Osteoporosis Risk in Hemodialysis Patients: The Roles of Gender,Comorbidities, Biochemical Parameters,Health and Diet Literacy

Osteoporosis is a common bone health disorder in hemodialysis patients that is linked with a higher morbidity and mortality rate. While previous studies have explored the associated factors of osteoporosis, there is a lack of studies investigating the impacts of health literacy (HL) and digital healthy diet literacy (DDL) on osteoporosis. Therefore, we aimed to investigate the associations of HL, DDL, and other factors with osteoporosis among hemodialysis patients. From July 2020 to March 2021, a cross-sectional study was conducted on 675 hemodialysis patients in eight hospitals in Vietnam. The data were collected by using the osteoporosis self-assessment tool for Asians (OSTA) and the 12-item short form of the health literacy questionnaire (HLS-SF12) on digital healthy diet literacy (DDL) and hemodialysis dietary knowledge (HDK). In addition, we also collected information about the socio-demographics, the clinical parameters, the biochemical parameters, and physical activity. Unadjusted and adjusted multinomial logistic regression models were utilized in order to investigate the associations. The proportion of patients at low, medium, and high levels of osteoporosis risk was 39.6%, 40.6%, and 19.8%, respectively. In the adjusted models, women had a higher likelihood of osteoporosis risk than men (odds ratio, OR, 3.46; 95% confidence interval, 95% CI, 1.86, 6.44; p < 0.001; and OR, 6.86; 95% CI, 2.96, 15.88; p < 0.001). The patients with rheumatoid arthritis (OR, 4.37; 95% CI, 1.67, 11.52; p = 0.003) and stomach ulcers (OR, 1.95; 95% CI, 1.01, 3.77; p = 0.048) were more likely to have a higher likelihood of osteoporosis risk than those without. The patients who had a higher waist circumference (WC), HL, and DDL were less likely to have a medium level of osteoporosis risk (OR, 0.95; 95% CI, 0.92, 0.98; p = 0.004; OR, 0.92; 95% CI, 0.88, 0.96; p < 0.001; OR, 0.96; 95% CI, 0.93, 0.99; p = 0.017, respectively) and a high level of osteoporosis risk (OR, 0.93; 95% CI, 0.89, 0.97; p = 0.001; OR, 0.89; 95% CI, 0.84, 0.94; p < 0.001; OR, 0.95; 95% CI, 0.91, 0.99; p = 0.008, respectively) compared with a low level of osteoporosis risk and to those with a lower WC, HL, and DDL. In addition, higher levels of hemoglobin (Hb) (OR, 0.79; 95% CI, 0.66, 0.95; p = 0.014), hematocrit (Hct) (OR, 0.95; 95% CI, 0.92, 0.99; p = 0.041), albumin (OR, 0.91; 95% CI, 0.83, 0.99; p = 0.030), and education (OR, 0.37; 95% CI, 0.16, 0.88; p = 0.025) were associated with a lower likelihood of a high level of osteoporosis risk. In conclusion, osteoporosis risk is highly prevalent in hemodialysis patients. Improved HL, DDL, education, WC, albumin, Hb, and Hct levels should be considered in preventing hemodialysis patients from developing osteoporosis.     

Artificial intelligence‐driven consensus gene signatures for improving bladder cancer clinical outcomes identified by multi‐center integration analysis

To accurately predict the prognosis and further improve the clinical outcomes of bladder cancer (BLCA), we leveraged large‐scale data to develop and validate a robust signature consisting of small gene sets. Ten machine‐learning algorithms were enrolled and subsequently transformed into 76 combinations, which were further performed on eight independent cohorts (n = 1218). We ultimately determined a consensus artificial intelligence‐derived gene signature (AIGS) with the best performance among 76 model types. In this model, patients with high AIGS showed a higher risk of mortality, recurrence, and disease progression. AIGS is not only independent of traditional clinical traits [(e.g., American Joint Committee on Cancer (AJCC) stage)] and molecular features (e.g., TP53 mutation) but also demonstrated superior performance to these variables. Comparisons with 58 published signatures also indicated that AIGS possessed the best performance. Additionally, the combination of AIGS and AJCC stage could achieve better performance. Patients with low AIGS scores were sensitive to immunotherapy, whereas patients with high AIGS scores might benefit from seven potential therapeutics: BRD‐K45681478, 1S,3R‐RSL‐3, RITA, U‐0126, temsirolimus, MRS‐1220, and LY2784544. Additionally, some mutations (TP53 and RB1), copy number variations (7p11.2), and a methylation‐driven target were characterized by AIGS‐related multi‐omics alterations. Overall, AIGS provides an attractive platform to optimize decision‐making and surveillance protocol for individual BLCA patients.     

Obesity-Associated Anxiety Is Prevalent among College Students and Alleviated by Calorie Restriction

Anxiety is a common disorder among college students, especially those with obesity. Obesity contributes to metabolic disorders and disturbs the neural functions, further leading to anxiety. In this cross-sectional study, we aimed to determine the association between obesity and anxiety among college students and identified the potential factors for obesity-associated anxiety. We evaluated the intervention effects of calorie restriction on anxiety. Self-reported questionnaires were distributed to 1381 college students from January to March in 2021. Anxiety was measured by the State-Trait Anxiety Inventory (STAI). Participants were classified into anxiety and non-anxiety groups according to their STAI scores. Chi-squared test and logistic regression were used to analyze the potential factors. We found that 383 college students exhibited anxiety, accounting for 30.1% among all included college students, which was higher than the global average. The association between anxiety and obesity was observed among college students (p = 0.009), especially in males (p = 0.007). We identified that pre-obesity (p = 0.012), unhealthy calorie intake (p = 0.001), dieting (p = 0.003) and high academic year (p = 0.006) as the risk factors for anxiety and found that the long sleep duration was a protective factor for anxiety (p < 0.001). We found that more obese students showed an improvement of anxiety than the underweight students after calorie restriction (p < 0.001). Collectively, our findings suggest that obesity-associated anxiety is prevalent among the college students and could be alleviated by moderate calorie restriction. It is necessary for students to receive anxiety management in their college life. Additionally, the proper calorie restriction should be promoted to help students protect against obesity and obesity-associated anxiety.     

Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough

The vast majority of people with cystic fibrosis (CF) are now eligible for CF transmembrane regulator (CFTR) modulator therapy. The remaining individuals with CF harbor premature termination codons (PTCs) or rare CFTR variants with limited treatment options. Although the clinical modulator response can be reliably predicted using primary airway epithelial cells, primary cells carrying rare CFTR variants are scarce. To overcome this obstacle, cell lines can be created by overexpression of mouse Bmi-1 and human TERT (hTERT). Using this approach, we developed 2 non-CF and 6 CF airway epithelial cell lines, 3 of which were homozygous for the W1282X PTC variant. The Bmi-1/hTERT cell lines recapitulated primary cell morphology and ion transport function. The 2 F508del-CFTR cell lines responded robustly to CFTR modulators, which was mirrored in the parent primary cells and in the cell donors’ clinical response. Cereblon E3 ligase modulators targeting eukaryotic release factor 3a (eRF3a) rescued W1282X-CFTR function to approximately 20% of WT levels and, when paired with G418, rescued G542X-CFTR function to approximately 50% of WT levels. Intriguingly, eRF3a degraders also diminished epithelial sodium channel (ENaC) function. These studies demonstrate that Bmi-1/hTERT cell lines faithfully mirrored primary cell responses to CFTR modulators and illustrate a therapeutic approach to rescue CFTR nonsense mutations.     

Functional mutations of SARS-CoV-2: implications to viral transmission,pathogenicity and immune escape

The pandemic of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to major public health challenges globally. The increasing viral lineages identified indicate that the SARS-CoV-2 genome is evolving at a rapid rate. Viral genomic mutations may cause antigenic drift or shift, which are important ways by which SARS-CoV-2 escapes the human immune system and changes its transmissibility and virulence. Herein, we summarize the functional mutations in SARS-CoV-2 genomes to characterize its adaptive evolution to inform the development of vaccination, treatment as well as control and intervention measures.     

The value of quantitative magnetic resonance imaging signal intensity in distinguishing between spinal meningiomas and schwannomas

Background: Prior studies have suggested a number of the subjective visual characteristics that help distinguish between spinal meningiomas and schwannomas on magnetic resonance imaging and computed tomography; however, objective quantification of the signal intensity can be useful information. This study assessed whether quantitative magnetic resonance imaging (MRI) signal intensity (SI) measurements could distinguish intradural-extramedullary schwannomas from meningiomas.Methods: From July 2019 to September 2021, 54 patients with intradural-extramedullary tumors (37 meningiomas and 17 schwannomas) underwent surgery, and tumors were verified pathologically. Defined regions of interest were used to quantify SI values on T1- (T1W) and T2-weighted images (T2W). Receiver operating characteristic curve analysis was used to obtain cutoff values and calculate the area under the curve (AUC), sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV).Results: Both Maximum (T2_max) and mean (T2_mean) T2W SI values demonstrated outstanding (AUC: 0.91) abilities to differentiate meningiomas from schwannomas with Se, Sp, PPV, and NPV values of 94.6%, 70.6%, 87.5%, and 85.7%, respectively, for T2_max and 81.1%, 88.2%, 93.8%, and 68.2% for T2_mean. The maximum SI value on contrast-enhanced T1W (T1CE_max) and the T2W tumor: fat SI ratio (rTF) demonstrated acceptable abilities (AUC: 0.73 and 0.79, respectively) to differentiate meningiomas from schwannomas with Se, Sp, PPV, and NPV values of 94.6%, 70.6%, 87.5%, and 85.7%, respectively, for T1CE_max and 81.1%, 88.2%, 93.8%, and 68.2% for rTF.Conclusions: Quantitative SI values (T2_max, T2_mean, T2_min, T1CE_max, rTF) can be used to differentiate intradural-extramedullary schwannomas from meningiomas.     

Avermectins菌丝提取液的分析与主要成分的分离富集

采用高效液相色谱（HPLC）-紫外检测（UVD）／蒸发光散射检测（ELSD）的方法分析avermectins菌丝提取液，发现主要成分为具有紫外吸收和无紫外吸收的物质。利用硅胶吸附柱层析方法分离富集了其中的主要成分。对几种有紫外吸收的组分（A1a、A2a、B1a、B2a）进行了核磁共振（NMR）分析，根据异核单量子相干谱（HSQC）对所有的^13C—NMR和^1H—NMR谱带进行了归属。鉴定了无紫外吸收的物质中含有糖类物质。     

微波辅助提取鼠尾藻多酚及抗氧化活性研究

本文研究了微波辅助提取鼠尾藻多酚的工艺条件。探讨了微波功率、微波提取时间、料液比及乙醇的浓度对鼠尾藻多酚的提取率和纯度的影响。结果表明微波辅助提取优于超声辅助提取,微波提取最佳条件为：微波提取功率700w,乙醇浓度15%,液固比25（m l/g）,微波处理时间40 s。     

Effects of hypocrellin A on expression of vascular endothelial growth factor and endothelin-1 in human umbilical endothelial cells

Increased endothelin-1 (ET-1), vascular endothelial growth factor (VEGF) and activation of protein kinase C (PKC) are co-contributors to endothelial hyperpermeability in diabetes. Several lines of evidence have suggested a hypothesis that activation of specific PKC isoforms are the causative factor in ET-1 and VEGF mediated endothelial dysfunction. In the present study, we tested this hypothesis with hypocrellin A, a naturally occurring PKC inhibitor from a Chinese plant. Human umbilical vein endothelial cells (HUVECs) were incubated with 20 mM glucose in both the presence and absence of hypocrellin A, after which, the protein expression and release of VEGF and mRNA expression and release of ET-1 were measured. VEGF and ET-1 were released into the medium and expressions of VEGF protein and ET-1 mRNA were significantly increased in HUVECs incubated with 20 mM glucose. Hypocrellin A (150 nM) significantly decreased VEGF release (117 +/- 3 vs. 180 +/- 11 pg/mg, p < 0.05) and VEGF protein expression (from 130 +/- 14% to 88 +/- 18.5%, p < 0.05). ET-1 release was also reduced in hypocrellin A treated HUVECs (63.3 +/- 9.9 vs. 75.2 +/- 12.6 ng/mg). Hypocrellin A significantly reversed the effect of high glucose on ET-1 mRNA expression (p < 0.05). The results revealed that PKC activation plays a pivotal role in VEGF and ET-1 mediated endothelial permeability. The naturally occurring compound hypocrellin A may be a potentially novel treatment for endothelial dysfunction in diabetes.