved contactless trace nucleic acid detection with a sensitivity of 0.21 copy µL-1 in only 6-14 min, which is 30.3-43.3% shorter than the conventional RPA approach. Such a programmable containerless microdroplet platform can be used for toxic, hazardous, or infectious samples sensing, opening up new avenues for developing future fully automated detection systems.

Clinicopathologic Features and Pathogens of Granulomatous Lobular Mastitis.

Background: Granulomatous lobular mastitis (GLM) is a rare, benign, and complex breast disease that can be easily misdiagnosed as breast cancer. The etiology of GLM is unclear, and optimal treatment has not been established. Methods: Medical records for 333 patients with GLM in recent 5 years at Longhua Hospital, Shanghai, China, were analyzed. Potential pathogens in 33 fresh tissue specimens were also analyzed using 16S rDNA sequencing technology, matrix-assisted laser desorption ionization time of flight mass spectrometry, and bacterial cultures. Results: The median age of patients was 32 years (range 22-47 years). Among 333 patients, 38.7% displayed elevated prolactin, while 23.7% displayed high interleukin-2. In the granulomatous lesion, CD3-positive T lymphocytes were significantly more than CD20-positive B lymphocytes around the vacuoles or microabscesses. Gram-positive organisms were observed in 82 cases, including in 22 cases from fresh tissue specimens. Thirty-three cases yielded associated pathogens and all displayed multiple pathogenic infections, as identified using 16S rDNA sequencing technology. Pathogenic infections were further identified as belonging to 16 main genera and 8 main pathogenic species. Conclusions: GLM displays distinct histological and clinical features similar to those that have been previously reported in the literature. Using 16S rDNA sequencing technology, all of our cases demonstrated multiple pathogenic infections, which provided more useful information for clinical treatment.

Copper Single-Atom Jellyfish-like Nanomotors for Enhanced Tumor Penetration and Nanocatalytic Therapy.

Single-atom catalysts with extraordinary catalytic activity have been receiving great attention in tumor therapy. However, most single-atom catalysts lack self-propulsion properties, restricting them from actively approaching cancer cells or penetrating the interior of tumors. Herein, we design N-doped jellyfish-like mesoporous carbon nanomotors coordinated with single-atom copper (Cu-JMCNs). It is a combination of single-atom nanocatalytic medicine and nanomotor self-propulsion for cancer therapy. The Cu single atom can catalyze H2O2 into toxic hydroxyl radical (•OH) for chemodynamic therapy (CDT). Near-infrared light triggers Cu-JMCNs to achieve self-thermophoretic motion because of the jellyfish-like asymmetric structure and photothermal property of carbon, which significantly improves the cellular uptake and the penetration of three-dimensional tumors. In vivo experiments indicate that the combination of single-atom Cu for CDT and near-infrared light propulsion can achieve over 85% tumor inhibition rate. This work sheds light on the development of advanced nanomotors with single-atom catalysts for biomedical applications.

Active Enrichment of Nanoparticles for Ultra-Trace Point-of-Care COVID-19 Detection.

Active enrichment can detect nucleic acid at ultra-low concentrations without relatively time-consuming polymerase chain reaction (PCR), which is an important development direction for future rapid nucleic acid detection. Here, we reported an integrated active enrichment platform for direct hand-held detection of nucleic acid of COVID-19 in nanoliter samples without PCR. The platform consists of a capillary-assisted liquid-carrying system for sampling, integrated circuit system for ultrasound output, and cell-phone-based surface-enhanced Raman scattering (SERS) system. Considering the acoustic responsiveness and SERS-enhanced performance, gold nanorods were selected for biomedical applications. Functionalized gold nanorods can effectively capture and enrich biomarkers under ultrasonic aggregation. Such approaches can actively assemble gold nanorods in 1-2 s and achieved highly sensitive (6.15 × 10-13 M) SERS detection of COVID-19 biomarkers in nanoliter (10-7 L) samples within 5 min. We further demonstrated the high stability, repeatability, and selectivity of the platform, and validated its potential for the detection of throat swab samples. This simple, portable, and ultra-trace integrated active enrichment detection platform is a promising diagnostic tool for the direct and rapid detection of COVID-19.

Anxiety, depression, and stress prevalence among college students during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: Since the end of 2019, the coronavirus disease (COVID-19) outbreak rapidly became a pandemic. The psychological state of people during the COVID-19 pandemic has gained interest. Our aim was to study the prevalence of anxiety, depression, and stress in college students during the COVID-19 pandemic. Methods: A systematic search of Medline, Embase, Web of Science, and the Cochrane Library was conducted up to September 20, 2020. Reviewers independently assessed full-text articles according to predefined criteria. Stata14/SE was used to calculate the prevalence and 95% confidence intervals (CIs) of anxiety, depression, and stress among college students from different countries. A random effects model was adopted. The Egger test was used to determine publication bias. Results: A total of 280 references were retrieved, and 28 papers met our inclusion criteria, for a total of 436,799 college students. Thirteen studies involved non-Chinese college students, and 15 studies involved Chinese college students. The prevalence of anxiety, depression, and stress was 29% (95% CI, 19-25%), 37% (95% CI, 32-42%), and 23% (95% CI, 8-39%), respectively. Conclusion: The COVID-19 pandemic has had a negative psychological effect on college students, and the prevalence of anxiety, depression, and stress among Chinese college students is lower than among non-Chinese college students.

Metabolic-associated fatty liver disease and the risk of cardiovascular disease.

BACKGROUND: With the gradual adoption of new metabolic-associated fatty liver disease (MAFLD) definitions in clinical practice, the relationship between MAFLD and cardiovascular disease (CVD) risk remains unclear. Similarly, clinical differences between MAFLD and nonalcoholic fatty liver disease (NAFLD), and the relationship between MAFLD and CVD risk are unclear. METHODS: We conducted a retrospective study using the 1988-1994 National Health and Nutrition Examination Surveys (NHANES III) database, including 11,673 individuals. Multivariate logistic regression analysis was performed to test relationships between MAFLD and the 10-year CVD risk. RESULTS: MAFLD was more significant than NAFLD in medium/high 10-year CVD risk (according to Framingham risk score) (1064 (29.92%) vs. 1022 (26.37%), P < 0.005). MAFLD patients were stratified according to NAFLD fibrosis scores (NFS's). In univariate regression analysis, when compared with non-MAFLD patients, unadjusted-OR values for MAFLD with different liver fibrosis stages, which were tiered by NFS (NFS < -1.455,-1.455 ≤ NFS < 0.676, and NFS ≥ 0.676) in the medium 10-year CVD risk (according to Framingham scores) were 1.175 (95% CI 1.030-1.341), 3.961 (3.449-4.549), and 5.477 (4.100-7.315), and the unadjusted or values of different MAFLD groups in the high 10-year CVD risk were 1.407 (95% CI 1.080-1.833), 5.725 (4.500-7.284), and 5.330 (3.132-9.068). Then, after adjusting for age, sex, race, alcohol consumption, and smoking, or adjusting for age, race, alcohol consumption, smoking, type 2 diabetes mellitus (T2DM), and other confounding factors, the incidence of medium and high 10-year CVD risk was statistically significant (P < 0.05). CONCLUSIONS: We showed that patients with MAFLD had a higher 10-year CVD risk when compared with patients with NAFLD. Increased MAFLD hepatic fibrosis scores were associated with a 10-year CVD risk.

Integrated microdroplet array platform with temperature controller and micro-stirring for ultra-fast SARS-CoV-2 detection.

The outbreak of COVID-19 has created a huge challenge to global health systems. Experience in fighting the epidemic shows that the development of a rapid and sensitive POCT diagnostic platform for SARS-CoV-2 that can be deployed in situ is crucial to contain the outbreak. Here, we have developed a portable microdroplet detection platform that integrated temperature controller and micro-stirring for high-throughput and ultrafast COVID-19 diagnosis. Such a device uses a p-n junction (PN junction) as the temperature controller to adjust the temperature in a single microdroplet independently and precisely, ensuring the amplification of reverse transcription loop-mediated isothermal amplification (RT-LAMP). Meanwhile, the platform incorporates an ultrasonic micro-stirring unit, greatly increasing the interaction between RT-LAMP molecules and accelerating the amplification. The results show good linearity over a wide linear range (1 to 105 copies/µL) and low LOD (0.48 copy/µL). Our method reports in only 6.1 min for high-viral load samples, and combines with sample preparation, the total detection process could be done within 30 min. Such a portable and fully integrated microdroplet molecular diagnostic platform is a promising tool for point-of-care diagnosis of COVID-19 and other infectious diseases in resource-limited settings.