Cholinergic hyperintensity pathways are associated with cognitive performance in patients with asymptomatic carotid artery stenosis.

OBJECTIVES: We aimed to determine whether asymptomatic carotid artery stenosis (ACS) induced cognitive impairments were related to the cholinergic hyperintensity pathway. METHODS: This cross-sectional study included patients with moderate-to-severe ACS, who were categorized into mild cognitive impairment (MCI) and normal cognition groups on the basis of Montreal Cognitive Assessment (MoCA) scores. The cholinergic pathway hyperintensity scale (CHIPS), Fazekas, and medial temporal atrophy (MTA) scores were assessed. SPSS software was used for statistical analyses. RESULTS: A total of 117 ACS patients (70.89 ± 8.81 years) and 105 controls (67.87 ± 9.49 years) were evaluated (t = 2.46, p = 0.015). The ACS group showed a worse median Mini-Mental Status Examination (MMSE) score (z = -2.41, p = 0.016) and MoCA score (z = -3.51, p < 0.001), and a significantly higher median total CHIPS score (z = 4.88, p < 0.001) and mean Fazekas score (t = 2.39, p = 0.018). In the correlation analysis, the MoCA score showed a significant negative correlation with the CHIPS score (ρ = -0.41, p < 0.001) and Fazekas score (ρ = -0.31, p < 0.001) in ACS group. Logistic regression analyses suggested that CHIPS scores were risk factors for MCI in patients with ACS (odds ratio [OR] = 1.07, 95% Confidence Interval [CI]1.01-1.13 and controls (OR = 1.09, 95%CI 1.01-1.17), while the MTA and Fazekas scores showed no predictive power. The receiver operating characteristic curve showed that the area under the curve of the CHIPS score for predicting MCI was 0.71 in ACS group, but was only 0.57 in controls. CONCLUSIONS: Patients with ACS showed poorer cognitive performance and higher CHIPS and Fazekas scores. CHIPS, but not Fazekas, scores were risk factors for cognitive impairment and were a valuable factor to predict MCI in patients with ACS.

Convolutional neural network applied to preoperative venous-phase CT images predicts risk category in patients with gastric gastrointestinal stromal tumors.

OBJECTIVE: The risk category of gastric gastrointestinal stromal tumors (GISTs) are closely related to the surgical method, the scope of resection, and the need for preoperative chemotherapy. We aimed to develop and validate convolutional neural network (CNN) models based on preoperative venous-phase CT images to predict the risk category of gastric GISTs. METHOD: A total of 425 patients pathologically diagnosed with gastric GISTs at the authors' medical centers between January 2012 and July 2021 were split into a training set (154, 84, and 59 with very low/low, intermediate, and high-risk, respectively) and a validation set (67, 35, and 26, respectively). Three CNN models were constructed by obtaining the upper and lower 1, 4, and 7 layers of the maximum tumour mask slice based on venous-phase CT Images and models of CNN_layer3, CNN_layer9, and CNN_layer15 established, respectively. The area under the receiver operating characteristics curve (AUROC) and the Obuchowski index were calculated to compare the diagnostic performance of the CNN models. RESULTS: In the validation set, CNN_layer3, CNN_layer9, and CNN_layer15 had AUROCs of 0.89, 0.90, and 0.90, respectively, for low-risk gastric GISTs; 0.82, 0.83, and 0.83 for intermediate-risk gastric GISTs; and 0.86, 0.86, and 0.85 for high-risk gastric GISTs. In the validation dataset, CNN_layer3 (Obuchowski index, 0.871) provided similar performance than CNN_layer9 and CNN_layer15 (Obuchowski index, 0.875 and 0.873, respectively) in prediction of the gastric GIST risk category (All P >.05). CONCLUSIONS: The CNN based on preoperative venous-phase CT images showed good performance for predicting the risk category of gastric GISTs.

Geniposide reduced oxidative stress-induced apoptosis in HK-2 cell through PI3K/AKT3/FOXO1 by m6A modification.

Exogenous hydrogen peroxide (H2O2) may generate excessive oxidative stress, inducing renal cell apoptosis related with kidney dysfunction. Geniposide (GP) belongs to the iridoid compound with anti-inflammatory, antioxidant and anti-apoptotic effects. This study aimed to observe the intervention effect of GP on H2O2-induced apoptosis in human kidney-2 (HK-2) cells and to explore its potential mechanism in relation to N6-methyladenosine (m6A) RNA methylation. Cell viability, apotosis rate and cell cycle were tested separately after different treatments. The mRNA and protein levels of m6A related enzymes and phosphoinositide 3-kinase (PI3K)/a serine/threonine-specific protein kinase 3 (AKT3)/forkhead boxo 1 (FOXO1) and superoxide dismutase 2 (SOD2) were detected by reverse transcription-quantitative real-time PCR (RT-qPCR) and Western blot. The whole m6A methyltransferase activity and the m6A content were measured by ELISA-like colorimetric methods. The changes of m6A methylation levels of PI3K/AKT3/FOXO1 and SOD2 were determined by methylated RNA immunoprecipitation (MeRIP)-qPCR. Multiple comparisons were performed by ANOVA with Turkey's post hoc test. Exposed to 400 µmol/L H2O2, cells were arrested in G1 phase and the apoptosis rate increased, which were significantly alleviated by GP. Compared with the H2O2 apoptosis group, both the whole m6A RNA methyltransferase activity and the m6A contents were increased due to GP intervention. Besides, the SOD2 protein was increased, while PI3K and FOXO1 decreased. The m6A methylation level of AKT3 was negatively correlated with its protein level. Taken together, GP affects the global m6A methylation microenvironment and regulates the expression of PI3K/AKT3/FOXO1 signaling pathway via m6A modification, alleviating cell cycle arrest and apoptosis caused by oxidative stress in HK-2 cells with a good application prospect.

Geniposide alleviated hydrogen peroxide-induced apoptosis of human hepatocytes via altering DNA methylation.

Geniposide (GP) is the homology of medicine and food with bioactive effects of antioxidation and resistance to apoptosis in the liver. It's of great significance to explore the biosafety exposure limits and action mechanisms of GP. This study detected the global DNA methylation microenvironment and the regulation of specific genes in GP against cellular apoptosis induced by hydrogen peroxide (H2O2) of human hepatocyte L-02 cells. The half inhibitory concentration (IC50) of GP on normal L-02 cells was 57.7 mg/mL. GP exerted new epigenetic activity, increased DNMT1, decreased TET1 and TET2 expression, and reversed the demethylation effect to some extent, thereby increasing the overall genomic DNA methylation level at the concentration of 900 µg/mL. GP pretreatment could also adjust the level of P53, Bcl-2 and AKT altered by H2O2, reducing their specific DNA methylation levels in the promoter regions of AKT and Bcl-2 to inhibit apoptosis. Taken together, GP regulates the global DNA methylation level and controls the expression changes of P53, Bcl-2 and AKT, jointly inhibiting the occurrence of apoptosis in human hepatocytes and providing the newly theoretical references for its safety evaluation.

Epidemiological characteristics of community-acquired pneumonia and effects from the COVID-19 pandemic in Shenzhen of China.

OBJECTIVE: This study aimed to observe the impact of the coronavirus disease 2019 (COVID-19) pandemic on the incidence of non-COVID-19 community-acquired pneumonia (CAP) in Shenzhen of China, offering new ideas for evaluating the effects of non-pharmaceutical interventions. METHODS: A retrospective analysis was conducted of inpatients with pneumonia from 2017 to 2021. Epidemiological characteristics of CAP and effects from the COVID-19 pandemic were analyzed by the basic characteristics, time distribution, etiology and disease burden. RESULTS: There were a total of 5746 CAP inpatient cases included from 2017 to 2021. The number of CAP hospitalizations decreased during the pandemic from 2020 to 2021, with seasonal variations of being higher in spring and winter and lower in summer and autumn, whereas it was prevalent throughout the year prior to the pandemic. The children group decreased significantly during the pandemic, with a 15% decrease in the share of CAP inpatients. The detection rates of bacteria and mycoplasma decreased in CAP patients, while the detection rate of the virus increased, and the number of moderate and severe cases reduced more than that of the mild. CONCLUSION: Non-pharmaceutical interventions from COVID-19 have led to a decrease in the number of CAP inpatients, especially for children, with a specific seasonal prevalence in spring and winter, when the prevention interventions should be strengthened further for adults during the pandemic.

Novel Roles of RNA m6A Methylation Regulators in the Occurrence of Alzheimer's Disease and the Subtype Classification.

Alzheimer's disease (AD) is one of the most common forms of dementia, closely related to epigenetic factors. N6-methyladenosine (m6A) is the most abundant RNA modification, affecting the pathogenesis and development of neurodegenerative diseases. This study was the first exploration of the combined role of 25 common m6A RNA methylation regulators in AD through the integrated bioinformatics approaches. The 14 m6A regulators related to AD were selected by analyzing differences between AD patients and normal controls. Based on the selected m6A regulators, AD patients could be well classified into two m6A models using consensus clustering. The two clusters of patients had different immune profiles, and m6A regulators were associated with the components of immune cells. Additionally, there were 19 key AD genes obtained by screening differential genes through weighted gene co-expression network and least absolute shrinkage and selection operator regression analysis, which were highly associated with important m6A regulators during the occurrence of AD. More interestingly, NOTCH2 and NME1 could be potential targets for m6A regulation of AD. Taken together, these findings indicate that dysregulation of m6A methylation affects the occurrence of AD and is vital for the subtype classification and immune infiltration of AD.

Effect of theaflavin-3,3'-digallate on leptin-deficient induced nonalcoholic fatty liver disease might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota.

Nonalcoholic fatty liver disease (NAFLD), one of the risk factors for hepatitis, cirrhosis, and even hepatic carcinoma, has been a global public health problem. The polyphenol compound theaflavin-3,3'-digallate (TF3), mainly extracted from black tea, has been reported to produce an effect on hypoglycemic and antilipid deposition in vitro. In our study, we further investigated the function and novel mechanisms of TF3 in protecting NAFLD in vivo. By using leptin-deficient obese (ob/ob) mice with NAFLD symptoms, TF3 treatment prevented body weight and waistline gain, reduced lipid accumulation, and alleviated liver function injury, as well as decreased serum lipid levels and TG levels in livers in ob/ob mice, observing no side effects. Furthermore, the transcriptome sequencing of liver tissue showed that TF3 treatment corrected the expression profiles of livers in ob/ob mice compared with that of the model group. It is interesting to note that TF3 might regulate lipid metabolism via the Fads1/PPARδ/Fabp4 axis. In addition, 16S rRNA sequencing demonstrated that TF3 increased the abundance of Prevotellaceae_UCG-001, norank_f_Ruminococcaceae, and GCA-900066575 and significantly decreased that of Parvibacter. Taken together, the effect of TF3 on NAFLD might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota. TF3 might be a promising candidate for NAFLD therapy.

New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC.

Non-alcoholic fatty liver disease (NAFLD) has become a major chronic disease in contemporary society, affected by N6-methyladenosine (m6A) RNA methylation, one of the most common RNA modifications. Compared with healthy control, m6A RNA methyltransferase 3 (METTL3) and METTL14 increased, while Wilms tumor 1-associated protein (WTAP) and RNA-binding motif protein 15 (RBM15) decreased significantly in NAFLD, and the m6A demethylases fat mass and obesity-associated protein (FTO) elevated. Meanwhile, the m6A binding proteins, YT521-B homology (YTH) domain-containing 1 (YTHDC1), YTHDC2, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), and HNRNPA2B1 were decreased, while eukaryotic translation initiation factor 3 subunit H (EIF3H) was increased significantly. All these changes of m6A regulators had significant differences between healthy control and NAFLD, but no differences between the NAFL and NASH group. The expression level of RBM15, HNRNPC, and HNRNPA2B1 were related to body fat index. RBM15, YTHDC2, HNRNPC, HNRNPA2B1, and EIF3H were related to steatosis. Also, KIAA1429 and YTH domain family 1 (YTHDF1) were related to lobular inflammation. Taken together, m6A regulators were involved in the occurrence of NAFLD. More importantly, abnormal MYC was determined as a key link to m6A regulation of NAFLD. The higher MYC mRNA level was accompanied by higher HDL cholesterol and unsaturated fatty acid proportions, as well as lower fat mass, glucose, and transaminase. Taken together, dysregulation of m6A methylation caused steatosis and fibrosis, affecting the occurrence of NAFLD, and MYC might be its potential target.

Dynamic Alteration Profile and New Role of RNA m6A Methylation in Replicative and H2O2-Induced Premature Senescence of Human Embryonic Lung Fibroblasts.

N6-methyladenosine (m6A) methylation is one of the most common RNA modifications, regulating RNA fate at the posttranscriptional level, and is closely related to cellular senescence. Both models of replicative and premature senescence induced by hydrogen peroxide (H2O2) were used to detect m6A regulation during the senescence of human embryonic lung fibroblasts (HEFs). The ROS level accumulated gradually with senescence, leading to normal replicative senescence. H2O2-treated cells had dramatically increased ROS level, inducing the onset of acute premature senescence. Compared with replicative senescence, ROS changed the expression profiles for m6A-related enzymes and binding proteins, including higher levels of METTL3, METTL14, WTAP, KIAA1429, and FTO, and lower levels of METTL16, ALKBH5, YTHDC1, and YTHDF1/2/3 in the premature senescence persistence group, respectively. Meanwhile, senescent cells decreased total m6A content and RNA methylation enzymes activity, regardless of replicative or premature senescence. Moreover, specific m6A methylation levels regulated the expression of SIRT3, IRS2, and E2F3 between replicative and premature senescence separately. Taken together, differential m6A epitranscription microenvironment and the targeted genes can be used as epigenetic biomarkers to cell senescence and the related diseases, offering new clues for the prevention and intervention of cellular senescence.

Cadmium chloride-induced apoptosis of HK-2 cells via interfering with mitochondrial respiratory chain.

Cadmium could induce cell apoptosis, probably related to the dysfunction of the mitochondrial respiratory chain. The human renal proximal tubule (HK-2) was used to explore the mechanism of mitochondrial respiratory chain dysfunction during apoptosis induced by cadmium chloride (CdCl2). Cell viability was evaluated by cell proliferation assay and different concentrations of 60, 80 and 100 µM were selected to evaluate the mitochondrial toxicity of CdCl2 respectively. Under the CdCl2 treatment for 24 h, the mitochondrial reactive oxygen species (ROS) of HK-2 cells increased and the superoxide dismutase (SOD) activity was inhibited at the above three concentrations separately. Both ATP content and mitochondrial membrane potential decreased significantly at 100 µM concentration. The levels of procaspase-3 and Bcl-2 had fallen in a concentration-dependent manner and Bax was significantly increased at 60, 80 and 100 µM concentration compared with no CdCl2 treatment respectively, which activated the mitochondrial apoptosis pathway. N-acetyl-cysteine (NAC) could partially resist CdCl2-induced cell apoptosis, while myxothiazol (Myx) promoted the process. Mitochondria relative alterations manifested as inhibition of complex III and V. In addition, both the quantity of mitochondrial coenzyme Q-binding protein CoQ10 homolog B (CoQ10B) and cytochrome c (Cyt c) had decreased significantly. Taken together, CdCl2 induced HK-2 apoptosis due to the mitochondrial respiratory chain dysfunction by reducing the CoQ10B level, offering a novel evaluating indicator for the environmental toxicity of CdCl2.

Time-concentration-dependent profile of histone modifications on human hepatocytes treated by trichloroacetic acid.

Trichloroacetic acid (TCA) is a common non-volatile by-product of chlorination disinfection for drinking water. It is necessary to know the epigenetic toxicity and mechanisms for establishing safe exposure limit for environmental TCA exposure. This study explored the histone modification variations of TCA-treated human hepatocytes L-02 at different time and concentrations. TCA (0.1 mM, 0.3 mM and 0.9 mM) had an inhibitory effect on the growth of L-02 cells, with no significant changes in morphology. Treated with TCA for 24 h and 48 h, L-02 cells showed decreased mRNA and protein level of histone deacetylases (HDACs), but increased after 72 h. The downregulation of HDACs in early stage of TCA exposure might be one of the important reasons for the increase of H3K9ac level. These changes of histone modification may serve as early epigenetic biomarkers for TCA exposure and the related diseases, offering the safe environmental exposure concentration reference.

An Epidemiological Retrospective and Predictive Analysis of Rubella in Beijing, Haidian District of China.

BACKGROUND: This study is aimed to investigate the epidemiological characteristics of rubella in Beijing, Haidian District of China, from 2005 to 2020, providing scientific basis for controlling rubella and the congenital rubella syndrome. METHODS: Data were collected via the legal infectious disease report cards from medical institutions in Haidian, 2005-2020. The descriptive epidemiological methods plus statistical analysis were used to analyze the distribution of rubella in terms of population, time and region. RESULTS: In total, there were 994 cases of rubella in Beijing, Haidian District, with an average incidence of 1.81/100 000. In 2007, it was hit by rubella with the highest incidence up to 8.37/100 000, in the past 16 years. The peak incident of rubella was in spring (March to May). The majority of rubella patients were students and employees (70.1%) who are infected mainly due to the gathering. The majority of patients aged 15-29 years (63.4%). And the male-to-female ratio was 1.45 : 1. Rubella had a feature of spatial aggregation and appeared in all the regions in Haidian. According to Joinpoint regression model, rubella would still exist in the next 3 years with 2-5 new cases per year. CONCLUSIONS: Rubella showed a downshift trend from 2008 to 2014, then a sporadic distribution till 2020 in Haidian. Not completely eliminated yet, it is quite impending to improve people's awareness of preventing rubella and their health literacy mentally and physically in the whole population by means of the policy issuing from government.

Biological and epigenetic alterations of mitochondria involved in cellular replicative and hydrogen peroxide-induced premature senescence of human embryonic lung fibroblasts.

The mitoepigenetic modifications may be closely related to cellular fate. Both the replicative and hydrogen peroxide (H2O2)-induced premature senescence models were used to detect the mitochondrial biological characteristics and the epigenetic factors during senescence of human embryonic lung fibroblasts. The mitochondrial quantity was decreased in two senescence stages, while the mitochondrial DNA (mtDNA) copy number was increased significantly and the methyltransferases activity likewise. And the acute mtROS accumulation could launch premature senescence. Later, the persistent premature senescence owned the higher level of adenosine triphosphate (ATP) and mitochondrial 5-methylcytosine (mt-5-mC), and the less level of 8-hydroxydeoxyguanosine (8-OHdG) than those of replicative senescence. The mtDNA methylation-related enzymes, binding protein and the mitochondrial transcription regulators presented the differentially expressed profiles in both senescent states. Interestingly, the hypermethylation in the CpG region of mitochondrial transcription factor B2 (TFB2M) contributed to its downregulation of mRNA level in replicative senescence. The alterations of the mitochondrial biological functions and mtDNA features would be novel candidate biomarkers involved in cellular senescence. The specific methylation status of mtDNA may also have a crosstalk with oxidative stress to the mitochondrial function, contributing to cellular senescence.

Tuberculosis infection and epidemiological characteristics in Haidian District, Beijing, 2005-2018.

BACKGROUND: This study was aimed to investigate the epidemiological characteristic of pulmonary tuberculosis (PTB) in Haidian District, Beijing from 2005 to 2018 and to provide suggestions for controlling tuberculosis (TB) development. METHODS: Epidemiological data about TB were obtained by the Infectious Disease Reporting System at different levels of medical institutions in Haidian District of Beijing from 2005 to 2018. The epidemiological methods combined with χ2 test were used to analyze the distribution of TB in population, time, region and TB diagnosis. RESULTS: In total, 14,449 cases of TB patients were reported in Haidian District from 2005 to 2018 and the average annual morbidity was 31.67/10,000. Of the total cases, housework and unemployed people (20.73%; 2996/14,449) accounted for the highest proportion of occupational distribution, followed by students, accounting for 17.18% (2482/14,449). 2433 patients with the age of 65 years and over accounting for 16.83% (2433/14,449); Laboratory confirmed diagnosis of TB was 26.60% and the diagnostic delays accounted for 54.96%. CONCLUSIONS: From 2005 to 2018, TB incidence was falling gradually in Haidian District. However, particular attention should be paid to the elderly and student groups, and the policy publicity and education should be strengthened to reduce the diagnosis delay of TB.

Hyperspectral Imaging for the Nondestructive Quality Assessment of the Firmness of Nanguo Pears Under Different Freezing/Thawing Conditions.

Firmness changes in Nanguo pears under different freezing/thawing conditions have been characterized by hyperspectral imaging (HSI). Four different freezing/thawing conditions (the critical temperatures, numbers of cycles, holding time and cooling rates) were set in this experiment. Four different pretreatment methods were used: multivariate scattering correction (MSC), standard normal variate (SNV), Savitzky-Golay standard normal variate (S-G-SNV) and Savitzky-Golay multiplicative scattering correction (S-G-MSC). Combined with competitive adaptive reweighted sampling (CARS) to identify characteristic wavelengths, firmness prediction models of Nanguo pears under different freezing/thawing conditions were established by partial least squares (PLS) regression. The performance of the firmness model was analyzed quantitatively by the correlation coefficient (R), the root mean square error of calibration (RMSEC), the root mean square error of prediction (RMSEP) and the root mean square error of cross validation (RMSECV). The results showed that the MSC-PLS model has the highest accuracy at different cooling rates and holding times; the correlation coefficients of the calibration set (Rc) were 0.899 and 0.927, respectively, and the correlation coefficients of the validation set (Rp) were 0.911 and 0.948, respectively. The accuracy of the SNV-PLS model was the highest at different numbers of cycles, and the Rc and the Rp were 0.861 and 0.848, respectively. The RMSEC was 65.189, and the RMSEP was 65.404. The accuracy of the S-G-SNV-PLS model was the highest at different critical temperatures, with Rc and Rp values of 0.854 and 0.819, respectively, and RMSEC and RMSEP values of 74.567 and 79.158, respectively.

Modulatory effect of Lactobacillus acidophilus KLDS 1.0738 on intestinal short-chain fatty acids metabolism and GPR41/43 expression in ß-lactoglobulin-sensitized mice.

We investigated the correlation between the beneficial effect of Lactobacillus acidophilus on gut microbiota composition, metabolic activities, and reducing cow's milk protein allergy. Mice sensitized with ß-lactoglobulin (ß-Lg) were treated with different doses of L. acidophilus KLDS 1.0738 for 4 weeks, starting 1 week before allergen induction. The results showed that intake of L. acidophilus significantly suppressed the hypersensitivity responses, together with increased fecal microbiota diversity and short-chain fatty acids (SCFAs) concentration (including propionate, butyrate, isobutyrate, and isovalerate) when compared with the allergic group. Moreover, treatment with L. acidophilus induced the expression of SCFAs receptors, G-protein-coupled receptors 41 (GPR41) and 43 (GPR43), in the spleen and colon of the allergic mice. Further analysis revealed that the GPR41 and GPR43 messenger RNA expression both positively correlated with the serum concentrations of transforming growth factor-ß and IFN-γ (p < .05), but negatively with the serum concentrations of IL-17, IL-4, and IL-6 in the L. acidophilus-treated group compared with the allergic group (p < .05). These results suggested that L. acidophilus protected against the development of allergic inflammation by improving the intestinal flora, as well as upregulating SCFAs and their receptors GPR41/43.

Preparation and characterization of slow-release fertilizer encapsulated by biochar-based waterborne copolymers.

To enhance the effectiveness of polyvinyl alcohol (PVA) coated fertilizers, a novel slow-release fertilizer was developed using biochar and waterborne copolymer of PVA and polyvinylpyrrolidone (PVP) as coating materials. The effects of botanical origins and doses of biochar as well as copolymer concentrations on biochar-copolymer structures and properties were investigated. Our results indicated that the water absorbency of blend films differing in biochar origins showed different responses to these three factors. Generally, biochar decreased water absorbency of copolymer with an increased degradability, and contributed to improving the slow-release property of coated urea. In particular, rice biochar-based copolymer (S5 film) had less hydrophilic OH bonds and encapsulated urea granules more compactly and densely. The urea particles coated with rice biochar-based copolymer (S5 film) exhibited an excellent release behavior of 65.28% nutrient leaching on the 22th day. Therefore, this work has demonstrated the potential of biochar-based copolymer from different botanical biochar for improving the effectiveness of fertilizers.