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Introduction: This study aimed to evaluate the relationship between 2-h post-load minus fasting plasma glucose (2hPG-FPG) and 1-year clinical outcomes, such as death, stroke recurrence, and modified Rankin Scale (mRS) ≥2–3 among acute ischemic stroke (AIS) patients without diabetes mellitus (DM) history. Methods: 1,214 AIS patients without DM history, obtained from ACROSS-China, were divided into 4 quartiles, based on 2hPG-FPG measurements obtained 14 days post-admission. Four models were constructed using multivariate Cox and logistic regression analyses, based on the inclusion of age, gender, trial of ORG 10172 in acute stroke treatment, NIH Stroke Scale scores (model 1), plus 10 other clinical parameters (model 2), plus newly diagnosed DM (NDDM) post-admission (model 3), plus 2hPG and FPG (model 4). Associations found from those 4 models between 2hPG-FPG and 1-year clinical outcomes were confirmed via stratification, multiplicative interaction, sensitivity, and restricted cubic spline analyses. Results: The highest quartile of 2hPG-FPG, after adjusting for variables, such as stroke severity (model 2), was independently associated with death, stroke recurrence, and mRS ≥2–3 (odds ratio [OR] = 3.95, 2.96, 4.15, and 4.83, respectively, all p < 0.0001). Increased 2hPG-FPG remained independently associated with mRS ≥2–3 in models 3–4, as well as increased mRS ≥2 under stratification analyses among both non-NDDM and NDDM patients. Conclusion: 2hPG-FPG is a relatively specific indicator of poorer 1-year clinical prognoses among AIS patients, independent of NDDM, 2hPG, and FPG post-hospital admission. Therefore, the oral glucose tolerance test could be a useful approach for detecting a higher likelihood for developing poorer prognoses among patients without DM history.

To describe the information technology and artificial intelligence support in management experiences of the pediatric designated hospital in the wave of COVID-19 in Shanghai.: We retrospectively concluded the management experiences at the largest pediatric designated hospital from March 1The COVID-19 designated hospitals were built particularly for critical patients requiring high-level medical care, responded quickly and scientifically to prevent and control the epidemic situation. From March 1Information technology and artificial intelligence has provided significant supports in the management. The system optimizes the admission screening process, increases the communication inside and outside the ward, achieves early detection and diagnosis, timely isolates patients, and timely treatment of various types of children.

According to hard and soft acid base theory, a novel 3D butterfly shaped Eu4(OH)2 cluster-based metal organic framework with lewis basic triazole sites is successfully obtained and shows sensitive luminescence quenching responses to organic amines.

The aim of this study was to explore the potential mechanisms responsible for the different manifestations of bronchiectasis in patients with pulmonary non-tuberculous mycobacteria (pNTM) infection. We found that the necroptosis level increased significantly after NTM infection. Further, the 31 pNTM-infected patients were classified into two subtypes based on necroptosis-related genes (NRGs) by unsupervised cluster analysis. After that, we compared the differences in clinical parameters, immune cell infiltration, and gene expression between the two subtypes. We observed that the high-necroptosis subtype possessed higher CT scores for bronchiectasis extent (P = 0.008) and severity (P = 0.023). And, more neutrophil infiltration in the high-necroptosis subtype was demonstrated both by the CIBERSORT algorithm and by blood neutrophil count (P = 0.001). Next, 688 differentially expressed genes (DEGs) between two subtypes were identified. To explore the portion in DEGs that might contribute to bronchiectasis, we intersected the DEGs with two gene modules. These two gene modules were identified as the most associated with CT scores for bronchiectasis extent and severity by weighted gene co-expression network analysis (WGCNA). Ninety-three intersection genes were obtained. Finally, 7 hub genes including ACSL1, ANXA3, DYSF, HK3, SLC11A1, STX11, and TLR4 were further screened out by machine learning algorithms and protein-protein interaction network analysis. These results suggested that the differential levels of necroptosis in pNTM patients might lead to differential extent and severity of bronchiectasis on radiographic imaging. This process might be associated with neutrophil infiltration and the involvement of seven hub genes.

Abstract: Ischemia-reperfusion injury is a complex hemodynamic pathology that is a leading cause of death worldwide and occurs in many body organs. Numerous studies have shown that mitochon-dria play an important role in the occurrence mechanism of ischemia-reperfusion injury and that mi-tochondrial structural abnormalities and dysfunction lead to the disruption of the homeostasis of the whole mitochondria. At this time, mitochondria are not just sub-organelles to produce ATP but also important targets for regulating ischemia-reperfusion injury; therefore, drugs targeting mitochondria can serve as a new strategy to treat ischemia-reperfusion injury. Based on this view, in this review, we discuss potential therapeutic agents for both mitochondrial structural abnormalities and mito-chondrial dysfunction, highlighting the application and prospects of targeted mitochondrial drugs in the treatment of ischemia-reperfusion injury, and try to provide new ideas for the clinical treatment of the ischemia-reperfusion injury.

This study aimed to examine changes in electrolytes and acid-base status in primary and secondary hypokalaemic periodic paralysis (HypoPP), which will help early differential diagnosis of HypoPP. A total of 64 HypoPP patients were enrolled and relevant data from clinical records was collected. Overall, 64 patients (mean age 28.2±7.3 years) of which 58(91%) were males, with 39, 11 and 14 patients, respectively, diagnosed as primary HypoPP, thyrotoxic HypoPP, and other secondary HypoPPs at discharge, were assessed. Those with HypoPP secondary to conditions other than hyperthyroidism were more likely to develop acid-base imbalance (p

The startup process of pump as turbine (PAT) is actually unavoidable. In order to reveal the transient behavior of a small centrifugal pump reversing as a turbine during an atypical startup, transient experiments are carried out on PAT test rig in the case of two valve openings and four rotational speeds so as to obtain the evolution characteristic of the external performance parameters over time. Meanwhile, three dimensionless parameters are also employed to deeply reveal the transient characteristics. It is found that the shock phenomena in static pressure are prevalent at the outlet of PAT, and that it tends to lag and weaken with increasing stable rotational speed. All three dimensionless factors have maximum values at the initial stage of PAT startup, whereafter they demonstrate the different evolution characteristics.

The role of angiogenesis in health and disease have gained considerable momentum in recent years. Visualizing angiogenic patterns and associated events of surrounding vascular beds in response to therapeutic and laboratory-grade biomolecules have become a commonplace in regenerative medicine and the biosciences. To aid imaging investigations in angiogenesis, the two-photon excitation fluorescence microscopy (2PEF), or multiphoton fluorescence microscopy is increasingly utilized in scientific investigations. The 2PEF microscope confers several distinct imaging advantages over other fluorescence excitation microscopy techniques - for the observation of in-depth, three-dimensional vascularity in a variety of tissue formats, including fixed tissue specimens and in vivo vasculature in live specimens. Understanding morphological and subcellular changes that occur in cells and tissues during angiogenesis will provide insights to behavioral responses in diseased states, advance the engineering of physiologically-relevant tissue models and provide biochemical clues for the design of therapeutic strategies. We review the applicability and limitations of the 2PEF microscope on the biophysical and molecular-level signatures of angiogenesis in various tissue models. Imaging techniques and strategies for best practices in 2PEF microscopy will be reviewed.

Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is the second leading cause of death after COVID-19 pandemic. Here, we coupled multiple cross displacement amplification (MCDA) technique with CRISPR-Cas12a-based biosensing system to design a novel detection platform for tuberculosis diagnosis, termed MTB-MCDA-CRISPR. MTB-MCDA-CRISPR pre-amplified the specific sdaA gene of MTB by MCDA, and the MCDA results were then decoded by CRISPR-Cas12a-based detection, resulting in simple visual fluorescent signal readouts. A set of standard MCDA primers, an engineered CP1 primer, a quenched fluorescent ssDNA reporter, and a gRNA were designed targeting the sdaA gene of MTB. The optimal temperature for MCDA pre-amplification is 67°C. The whole experiment process can be completed within one hour, including sputum rapid genomic DNA extraction (15 minutes), MCDA reaction (40 minutes), and CRISPR-Cas12a-gRNA biosensing process (5 minutes). The limit of detection (LoD) of the MTB-MCDA-CRISPR assay is 40 fg per reaction. The MTB-MCDA-CRISPR assay does not cross reaction with non-tuberculosis mycobacterium (NTM) strains and other species, validating its specificity. The clinical performance of MTB-MCDA-CRISPR assay was higher than that of the sputum smear microscopy test and comparable to that of Xpert method. In summary, the MTB-MCDA-CRISPR assay is a promising and effective tool for tuberculosis infection diagnosis, surveillance and prevention, especially for point-of-care (POC) test and field deployment in source-limited regions.

Extreme climate events constitute a major risk to global food production. Among these, the extreme rainfall is often dismissed from historical analyses and future projections, whose impacts and mechanisms remain poorly understood. Here, we find that rice yield reductions due to extreme rainfall in China were comparable to those induced by extreme heat over the last two decades, reaching 7.6 ± 0.9% (one standard error) according to nationwide observations and 8.1 ± 1.1% according to the crop model incorporating the mechanisms revealed from manipulative experiments. Extreme rainfall reduces rice yield mainly by limiting nitrogen availability for tillering that lowers per-area effective panicles and by exerting physical disturbance on pollination that declines per-panicle filled grains. Considering these mechanisms, we projected ~8% additional yield reduction due to extreme rainfall under warmer climate by the end of the century. These findings demonstrate the critical importance to account for extreme rainfall in food security assessments, posing greater challenges to climate change adaptation.

With environmental protection becoming more and more important in recent years, the suitability of traditional regulation methods in rivers such as bank protection and river cutoff begins to be challenged. The regulation methods combined with ecology have become an important goal in natural rivers nowadays. In this research, a series of flume experiments were conducted to discuss the effect of bank erosion on vegetation roots between bare and vegetated banks.The experimental parameters of flow discharge, water depth, and channel slope are 0.014 , 9.5 cm, and 0.001, respectively. A kind of vegetation, Vigna radiate, is planted in cultivation boxes for 1 – 2 weeks and then moves into the channel as the vegetated banks. A laser scanner is set up on the flume channel to record the variation of initial and final topography. The results show that the erosion ratios of bare and vegetated banks are 40.24 % and 24.34 %, respectively. The root system of vegetation has a function of anti-erosion on river banks. In addition, we observe the exposed roots formed a protective layer along the flow direction on the bank over a period of time after beginning the experiment. The protective layer by roots helps the river bank resist water erosion and reduce the amount of erosion in the covered area.

As a common malignant tumor among women, ovarian cancer poses a serious threat to their health. This study demonstrates that long non-coding RNA NRSN2-AS1 is over-expressed in ovarian cancer tissues using patient sample and tissue microarrays. In addition, NRSN2-AS1 is shown to promote ovarian cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NRSN2-AS1 stabilizes protein tyrosine kinase 2 (PTK2) to activate the β-catenin pathway via repressing MG-53-mediated ubiquitinated degradation of PTK2, thereby facilitating ovarian cancer progression. Rescue experiments verify the function of the NRSN2-AS1/PTK2/β-catenin axis and the effects of MG53 on this axis in ovarian cancer cells. In conclusion, this study demonstrates the key role of the NRSN2-AS1/PTK2/β-catenin axis for the first time and explores its potential clinical applications in ovarian cancer.

To control the ongoing coronavirus disease-2019 (COVID-19) pandemic, CoronaVac (Sinovac), an inactivated vaccine, has been granted emergency use authorization by many countries. However, the underlying mechanisms of the inactivated COVID-19 vaccine-induced immune response remain unclear, and little is known about its features compared to (Severe acute respiratory syndrome coronavirus 2) SARS-CoV-2 infection. Here, we implemented single-cell RNA sequencing (scRNA-seq) to profile longitudinally collected PBMCs (peripheral blood mononuclear cells) in six individuals immunized with CoronaVac and compared these to the profiles of COVID-19 infected patients from a Single Cell Consortium. Both inactivated vaccines and SARS-CoV-2 infection altered the proportion of different immune cell types, caused B cell activation and differentiation, and induced the expression of genes associated with antibody production in the plasma. The inactivated vaccine and SARS-COV-2 infection also caused alterations in peripheral immune activity such as interferon response, inflammatory cytokine expression, innate immune cell apoptosis and migration, effector T cell exhaustion and cytotoxicity, however, the magnitude of change was greater in COVID-19 patients, especially those with severe disease, than in immunized individuals. Further analyses revealed a distinct peripheral immune cell phenotype associated with CoronaVac immunization (HLA class II upregulation and IL21R upregulation in naïve B cells) versus SARS-CoV-2 infection (HLA class II downregulation and IL21R downregulation in naïve B cells from severe disease individuals). There were also differences in the expression of important genes associated with proinflammatory cytokines and thrombosis. In conclusion, this study provides a single-cell atlas of the systemic immune response to CoronaVac immunization and revealed distinct immune responses between inactivated vaccines and SARS-CoV-2 infection.

Multiple sclerosis (MS) is a common chronic autoimmune disorder of the central nervous system that predominantly affects young adults. Mounting evidence indicates that deregulation of microRNAs (miRNAs) in cerebrospinal fluid (CSF) has been implicated in MS as a potential biomarker. However, comprehensive assessments of CSF miRNAs and their target genes are lacking. Here, aberrantly expressed CSF miRNAs of MS patients were obtained from numerous studies by manual search. With detailed information on these miRNAs, we utilized online databases to screen out immune-related target genes and further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. To identify MS high-risk pathways and pivotal genes, pathway crosstalk and pathway-gene networks were constructed, followed by the establishment of a protein-protein interaction (PPI) network. The datasets collected from ArrayExpress were used to assess pivotal genes. Overall, 21 MS-related CSF miRNAs were included in this study. Subsequently, we identified 469 MS-related genes and 14 high-risk pathways. In the pathway-gene network, 27 critical MS-related genes participated in at least half of the high-risk pathways, and these genes were used to identify pivotal genes. Finally, miR-150, miR-328, and miR-34c-5p were determined to be risk miRNAs via the regulation of the pivotal risk genes MAPK1, AKT1, and VEGFA. Among them, VEGFA was validated to be significantly decreased in the CSF cells of MS patients by transcriptomic datasets. These findings may provide potential biomarkers or therapeutic targets and help elucidate the molecular mechanisms underlying the pathogenesis of MS.

Human microtubule-associated protein Tau (τ) is abundant in the axons of neurons where it stabilizes microtubule bundles; abnormally hyperphosphorylated τ is a hallmark of Alzheimer's disease (AD) and related tauopathies. The hyperphosphorylation events can be recognized by phosphotyrosine-recognition domain SH2 (Src homology 2) to elicit downstream τ signaling in AD pathology. In this study, a comprehensive binary interaction map (CBIM) of all the 6 τ phosphotyrosine sites with 120 SH2 domains in the human genome was systematically created at structural level using computational analyses and binding assays, from which we were able to identify those of strong and moderate binding pairs of sites to domains. It is found that the SH2-recognition specificity of different τ phosphotyrosine sites has been evolutionally optimized to become roughly orthogonal to each other, and thus these site phosphorylations would regulate different but probably partially overlapped biological functions in τ signaling. Some SH2 groups such as SRC, RIN, PLCG, SOCS and SH2D were revealed to have effective binding potency as compared to others; they could be regarded as potential τ-associated proteins to transduce the downstream signaling. We further determined the systematic binding affinities of 6 τ-phosphopeptides to the 11 SH2 domains in SRC group, from which the FYN-τ

In order to reveal the influence of starting acceleration on starting process of a pump as turbine system, this paper carries out a numerical calculation of the three-dimensional viscous unsteady flow of pump as turbine circulating piping system under three starting acceleration conditions, and obtains the external and internal flow characteristics of each overflow component during the starting process, and also analyzes the energy loss of each component in the piping system in depth with the help of entropy production method and Q criterion method. The results show that during system start-up, the flow rate and outlet static pressure curves of the pump as turbine are hysteresis relative to the rotational speed, the head curve is similar to a linear rise during slow and medium speed start-up, while it shows a parabolic rise during rapid start-up, the entropy production and vorticity in the impeller domain of the pump as turbine are mainly distributed between the blades, and the distribution decreases during start-up. In addition, the pump similarity law does not apply to the performance prediction during the transient start of the pump as turbine.

Background: Migraine and multiple sclerosis (MS) are frequent clinical partners, but the mechanisms and treatments of the comorbidity of the two are still unclear. This study aimed to investigate the shared mechanisms and predict potential drugs of migraine and MS with a view to provide new clues and approaches for clinical management. Methods: So firstly, PRJEB40032 (migraine) from ENA and GSE21942 (MS) from GEO were analyzed for differentially expressed genes (DEGs). And then, gene clusters and hub genes for common DEGs were identified, as well as functional annotation and pathway enrichment analysis were performed for exploring the gene signatures and molecular mechanisms of the comorbidity. Further, hub genes and critical pathways were evaluated by the receiver operating characteristic curves (ROC) and previous studies. Finally, the drugs targeting hub genes and critical pathways were predicted, of which drugs targeting both hub genes and critical pathways were further screened. Results: 112 DEGs were identified to be related to the comorbidity of migraine and MS, of which 9 hub genes (IL1B,JUN, CXCL8, FOS, ICAM1, MMP9, EGR1,LCN2, MMP8) were of high diagnostic value for the comorbidity. Functional annotation and pathway enrichment analysis showed that inflammatory response regulation and reactive oxygen species metabolism played a major role, and multiple pathways such as IL17 signaling pathway were involved in the comorbidity. 5 hub genes and 17 critical pathways were further evaluated, with predicted 112 and 535 drugs, respectively, including aspirin (non-steroidal anti-inflammatory drugs (NSAIDs)), baclofen (gamma-aminobutyric acid (GABA) receptor agonist), and melatonin (antioxidant). Ultimately, 10 drugs targeting both hub genes and critical pathways were screened, mainly anti-inflammatory drugs, immunological agents and antineoplastic drugs, in which there were three IL-1β inhibitors with high potential research value for the treatments of the comorbidity. Conclusions: We found that inflammation and oxidative stress were closely related to the comorbidity of migraine and multiple sclerosis. We also predicted some drugs for drawing on from each other and the comorbidity, such as NSAIDs, GABA receptor agonists/analogs andIL-1β inhibitors.

Background Nearly half of bronchiectasis patients receiving bronchial artery embolization (BAE) still have recurrent hemoptysis, which may be life-threatening. Worse still, the underlying risk factors of recurrence remain unknown. Methods A retrospective cohort was conducted of patients with idiopathic bronchiectasis who received BAE from 2015 to 2019 at eight centers. Patients were followed up for at least 24 months post BAE. Based on the outcomes of recurrent hemoptysis and recurrent severe hemoptysis, a Cox regression model was used to identify risk factors for recurrence. Results A total of 588 individuals were included. The median follow-up period was 34.0 months (interquartile range: 24.3–53.3 months). The 1-month, 1-year, 2-year, and 5-year cumulative recurrent hemoptysis-free rates were 87.2%, 67.5%, 57.6%, and 49.4%, respectively. The following factors were relative to recurrent hemoptysis: 24-h sputum volume (hazard ratio [HR] = 1.99 [95% confidence interval [95% CI]: 1.25–3.15, p = 0.015]), isolation of Pseudomonas aeruginosa (HR = 1.50 [95% CI: 1.13–2.00, p = 0.003]), extensive bronchiectasis (HR = 2.00 [95% CI: 1.29–3.09, p = 0.002]), and aberrant bronchial arteries (AbBAs) (HR = 1.45 [95% CI: 1.09–1.93, p = 0.014]). The area under the receiver operating characteristic curve of the nomogram was 0.728 [95% CI: 0.688–0.769]. Conclusions Isolation of Pseudomonas aeruginosa is an important independent predictor of recurrent hemoptysis. The clearance of Pseudomonas aeruginosa might effectively reduce the hemoptysis recurrence rate.

Circular RNA (circRNA) is a type of non-coding RNA (ncRNA) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic nephropathy (DN) for their stability and enrichment in exosomes. However, the role of circRNAs from exosome of tubular epithelial cells in DN development has not been fully illustrated. In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. We found the exosome concentration was higher in HG stimulated HK-2 cells compared with controls. 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of HG group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis indicated that circRNA parental genes were associated with glucose metabolism, lipid metabolism and inflammatory process, which are important in DN development. Further analysis of circRNA/miRNA interaction indicated that some differentially expressed circRNAs interacted with one or more binding sites of miRNAs, which are associated with diabetes or DN. In conclusion, our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers and play a critical role in the progression of DN.

Background Hair follicle stem cells (HFSCs) are considered as a promising cell type in the stem cell transplantation treatment of neurological diseases because of their rich sources, easy access, and the same ectoderm source as the nervous system. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that shows neuroprotective function in ischemic stroke. Here we assessed the therapeutic effects of HFSCs on ischemic stroke injury and the synthetic effect of HGF along with HFSCs. Methods Rat HFSCs were intravenously transplanted into a middle cerebral artery ischemia/reperfusion (I/R) rat model. Neurological scoring and TTC staining were performed to assess the benefits of HFSC transplantation. Inflammatory cytokines, blood–brain barrier integrity and angiogenesis within penumbra were estimated by Western blot and immunohistochemistry. The differentiation of HFSCs was detected by immunofluorescence method 2 weeks after transplantation. Results HFSC transplantation could significantly inhibit the activation of microglia, improve the integrity of blood–brain barrier and reduce brain edema. Moreover, the number of surviving neurons and microvessels density in the penumbra were upregulated by HFSC transplantation, leading to better neurological score. The combination of HFSCs and HGF could significantly improve the therapeutic benefit. Conclusion Our results indicate for the first time that HGF modified HFSCs can reduce I/R injury and promote the neurological recovery by inhibiting inflammatory response, protecting blood–brain barrier and promoting angiogenesis.

BackgroundThe high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient.MethodsWe retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months.ResultsThe HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1–2, 20.3% based on SPSP 1–3, and 20.8% based on SPSPII 1–3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months.ConclusionThe HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis.Trial registrationClinicalTrial.gov, identifier: NCT04516577.

Bronchiectasis is a debilitating chronic suppurative airway disease that confers a substantial burden globally. Despite the notable prevalence, research on bronchiectasis in mainland China remains in its infancy. Nevertheless, there has been a significant leap in the quantity and quality of research, which has contributed to the ever-improving clinical practice. A nationwide collaborative platform has been established to foster multicentre studies, which will help increase the level of evidence further. Here, we summarise the status quo of clinical management and consider the research priorities for bronchiectasis that have been published previously. We also highlight the efforts of the Chinese medical communities to outline the core tasks that need to be addressed within the next decade.

Obesity is an important independent risk factor for cardiovascular diseases, remaining an important health concern worldwide. Evidence shows that saturated fatty acid-induced inflammation in cardiomyocytes contributes to obesity-related cardiomyopathy. Dapagliflozin (Dapa), a selective SGLT2 inhibitor, exerts a favorable preventive activity in heart failure. In this study, we investigated the protective effect of Dapa against cardiomyopathy caused by high fat diet-induced obesity in vitro and in vivo. Cultured rat cardiomyocyte H9c2 cells were pretreated with Dapa (1, 2.5 μM) for 1.5 h, followed by treatment with palmitic acid (PA, 200 μM) for 24 h. We showed that Dapa pretreatment concentration-dependently attenuated PA-induced cell hypertrophy, fibrosis and apoptosis. Transcriptome analysis revealed that inhibition of PA-activated MAPK/AP-1 pathway contributed to the protective effect of Dapa in H9c2 cells, and this was confirmed by anti-p-cJUN fluorescence staining assay. Using surface plasmon resonance analysis we found the direct binding of Dapa with NHE1. Gain and loss of function experiments further demonstrated the role of NHE1 in the protection of Dapa. In vivo experiments were conducted in mice fed a high fat diet for 5 months. The mice were administered Dapa (1 mg·kg

Chao Zhuo,1 Yijiang Huang,2 Wenyuan Liu,3 Jin-Fu Xu,4 Wei Yun Zhu,5 Gregory G Stone,6 Jean Li Yan,7 Naglaa Mohamed8 1State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Respiratory Clinical Medical Center, Hainan Cancer Hospital, Hainan, People’s Republic of China; 3Respiratory Department, Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 5Medical Department, Pfizer Investment Co. Ltd., Beijing, People’s Republic of China; 6Biopharmaceuticals Group, Pfizer Inc., Groton, CT, USA; 7Biopharmaceuticals Group, Pfizer Inc., Cambridge, MA, USA; 8Biopharmaceuticals Group, Pfizer Inc., New York, NY, USACorrespondence: Chao Zhuo, Email chaosheep@sina.comBackground: Ceftaroline fosamil has demonstrated superior clinical efficacy versus ceftriaxone for hospitalized adults with moderate-to-severe community-acquired pneumonia (CAP) in a Phase 3 trial in Asia and in a meta-analysis of three trials in Asia, North America, and Europe. Efficacy and safety outcomes for the subset of patients in China in the ASIA CAP trial were analyzed to determine if the same conclusions hold in the China subpopulation.Methods: Hospitalized adults with Pneumonia Outcomes Research Team risk class III–IV CAP were randomized (1:1) to receive either intravenous ceftaroline fosamil 600 mg every 12 h or ceftriaxone 2 g every 24 h for 5– 7 days. The primary efficacy variable was clinical response at test-of-cure (TOC) in the clinically evaluable (CE) population. Secondary endpoints included microbiological responses and safety.Results: Of 302 patients randomized in China, 205 were included in the CE population. Clinical cure rates at TOC were 80/105 (76.2%) for ceftaroline fosamil and 61/100 (61.0%) for ceftriaxone (difference 15.2%, 95% CI 2.5, 27.6), thereby meeting predefined non-inferiority and superiority criteria for the overall study. Subgroup analyses of the primary endpoint demonstrated consistency of favourable efficacy of ceftaroline fosamil across age groups, Pneumonia Outcomes Research Team risk classes and CURB-65 scores. Microbiological responses were presumed from clinical outcomes. Adverse events were consistent with the study treatments’ known safety profiles.Conclusion: The China subset results are consistent with the overall study population, despite the smaller sample size. Ceftaroline fosamil was both non-inferior and superior to ceftriaxone for empiric treatment of Chinese patients with moderate-to-severe CAP.Trial Registration: ClinicalTrials.gov identifier NCT01371838.Keywords: ceftriaxone, CURB-65, treatment outcomes, clinical trial

MicroRNAs (miRNAs) function as potential diagnostic biomarkers in various cancers. This study aimed to evaluate the roles of miR-205-5p in lung cancer progression and diagnosis.MiR-205-5p was detected by quantitative real-time PCR. The effect of miR-205-5p on cell proliferation and metastasis was estimated by MTT and flow cytometry. The expression of TP53INP1 and related genes was analyzed by immunoblotting. The diagnostic value of miR-205-5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity.The miR-205-5p was increased in lung cancer tissues. MiR-205-5p mimics were promoted but its inhibitor suppressed cell proliferation and metastasis compared with control treatment in vitro and in vivo. By regulating the 3' untranslated region, miR-205-5p could negatively regulate TP53INP1 expression, which further inhibited the expression of RB1 and P21, but increased that of cyclinD1. Moreover, the serum miR-205-5p levels of patients with lung cancer were significantly higher than those of normal controls, and they were correlated with patients' gender, drinking status, and clinical stage. The area under the ROC curve of serum miR-205-5p in the diagnosis of non-small-cell lung cancer was 0.8250, respectively. The finding supported its possession of high diagnostic efficiency for lung cancer.MiR-205-5p promoted lung cancer cell proliferation and metastasis by negatively regulating the novel target TP53INP1, which further affected the expression of P21, RB1, and cyclin D1. Serum miR-205-5p is a novel and valuable biomarker for lung cancer diagnosis.

Mycoplasma pneumoniae (MP), which is responsible for a majority of community-acquired pneumonia (CAP) in children, has been largely underestimated. Here, we coupled multiple cross displacement amplification (MCDA) technique with CRISPR-Cas12a-based biosensing system to design a novel detection platform termed MP-MCDA-CRISPR assay for MP infection diagnosis and clinical application. The MP-MCDA-CRISPR assay amplified the CARDS gene of MP by MCDA method, followed by trans-cleavage of the reporter molecular upon the formation of CRISPR-Cas12a-gRNA-target DNA complex, which was confirmed by the release of fluorescent signals. A set of standard MCDA primers, an engineered CP1 primer, a quenched fluorescent ssDNA reporter, and a gRNA were designed targeting the CARDS gene of MP. The optimal temperature for MCDA pre-amplification is 64°C, and the time for CRISPR-Cas12a-gRNA biosensing process is 5 min. The limit of detection (LoD) of the MP-MCDA-CRISPR assay is 50 fg per reaction without any cross-reaction with other non-MP pathogens. The MP-MCDA-CRISPR assay accurately identified the 50 real time-PCR positive clinical samples and 78 negative ones. Taken together, the MP-MCDA-CRISPR assay designed here is a promising diagnostic tool for point-of care (POC) testing of MP infection.

The current outbreak of monkeypox virus (MPXV) has become a public health emergency of international concern that highlights the need for rapid, sensitive MPXV diagnostic assays. Here, we combined isothermal multiple cross displacement amplification (MCDA) with nanoparticle-based lateral flow biosensor (LFB) to devise a diagnostic test for the diagnosis of MPXV infection (called MPXV-MCDA-LFB) and differentiation of West and Central African MPXV isolates. The MPXV-MCDA-LFB protocol conducts isothermal MCDA reaction for DNA templates followed by LFB detection of preamplification target sequences. Two MCDA primer sets were designed targeting the D41L and ATI genes of Central and West African MPXV isolates, respectively, and the optimal condition of two MCDA reactions was 64 ºC for 30 min. The two MCDA reactions were decoded by LFB, which was devised for detecting three targets, including two amplicons yielded from two MCDA reactions and a chromatography control. Thus, the MPXV-MCDA-LFB assay could be completed within 50 min including rapid template preparation (15 min), MCDA reaction (30 min) and reporting of result (5 min). The MPXV-MCDA-LFB method is very sensitive and can detect the target genes (D14L and ATI) with as low as five copies of plasmid template per reaction and 12.5 copies of pseudovirus in human blood samples. MPXV-MCDA-LFB assay does not cross-react with non-MPXV templates, validating its specificity. Therefore, the MPXV-MCDA-LFB assay developed here is a useful tool for rapid and reliable diagnosis of MPXV infection. This article is protected by copyright. All rights reserved.

Based on the transcriptome data of Isatis indigotica, a total of 110 putative glycosytransferases were identified. Through prokaryotic expression and enzymic activity assay in vitro, a novel lignan glycosyltransferase gene was screened out and named IiUGT349, which catalyzed lariciresinol into lariciresinol-4-O-β-D-glucoside and lariciresinol-4'-O-β-D-glucoside. Bioinformatics analysis suggested that IiUGT349 contained an open reading frame(ORF) of 1 401 bp encoding a protein of 467 amino acids. A protein analysis indicated that IiUGT349 have a predecited molecular weight of 52.77 kDa and pI of 5.96. Phylogenetic analysis showed that IiUGT349 belonging to UGT90 family shared low amino acid sequence identity with the reported lignan glycosyltransferases, which may represent a novel type of lignan glycosyltransferases. Quantitative real-time PCR(qRT-PCR) analysis showed that IiUGT349 was expressed in roots, stems, young leaves and leaves, with the highest expression level in stems. Further biochemical analysis showed that the optimal reaction time of IiUGT349 recombinant protein was 12 h and the optimal temperature was 45 ℃. Subcellular localization demonstrated that IiUGT349 was located in the cytoplasm and nucleus of plants. In this study, a new glucosyltransferase gene IiUGT349 from I. indigotica belonging to the UGT90 family was cloned, which laid a foundation to further investigate itsapos; function and elucidate the lignan glycosides biosynthesis pathway and plays an important role for great significance for the synthetic biology of active lignan glycosides.

Additional file 4: Table S1. Univariate Cox regression and multivariate Cox regression analysis of the factors associated with recurrent hemoptysis of patients with idiopathic bronchiectasis after BAE. Table S2. Univariate Cox regression and multivariate Cox regression analysis of the factors associated with recurrent severe hemoptysis of patients with idiopathic bronchiectasis after BAE.

Additional file 3: Figure S3. Specific origination, the recurrence rate, and the severe recurrence rate of abnormal AbBAs on CTA. (A) The proportion of certain abnormal AbBAs on CTA to all abnormal AbBAs on CTA. (B) Ratio of recurrent hemoptysis group to all patients per abnormal AbBAs on CTA. (C) Ratio of recurrent severe hemoptysis group to all patients per abnormal AbBAs on CTA.

The stochastic thermodynamics of systems with a few degrees of freedom has been studied extensively so far. We would like to extend the study to systems with more degrees of freedom and even further-continuous fields with infinite degrees of freedom. The simplest case for a continuous stochastic field is the Edwards-Wilkinson elastic manifold. It is an exactly solvable model of which the heat statistics in the relaxation process can be calculated analytically. The cumulants require a cutoff spacing to avoid ultra-violet divergence. The scaling behavior of the heat cumulants with time and the system size as well as the large deviation rate function of the heat statistics in the large size limit is obtained.

Additional file 1: Figure S1. The cumulative rates of patients with recurrent hemoptysis-free or recurrent severe hemoptysis-free with Pseudomonas aeruginosa, abnormal AbBAs on CTA, extensive bronchiectasis, and high 24-h sputum volume.

Additional file 2: Figure S2. Distribution characteristics of abnormal arteries in 588 patients. BAs, bronchial arteries; NBSAs, non-bronchial system arteries.

Nozzle flowmeter is widely used in industry. In this paper, in order to study the influence of different flow rates and inner wall temperatures on the thermal effect and flow field of the nozzle flowmeter, the fluid-solid coupling numerical calculation of the thermal effect and flow field of nozzle flowmeter is carried out under four different flow rates and five different inner wall temperatures. It is found that, with the increase of flow rate, the heat transfer effect of the nozzle flowmeter is weakened under different inner wall temperatures. The pressure distribution in the fluid domain, the dynamic stress, and fluid-induced vibration deformation generated by the fluid of the nozzle flowmeter are less affected by inner wall temperatures.

The effective detection of organic amines is particularly important for environmental protection and human health. Herein, according to hard and soft acid base theory, a novel three-dimensional (3D) butterfly shaped Eu

Background Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. Methods The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at − 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. Conclusions Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653