Automated machine learning for the identification of asymptomatic COVID-19 carriers based on chest CT images.

BACKGROUND: Asymptomatic COVID-19 carriers with normal chest computed tomography (CT) scans have perpetuated the ongoing pandemic of this disease. This retrospective study aimed to use automated machine learning (AutoML) to develop a prediction model based on CT characteristics for the identification of asymptomatic carriers. METHODS: Asymptomatic carriers were from Yangzhou Third People's Hospital from August 1st, 2020, to March 31st, 2021, and the control group included a healthy population from a nonepizootic area with two negative RT‒PCR results within 48 h. All CT images were preprocessed using MATLAB. Model development and validation were conducted in R with the H2O package. The models were built based on six algorithms, e.g., random forest and deep neural network (DNN), and a training set (n = 691). The models were improved by automatically adjusting hyperparameters for an internal validation set (n = 306). The performance of the obtained models was evaluated based on a dataset from Suzhou (n = 178) using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and F1 score. RESULTS: A total of 1,175 images were preprocessed with high stability. Six models were developed, and the performance of the DNN model ranked first, with an AUC value of 0.898 for the test set. The sensitivity, specificity, PPV, NPV, F1 score and accuracy of the DNN model were 0.820, 0.854, 0.849, 0.826, 0.834 and 0.837, respectively. A plot of a local interpretable model-agnostic explanation demonstrated how different variables worked in identifying asymptomatic carriers. CONCLUSIONS: Our study demonstrates that AutoML models based on CT images can be used to identify asymptomatic carriers. The most promising model for clinical implementation is the DNN-algorithm-based model.

Protocol for determining protein dynamics using FT-IR spectroscopy.

In biological systems, protein function depends on spatial and temporal changes known as protein dynamics, which can be probed by amide hydrogen/deuterium (H/D) exchange. Here, we present a protocol for determining protein dynamics by Fourier-transform infrared (FT-IR) spectroscopy. We describe steps for protein sample preparation and FT-IR spectra collection. We then detail procedures for spectra analysis. Applications include the effects of protein mutation or protein and metal ion or ligand interactions on the protein H/D exchange rate. For complete details on the use and execution of this protocol, please refer to Yu et al. (2013).1.

Exploring the therapeutic potential of ADC combination for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. Currently, standard treatment options for TNBC are limited to surgery, adjuvant chemotherapy, and radiotherapy. However, these treatment methods are associated with a higher risk of intrinsic or acquired recurrence. Antibody-drug conjugates (ADCs) have emerged as a useful and promising class of cancer therapeutics. ADCs, also known as "biochemical missiles", use a monoclonal antibody (mAb) to target tumor antigens and deliver a cytotoxic drug payload. Currently, several ADCs clinical studies are underway worldwide, including sacituzumab govitecan (SG), which was recently approved by the FDA for the treatment of TNBC. However, due to the fact that only a small portion of TNBC patients respond to ADC therapy and often develop resistance, growing evidence supports the use of ADCs in combination with other treatment strategies to treat TNBC. In this review, we described the current utilization of ADCs and discussed the prospects of ADC combination therapy for TNBC.

Value of Laboratory Indicators in Predicting Pneumonia in Symptomatic COVID-19 Patients Infected with the SARS-CoV-2 Omicron Variant.

Background: The pathogenicity of Omicron is different from that of the previous strains. The value of hematological indicators in patients at high risk of Omicron infection remains unclear. We need rapid, inexpensive and widely available biomarkers to guide the early detection of people at risk of pneumonia and to provide early intervention. We aimed to assess the value of hematological indicators as risk factors for pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant. Patients and Methods: The study enrolled 144 symptomatic COVID-19 patients with Omicron infection. We collected available clinical details, including laboratory tests and CT examinations. Univariate and multivariate logistic analyses and receiver operating characteristic (ROC) curve analyses were used to assess the value of laboratory markers in predicting the development of pneumonia. Results: Among the 144 patients, 50 (34.7%) had pneumonia. The ROC analysis revealed that the areas under the ROC curve (AUC) for leukocytes, lymphocytes, neutrophils, and fibrinogen were 0.603 (95% confidence interval (CI): 0.501-0.704, P=0.043), 0.615 (95% CI: 0.517-0.712, P=0.024), 0.632 (95% CI: 0.534-0.730, P=0.009) and 0.635 (95% CI: 0.539-0.730, P=0.008), respectively. The AUC for neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), fibrinogen to lymphocyte ratio (FLR), and fibrinogen to D-dimer ratio (FDR) were 0.670 (95% CI: 0.580-0.760, P=0.001), 0.632 (95% CI: 0.535-0.728, P=0.009), 0.669 (95% CI: 0.575-0.763, P=0.001) and 0.615 (95% CI: 0.510-0.721, P=0.023), respectively. Univariate analysis showed that elevated levels of NLR (odds ratio (OR): 1.219, 95% CI: 1.046-1.421, P=0.011), FLR (OR: 1.170, 95% CI: 1.014-1.349, P=0.031) and FDR (OR: 1.131, 95% CI: 1.039-1.231, P=0.005) were significantly correlated with the presence of pneumonia. Multivariate analysis indicated elevated NLR (OR: 1.248, 95% CI: 1.068-1.459, P=0.005) and FDR (OR: 1.160, 95% CI: 1.054-1.276, P=0.002) levels were associated with the existence of pneumonia. The AUC for the combination of NLR and FDR was 0.701 (95% CI: 0.606-0.796, P<0.001, sensitivity 56.0%, specificity 83.0%). Conclusion: NLR and FDR can predict the presence of pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant.

Mental health symptoms and sleep quality of asymptomatic/mild SARS-CoV-2 infected individuals during the Omicron wave of the COVID-19 pandemic in Shanghai China.

OBJECTIVE: To investigate mental health symptoms (anxiety, depression, and sleep status) and their associated factors among people infected with the SARS-CoV-2 omicron variant during the quarantine period in Shanghai. METHODS: To investigate the mental health symptoms among participants with SARS-CoV-2 omicron infection, an anonymous online survey questionnaire was used. The survey panel included the 9-item Patient Health Questionnaire-9 (PHQ-9), 7-item Generalized Anxiety Disorder Scale (GAD-7), Pittsburgh Sleep Quality Index (PSQI), and 22-item Ruminative Responses Scale (RRS). Group comparisons and correlation analyses were employed to explore the epidemiological characteristics of patients and factors related to depression and anxiety symptoms. RESULTS: A total of 960 participants completed the survey. Of the total respondents, 583 participants (60.7%) were male, and the mean (SD) age was 34.33 (9.21) years (95% CI: 33.74-34.91). The prevalence of depressive and anxiety symptoms among the participants was 13.7% (n = 151, 95% CI: 11.6%-15.7%) and 8.6% (n = 90, 95% CI: 6.9%-10.3%), respectively. Age-stratified analysis showed that the prevalence of anxiety among the 36- to 45-year-old group (12.9%; n = 35, 8.9%-16.9%) was significantly higher than that of the 18- to 15-year-old group (7.4%; n = 42, 5.3%-9.6%, p = .011). Spearman's correlation analyses showed that rumination (assessed by the RRS) was significantly and positively correlated with depression (rho = .706, p < .001) and anxiety symptoms (rho = .758, p < .001). CONCLUSION: The results suggest that female and middle-aged populations manifest higher susceptibility to mental health distress during the current Omicron wave of the COVID-19 pandemic. Population-specific psychological crisis intervention is warranted to improve the quality of epidemic prevention methods and to promote the mental well-being of the public.

Chemodrug-gated mesoporous nanoplatform for new near-infrared light controlled drug release and synergistic chemophotothermal therapy of tumours.

Controlled drug release and synergistic therapies have an important impact on improving therapeutic efficacy in cancer theranostics. Herein, a new near-infrared (NIR) light-controlled multi-functional nanoplatform (GNR@mSiO2-DOX/PFP@PDA) was developed for synergistic chemo-photothermal therapy (PTT) of tumours. In this nano-system, doxorubicin hydrochloride (DOX) and perfluoro-n-pentane (PFP) were loaded into the channels of mesoporous SiO2 simultaneously as a first step. A polydopamine (PDA) layer as the gatekeeper was coated on their surface to reduce premature release of drugs at physiological temperature. Upon 808 nm NIR irradiation, the gold nanorods (GNR) in the core of the nanoplatform show high photothermal conversion efficiency, which not only can provide the heat for PTT, but also can decompose the polymer PDA to allow DOX release from the channels of mesoporous SiO2. Most importantly, the photothermal conversion of GNR can also lead the liquid-gas phase transition of PFP to generate bubbles to accelerate the release of DOX, which can realize the chemotherapy of tumours. The subsequent synergistic chemo-PTT (contributed by the DOX and GNR) shows good anti-cancer activity. This work shows that the NIR-triggered multi-functional nanoplatform is of capital significance for future potential applications in drug delivery and cancer treatment.

Clinical characteristics and image features of pulmonary cryptococcosis: a retrospective analysis of 50 cases in a Chinese hospital.

OBJECTIVE: To investigate the clinical manifestations and imaging characteristics of pulmonary cryptococcosis, and discuss its guidance in diagnosing. METHODS: The clinical data of patients diagnosed with cryptococcosis in our hospital from January 2014 to May 2020 were collected and retrospectively analyzed. Patients were divided into the immunocompromised group and the immunocompetent group. The symptomatic features, laboratory examination, imaging manifestations, and curative effect were analyzed. RESULTS: The most common symptoms of patients were cough and sputum production, followed by fever. The immunocompetent group has a significantly higher accident rate of cough and fever than the immunocompromised group, while the immunocompromised group has a significantly higher accident rate of headache and dizziness (P < 0.05). The positive rate of serum cryptococcal capsular antigen (CrAg) test of the two groups were 83.33% and 86.96%, respectively. While the positive rate of CrAg test in cerebrospinal fluid of the immunocompromised group was significantly higher than that of the immunocompetent group (P < 0.05). The lesions of pulmonary cryptococcosis were predominantly present in the lower part of the lung periphery and significantly distributed in the right lung (P < 0.05). The most common imaging finding of pulmonary cryptococcosis was halo sign (64.58%), followed by multiple nodules, and trachea sign was significantly more common in the immunocompetent group. CONCLUSIONS: Cryptococcosis has an insidious onset, which can infect healthy people as well. Conducting a CrAg test is good for screening and diagnosing cryptococcosis. We should be alert for the high risk of cryptococcal meningoencephalitis in patients with compromised immune function.

Laser ablative TiO2 and tremella-like CuInS2 nanocomposites for robust and ultrasensitive photoelectrochemical sensing of let-7a.

A photoelectrochemical (PEC) biosensor based on a multiple signal amplification strategy was established for highly sensitive detection of microRNA (miRNA). TiO2 was prepared on the surface of titanium sheet by laser etching to improve its stability and photoelectrical properties, and CuInS2-sensitized TiO2 was used to form a superior photoelectrical layer, which realized the initial signal amplification. The electron donor dopamine (DA) was modified to H2 as a signal regulator, which effectively increased the photocurrent signal. To further amplify the signal, an enzyme-free hybridization reaction was implemented. When target let-7a and fuel-DNA (F-DNA) were present, the base of H1 specifically recognized let-7a and forced dopamine@AuNPs-H2 away from the electrode surface. Subsequently, the end base of H1 specifically recognized F-DNA, and let-7a was replaced and recycled to participate in the next cycle. Enzyme-free circulation, as a multifunctional amplification method, ensured the recycling of target molecules. This PEC sensor for let-7a detection showed an excellent linear response from 0.5 to 1000 pM with a detection limit of 0.12 pM. The intra-batch RSD was 3.8% and the recovery was 87.74-108.1%. The sensor was further used for clinical biomolecular monitoring of miRNA, showing excellent quantitative detection capability.

The effect of Tai Chi on the pulmonary rehabilitation of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of Tai Chi for chronic obstructive pulmonary disease (COPD) so far is unclear. The present systematic review aimed to determine the influence of Tai Chi among people with COPD. METHODS: We searched six electronic databases for relevant studies in September, 2019. The methods of standard meta-analysis were used for identifying relevant studies, quality appraisal, and synthesis. The primary outcomes were six-minute walking distance (6MWD), percentage predicted forced expiratory flow volume in the first second (%PredFEV1), and St. George's Respiratory Questionnaire (SGRQ) score. RESULTS: A total of 23 studies including 1663 participants were included in the meta-analysis. The pooled data showed that the Tai Chi group was associated with a significant improvement in 6MWD [mean difference (MD) 40.83 m, 95% CI: 32.47 to 49.19], %PredFEV1 (MD 1.67%, 95% CI: 0.41 to 2.93), SGRQ score (MD -6.57, 95% CI: -10.17 to -2.98), and Chronic Respiratory Disease Questionnaire (CRQ) (MD 1.60, 95% CI: 0.89 to 2.30) relative to the blank control population. When compared with breathing exercises, the 6MWD was significantly enhanced with Tai Chi (MD 14.15 m, 95% CI: 3.76 to 24.53). Finally, when compared with breathing and walking exercises, Tai Chi was associated with a significant improvement in 6MWD (MD 7.68 m, 95% CI: 2.28 to 13.09 m) and SGRQ score (MD -6.31, 95% CI: -9.13 to -1.48). CONCLUSIONS: Tai Chi may have the potential to reduce dyspnoea, enhance exercise capacity, and improve the quality of life in COPD patients. People with COPD may obtain benefit from practicing Tai Chi.

Clinical risk factors for mortality of hospitalized patients with COVID-19: systematic review and meta-analysis.

BACKGROUND: New evidence from retrospective cohort studies on risk of death from COVID-19 infection became available. We aimed to systematically review the clinical risk factors for fatal outcome of COVID-19. METHODS: We performed meta-analysis, using PubMed, EMBASE and Cochrane databases from December 1 2019 to June 10 2020. The meta-analysis summarized clinical, laboratory, radiological features, and complications of non-survivors with confirmed COVID-19. In addition, a fixed- or random-effects model was adopted based on the heterogeneity among studies. We also used funnel-plot with Egger's tests to screen potential publication bias. RESULTS: In total, twenty studies with 15,408 COVID-19 cases were included in our meta-analysis. Male, current smoking, and older age were associated with in-hospital death. Patients aged 60 years or over had the highest pooled ORs [OR 4.94 (2.89, 8.44)]. Non-survivors were more likely to have diabetes, hypertension, cardiovascular disease (CVD), respiratory disease, or chronic kidney disease (CKD). Respiratory disease had the highest pooled ORs [OR 2.55 (2.14, 3.05)]. Dyspnea [OR 3.31 (1.78, 6.16); I2 : 83%] and fatigue [OR 1.36 (1.07, 1.73); I2 : 0%] were associated with increased risk of death. Increased white blood cell count, decreased lymphocyte and platelet counts, were also associated with increased risk of death. Biomarkers of coagulation function, inflammation, liver and kidney function, cardiac and muscle injury were also elevated in nonsurvivors. CONCLUSIONS: Male, current smoking patients aged 60 years or over might face a greater risk of in-hospital death and the comorbidities such as diabetes, hypertension, CVD, respiratory disease, and CKD could also influence the prognosis of the COVID-19. Clinical feature such as dyspnea and fatigue could imply the exacerbation and even death. Our findings highlighted early markers of mortality which were beneficial to identify fatal COVID-19.

The effect of coagulation factors in 2019 novel coronavirus patients: A systematic review and meta-analysis.

BACKGROUND: The role of coagulation dysfunction in Severe Coronavirus Disease 2019 (COVID-19) is inconsistent. We aimed to explore the impact of coagulation dysfunction amongst patients with COVID-19. METHODS: We searched PubMed, Cochrane and Embase databases from December 1, 2019 to April 27, 2020 following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data about coagulation (Platelets, PT, APTT, fibrin, fibrinogen degradation products, D-dimer), prevalence of coagulation dysfunction and mortality were extracted. Meta regression was used to explore the heterogeneity. RESULTS: Sixteen observational studies were included, comprising 2, 139 patients with confirmed COVID-19. More severe COVID-19 cases tended to have higher mean D-dimer (SMD 0.78, 95% CI 0.53 to 1.03, P < .001). The similar pattern occurred with PT and fibrin, with a contrary trend for PLTs. Coagulation dysfunction was more frequent in severe cases compared to less severe (SMD 0.46, 95% CI 0.25 to 0.67, P < .001). Higher mortality was associated with COVID-19-related coagulopathy (RR 10.86, 2.86 to 41.24, P < .001). Prevalence of ARDS was increased in more severe patients than less severe cases (RR 16.52, 11.27 to 24.22, P < .001). PT, fibrin and D-dimer levels elevated significantly in non-survivors during hospitalization. CONCLUSION: Presence of coagulation dysfunction might be associated with COVID-19 severity, and coagulopathy might be associated with mortality. Coagulation markers including PT, fibrin and D-dimer may imply the progression of COVID-19. This illuminates the necessity of effectively monitoring coagulation function for preventing COVID-19-related coagulopathy, especially in severe patients. For the obvious heterogeneity, the quality of the evidence is compromised. Future rigorous randomized controlled trials that assess the correlation between coagulation and COVID-19 are needed. TRIAL REGISTRATION: PROSPERO (CRD42020183514).

Exposure to particulate matter 2.5 and cigarette smoke induces the synthesis of lipid droplets by glycerol kinase 5.

Particulate matter (PM2.5) and cigarette smoke exposure are leading factors contributing to various diseases, especially respiratory diseases. The purpose of this research was to study the effects of PM2.5 and cigarette smoke on glycerol kinase 5 (GK5) expression and the possible mechanisms by which GK5 participates in lipid droplet (LD) synthesis in alveolar epithelial A549 cells. Real-time polymerase chain reaction (RT-PCR) and western blotting have been used for the detection of messenger RNA (mRNA) and protein expression respectively. GK5 overexpressing cells were established by lentivirus transfection, whereby lentiviral vectors deliver the gene into chromosomes, allowing stable expression. Affymetrix microarray analysis, a widely used tool for measuring genome-wide gene expression, has been used to explore differential gene expression profiles. A549 cells stimulated with PM2.5 and cigarette smoke extract (CSE) showed elevated GK5 expression in a dose-dependent manner. Transmission electron microscopy and oil red O staining were used to observe LDs in cells. Further, GK5 overexpressing cells showed increased LDs and upregulation of genes and proteins related to lipogenesis and lipid transportation. Affymetrix microarray analysis revealed that GK5 overexpression resulted in the differential expression of more than 109 genes, which were mainly involved in the regulation of cell death, cell survival, cellular movement and migration, and those involved in cellular growth and proliferation pathways. Overall, this study demonstrates that GK5 is upregulated during PM2.5 and cigarette smoke exposure and induces LD synthesis.

Engineering Near-Infrared-Excitable Metal-Organic Framework for Tumor Microenvironment Responsive Therapy.

Luminescent metal-organic frameworks (MOFs), which incorporate some guest luminescent molecules/ions into MOFs, have attracted extensive attention because of their exceptional optical properties. However, traditional luminescent MOFs are mainly responsive to ultraviolet (UV) or visible light, which has limited their bioapplications due to the restrained tissue penetration depths. In this study, we have constructed a diagnostic nanoplatform UCNP@MOF consisting of upconverting metal-organic frameworks, which combine the photo-upconverting characteristics of the upconversion nanoparticles (UCNPs) with the unique physicochemical properties of Al-MOFs. Specifically, the core-shell structured UCNP@MOF nanocomposites were prepared by poly(vinylpyrrolidone) (PVP)-regulated nucleation of Al-MOF layer on the UCNP surface. When excited by a 980 nm laser light, the green signal released from UCNPs can trigger the photosensitive Al-MOFs to produce a large amount of singlet oxygen (1O2) for photodynamic therapy (PDT). Meanwhile, the anticancer drug, doxorubicin hydrochloride (DOX), was further incorporated into the porous structures of Al-MOFs and demonstrated the pH-responsive drug release behavior. Our results show that the near-infrared (NIR) light-induced PDT with chemotherapy (CMT) exhibits excellent antitumor effects. It is believed that the present work highlights the potential of the combination of UCNPs and MOFs and holds great promise for biomedical applications.

Paper-Based Bipolar Electrode Electrochemiluminescence Platform for Detection of Multiple miRNAs.

This paper introduces a novel potential-resolved paper-based biosensor for simultaneous detection of multiple microRNAs (miRNAs) (taking miRNA-155 and miRNA-126 as examples) based on the bipolar electrode (BPE) electrochemiluminescence (ECL) strategy. The proposed multiple-channel paper-based sensing microfluidic platform was prepared by wax-printing technology, screen-printing method, and in situ Au nanoparticles (AuNPs) growth to form hydrophilic areas, hydrophobic boundaries, waterproof electronic bridge, driving electrode regions, and parallel bipolar electrode regions. CdTe quantum dots (QDs)-H2 and Au@g-C3N4 nanosheets (NSs)-DNA1 were used as dual electrochemiluminescence signal probes, and carboxylated Fe3O4 magnetic nanoparticles existed as carriers. CdTe QDs-H2/S2O82- and Au@g-C3N4 NSs-DNA1/S2O82- could exhibit two strong and stable ECL emissions at a drive voltage of 9 and 12 V, respectively, which can be used as effective potential-resolved signal tags. In addition, the proposed three-dimensional (3D) DNA nanomachine model and the target miRNA cycle strategy were used to achieve double amplification of electrochemiluminescence intensity. More importantly, the combination of the bipolar electrode system and the potential-resolved multitarget electrochemiluminescence method can greatly reduce the spatial interference between substances. The prepared ECL biosensor showed a favorable linear response for the detection of miRNA-155 and miRNA-126 with relatively low detection limits of 5.7 and 4.2 fM, respectively. With excellent sensitivity, the strategy may provide an efficient method for clinical application, especially in detection of trace multiple targets.

Ultrasensitive sandwich-like electrochemical biosensor based on core-shell Pt@CeO2 as signal tags and double molecular recognition for cerebral dopamine detection.

In this report, 4-mercaptophenylboronic acid (MBA) and dithiobis (succinimidyl propionate) (DSP) were used as DA molecular recognizer, which bounded onto the prepared Pt@CeO2 nanomaterial and the electrode surface. A sandwich-like electrochemical biosensor was constructed for sensitive detection of dopamine (DA) based on double molecular recognition and Pt@CeO2 (MBA-DSP- Pt@CeO2) as an electrochemical probe for signal amplification. It is worth noting that the diol and amine groups of DA were reacted by the boronic acid of MBA and the succinimide residue of DSP, respectively. This sandwich-like double molecular interaction can efficiently and accurately identify DA. The uniform Pt@CeO2 multicore@shell nanospheres as signal tags and signal amplifiers in electrochemical biosensor were synthesized by hydrothermal, which has excellent catalytic activity for H2O2. Interestingly, more oxygen vacancies were produced in the lattice structure of CeO2 doped with Pt, so that the catalytic and redox performance of the obtained Pt@CeO2 was much better than that of pure CeO2, thus greatly improving the performance of the proposed sensor. The proposed electrochemical biosensor provided a wide detection range of 2-180 nM and a low detection limit (0.71 nM) by the electrochemical measurement. And it also showed ultra-high sensitivity, accuracy and broad application prospect, which developed a new research method for early clinical diagnosis.

Efficiency of High-Flow Nasal Cannula on Pulmonary Rehabilitation in COPD Patients: A Meta-Analysis.

INTRODUCTION: The clinical benefit of high-flow nasal cannula (HFNC) on factors related to pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) patients remains unclear. This meta-analysis aimed at synthesizing the available evidence on the efficacy of HFNC on exercise capacity, lung function, and other factors related to pulmonary rehabilitation in COPD patients. METHODS: Electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science) were searched for randomized trials comparing with conventional oxygen therapy (COT) or noninvasive ventilation (NIV). Primary outcomes were respiratory rate, FEV1, tidal volume, oxygen partial pressure, total score of St. George's respiratory questionnaire, 6-minute walk test, and exercise endurance time. RESULTS: Ten trials met the criteria for inclusion. Combined data from six studies showed that HFNC showed a lower respiratory rate in COPD patients [mean difference -1.27 (95% CI: -1.65-(-0.89)]. Combined data from three studies showed a lower forced expiratory volume in one second (FEV1) in the group of HFNC. No difference in tidal volume was showed between the HFNC and control groups in COPD patients. No significant oxygen improvement between the HFNC groups and control groups. The total score of St. George's respiratory questionnaire was improved by the subgroup analysis of HFNC versus COT but no NIV. Two multicenter RCTs showed the six-minute walk test, and statistical results showed that the length of the six-minute walk capacity was increased after usage of HFNC compared to the control group [mean difference -8.65 (95% CI: -9.12-(-8.19)]. No increase of exercise capacity after usage of HFNC (mean difference -12.65). CONCLUSION: In the first meta-analysis of the area, the current evidence did not show so much positive effect on tidal volume or oxygen improvement in COPD patients. Length of the six-minute walk capacity was increased after using HFNC, while other pulmonary rehabilitation parameters, namely, the score of St. George's respiratory questionnaire and exercise capacity show no increase in the group of HFNC. The variance in the quality of the evidence included in this meta-analysis highlights the need for this evidence to be followed up with further high-quality and more randomized trials.

AgInSe2-Sensitized ZnO Nanoflower Wide-Spectrum Response Photoelectrochemical/Visual Sensing Platform via Au@Nanorod-Anchored CeO2 Octahedron Regulated Signal.

Herein an ultrasensitive photoelectrochemical (PEC)/visual biosensor coupled with a multiple signal amplification strategy was proposed for the detection of nucleic acids. The initial signal amplification was achieved via ternary AgInSe2 quantum dot (QD)-sensitized ZnO nanoflowers (ZnO NFs) to form an excellent photoelectric layer. A gold-modified nanorod-anchored CeO2 (Au@NR-CeO2) octahedron was introduced as a multifunctional signal regulator via the formation of triple helix molecules. The Au@NR-CeO2 octahedron could not only quench the photocurrent signal due to the competitive capture of photon energy and electron donors with the photoelectric layer but could also act like a peroxidase to catalyze the formation of mimetic enzymatic catalytic precipitation (MECP) on the surface of the photoelectric layer. Furthermore, the steric hindrance effect from the Au@NR-CeO2 octahedron further reduced the output of the photocurrent signal. After incubation with t-DNA, the triple helix conformation was disassembled and the Au@NR-CeO2 octahedron was released from the electrode surface, leading to the significant increase of photocurrent signal. Meanwhile, the released Au@NR-CeO2 octahedron could flow into the colorimetric area of the lab-on-paper device to catalyze the occurrence of the color reaction, achieving a visual detection for t-DNA. On the basis of the multiple signal amplification strategy, t-DNA was detected specifically with a lower limit of detection of 0.28 fM and a wider linear range from 0.5 fM to 50 nM. The proposed method has the potential utility to detect a variety of nucleic acids and biomarkers.

Heterozygous SOD2 deletion deteriorated chronic intermittent hypoxia-induced lung inflammation and vascular remodeling through mtROS-NLRP3 signaling pathway.

Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2+/-) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1ß elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.

SOD2 ameliorates pulmonary hypertension in a murine model of sleep apnea via suppressing expression of NLRP3 in CD11b+ cells.

BACKGROUND: High prevalence of obstructive sleep apnea (OSA) in the pulmonary hypertension (PH) population suggests that chronic intermittent hypoxia (CIH) is an important pathogenic factor of PH. However, the exact mechanism of CIH induced PH is not clear. One of the molecules that plays a key role in regulating pulmonary artery function under hypoxic conditions is superoxide dismutase 2 (SOD2). METHODS: Our study utilized heterozygous SOD2-/+ mice firstly in CIH model to explore the exact role of SOD2 in CIH causing PH. Expression of SOD2 was analyzed in CIH model. Echocardiography and pulmonary hypertension were measured in wild type (WT) and SOD2-/+ mice under normal air or CIH condition. Hematoxylin-Eosin (H&E) staining and masson staining were carried out to evaluate pulmonary vascular muscularization and remodeling. Micro-PET scanning of in vivo 99mTc-labelled- MAG3-anti-CD11b was applied to assess CD11b in quantification and localization. Level of nod-like receptor pyrin domain containing 3 (NLRP3) was analyzed by real time PCR and immunohistochemistry (IHC). RESULTS: Results showed that SOD2 was down-regulated in OSA/CIH model. Deficiency of SOD2 aggravated CIH induced pulmonary hypertension and pulmonary vascular hypertrophy. CD11b+ cells, especially monocytic myeloid cell line-Ly6C+Ly6G- cells, were increased in the lung, bone marrow and the blood under CIH condition, and down-regulated SOD2 activated NLRP3 in CD11b+ cells. SOD2-deficient-CD11b+ myeloid cells promoted the apoptosis resistance and over-proliferation of human pulmonary artery smooth muscle cells (PASMCs) via up-regulating NLRP3. CONCLUSION: CIH induced down-regulating of SOD2 increased pulmonary hypertension and vascular muscularization. It could be one of the mechanism of CIH leading to PH.

Paper-based closed Au-Bipolar electrode electrochemiluminescence sensing platform for the detection of miRNA-155.

This paper introduces a paper-based closed Au-bipolar electrode (BPE) biosensing system for the rapid and sensitive electrochemiluminescence (ECL) detection of miRNA-155. This microfluidic paper-based sensing platform is formed by wax-printing technology, screen printing method and in-situ Au nanoparticles (NPs) growth to form hydrophilic cells, hydrophobic boundaries, water proof electronic bridge, driving electrode regions and bipolar electrode regions. For rapid and sensitive detection, the cathode of bipolar electrode was modified with the prepared DNA (S1)-AuPd NPs by hybridization chain reaction, in which the target could initiate multiple cycles reaction to load more AuPd NPs which catalyzed H2O2 reduction. In addition, a classical ECL system tris (2,2'-bipyridine) ruthenium (II)- tripropylamine (Ru(bpy)32+/TPrA) exists at the anode of the bipolar electrode. Due to the charge balance between the anode and the cathode of BPE, the ECL signal response of Ru(bpy)32+/TPrA system was enhanced in the reporting cell. The intensity of ECL was quantitatively correlated with the concentration of miRNA-155 in the range of 1 pM-10 µM with the detection limit 0.67 pM. Moreover, this method paves a novel way for highly sensitive detection of miRNA-155 in clinical application.