The close association of micronutrients with COVID-19.

Objectives: The present study was conducted to explore the performance of micronutrients in the prediction and prevention of coronavirus disease 2019 (COVID-19). Methods: This is an observational case-control study. 149 normal controls (NCs) and 214 COVID-19 patients were included in this study. Fat-soluble and water-soluble vitamins were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and inorganic elements were detected by inductively coupled plasma-mass spectrometry (ICP-MS) analysis. A logistic regression model based on six micronutrients were constructed using DxAI platform. Results: Many micronutrients were dysregulated in COVID-19 compared to normal control (NC). 25-Hydroxyvitamin D3 [25(OH)D3], magnesium (Mg), copper (Cu), calcium (Ca) and vitamin B6 (pyridoxic acid, PA) were significantly independent risk factors for COVID-19. The logistic regression model consisted of 25(OH)D3, Mg, Cu, Ca, vitamin B5 (VB5) and PA was developed, and displayed a strong discriminative capability to differentiate COVID-19 patients from NC individuals [area under the receiver operating characteristic curve (AUROC) = 0.901]. In addition, the model had great predictive ability in discriminating mild/normal COVID-19 patients from NC individuals (AUROC = 0.883). Conclusions: Our study showed that micronutrients were associated with COVID-19, and our logistic regression model based on six micronutrients has potential in clinical management of COVID-19, and will be useful for prediction of COVID-19 and screening of high-risk population.

Clinical prediction of HBV-associated cirrhosis using machine learning based on platelet and bile acids.

OBJECTIVES: The present study was conducted to evaluate the performance of serum bile acids in the prediction of cirrhosis in chronic hepatitis B (CHB) population. METHODS: Dysregulated metabolites were explored using untargeted and targeted metabolomic analyses. A machine learning model based on platelet (PLT) and several bile acids was constructed using light gradient boosting machine (LightGBM), to differentiate HBV-associated cirrhosis (BAC) from CHB patients. RESULTS: Serum bile acids were dysregulated in BAC compared to CHB patients. The LightGBM model consisted of PLT, TUDCA, UDCA, TLCA, LCA and CA. The model demonstrated a strong discrimination ability in the internal test subset of the training cohort to diagnose BAC from CHB patients (AUC = 0.97). The high diagnostic accuracy of the model was further validated in an independent validation cohort. In addition, the model had high predictive efficacy in discriminating compensated BAC from CHB patients (AUC = 0.89). The performance of the model was better than AST/ALT ratio and the gradient boosting (GB)-based model reported in previous studies. CONCLUSIONS: Our study showed that this LightGBM model based on PLT and 5 bile acids has potential in clinical assessments of CHB progression and will be useful for early detection of cirrhosis in CHB patients.

T4 bacteriophage nanoparticles engineered through CRISPR provide a versatile platform for rapid development of flu mucosal vaccines.

Vaccines that trigger mucosal immune responses at the entry portals of pathogens are highly desired. Here, we showed that antigen-decorated nanoparticle generated through CRISPR engineering of T4 bacteriophage can serve as a universal platform for the rapid development of mucosal vaccines. Insertion of Flu viral M2e into phage T4 genome through fusion to Soc (Small Outer Capsid protein) generated a recombinant phage, and the Soc-M2e proteins self-assembled onto phage capsids to form 3M2e-T4 nanoparticles during propagation of T4 in E. coli. Intranasal administration of 3M2e-T4 nanoparticles maintains antigen persistence in the lungs, resulting in increased uptake and presentation by antigen-presenting cells. M2e-specific secretory IgA, effector (TEM), central (TCM), and tissue-resident memory CD4+ T cells (TRM) were efficiently induced in the local mucosal sites, which mediated protections against divergent influenza viruses. Our studies demonstrated the mechanisms of immune protection following 3M2e-T4 nanoparticles vaccination and provide a versatile T4 platform that can be customized to rapidly develop mucosal vaccines against future emerging epidemics.

Analysis of Dual Combination Therapies Used in Treatment of Hypertension in a Multinational Cohort.

Importance: More than 1 billion adults have hypertension globally, of whom 70% cannot achieve their hypertension control goal with monotherapy alone. Data are lacking on clinical use patterns of dual combination therapies prescribed to patients who escalate from monotherapy. Objective: To investigate the most common dual combinations prescribed for treatment escalation in different countries and how treatment use varies by age, sex, and history of cardiovascular disease. Design, Setting, and Participants: This cohort study used data from 11 electronic health record databases that cover 118 million patients across 8 countries and regions between January 2000 and December 2019. Included participants were adult patients (ages ≥18 years) who newly initiated antihypertensive dual combination therapy after escalating from monotherapy. There were 2 databases included for 3 countries: the Iqvia Longitudinal Patient Database (LPD) Australia and Electronic Practice-based Research Network 2019 linked data set from South Western Sydney Local Health District (ePBRN SWSLHD) from Australia, Ajou University School of Medicine (AUSOM) and Kyung Hee University Hospital (KHMC) databases from South Korea, and Khoo Teck Puat Hospital (KTPH) and National University Hospital (NUH) databases from Singapore. Data were analyzed from June 2020 through August 2021. Exposures: Treatment with dual combinations of the 4 most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; ß-blocker; and thiazide or thiazide-like diuretic). Main Outcomes and Measures: The proportion of patients receiving each dual combination regimen, overall and by country and demographic subgroup. Results: Among 970 335 patients with hypertension who newly initiated dual combination therapy included in the final analysis, there were 11 494 patients from Australia (including 9291 patients in Australia LPD and 2203 patients in ePBRN SWSLHD), 6980 patients from South Korea (including 6029 patients in Ajou University and 951 patients in KHMC), 2096 patients from Singapore (including 842 patients in KTPH and 1254 patients in NUH), 7008 patients from China, 8544 patients from Taiwan, 103 994 patients from France, 76 082 patients from Italy, and 754 137 patients from the US. The mean (SD) age ranged from 57.6 (14.8) years in China to 67.7 (15.9) years in the Singapore KTPH database, and the proportion of patients by sex ranged from 24 358 (36.9%) women in Italy to 408 964 (54.3%) women in the US. Among 12 dual combinations of antihypertensive drug classes commonly used, there were significant variations in use across country and patient subgroup. For example starting an ACEI or ARB monotherapy followed by a CCB (ie, ACEI or ARB + CCB) was the most commonly prescribed combination in Australia (698 patients in ePBRN SWSLHD [31.7%] and 3842 patients in Australia LPD [41.4%]) and Singapore (216 patients in KTPH [25.7%] and 439 patients in NUH [35.0%]), while in South Korea, CCB + ACEI or ARB (191 patients in KHMC [20.1%] and 1487 patients in Ajou University [24.7%]), CCB + ß-blocker (814 patients in Ajou University [13.5%] and 217 patients in KHMC [22.8%]), and ACEI or ARB + CCB (147 patients in KHMC [15.5%] and 1216 patients in Ajou University [20.2%]) were the 3 most commonly prescribed combinations. The distribution of 12 dual combination therapies were significantly different by age and sex in almost all databases. For example, use of ACEI or ARB + CCB varied from 873 of 3737 patients ages 18 to 64 years (23.4%) to 343 of 2292 patients ages 65 years or older (15.0%) in South Korea's Ajou University database (P for database distribution by age < .001), while use of ACEI or ARB + CCB varied from 2121 of 4718 (44.8%) men to 1721 of 4549 (37.7%) women in Australian LPD (P for drug combination distributions by sex < .001). Conclusions and Relevance: In this study, large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries and by demographic group. These findings suggest that future research may be needed to investigate what dual combinations are associated with best outcomes for which patients.

A Fischer-Type Ruthenium Carbene Complex as a Metathesis Catalyst for the Synthesis of Enol Ethers.

The Grubbs G-I or G-II catalyst gives the ruthenium ethoxy carbene complex, which catalyzes ring-opening cross metathesis (ROCM) of a strained cyclic alkene to give a diene where one of the two alkene moieties in the product contains an ethoxy substituent. No polymeric products are detected. Hydrocarbons such as parent norbornene or substituted cyclopropenes can proceed with the reaction smoothly. Tertiary amines, N-alkylimides, esters, and aryl or alkyl bromides remain intact under the reaction conditions. In addition to vinyl ethers, vinylic esters can also be used. The time required to reach a 50% yield of the ROCM product t50 varies from 0.01 to 140 h depending on the strain and nucleophilicity of the double bond. Anchimeric participation of an electron-rich group would result in significant enhancement of the reactivity, and the t50 could be as short as several minutes. A similar substrate without such a neighboring group shows a much slower rate. An exo-norborne derivative reacts much faster than the corresponding endo-isomer. Alkenes with poor nucleophilicity are less favored for the ROCM process, so is less strained cyclooctene.

[Investigation of nitrobenzene removal by iron sulfide (FeS)].

The nitrobenzene removal performance by iron sulfide was investigated in batch experiments. The effects of different factors were studied. The results showed that the removal efficiency of nitrobenzene was 90% as initial nitrobenzene concentration was 0.96 mmol x L(-1), dosage of FeS was 1.2 g and the reaction time was 180 minutes. Initial nitrobenzene concentration, dosage of FeS, temperature and reused times of FeS had a significant influence on the removal efficiency of nitrobenzene. As the initial nitrobenzene concentration was in range of 0.74 to 1.74 mmol x L(-1), the removal efficiency of nitrobenzene decreased by 4.7% with every 0.1 mmol x L(-1) increasing of initial nitrobenzene concentration. As the dosage of FeS was in the range of 0.3 to 1.5 g, the removal efficiency of nitrobenzene increased by 20% with every 0.3 g increasing of FeS. As the dosage of FeS was 1.8 g, the removal efficiency of nitrobenzene was 100%. In the temperature range of 10 to 25 degrees C, the removal efficiency of nitrobenzene increased by 1.6% with 1 degrees C increasing. As the temperature was 30 degrees C, the removal efficiency of nitrobenzene was 100%. The removal efficiency of nitrobenzene decreased as the reused times of FeS increased. Rotational speed hardly had any influence on the removal efficiency of nitrobenzene. As the rotational speed was in the range of 10 to 80 r x min(-1), the removal efficiency of nitrobenzene was around 75%. The nitrobenzene removal performance by iron sulfide was satisfied in the treatment of simulated chemical industrial wastewater, and after 60 min, the removal efficiency of nitrobenzene was 100%.