A ratiometric fluorescent probe for imaging the fluctuation of HOBr during endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress is closely associated with cell apoptosis, autophagy, DNA damage, metabolism, and migration. When ER stress occurs, a large number of reactive oxygen species, including hypobromous acid (HOBr), are generated. The degree of ER stress can be understood by accurately detecting the HOBr concentration in the ER. Unfortunately, no ER-targetable probes for detecting HOBr have been reported to date. To solve this problem, we developed a naphthalimide-based fluorescent probe (ER-NABr) for imaging HOBr in the ER. Upon reaction with HOBr, a red shift in the fluorescence spectrum occurs due to the difference in the molecular conjugation between the original ER-NABr and the reaction product. ER-NABr showed a fast response (within 30 s) and high selectivity towards HOBr, with a ratiometric quantitative response (5-40 µM) and high sensitivity (138 nM). With its excellent biocompatibility and remarkable ER-targetable ability, ER-NABr was successfully utilized to ratiometrically image intracellular HOBr, particularly during ER stress, which is beneficial for revealing the role of HOBr in ER-associated diseases.

PDI-Based Organic Small Molecule Regulated by Inter/Intramolecular Interactions for Efficient Solar Vapor Generation.

Organic small molecules with processing feasibility, structural diversity, and fine-tuned properties have the potential applications in solar vapor generation. However, the common defects of narrow solar absorption, low photothermal conversion efficiency, and photobleaching result in limited materials available and unsatisfactory evaporation performance. Herein, the perylene diimide (PDI) derivatives are exploited as stable sunlight absorbers for solar vapor generation. Particularly, the N,N'-bis(3,4,5-trimethoxyphenyl)-3,4,9,10-perylenetetracarboxylic diimide (PDI-DTMA) is well-designed with donor-acceptor-donor configuration based on plane rigid PDI core. The efficient photothermal conversion is enabled through strong intermolecular π-π stacking and intramolecular charge transfer, as revealed by experimental demonstration and theoretical calculation. The PDI-DTMA with a narrow band gap of 1.17 eV exhibits expanded absorption spectrum and enhanced nonradiative transition capability. The 3D hybrid hydrogels (PPHs) combining PDI-DTMA and polyvinyl alcohol are constructed. With the synergistic effect of solar-to-heat conversion, thermal localization management, water activation, and unobstructed water transmission of PPHs, the high water evaporation rates can reach 3.61-10.07 kg m-2 h-1 under one sun. The hydrogels also possess great potential in seawater desalination and sewage treatment. Overall, this work provides valuable insights into the design of photothermal organic small molecules and demonstrates their potentials in solar water evaporation.

An endoplasmic reticulum-specific ratiometric fluorescent probe for imaging esterase in living cells.

Esterase is primarily distributed in the endoplasmic reticulum (ER) and often overexpressed in cancer cells. Therefore, the detection of esterase in ER is significant for monitoring the metabolic process of various esters and evaluating the efficacy of chemotherapeutic prodrugs. However, only few fluorescent probes can detect esterase in the ER due to the lack of ER-specificity. More seriously, these probes are often limited by low pearson's colocalization coefficient and one single wavelength emission. To solve those problems, an ER-specific ratiometric fluorescent probe (ER-EST) is designed for detecting esterase in living cells. The ER-EST shows a ratiometric and red-shifted emission (125 nm) from 435 to 560 nm after hydrolysis by esterase. The fluorescence intensity ratio of ER-EST displays quantitative response to the esterase activity (0-0.5 U/mL) with low detection limit of 1.8 × 10-4 U/mL. Importantly, the ER-EST with good biocompatibility and excellent ER-targeted ability was successfully employed to ratiometric image the endogenous endoplasmic reticulum esterase in living cells.

Comprehensive characterization reveals sputum supernatant as a valuable alternative liquid biopsy for genome profiling in advanced non-small cell lung cancer.

BACKGROUND: Sputum biopsies offer unique advantages such as non-invasiveness and convenient collection. The one investigation so far on sputum for genome profiling in advanced non-small cell lung cancer (aNSCLC) suggested promising performance. However, it remains undefined whether clinicohistologic characteristics were associated with performance and how this knowledge could help guide choice of liquid biopsy. METHODS: Targeted sequencing with a 520-gene panel was performed on prospectively collected matched tumor tissue (TIS), plasma (PLA), and sputum supernatant (SPU) from 71 aNSCLC patients (NCT05034445). Genomic alteration detection was characterized in a series of aspects and interrogated for association with 14 clinicohistologic features. Nomograms were constructed with logistic regression for predicting the liquid biopsy type with greater sensitivity. RESULTS: Compared with PLA, SPU showed comparable quality control metrics, mutation detection rate (SPU: 67.6%, PLA: 70.4%), concordance with tumor tissue (67.6% vs. 73.2%), and correlation with tissue-based tumor mutation burden levels (r = 0.92 vs. 0.94). For driver alterations, detection was less sensitive with SPU (50.0%) than PLA (63.5%) in the entire cohort but similarly or more sensitive in patients with centrally located lung tumors or smoking history or for altered ALK or KRAS. Two nomograms were constructed and enabled predicting the probability of superior sensitivity with SPU with moderate to borderline high accuracy. CONCLUSION: In addition to demonstrating comparable performance in multiple aspects, this study is the first to propose nomograms for choosing liquid biopsy based on clinicohistologic characteristics. Future research is warranted to delineate the clinical utility of sputum for genome profiling.

A Matrix Prediction Model for the 6-Month Mortality Risk in Patients With Anti-Melanoma Differentiation-Associated Protein-5-Positive Dermatomyositis.

Objectives: The purpose of this study was to investigate the baseline independent risk factors for predicting 6-month mortality of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis (DM) and develop a matrix prediction model formed by these risk factors. Methods: The hospitalized patients with DM who completed at least 6-month follow-up were recruited as a derivation cohort. The primary exposure was defined as positive anti-MDA5 at the baseline. The primary outcome was all-cause 6-month mortality after enrollment. A matrix prediction model was developed in the derivation cohort, and another published cohort was used for external validation. Results: In derivation cohort, 82 patients with DM were enrolled (mean age of onset 50 ± 11 years and 63% women), with 40 (49%) showing positive anti-MDA5. Gottron sign/papules (OR: 5.135, 95%CI: 1.489-17.708), arthritis (OR: 5.184, 95%CI: 1.455-18.467), interstitial lung disease (OR: 7.034, 95%CI: 1.157-42.785), and higher level of C4 (OR: 1.010, 95%CI: 1.002-1.017) were the independent associators with positive anti-MDA5 in patients with DM. Patients with anti-MDA5-positive DM had significant higher 6-month all-cause mortality than those with anti-MDA5-negative (30 vs. 0%). Among the patients with anti-MDA5-positive DM, compared to the survivors, non-survivors had significantly advanced age of onset (59 ± 6 years vs. 46 ± 9 years), higher rates of fever (75 vs. 18%), positive carcinoma embryonic antigen (CEA, 75 vs. 14%), higher level of ferritin (median 2,858 ug/L vs. 619 ug/L, all p < 0.05). A stepwise multivariate Cox regression showed that ferritin ≥1,250 µg/L (HR: 10.4, 95%CI: 1.8-59.9), fever (HR: 11.2, 95%CI: 2.5-49.9), and positive CEA (HR: 5.2, 95%CI: 1.0-25.7) were the independent risk factors of 6-month mortality. A matrix prediction model was built to stratify patients with anti-MDA5-positive DM into different subgroups with various probabilities of 6-month mortality risk. In an external validation cohort, the observed 6-month all-cause mortality was 78% in high-risk group, 43% in moderate-risk group, and 25% in low-risk group, which shows good accuracy of the model. Conclusion: Baseline characteristics such as fever, ferritin ≥1,250 µg/L, and positive CEA are the independent risk factors for 6-month all-cause mortality in patients with anti-MDA5-positive DM. A novel matrix prediction model composed of these three clinical indicators is first proposed to provide a chance for the exploration of individual treatment strategies in anti-MDA5-positive DM subgroups with various probabilities of mortality risk.

A Computed Tomography Radiomics-Based Prediction Model on Interstitial Lung Disease in Anti-MDA5-Positive Dermatomyositis.

Objectives: Anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated interstitial lung disease (MDA5+ DM-ILD) is a life-threatening disease. The current study aimed to quantitatively assess the pulmonary high-resolution computed tomography (HRCT) images of MDA5+ DM-ILD by applying the radiomics approach and establish a multidimensional risk prediction model for the 6-month mortality. Methods: This retrospective study was conducted in 228 patients from two centers, namely, a derivation cohort and a longitudinal internal validation cohort in Renji Hospital, as well as an external validation cohort in Guangzhou. The derivation cohort was randomly divided into training and testing sets. The primary outcome was 6-month all-cause mortality since the time of admission. Baseline pulmonary HRCT images were quantitatively analyzed by radiomics approach, and a radiomic score (Rad-score) was generated. Clinical predictors selected by univariable Cox regression were further incorporated with the Rad-score, to enhance the prediction performance of the final model (Rad-score plus model). In parallel, an idiopathic pulmonary fibrosis (IPF)-based visual CT score and ILD-GAP score were calculated as comparators. Results: The Rad-score was significantly associated with the 6-month mortality, outperformed the traditional visual score and ILD-GAP score. The Rad-score plus model was successfully developed to predict the 6-month mortality, with C-index values of 0.88 [95% confidence interval (CI), 0.79-0.96] in the training set (n = 121), 0.88 (95%CI, 0.71-1.0) in the testing set (n = 31), 0.83 (95%CI, 0.68-0.98) in the internal validation cohort (n = 44), and 0.84 (95%CI, 0.64-1.0) in the external validation cohort (n = 32). Conclusions: The radiomic feature was an independent and reliable prognostic predictor for MDA5+ DM-ILD.

An AIEgen as an Intrinsic Antibacterial Agent for Light-Up Detection and Inactivation of Intracellular Gram-Positive Bacteria.

Infections caused by Gram-positive bacteria, especially those able to invade and survive in host cells, threaten human health severely. It is therefore highly desirable to develop therapeutics that can selectively target and kill intracellular Gram-positive pathogens with minimal toxicity to host cells. Herein, it is described that the aggregation-induced emission luminogen (AIEgen) TPEPy-Et, containing a positively charged pyridinium group and a hydrophobic tetraphenylethylene fragment, is effective for Gram-positive bacteria detection and elimination. The fluorescence of TPEPy-Et is greatly enhanced after incubation with Gram-positive bacteria, which can be used to detect and trace the bacteria in cells. TPEPy-Et also shows excellent killing effects against both extracellular and intracellular Gram-positive bacteria through a membrane depolarization mechanism. The luminescent antibacterial agent TPEPy-Et is thus promising for diagnosis and therapy against intracellular bacterial infection.

The Application of Transbronchial Lung Cryobiopsy and Uniportal and Tubeless Video-Assisted Thoracic Surgery in the Multidisciplinary Diagnosis of Interstitial Lung disease-A Real-World Prospective Study.

The application of transbronchial lung cryobiopsy (TBLC) and uniportal and tubeless video-assisted thoracic surgery (UT-VATS) in the multidisciplinary diagnosis of interstitial lung disease (ILD) has not been demonstrated in real-world clinical practice. This prospective study included 137 patients with no definitive diagnosis who were the subject of two multidisciplinary discussion (MDD) sessions. As indicated in the first MDD, 67 patients underwent UT-VATS and 70 underwent TBLC. The specificity of biopsy information and its contribution to final MDD diagnosis were evaluated in the second MDD. The post-operative complications and hospitalization costs associated with the two biopsy methods were compared. UT-VATS was favored for patients initially diagnosed with idiopathic pulmonary fibrosis (IPF), bronchiolitis-associated interstitial lung disease (RB-ILD)/desquamative interstitial pneumonia (DIP) and undefined idiopathic interstitial pneumonia (UIIP), while TBLC was preferred for pulmonary lymphangioleiomyomatosis (PLAM) and pulmonary alveolar proteinosis (PAP). The spirometry parameters were better in patients who underwent UT-VATS than those who underwent TBLC. UT-VATS provided more specific pathological results than TBLC (85.7 vs 73.7%, p = 0.06). In patients initially diagnosed with UIIP, pathological information from UT-VATS was more clinically useful than that obtained from TBLC, although both tests contributed similarly to cases initially diagnosed as interstitial pneumonia with auto-immune features (IPAF)/connective tissue disease-related ILD (CTD-ILD). The safety of UT-VATS was comparable with TBLC although TBLC was cheaper during hospitalization (US$4,855.7 vs US$3,590.9, p < 0.001). multidisciplinary discussion decisions about biopsies were driven by current knowledge of sampling and diagnosis capacity as well as potential risks of different biopsy methods. The current MDD considered UT-VATS more informative than TBLC in cases initially diagnosed as UIIP although they were equally valuable in patients initially diagnosed with IPAF/CTD-ILD.

Complex Involvement of the Extracellular Matrix, Immune Effect, and Lipid Metabolism in the Development of Idiopathic Pulmonary Fibrosis.

Background and objective: Idiopathic pulmonary fibrosis (IPF) is an aggressive fibrotic pulmonary disease with spatially and temporally heterogeneous alveolar lesions. There are no early diagnostic biomarkers, limiting our understanding of IPF pathogenesis. Methods: Lung tissue from surgical lung biopsy of patients with early-stage IPF (n = 7), transplant-stage IPF (n = 2), and healthy controls (n = 6) were subjected to mRNA sequencing and verified by real-time quantitative PCR (RT-qPCR), immunohistochemistry, Western blot, and single-cell RNA sequencing (scRNA-Seq). Results: Three hundred eighty differentially expressed transcripts (DETs) were identified in IPF that were principally involved in extracellular matrix (ECM) remodeling, lipid metabolism, and immune effect. Of these DETs, 21 (DMD, MMP7, POSTN, ECM2, MMP13, FASN, FADS1, SDR16C5, ACAT2, ACSL1, CYP1A1, UGT1A6, CXCL13, CXCL5, CXCL14, IL5RA, TNFRSF19, CSF3R, S100A9, S100A8, and S100A12) were selected and verified by RT-qPCR. Differences in DMD, FASN, and MMP7 were also confirmed at a protein level. Analysis of scRNA-Seq was used to trace their cellular origin to determine which lung cells regulated them. The principal cell sources of DMD were ciliated cells, alveolar type I/II epithelial cells (AT cells), club cells, and alveolar macrophages (AMs); MMP7 derives from AT cells, club cells, and AMs, while FASN originates from AT cells, ciliated cells, and AMs. Conclusion: Our data revealed a comprehensive transcriptional mRNA profile of IPF and demonstrated that ECM remodeling, lipid metabolism, and immune effect were collaboratively involved in the early development of IPF.

Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD.

OBJECTIVES: To evaluate the efficacy and safety of ultra-low dose (100 mg) rituximab (RTX) administration in anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with polymyositis/dermatomyositis (PM/DM) associated interstitial lung disease. METHODS: This retrospective study included anti-MDA5 antibody positive ILD subjects in the First Affiliated Hospital of Guangzhou Medical University from November 2017 to March 2019. Independent predictors for 180-day mortality were measured by Cox regression analysis. Patients were divided into 3 groups: Group 1 (non-cyclophosphamide (CTX)/RTX) (n = 10), Group 2 (CTX only) (n = 19) and Group 3 (RTX with/without CTX) (n = 11). The 180-day mortality was compared among 3 groups with Kaplan-Meier analysis. Post-RTX serological parameters as well as adverse events were evaluated. RESULTS: Forty patients were included with the mean age of 51.3 years. Elevated IL-10 level and CD4+/8+ ratio were considered as risk factors of 180-day mortality. Kaplan-Meier analysis showed a trend toward decrease, albeit non-significant, in 180-day mortality in Group 3 (P = 0.26). The administration of 100 mg RTX brought down B cell within 7 days that lasted for 180 days. There were 7 and 6 infection events observed within 2 months of CTX/RTX treatment in Group 2 and 3, with 5 and 2 fatal cases respectively. Cytomegalovirus infection accounted for half infection events in Group 3. CONCLUSION: We found a pronounced and prolonged B cell depletion following 100 mg RTX infusion and RTX add-on may be effective in anti-MDA5 positive ILD patients. However, infection, especially opportunistic infection, should be concerned during the treatment.

The interstitial lung disease spectrum under a uniform diagnostic algorithm: a retrospective study of 1,945 individuals.

BACKGROUND: Reported data on the disease spectrum of interstitial lung diseases (ILDs) of China are sparse and varied. We aimed to investigate the spectrum of ILDs and the distribution of diagnostic methods under a uniform diagnosis. METHODS: This retrospective study enrolled ILDs cases from Guangzhou Institute of Respiratory Health (GIRH). All cases were classified into specific subgroups of ILDs according to updated guidelines. RESULTS: A total of 1,945 subjects were enrolled from January 2012 to December 2017. The mean age was 57.9 years, and 1,080 (55.5%) patients were male. The most common subtype of ILDs was idiopathic pulmonary fibrosis (IPF, 20.3%), followed by interstitial pneumonia with autoimmune features (IPAF, 17.9%), connective tissue disease associated ILD (CTD-ILD, 18.3%) and unclassifiable idiopathic interstitial pneumonia (UIIP, 14.7%). A total of 818 (42.1%) patients underwent lung biopsy in order to obtain a histological diagnose. TBLB was performed in 565 (29.0%) patients, eleven of whom underwent SLB because TBLB failed to obtain lung samples. SLB was performed in 213 (11.0%) patients and TBCB was performed in 51 (2.6%) patients. Among them, histological results were considered clinically helpful in 722 (88.3%) cases, and provided definitive histopathological diagnoses in 368 cases. Surgical lung biopsy (SLB) was performed in 213 (10.9%) subjects, while 115 (54.0%) cases were performed among the idiopathic interstitial pneumonia (IIP). Among SLB cases in IIP, the highest rate of SLB was desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lung disease (DIP/RB-ILD, 10/10), lymphoid interstitial pneumonia (LIP, 9/9), followed by cryptogenic organizing (COP, 18/26), nonspecific interstitial pneumonia (NSIP, 22/53), IPF (43/395), UIIP (13/285). CONCLUSIONS: IPF was the most common ILDs in our ILD center, followed by IPAF, CTD-ILD and UIIP. Histological information may help to establish diagnostic algorithm in ILD.

Successful therapy with bevacizumab combined with corticosteroids for crizotinib-induced interstitial lung disease.

We present the case of an old woman with ALK-rearranged stage IV lung adenocarcinoma who received crizotinib. She presented with severe dyspnea on the 34th day, and diffuse ground-glass opacifications in her chest. A diagnosis of crizotinib-induced ILD was confirmed. Corticosteroids were administered. However, the disease was still progressing rapidly. Therefore, as a monoclonal antibody against vascular endothelial growth factor, bevacizumab was administered in low doses (200 mg on days one and three). Her symptoms began to improve. Our clinical experience indicates that bevacizumab combined with corticosteroids might be a promising treatment in crizotinib-induced ILD patients.

Synthesis of N-Doped Micropore Carbon Quantum Dots with High Quantum Yield and Dual-Wavelength Photoluminescence Emission from Biomass for Cellular Imaging.

Pursuit of a simple, fast, and cost-effective method to prepare highly and dual-wavelength fluorescent carbon quantum dots (CQDs) is a persistent objective in recent years. Here, we fabricated N-doped micropore carbon quantum dots (NM-CQDs) with a high quantum yield and dual-wavelength photoluminescence (PL) emission from sustainable biomass using a pulsed laser ablation method. Interestingly, two coexisting indigo⁻blue photoluminescence (PL) emissions were clearly observed, elucidating that the excited electrons transited from the intrinsic π* orbital to the surface state (SS) formed from the saturation passivation. The quantum yield (QY) and fluorescence lifetime (FL) of the obtained NM-CQDs were as high as 32.4% and 6.56 ns. Further investigations indicated that the emission behaviors of NM-CQDs were still stable and independent in various conditions such as various excitation wavelengths, salt ionic concentrations, pH values, irradiation times, and temperatures. The obtained NM-CQDs are very suitable for cellular staining images due to strong and stable PL emission and show good internalization in different cells. Therefore, we propose a new and cost-effective preparation strategy for highly fluorescent NM-CQDs with great potential in biomedical imaging and engineering.

A two-photon fluorescent probe for basal formaldehyde imaging in zebrafish and visualization of mitochondrial damage induced by FA stress.

The detection of mitochondrial formaldehyde (FA) is of great significance because FA is generated through a one-carbon formaldehyde cycle in mitochondria, and abnormal elevations in FA levels can damage mitochondria by decreasing the mitochondrial membrane potential and inhibiting mitochondrial respiration. Herein, a mitochondria-targetable two-photon probe (Mito-FA-FP) has been well demonstrated. Mito-FA-FP is conjugated with hydrazine as the FA-reactive site and a pyridine derivate as the mitochondria-targetable moiety. After reacting with FA, Mito-FA-FP exhibits dramatic fluorescence enhancement (12-fold) due to suppression of the PET process in the probe and presents good selectivity as well as high sensitivity (LOD: 12.4 µM). Moreover, Mito-FA-FP can be utilized to monitor endogenous FA in mitochondria and evaluate mitochondrial damage caused by FA stress through observing mitochondrial morphology changes. With good two-photon absorption cross-section and high two-photon fluorescence contrast, Mito-FA-FP has been successfully employed for the two-photon fluorescence imaging of basal FA in zebrafish.

Methacholine induces extracellular matrix production by human airway smooth muscle cells through ß-catenin signaling.

Altered extracellular matrix (ECM) production by airway smooth muscle cells (ASMCs) is an important feature of airway remodeling. Muscarinic receptor agonists contribute to ECM production in vivo, but the mechanisms involved remain unclear. This study attempted to investigate the role of methacholine in promoting ECM production by human ASMCs (HASMCs) and the underlying mechanism. We found that methacholine induced the expression of collagen I protein and multiple ECM genes. ß-catenin signaling was activated in this process upon GSK3ß phosphorylation, leading to upregulation of total and active ß-catenin. Silencing ß-catenin by specific small interfering RNA (siRNA) or with the ß-catenin inhibitor, PKF115-584, decreased collagen I expression. Conversely, overexpression of active ß-catenin by adenoviruses carrying the S33Y-ß-catenin mutant increased the methacholine-induced collagen I expression. Furthermore, methacholine induced TGF-ß expression in HASMCs, while pan-TGF-ß-neutralizing antibody only partially decreased collagen I expression. These findings suggest that methacholine induced ECM production through ß-catenin signaling and partially through TGF-ß.

Chinese version of the severe respiratory insufficiency questionnaire for patients with COPD receiving long-term oxygen therapy.

Purpose: Patients with advanced-stage COPD often experience severe hypoxemia. Treatment with long-term oxygen therapy (LTOT) may relieve patients' symptoms and increase survival. As COPD is incurable, improving patients' health-related quality of life is important. The Chinese version of the Severe Respiratory Insufficiency Questionnaire (SRI) is valid for patients with hypercapnic COPD undergoing noninvasive positive airway pressure ventilation at home. However, the reliability and validity of the Chinese SRI for patients with COPD undergoing LTOT have not been investigated. Patients and methods: We analyzed reliability using Cronbach's α coefficient. Construct validity was assessed with principal, exploratory, and confirmatory factor analysis. Concurrent validity was evaluated through the correlation between SRI domains and Chronic Respiratory Disease Questionnaire (CRQ) domains. Content validity was assessed by calculating the correlation between each SRI item score and the total score for the relevant domain. Results: In total, 161 patients participated in this study. The Cronbach's α coefficient for all SRI domains was >0.7, except for the attendant symptoms and sleep domain. Exploratory and confirmatory factor analysis showed a good model fit for each domain, but the factors extracted from each domain were correlated. SRI and CRQ domains correlated well with respect to similar aspects of health-related quality of life, indicating good concurrent validity. Content validity was indirectly shown by a good correlation between each item score and the total score of the relevant domain. Conclusion: The Chinese version of the SRI has a good reliability and validity for patients with COPD undergoing LTOT in China.

Efficacy of bilevel positive airway pressure and continuous positive airway pressure therapy in patients with obesity hypoventilation syndrome: protocol for systematic review and meta-analysis.

INTRODUCTION: Obesity hypoventilation syndrome (OHS) is a major respiratory complication caused by severe obesity, being associated with significant morbidity, negative impacts on quality of life and reduced survival if not treated appropriately. Positive airway pressure therapy is the first-line treatment for OHS although the optimal modality remains unclear. The goal of this study is to identify the efficacy of home bilevel positive airway pressure therapy by comparison to continuous positive airway pressure therapy and determine the best strategy for patients with OHS. METHODS AND ANALYSIS: This study will be conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. We will search the following databases: PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. Ongoing studies will be identified through the ClinicalTrials.gov and WHO International Clinical Trials Registry Platform Search Portal. Grey literature will be recognised through Google Scholar and other search engines. Only randomised controlled trials meeting the eligibility criteria will be included. The risk of bias of the included studies will be evaluated through the Cochrane Collaboration's tool. RevMan V.5.3.5 software will be used for data analysis. The Q statistic and I2 index will be used for investigating heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required because this study contains no primary data collected from humans. This systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42017078369.

Author Correction: High-pressure versus low-pressure home non-invasive positive pressure ventilation with built-in software in patients with stable hypercapnic COPD: a pilot study.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

A lysosome targetable versatile fluorescent probe for imaging viscosity and peroxynitrite with different fluorescence signals in living cells.

The lysosome, which acts as the cellular recycling centre, is filled with numerous hydrolases that can degrade most cellular macromolecules. The abnormalities of the lysosome are closely associated with diseases, such as Hermanský-Pudlák syndrome, Griscelli syndrome and Chédiak-Higashi syndrome. Studies have shown that abnormal viscosity and the accumulation of reactive oxygen species (ROS) in the lysosome will disorder the normal function of the lysosome. In this research, a versatile fluorescent probe Lyso-NA has been developed for the multi-channel imaging of lysosomal viscosity and peroxynitrite (ONOO-). When excited at 550 nm, the Lyso-NA exhibited about a 50-fold increase in fluorescence at 610 nm and also with the increasing viscosity from 1.0 cP to 1410 cP, and about a 3.5-fold increase in fluorescence at 510 nm (excitation at 440 nm) together with the increasing ONOO-. These satisfactory response properties make it possible to use Lyso-NA to monitor changes in both viscosity and ONOO- inside the lysosome. To achieve its practical application, it was further demonstrated that Lyso-NA exhibits low cytotoxicity, and good cell permeability, and could be used to monitor lysosomal viscosity and ONOO- in living cells.

Specific and sensitive imaging of basal cysteine over homocysteine in living cells.

Biological thiols play important roles in maintaining appropriate redox status of organisms. Accepting the challenge to differentiate structurally similar cysteine (Cys) and homocysteine (Hcy), we have successfully developed a miniature synthetic turn-on fluorescent probe based on 6-(2-benzothiazolyl)-2-naphthalenol for Cys. This probe is able to specifically react with Cys to yield its naphthalenol derivative, accompanied by remarkable green fluorescence enhancement with a detection limit of 14.8 nM. Besides, this probe displays much greater selectivity for Cys over other biological thiols, including homocysteine (Hcy) and glutathione (GSH). Practically, good cell permeability and low cytotoxicity make it suitable for monitoring basal Cys in living cells.