Identification of biomarkers and pathways for the SARS-CoV-2 infections in obstructive sleep apnea patients based on machine learning and proteomic analysis.

BACKGROUND: The prevalence of obstructive sleep apnea (OSA) was found to be higher in individuals following COVID-19 infection. However, the intricate mechanisms that underscore this concomitance remain partially elucidated. The aim of this study was to delve deeper into the molecular mechanisms that underpin this comorbidity. METHODS: We acquired gene expression profiles for COVID-19 (GSE157103) and OSA (GSE75097) from the Gene Expression Omnibus (GEO) database. Upon identifying shared feature genes between OSA and COVID-19 utilizing LASSO, Random forest and Support vector machines algorithms, we advanced to functional annotation, analysis of protein-protein interaction networks, module construction, and identification of pivotal genes. Furthermore, we established regulatory networks encompassing transcription factor (TF)-gene and TF-miRNA interactions, and searched for promising drug targets. Subsequently, the expression levels of pivotal genes were validated through proteomics data from COVID-19 cases. RESULTS: Fourteen feature genes shared between OSA and COVID-19 were selected for further investigation. Through functional annotation, it was indicated that metabolic pathways play a role in the pathogenesis of both disorders. Subsequently, employing the cytoHubba plugin, ten hub genes were recognized, namely TP53, CCND1, MDM2, RB1, HIF1A, EP300, STAT3, CDK2, HSP90AA1, and PPARG. The finding of proteomics unveiled a substantial augmentation in the expression level of HSP90AA1 in COVID-19 patient samples, especially in severe conditions. CONCLUSIONS: Our investigation illuminate a mutual pathogenic mechanism that underlies both OSA and COVID-19, which may provide novel perspectives for future investigations into the underlying mechanisms.

Efficient Adsorbent Derived from Phytolith-Rich Ore for Removal of Tetracycline in Wastewater.

In recent decades, the tetracycline (TC) concentration in aquatic ecosystems has gradually increased, leading to water pollution problems. Various mineral adsorbents for the removal of tetracyclines have garnered considerable attention. However, efficient adsorbents suitable for use in a wide pH range environment have rarely been reported. Herein, a phytolith-rich adsorbent (PRADS) was prepared by a simple one-step alkali-activated pyrolysis treatment using phytolith as a raw material for effectively removing TC. PRADS, benefiting from its porous structure, which consists of acid- and alkali-resistant, fast-adsorbing macroporous silica and mesoporous carbon, is highly desirable for efficient TC removal from wastewater. The results indicate that PRADS exhibited excellent adsorption performance and stability for TC over a wide pH range of 2.0-12.0 under the coexistence of competing ions, which could be attributed to the fact that PRADS has a porous structure and contains abundant oxygen-containing functional groups and a large number of bonding sites. The adsorption mechanisms of PRADS for TC were mainly attributed to pore filling, hydrogen bonding, π-π electron-donor-acceptor, and electrostatic interactions. This work could offer a novel preparation strategy for the effective adsorption of pollutants by new functionalized phytolith adsorbents.

Fast and sensitive CRISPR detection by minimized interference of target amplification.

Despite the great potential of CRISPR-based detection, it has not been competitive with other market diagnostics for on-site and in-home testing. Here we dissect the rate-limiting factors that undermine the performance of Cas12b- and Cas13a-mediated detection. In one-pot testing, Cas12b interferes with loop-mediated isothermal amplification by binding to and cleaving the amplicon, while Cas13a directly degrades the viral RNA, reducing its amplification. We found that the protospacer-adjacent motif-interacting domain engineered Cas12b accelerated one-pot testing with 10-10,000-fold improved sensitivity, and detected 85 out of 85 SARS-CoV-2 clinical samples with a sensitivity of 0.5 cp µl-1, making it superior to wild-type Cas12b. In parallel, by diminishing the interference of Cas13a with viral RNA, the optimized Cas13a-based assay detected 86 out of 87 SARS-CoV-2 clinical samples at room temperature in 30 min with a sensitivity of 0.5 cp µl-1. The relaxed reaction conditions and improved performance of CRISPR-based assays make them competitive for widespread use in pathogen detection.

Incomplete immune reconstitution and its predictors in people living with HIV in Wuhan, China.

OBJECTIVE: This study aimed to build and validate a nomogram model to predict the risk of incomplete immune reconstitution in people living with HIV (PLWH). METHODS: Totally 3783 individuals with a confirmed diagnosis of HIV/AIDS were included. A predictive model was developed based on a retrospective set (N = 2678) and was validated using the remaining cases (N = 1105). Univariate and multivariate logistic regression analyses were performed to determine valuable predictors among the collected clinical and laboratory variables. The predictive model is presented in the form of a nomogram, which is internally and externally validated with two independent datasets. The discrimination of nomograms was assessed by calculating the area under the curve (AUC). Besides, calibration curve and decision curve (DCA) analyses were performed in the training and validation sets. RESULTS: The final model comprised 5 predictors, including baseline CD4, age at ART initiation, BMI, HZ and TBIL. The AUC of the nomogram model was 0.902, 0.926, 0.851 in the training cohort, internal validation and external cohorts. The calibration accuracy and diagnostic performance were satisfactory in both the training and validation sets. CONCLUSIONS: This predictive model based on a retrospective study was externally validated using 5 readily available clinical indicators. It showed high performance in predicting the risk of incomplete immune reconstitution in people living with HIV.

Development and validation of a scoring system for the prediction of HIV drug resistance in Hubei province, China.

Objective: The present study aimed to build and validate a new nomogram-based scoring system for the prediction of HIV drug resistance (HIVDR). Design and methods: Totally 618 patients with HIV/AIDS were included. The predictive model was created using a retrospective set (N = 427) and internally validated with the remaining cases (N = 191). Multivariable logistic regression analysis was carried out to fit a model using candidate variables selected by Least absolute shrinkage and selection operator (LASSO) regression. The predictive model was first presented as a nomogram, then transformed into a simple and convenient scoring system and tested in the internal validation set. Results: The developed scoring system consisted of age (2 points), duration of ART (5 points), treatment adherence (4 points), CD4 T cells (1 point) and HIV viral load (1 point). With a cutoff value of 7.5 points, the AUC, sensitivity, specificity, PLR and NLR values were 0.812, 82.13%, 64.55%, 2.32 and 0.28, respectively, in the training set. The novel scoring system exhibited a favorable diagnostic performance in both the training and validation sets. Conclusion: The novel scoring system can be used for individualized prediction of HIVDR patients. It has satisfactory accuracy and good calibration, which is beneficial for clinical practice.

GIS model for geothermal advantageous target selection.

As the particularly popular green energy, geothermal resources are gradually favored by countries around the world, and the development model centered on geothermal dew point cannot meet the increasing geothermal demand. In this paper, a GIS model combining PCA and AHP is proposed, aiming to select the advantages of geothermal resources at the regional scale and analyze the main influencing indicators. Through the combination of the two methods, both data and empirical can be considered, then the geothermal advantage distribution on the area can be displayed through GIS software images. A multi-index evaluation system is established to qualitatively and quantitatively evaluate the mid-high temperature geothermal resources in Jiangxi Province, and carry out the evaluation of the dominant target areas and the analysis of geothermal impact indicators. The results show that it is divided into 7 geothermal resource potential areas and 38 geothermal advantage targets, and the determination of deep fault is the most critical index of geothermal distribution. This method is suitable for large-scale geothermal research, multi-index and multi-data model analysis and precise positioning of high-quality geothermal resource targets, which can meet the needs of geothermal research at the regional scale.

Investigation of Poly(MM-EM-BM) as Nanosealing Materials in Oil-Based Drilling Fluids: Synthesis and Evaluation.

Nanosealing technology has become the key to overcoming the wellbore instability problem in deep and ultradeep shale formations. In this Article, the terpolymer poly(MM-EM-BM) was synthesized from methyl methacrylate, ethyl methacrylate, and butyl methacrylate by a Michael addition reaction. The poly(MM-EM-BM) nanoparticles were investigated by Fourier transform infrared spectroscopy, laser scattering analysis, and thermogravimetric analysis. The results imply that the particle size range of poly(MM-EM-BM) is between 33.90 and 135.62 nm and the average diameter is about 85.95 nm at room temperature, which can maintain excellent stability at 382.75 °C. The effects of poly(MM-EM-BM) on the properties of oil-based drilling fluids (OBDFs) were ascertained through experiments on the rheological performance, electrical stability, and high-temperature and high-pressure (HTHP) filtration loss. The results suggested that when the amount of added poly(MM-EM-BM) increases, the apparent viscosity, plastic viscosity, dynamic shear force, and demulsification voltage of the drilling fluids will increase correspondingly; in contrast, the HTHP filtration loss gradually decreased. When poly(MM-EM-BM) is added at 0.75%, the kinetic-to-plastic ratio of the drilling fluids is 0.24 and the filtration loss is 0.6 mL, showing excellent overall performance. The drilling fluids have a good rock-carrying ability and water loss wall-building property. The sealing performance and mechanism of poly(MM-EM-BM) were researched by the method of a sealing performance test under high temperature. The results indicated that the more poly(MM-EM-BM) used, the higher the sealing efficiency of the mud cake and the core as the sealing medium. When poly(MM-EM-BM) was added at 0.75%, the sealing rates of the mud cake and the core as the sealing medium reached the maximum sealing rates of 40.30% and 91.48%, respectively. When poly(MM-EM-BM) enters the core nanopore joint for a certain distance under formation pressure, a tight sealing layer will be formed to effectively prevent the entry of filtrate. Poly(MM-EM-BM) as a potential oil-based nanosealing agent is expected to solve the problem caused by wellbore instability in shale horizontal wells.

A Scoring System Based on Laboratory Parameters and Clinical Features to Predict Unfavorable Treatment Outcomes in Multidrug- and Rifampicin-Resistant Tuberculosis Patients.

Background: The growth of antibiotic resistance to Mycobacterium TB represents a major barrier to the goal of "Ending the global TB epidemics". This study aimed to develop and validate a simple clinical scoring system to predict the unfavorable treatment outcomes (UTO) in multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) patients. Methods: A total of 333 MDR/RR-TB patients were recruited retrospectively. The clinical, radiological and laboratory features were gathered and selected by lasso regression. These variables with area under the receiver operating characteristic curve (AUC)>0.6 were subsequently submitted to multivariate logistic analysis. The binomial logistic model was used for establishing a scoring system based on the nomogram at the training set (N = 241). Then, another independent set was used to validate the scoring system (N = 92). Results: The new scoring system consists of age (8 points), education level (10 points), bronchiectasis (4 points), red blood cell distribution width-coefficient of variation (RDW-CV) (7 points), international normalized ratio (INR) (7 points), albumin to globulin ratio (AGR) (5 points), and C-reactive protein to prealbumin ratio (CPR) (6 points). The scoring system identifying UTO has a discriminatory power of 0.887 (95% CI=0.835-0.939) in the training set, and 0.805 (95% CI=0.714-0.896) in the validation set. In addition, the scoring system is used exclusively to predict the death of MDR/RR-TB and has shown excellent performance in both training and validation sets, with AUC of 0.930 (95% CI=0.872-0.989) and 0.872 (95% CI=0.778-0.967), respectively. Conclusion: This novel scoring system based on seven accessible predictors has exhibited good predictive performance in predicting UTO, especially in predicting death risk.

Synthesis of the Oil-Based Nanoblocker Poly(MMA-BMA-BA-St) and the Study of the Blocking Mechanism.

Well wall instability is one of the problems that seriously affect the efficiency of oil and gas drilling and extraction, and the economic losses caused by accidents due to well wall instability amount to billions of dollars every year. Aiming at the fact that well wall stabilization is the current technical difficulty of drilling shale gas horizontal wells with oil-based drilling fluids, the oil-based nanoplugging agent poly(MMA-BMA-BA-St) was synthesized by the Michael addition reaction with compounds such as styrene, methyl methacrylate, and butyl methacrylate as raw materials. The structure and characteristics of the oil-based nanoblocker poly(MMA-BMA-BA-St) were characterized by infrared spectroscopy, particle size analysis, and thermal weight loss analysis. The particle size distribution of poly(MMA-BMA-BA-St) is 80.56-206.61 nm, with an average particle size of 137.10 nm, and it can resist the high temperature of 372 °C. The effects of poly(MMA-BMA-BA-St) on the performance parameters of oil-based drilling fluids were investigated by rheological experiments, electrical stability tests, and HTHP filtration loss experiments. The results show that when poly(MMA-BMA-BA-St) is added at 0.5 wt %, it has less influence on the rheological parameters of drilling fluids, the breaking emulsion pressure remains basically unchanged, the stability of the drilling fluid is better, the dynamic-plastic ratio of the drilling fluid is higher than 0.27, the filtration loss is the lowest, and it shows good rock-carrying properties. The results of mud cake experiments and artificial lithology experiments show that poly(MMA-BMA-BA-St) has the best sealing effect, with a mud cake permeability of 1.12 × 10-4 mD and a sealing rate of 30.00% when added at 0.5 wt %; the artificial core permeability was 4.0 × 10-4 mD, and the sealing rate was 91.23%. Poly(MMA-BMA-BA-St) showed good sealing performance. The oil-based nanoplugging agent poly(MMA-BMA-BA-St) has good dispersion in oil-based drilling fluids and can enter the nanopore joints to form a dense plugging layer under the action of formation pressure to prevent the intrusion of drilling fluids, thus reducing the impact of drilling fluids on the formation, maintaining the stability of the well wall and reducing downhole complications.

High-dose gatifloxacin-based shorter treatment regimens for MDR/RR-TB.

SETTING: The shorter treatment regimen (STR) for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) has achieved successful outcomes in many countries. However, there are few studies on high-dose gatifloxacin-based STR with adverse drug reactions (ADRs) and management. DESIGN: A prospective observational study was conducted with MDR/RR-TB patients who were treated with a standardized 9 or 12 - month regimen: including gatifloxacin (Gfx), clofazimine (Cfz), ethambutol (EMB), and pyrazinamide (PZA), and supplemented by amikacin (Am), isoniazid (INH), and prothionamide (Pto) during an intensive phase of 4 or 6 - month. Monitored ADRs monthly until treatment completion and then followed up every three months for one year. RESULTS: Among the 42 eligible patients, 35 (83.3%) completed treatment successfully, 1 (2.4%) lost to follow-up (LTFU), and 6 (14.3%) failed due to ADRs, with no death. The most important ADR was drug-induced liver damage, which occurred in 24 out of 42 (57.1%) patients and resulted in 4 (9.5%) failed treatments and 4 (9.5%) adjusted treatments. QT interval prolongation occurred in 17 out of 42 (40.5%) patients, 9 (21.4%) of them with the corrected QT interval according to Fridericia (QTcF) > 500 ms resulting in 7 (16.7%) adjusted treatments. CONCLUSIONS: This study confirmed the effectiveness of the high-dose gatifloxacin-based STR but severe ADRs, especially hepatotoxicity and QT interval prolongation should never be ignored.

Black Talc-Based TiO2/ZnO Composite for Enhanced UV-Vis Photocatalysis Performance.

Herein, using black talc as a carrier, a ternary black talc-TiO2/ZnO composite photocatalyst was prepared by the sol-gel method, and the effect of the black talc on the hetero-structure properties of the TiO2 and ZnO was systematically studied. The prepared composite photocatalyst showed an excellent degradation performance of the pollutant, where black talc plays an important role in promoting the interface interaction by enhancing the contact area between the TiO2 and ZnO. Moreover, the free carbon element doping in black talc favors the formation of more oxygen vacancies, thereby improving the response as a photocatalyst in visible light. In addition, the carbon in the black talc can also adsorb organic pollutants and enrich the surroundings of the photocatalyst with pollutants, so it further improves the catalytic efficiency of the photocatalyst. Under UV irradiation, the degradation rate of Rhodamine B on black talc-TiO2/ZnO was found 3.3 times higher than that of black talc-TiO2 with good stability.

1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study.

BACKGROUND: The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19. METHODS: We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes. FINDINGS: 1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls. INTERPRETATION: Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.

A pneumonia outbreak associated with a new coronavirus of probable bat origin.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.