Visible-Light-Mediated Annulation/Thiolation of 2-Isocyanobiaryls with Disulfides to Organoylthiophenanthridines Derivatives.

A visible-light-induced annulation/thiolation of 2-isocyanobiaryls with dialkyl(aryl)disulfides has been established, delivering a sustainable and atom-economic route to 6-organoylthiophenanthridines with wild functional group tolerance and good to excellent yields under oxidant-, base-, and transition-metal-free conditions.

Exogenous Ang-(1-7) inhibits autophagy via HIF-1α/THBS1/BECN1 axis to alleviate chronic intermittent hypoxia-enhanced airway remodelling of asthma.

Obstructive sleep apnoea (OSA)-induced chronic intermittent hypoxia (CIH) has been considered a risk factor for severe asthma. Airway remodelling, which could be modulated by autophagy, plays a key role in severe asthma. However, the extent of autophagy's involvement in CIH-potentiated airway remodelling remains largely unexplored. Furthermore, we had found that angiotensin-(1-7) [Ang-(1-7)] has therapeutic effects on airway remodelling in asthma, but the underlying mechanism is either unclear. This study aimed to explore how CIH aggravates asthma and mechanism of protective effects of Ang-(1-7) on airway remodelling, with a focus on autophagy. We observed that CIH promoted epithelial-to-mesenchymal transition (EMT), indicated by elevated EMT and fibrotic markers such as Snail and Collagen IV, both in vitro and in vivo. CIH intensified cell autophagy, evident from increased LC3B expression and reduced p62 levels. Ang-(1-7) reversed the CIH-enhanced expression of Snail, Collagen IV, and LC3B. To explore how CIH enhanced autophagy in cellular and animal model of asthma, overexpression of hypoxia-inducible factor 1-alpha (HIF-1α) and Thrombospondin 1 (THBS1) were identified in CIH-exposure mice lung compared with normal mice lung tissues from the GEO database. Finally, through chromatin immunoprecipitation and immunoprecipitation assays, we verified that Ang-(1-7) inhibits CIH-induced binding of HIF-1α to the promoter of THBS1, and also disrupts the protein-protein interaction between THBS1 and the autophagy-associated protein Beclin 1 (BECN1), ultimately leading to autophagy inhibition. Our findings suggest that exogenous Ang-(1-7) can inhibit autophagy via HIF-1α/THBS1/BECN1 axis, thereby alleviating CIH-enhanced airway remodelling in asthma. These findings imply the potential therapeutic effect of Ang-(1-7) in asthma with OSA.

Combined aspartate aminotransferase level and PE-SARD score predict 1-month bleeding risk in acute pulmonary embolism.

BACKGROUND: Anti-coagulation is the cornerstone management of acute pulmonary embolism (PE), which is a double-edged sword, as it increases the risk of bleeding. Thus, predicting bleeding risk is necessary. The liver produces most coagulation factors to maintain the coagulation balance. However, the association between liver dysfunction markers and bleeding risk has not been thoroughly investigated. METHODS: A single-center, retrospective analysis of patients with acute PE was performed. First, the authors studied the association between liver dysfunction indexes and the 1-month bleeding risk. Then, they investigated whether it is more effective to predict the bleeding risk using a new joint model, i.e., adding liver dysfunction indexes to the PE-SARD score, which is the first score to assess the bleeding risk of acute PE. RESULTS: Among 469 patients with acute PE, 34 patients (7.2%) had bleeding events within 1 month after the onset. The levels of aspartate aminotransferase (AST) were higher in the bleeding group compared with the non-bleeding group (36.0 [18.25-90.0] vs. 23.0 [18.0-31.0], p = 0.008). Compared with AST<40, the odds ratios of 80≤AST<120 and AST≥120 were significant (8.825 [2.449-31.804] and 8.023 [2.543-25.315] respectively, p<0.01), even when adjusted for nine confounding factors (p<0.05). The area under the curve of PE-SARD combined with AST was significantly higher than that of the PE-SARD score (p = 0.02). CONCLUSIONS: In PE patients, AST is an independent factor in predicting the 1-month bleeding risk, and a novel joint model that combines AST and PE-SARD score improved the predictive efficiency for the 1-month bleeding risk.

Short Sleep Duration is Associated with Prolonged Virus Shedding in SARS-CoV-2 Omicron-Infected Patients.

Purpose: Sleep disturbance has been implicated in poor prognosis of coronavirus disease 2019 (COVID-19), but less is known about the influence of short sleep duration on COVID-19 outcomes. We aim to investigate whether short sleep duration is associated with prolonged virus shedding duration in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-infected patients. Patients and Methods: A total of 270 patients with a laboratory confirmed COVID-19 diagnosis during SARS-CoV-2 Omicron-predominant period were recruited. Self-reported sleep duration of the patients was collected. The two-way analysis of variance (ANOVA) was used to determine the interactions between sleep duration and variables, and multivariate logistic regression analysis was used to analyze the effect of independent variables on longer virus shedding duration. Results: The two-way ANOVA revealed a significant sleep duration × snoring interaction effect for virus shedding duration, and a sleep duration × sex interaction effect for virus shedding duration. Multivariate logistic regression model illustrated that patients sleeping <6 h were at greater risk of prolonged virus shedding duration compared to those sleeping ≥6 hours (OR = 1.80, 95% CI = 1.01-3.26), independent of age, sex, co-existing diseases, vaccination condition, and antiviral treatment. Conclusion: Short sleep duration (<6 h) was associated with increased virus shedding in SARS-CoV-2 Omicron-infected patients.

SOCS3 protein expression predicts the responses of advanced non-small cell lung cancer patients to platinum-based chemotherapy.

Background: This study sought to assess the relationship between suppressor of cytokine signaling 3 (SOCS3) expression, SOCS3 promoter methylation status, and platinum-based chemotherapy responses in advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 400 advanced NSCLC patients with inoperable disease were enrolled in this study. All the patients underwent platinum-based chemotherapy treatment, and the clinical and prognostic outcomes of these patients were analyzed. The SOCS3 protein expression and SOCS3 promoter methylation status of the tumor tissues in these patients were also tested by immunohistochemistry and polymerase chain reaction (PCR), respectively. In addition, we knocked down SOCS3 expression via small-interfering RNA (siRNA) in the lung cancer cell lines and conducted in vitro analyses to examine cell viability and apoptosis. Results: Patients with higher expression levels of SOCS3 were found to have a lower average tumor stage, higher average tumor differentiation, and higher rates of positive chemotherapy responses than those with lower expression levels of SOCS3. SOCS3 promoter methylation was also found to be correlated with chemotherapy responses in these patients. In the prognostic analyses, only SOCS3 expression, but not SOCS3 promoter methylation, was found to be predictive of outcomes in advanced NSCLC patients. We also found that the pro-apoptotic effects of SOCS3 were mediated by the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways in the lung cancer cells. Conclusions: Currently, there is a lack of reliable biomarkers for predicting the responses of NSCLC patients to chemotherapy. Our results may aid in clinical evaluations of NSCLC patients.

Cloning, expression, and characterization of two pectate lyases isolated from the sheep rumen microbiome.

Pectate lyases (Pels) have a vital function in degradation of the primary plant cell wall and the middle lamella and have been widely used in the industry. In this study, two pectate lyase genes, IDSPel16 and IDSPel17, were cloned from a sheep rumen microbiome. The recombinant enzymes were expressed in Escherichia coli and functionally characterized. Both IDSPel16 and IDSPel17 proteins had an optimal temperature of 60 ℃, and an optimal pH of 10.0. IDSPel16 was relatively stable below 60 °C, maintaining 77.51% residual activity after preincubation at 60 °C for 1 h, whereas IDSPel17 denatured rapidly at 60 °C. IDSPel16 was relatively stable between pH 6.0 and 12.0, after pretreatment for 1 h, retaining over 60% residual activity. IDSPel16 had high activity towards polygalacturonic acid, with a Vmax of 942.90 ± 68.11, whereas IDSPel17 had a Vmax of only 28.19 ± 2.23 µmol/min/mg. Reaction product analyses revealed that IDSPel17 liberated unsaturated digalacturonate (uG2) and unsaturated trigalacturonate (uG3) from the substrate, indicating a typical endo-acting pectate lyase (EC 4.2.2.2). In contrast, IDSPel16 initially generated unsaturated oligogalacturonic acids, then converted these intermediates into uG2 and unsaturated galacturonic acid (uG1) as end products, a unique depolymerization profile among Pels. To the best of our knowledge, the IDSPel16 discovered with both endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities. These two pectate lyases, particularly the relatively thermo- and pH-stable IDSPel16, will be of interest for potential application in the textile, food, and feed industries. KEY POINTS: • Two novel pectate lyase genes, IDSPel16 and IDSPel17, were isolated and characterized from the sheep rumen microbiome. • Both IDSPel16 and IDSPel17 are alkaline pectate lyases, releasing unsaturated digalacturonate and unsaturated trigalacturonate from polygalacturonic acid. • IDSPel16, a bifunctional pectate lyase with endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities, could be a potential candidate for industrial application.

Quantum manifestations in electronic properties of bilayer phosphorene nanoribbons.

Recently, a new edge structure named ZZ(U) has been evidenced as the lowest-energy structure for bilayer phosphorene nanoribbons (PNRs). Owing to strong quantum confinement effects and edge states, width and edge are the two most important factors that influence the properties of PNRs in nanosized microelectronics. In this study, we systematically investigated the evolution of the electronic properties of bilayer PNRs with different edge configurations as the widths vary. The four types of edges explored include ZZ(Pristine), ZZ(Klein), ZZ(Tube), and newly found ZZ(U). As the widths change from 14 to 40 Å, the ZZ(Pristine) are always metallic with edge states penetrating the Fermi level, while the others are semiconductors. The edge states in ZZ(Klein) are located in the two lowest conduction bands. However, in ZZ(U), the edge states are nearly hidden in the bulk band structure, and its carrier transportation exhibits almost perfect 2D layers, nearly eliminating the U-edge influence. Our results pave the way for phosphorene's utilization in electronics and optoelectronics.

SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The mechanism of lung cancer (LC) in male patients with chronic obstructive pulmonary disease (COPD) has not been well understood, and the early diagnosis is currently challenging. The study aimed to explore the association of DNA methylation levels with LC development in male COPD patients. Patients and Methods: A total of 147 male participants were divided into four groups, ie, COPD+LC group, COPD group, LC group, and control (CON) group. The methylation levels of human serine protease inhibitor A1 (SERPINA1) and the serum levels of inflammatory biomarkers were compared among groups. Multivariate logistic regression was performed to explore the correlation of inflammatory biomarkers and gene methylation with lung cancer combining COPD. Results: SERPINA1 methylation levels were significantly higher in the COPD+LC group than that in the COPD group and LC group, respectively (all p < 0.05). The serum levels of interleukin (IL)-1ß, IL-17, and transforming growth factor (TGF)-ß1 were significantly higher in the COPD+LC group than in the LC group (all p < 0.05). The SERPINA1 methylation levels were positively correlated with the IL-1ß levels (r = 0.5188, p = 0.0012). The AUC (area under curve) of SERPINA1 methylation for the diagnosis of LC in COPD was 0.677 (sensitivity of 52.2% and specificity of 78.2%). Conclusion: The methylation of SERPINA1 is linked to LC in patients with COPD. The SERPINA1 methylation levels were positively correlated with the IL-1ß levels. These findings may be of diagnostic value.

Voxel-Mirrored Homotopic Connectivity Is Altered in Meibomian Gland Dysfunction Patients That Are Morbidly Obese.

PURPOSE: To investigate the altered functional connectivity (FC) of the cerebral hemispheres in patients with morbid obesity (MO) with meibomian gland dysfunction (MGD) by voxel-mirrored homotopic connectivity (VMHC). METHODS: Patients and matched healthy controls (HCs) were recruited, and all subjects underwent functional resonance magnetic imaging (fMRI), and VMHC results were processed statistically to assess the differences in FC in different brain regions between the two groups. We further used ROC curves to evaluate the diagnostic value of these differences. We also used Pearson's correlation analysis to explore the relationship between changes in VMHC values in specific brain regions, visual acuity, and Mini-Mental State Examination (MMSE) score. CONCLUSIONS: Patients with morbid obesity and MGD had abnormal FC in the cerebral hemispheres in several specific brain areas, which were mainly concentrated in pathways related to vision and perception and may correlate to some extent with the clinical presentations of the patients.

Neuroimaging Markers of Chronic Eye Diseases and Their Application Values.

In recent years, the impact of various chronic eye diseases on quality of life has become increasingly apparent. Therefore, it is particularly important to control the progress of chronic diseases at an early stage. Many studies have used neuroimaging methods to explore the effects of chronic eye diseases on the brain, and to identify changes in brain function that may act as markers for early diagnosis and treatment. This article reviews the clinical application of different techniques of functional magnetic resonance imaging in chronic eye diseases.

Changes of circulating biomarkers of inflammation and glycolipid metabolism by CPAP in OSA patients: a meta-analysis of time-dependent profiles.

Background: Continuous positive airway pressure (CPAP) is the first-line therapy for moderate-to-severe obstructive sleep apnea (OSA). Specifying timing of CPAP benefits on OSA-related biomarkers will help to assess the effectiveness of CPAP and to optimize the treatment strategies. Purpose: To explore the time-dependent changes of circulating biomarkers to CPAP treatment in patients with OSA, including inflammatory biomarkers [C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α)] and glycolipid metabolic biomarkers [fasting blood glucose (FBG), fasting insulin (FINS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglyceride (TG)]. Methods: Searches of PubMed and Embase database were completed. Two independent reviewers extracted data from 68 included studies. A meta-analysis was conducted using a random-effect (or fixed-effect) model and standardized mean difference (SMD) model. The timing profiles of circulating biomarkers changes of inflammation and glycolipid metabolism were analyzed based on different CPAP duration, that is, short-term (<3 months), mid-term (3-6 months), and long-term (⩾6 months). Results: Those first improved by short-term treatment include CRP [SMD: 0.73, 95% confidence interval (CI): 0.15-1.31; p = 0.014], TNF-α [SMD: 0.48 (95% CI: 0.10-0.86; p = 0.014)], FBG [SMD: 0.32 (95% CI: 0.07-0.57; p = 0.011)], and LDL [SMD: 0.40 (95% CI: 0.18-0.62; p = 0.000)]. Those first improved by the mid-term or long-term treatment include HDL [SMD: -0.20 (95% CI: -0.36 to -0.03; p = 0.018)] and TC [SMD: 0.20 (95% CI: 0.05-0.34; p = 0.007)]. There were insignificant changes for TG and FINS after short or long CPAP. Conclusion: Our results imply that changes of circulating biomarkers for patients with OSA under CPAP treatment have a time-dependent profile.

Two bis-ligand-coordinated Zn(ii)-MOFs for luminescent sensing of ions, antibiotics and pesticides in aqueous solutions.

Two organometallic complexes with two and three-dimensional architectures were constructed by using multiple ligands and Zn(ii) ions: [Zn3(BTC)2(DTP)4(H2O)2]·(H2O)4 (Zn-1) (BTC = benzene-1,3,5-tricarboxylic acid and DTP = 3,5-di(1,2,4-triazol-1-yl)pyridine) and [Zn2(NTD)2(DTP)] (Zn-2) (NTD = 1,4-naphthalenedicarboxylic acid). The as-prepared complexes were characterized by single-crystal X-ray diffraction (SCXRD), elemental analysis, powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and fluorescence analysis. Fluorescence sensing tests revealed that the two complexes are effective, sensitive and selective toward cationic Fe3+ and anionic MnO4 - and Cr2O7 2-. During the antibiotic sensing process, cefixime (CFX) for Zn-1 and nitrofurantoin (NFT) for Zn-2 exhibited the highest quenching efficiencies. For sensing pesticides, the highest quenching efficiencies were exhibited by imidacloprid (IMI) toward Zn-1 and Zn-2. The fluorescence quenching of the complexes that was induced by antibiotics, pesticides and MnO4 - was attributed to both the inner filter effect (IFE) and the fluorescence resonance energy transfer (FRET) effect.

Eliminating Edge Electronic and Phonon States of Phosphorene Nanoribbon by Unique Edge Reconstruction.

Edge termination plays a vital role in determining the properties of 2D materials. By performing compelling ab initio simulations, a lowest-energy U-edge [ZZ(U)] reconstruction is revealed in the bilayer phosphorene. Such reconstruction reduces 60% edge energy compared with the pristine one and occurs almost without an energy barrier, implying it should be the dominating edge in reality. The electronic band structure of phosphorene nanoribbon with such reconstruction resembles that of an intrinsic 2D layer, exhibiting nearly edgeless band characteristics. Although ZZ(U) changes the topology of phosphorene nanoribbons, simulated transmission electron microscope, scanning transmission electron microscope and scanning tunneling microscope images indicate it is very hard to be identified. One possible identified method is infrared/Raman analyses because the ZZ(U) edge alters vibrational modes dramatically. In addition, it also increases the thermal conductivity of PNR 1.4 and 2.3 times than the pristine and Klein edges.

Surfaxin attenuates PM2.5-induced airway inflammation via restoring surfactant proteins in rats exposed to cigarette smoke.

Epidemiologic studies have shown that the fine particulate matter 2.5 (PM2.5) exaggerates chronic airway inflammation involving in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Surfactant proteins (SPs) decreases significantly related to airflow limitation and airway inflammation. However, how to restore the reduction of SPs levels in airway inflammation exposed to PM2.5 has not been well understood. In the present study, the SPs including SPA, SPB, SPC and SPD levels in bronchoalveolar lavage fluid (BALF) were detected from patients with stable COPD. Rats were exposed to cigarette smoke and PM2.5. After given with Surfaxin, the expression of SPs, protein kinase C (PKC) and tight junction protein (ZO-1) in lung tissue and the levels of C-reactive protein (CRP) and fibrinogen (FIB) in plasma was observed. The results showed that SPA, SPB and SPD were significantly lower than those of the control group (p < 0.01). PM2.5 aggravated smoking-induced airway inflammation and oxidative stress demonstrated by pathological changes of lung tissue and increased levels of CRP and PKC in vivo. PM2.5 decreased the expression of all the SPs and ZO-1, which could be significantly restored by Surfaxin. These findings indicate that Surfaxin protects the alveolar epithelium from PM2.5 in airway inflammation through increasing SPs.

Moderate to severe OSA screening based on support vector machine of the Chinese population faciocervical measurements dataset: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnoea (OSA) has received much attention as a risk factor for perioperative complications and 68.5% of OSA patients remain undiagnosed before surgery. Faciocervical characteristics may screen OSA for Asians due to smaller upper airways compared with Caucasians. Thus, our study aimed to explore a machine-learning model to screen moderate to severe OSA based on faciocervical and anthropometric measurements. DESIGN: A cross-sectional study. SETTING: Data were collected from the Shanghai Jiao Tong University School of Medicine affiliated Ruijin Hospital between February 2019 and August 2020. PARTICIPANTS: A total of 481 Chinese participants were included in the study. PRIMARY AND SECONDARY OUTCOME: (1) Identification of moderate to severe OSA with apnoea-hypopnoea index 15 events/hour and (2) Verification of the machine-learning model. RESULTS: Sex-Age-Body mass index (BMI)-maximum Interincisal distance-ratio of Height to thyrosternum distance-neck Circumference-waist Circumference (SABIHC2) model was set up. The SABIHC2 model could screen moderate to severe OSA with an area under the curve (AUC)=0.832, the sensitivity of 0.916 and specificity of 0.749, and performed better than the STOP-BANG (snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference, and male gender) questionnaire, which showed AUC=0.631, the sensitivity of 0.487 and specificity of 0.772. Especially for asymptomatic patients (Epworth Sleepiness Scale <10), the SABIHC2 model demonstrated better predictive ability compared with the STOP-BANG questionnaire, with AUC (0.824 vs 0.530), sensitivity (0.892 vs 0.348) and specificity (0.755 vs 0.809). CONCLUSION: The SABIHC2 machine-learning model provides a simple and accurate assessment of moderate to severe OSA in the Chinese population, especially for those without significant daytime sleepiness.

A narrative review of exploring potential salivary biomarkers in respiratory diseases: still on its way.

Saliva is abundant with proteins, metabolites, DNA, and a diverse range of bacterial species. During the past two decades, saliva has emerged as a novel diagnostic and evaluation medium for several diseases. Collection of saliva samples is simple, minimally invasive, and convenient even in infants, children, and patients with anxious. Furthermore, with the development of hypersensitive techniques [e.g., microsensor arrays, enzyme-labeled immunosensors, nanoparticle-labeled immunosensors, capacitive or impedimetric immunosensors, magneto immunosensors, field effect transistor immunosensors, and surface enhanced Raman spectroscopy (SERS)], the sensitivity and accuracy of saliva diagnostic procedures have been improved. Nowadays, saliva has been used as a potential medium for several disease diagnosis and assessment, such as periodontitis, caries, cancers, diabetes mellitus, and cardiovascular diseases. Saliva has been used widely for studying microbiomics, genomics, transcriptomics, proteomics, and metabolomics of respiratory diseases, however, the use of salivary biomarkers for the diagnosis, prognosis, and monitoring of respiratory disease is still in its infancy. Herein, we review the progress of research on salivary biomarkers related to several respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), pneumonia, tuberculosis (TB), Langerhans cell histiocytosis (LCH) and cystic fibrosis (CF). Furthermore, several limitations of saliva test such as the lack of standard protocol for saliva collection and reasonable reference values for saliva test are also mentioned in this review.

Therapeutic Agents Rounding Up the Immunopathology of COVID-19.

COVID-19 pandemic has caused more than 3 million deaths globally during the past year. The direct attack from SARS-CoV-2 and hyperactivated immune response contribute to the progress and deterioration of COVID-19. After the virus invades, the activation and release of cytokines/chemokines cause "cytokine storm", leading to acute respiratory distress syndrome (ARDS) and multiple organs dysfunction syndrome (MODS). Eliminating virus and blocking cytokines are important checkpoints of COVID-19 therapy, and several agents targeting immunopathology, including interferons, thymosin, glucocorticoids and immunoglobulin, have shown therapeutic effects in severe patients with COVID-19. Herein, we reviewed the practice evidences and concluded that several agents rounding up the immunopathology of COVID-19 may be the alternative approaches under the scenario of the lacking of effective antiviral drugs.

Burden of Sleep Disturbance During COVID-19 Pandemic: A Systematic Review.

Coronavirus disease 2019 (COVID-19) pandemic may exert adverse impacts on sleep among populations, which may raise awareness of the burden of sleep disturbance, and the demand of intervention strategies for different populations. We aimed to summarize the current evidence for the impacts of COVID-19 on sleep in patients with COVID-19, healthcare workers (HWs), and the general population. We searched PubMed and Embase for studies on the prevalence of sleep disturbance. Totally, 86 studies were included in the review, including 16 studies for COVID-19 patients, 34 studies for HWs, and 36 studies for the general population. The prevalence of sleep disturbance was 33.3%-84.7%, and 29.5-40% in hospitalized COVID-19 patients and discharged COVID-19 survivors, respectively. Physiologic and psychological traumatic effects of the infection may interact with environmental factors to increase the risk of sleep disturbance in COVID-19 patients. The prevalence of sleep disturbance was 18.4-84.7% in HWs, and the contributors mainly included high workloads and shift work, occupation-related factors, and psychological factors. The prevalence of sleep disturbance was 17.65-81% in the general population. Physiologic and social-psychological factors contributed to sleep disturbance of the general population during COVID-19 pandemic. In summary, the sleep disturbance was highly prevalent during COVID-19 pandemic. Specific health strategies should be implemented to tackle sleep disturbance.