The MPS1 family of protein kinases.

MPS1 protein kinases are found widely, but not ubiquitously, in eukaryotes. This family of potentially dual-specific protein kinases is among several that regulate a number of steps of mitosis. The most widely conserved MPS1 kinase functions involve activities at the kinetochore in both the chromosome attachment and the spindle checkpoint. MPS1 kinases also function at centrosomes. Beyond mitosis, MPS1 kinases have been implicated in development, cytokinesis, and several different signaling pathways. Family members are identified by virtue of a conserved C-terminal kinase domain, though the N-terminal domain is quite divergent. The kinase domain of the human enzyme has been crystallized, revealing an unusual ATP-binding pocket. The activity, level, and subcellular localization of Mps1 family members are tightly regulated during cell-cycle progression. The mitotic functions of Mps1 kinases and their overexpression in some tumors have prompted the identification of Mps1 inhibitors and their active development as anticancer drugs.

Liebig's law of the minimum in the TGF-ß/SMAD pathway.

Cells use signaling pathways to sense and respond to their environments. The transforming growth factor-ß (TGF-ß) pathway produces context-specific responses. Here, we combined modeling and experimental analysis to study the dependence of the output of the TGF-ß pathway on the abundance of signaling molecules in the pathway. We showed that the TGF-ß pathway processes the variation of TGF-ß receptor abundance using Liebig's law of the minimum, meaning that the output-modifying factor is the signaling protein that is most limited, to determine signaling responses across cell types and in single cells. We found that the abundance of either the type I (TGFBR1) or type II (TGFBR2) TGF-ß receptor determined the responses of cancer cell lines, such that the receptor with relatively low abundance dictates the response. Furthermore, nuclear SMAD2 signaling correlated with the abundance of TGF-ß receptor in single cells depending on the relative expression levels of TGFBR1 and TGFBR2. A similar control principle could govern the heterogeneity of signaling responses in other signaling pathways.

Chandipura viral glycoprotein (CNV-G) promotes Gectosome generation and enables delivery of intracellular therapeutics.

Overexpression of vesicular stomatitis virus G protein (VSV-G) elevates the secretion of EVs known as gectosomes, which contain VSV-G. Such vesicles can be engineered to deliver therapeutic macromolecules. We investigated viral glycoproteins from several viruses for their potential in gectosome production and intracellular cargo delivery. Expression of the viral glycoprotein (viral glycoprotein from the Chandipura virus [CNV-G]) from the human neurotropic pathogen Chandipura virus in 293T cells significantly augments the production of CNV-G-containing gectosomes. In comparison with VSV-G gectosomes, CNV-G gectosomes exhibit heightened selectivity toward specific cell types, including primary cells and tumor cell lines. Consistent with the differential tropism between CNV-G and VSV-G gectosomes, cellular entry of CNV-G gectosome is independent of the Low-density lipoprotein receptor, which is essential for VSV-G entry, and shows varying sensitivity to pharmacological modulators. CNV-G gectosomes efficiently deliver diverse intracellular cargos for genomic modification or responses to stimuli in vitro and in the brain of mice in vivo utilizing a split GFP and chemical-induced dimerization system. Pharmacokinetics and biodistribution analyses support CNV-G gectosomes as a versatile platform for delivering macromolecular therapeutics intracellularly.

Tunable green syngas generation from CO2 and H2O with sunlight as the only energy input.

The carbon-neutral synthesis of syngas from CO2 and H2O powered by solar energy holds grand promise for solving critical issues such as global warming and the energy crisis. Here we report photochemical reduction of CO2 with H2O into syngas using core/shell Au@Cr2O3 dual cocatalyst-decorated multistacked InGaN/GaN nanowires (NWs) with sunlight as the only energy input. First-principle density functional theory calculations revealed that Au and Cr2O3 are synergetic in deforming the linear CO2 molecule to a bent state with an O-C-O angle of 116.5°, thus significantly reducing the energy barrier of CO2RR compared with that over a single component of Au or Cr2O3. Hydrogen evolution reaction was promoted by the same cocatalyst simultaneously. By combining the cooperative catalytic properties of Au@Cr2O3 with the distinguished optoelectronic virtues of the multistacked InGaN NW semiconductor, the developed photocatalyst demonstrated high syngas activity of 1.08 mol/gcat/h with widely tunable H2/CO ratios between 1.6 and 9.2 under concentrated solar light illumination. Nearly stoichiometric oxygen was evolved from water splitting at a rate of 0.57 mol/gcat/h, and isotopic testing confirmed that syngas originated from CO2RR. The solar-to-syngas energy efficiency approached 0.89% during overall CO2 reduction coupled with water splitting. The work paves a way for carbon-neutral synthesis of syngas with the sole inputs of CO2, H2O, and solar light.

Multiomic Analysis Reveals Disruption of Cholesterol Homeostasis by Cannabidiol in Human Cell Lines.

The nonpsychoactive cannabinoid, cannabidiol (CBD), is Food and Dug Administration approved for treatment of two drug-resistant epileptic disorders and is seeing increased use among the general public, yet the mechanisms that underlie its therapeutic effects and side-effect profiles remain unclear. Here, we report a systems-level analysis of CBD action in human cell lines using temporal multiomic profiling. FRET-based biosensor screening revealed that CBD elicits a sharp rise in cytosolic calcium, and activation of AMP-activated protein kinase in human keratinocyte and neuroblastoma cell lines. CBD treatment leads to alterations in the abundance of metabolites, mRNA transcripts, and proteins associated with activation of cholesterol biosynthesis, transport, and storage. We found that CBD rapidly incorporates into cellular membranes, alters cholesterol accessibility, and disrupts cholesterol-dependent membrane properties. Sustained treatment with high concentrations of CBD induces apoptosis in a dose-dependent manner. CBD-induced apoptosis is rescued by inhibition of cholesterol synthesis and potentiated by compounds that disrupt cholesterol trafficking and storage. Our data point to a pharmacological interaction of CBD with cholesterol homeostasis pathways, with potential implications in its therapeutic use.

Research on a Fault Diagnosis Method for Crankshafts Based on Improved Multi-Scale Permutation Entropy.

As the crucial part of a transmission assembly, the monitoring of the status of the crankshaft is essential for the normal working of a reciprocating machinery system. In consideration of the interaction between crankshaft system components, the fault vibration feature is typically non-stationary and nonlinear, and the single-scale feature extraction method cannot adequately assess the fault features, therefore a novel impact feature extraction method based on genetic algorithms to optimize multi-scale permutation entropy is proposed. Compared with other traditional feature extraction methods, the proposed method illustrates good robustness and high adaptability in the signal processing of crankshaft vibrations. Firstly, the improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) method is developed on the signal to obtain several intrinsic mode function (IMF) components, and the IMF components with a large kurtosis are selected for array reorganization. Then, the parameters of multi-scale permutation entropy (MPE) are optimized based on genetic algorithm (GA), the multi-scale permutation entropy is calculated and the feature vector set is constructed. The feature vector set is input into the support vector machine (SVM) and optimized by a particle swarm optimization (PSO) model for training and final pattern recognition, where the Variational Mode Decomposition(VMD)-GA-MPE with a PSO-SVM recognition model and the ICEEMDAN-MPE with PSO-SVM recognition model without GA optimization are constructed for a comparison with the proposed method. The research result illustrates that the proposed method, which inputs the genetic algorithm optimized multi-scale permutation entropy extracted from the ICEEMDAN decomposition into the PSO-SVM, performs well in impact feature extraction and the pattern recognition of crankshaft vibrations.

Antler-derived microRNA PC-5p-1090 inhibits HCC cell proliferation, migration, and invasion by targeting MARCKS, SMARCAD1, and SOX9.

The capability of microRNAs (miRNAs) to regulate gene expression across species has opened new avenues for miRNA-based therapeutics. Here, we investigated the potential of PC-5p-1090 (miR-PC-1090), a miRNA found in deer antlers, to control the malignant phenotypes of hepatocellular carcinoma (HCC) cells. Using Cell Counting Kit-8 and transwell assays, we found that heterologous expression of miR-PC-1090 inhibited HCC cell proliferation, migration, and invasion. Bioinformatics analysis indicated that predicted miR-PC-1090 targets, including MARCKS, SMARCAD1, and SOX9, were significantly elevated in HCC tissues, and their high expressions were associated with poor overall survival of HCC patients. Moreover, mechanistic investigations revealed that miR-PC-1090 promoted the degradation of MARCKS and SMARCAD1 mRNAs and hindered the translation of SOX9 mRNA by recognizing their 3' untranslated regions. Subsequent loss-of-function and rescue experiments confirmed the involvement of MARCKS, SMARCAD1, and SOX9 in miR-PC-1090-suppressed HCC cell proliferation, migration, and invasion. Notably, MARCKS knockdown induced the downregulation of phosphorylated MARCKS and a corresponding upregulation of phosphorylated AKT in HCC. Conversely, miR-PC-1090 repressed MARCKS phosphorylation and effectively circumvented the activation of the PI3K/AKT pathway. Furthermore, miR-PC-1090 regulates the Wnt/ß-catenin pathway through SMARCAD1- and SOX9-mediated reduction of ß-catenin expression. Overall, our results illustrate the tumor-suppressive activity and molecular mechanism of antler-derived miR-PC-1090 in HCC cells, indicating its potential as a multiple-target agent for HCC treatment.

Comparison of genome-wide DNA methylation patterns between antler precartilage and cartilage.

Deer antlers are the only mammalian organs that can fully regenerate after being lost and provide a valuable model for cartilage development. As one of the best-studied epigenetic mechanisms, DNA methylation is known to engage in organ and tissue development. This study aimed to investigate the role of DNA methylation in antler chondrogenesis by comparing whole-genome DNA methylation between precartilage and cartilage. Quantitative reverse transcription PCR (RT-qPCR) showed significant differences in the expression levels of DNA methyltransferase genes (DNMT1, DNMT3A, and DNMT3B) between precartilage and cartilage. Subsequently, we obtained DNA methylation profiles of antler precartilage and cartilage tissues by whole-genome bisulfite sequencing. Although sequencing data indicated that overall methylation levels at CpG and non-CpG sites were similar between precartilage and cartilage, 140,784 differentially methylated regions (DMRs, P < 0.05) and 3,941 DMR-related genes were identified. Gene ontology (GO) analysis of DMR-related genes demonstrated some significantly enriched GO terms (P < 0.05) related to chondrogenesis, including insulin receptor binding, collage trimer, integrin binding, and extracellular matrix structural constituent. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DMR-related genes uncovered that the PI3K/AKT, cortisol synthesis and secretion, glycosaminoglycan biosynthesis-keratan sulfate, Hippo, and NF-κB signaling pathways might play a pivotal role in the transition of precartilage to cartilage. Moreover, we found that 25 DMR-related genes, including CD44, IGF1, ITGAV, ITGB1, RUNX1, COL2A1, COMP, and TAGLN, were most likely involved in antler chondrogenesis. In conclusion, this study revealed the genome-wide DNA methylation patterns of antler precartilage and cartilage, which may contribute to understanding the epigenetic regulation of antler chondrogenesis.

Maize miR167-ARF3/30-polyamine oxidase 1 module-regulated H2O2 production confers resistance to maize chlorotic mottle virus.

Maize chlorotic mottle virus (MCMV) is the key pathogen causing maize lethal necrosis (MLN). Due to the sharply increased incidence of MLN in many countries, there is an urgent need to identify resistant lines and uncover the underlying resistance mechanism. Here, we showed that the abundance of maize (Zea mays) microR167 (Zma-miR167) positively modulates the degree of resistance to MCMV. Zma-miR167 directly targets Auxin Response Factor3 (ZmARF3) and ZmARF30, both of which negatively regulate resistance to MCMV. RNA-sequencing coupled with gene expression assays revealed that both ZmARF3 and ZmARF30 directly bind the promoter of Polyamine Oxidase 1 (ZmPAO1) and activate its expression. Knockdown or inhibition of enzymatic activity of ZmPAO1 suppressed MCMV infection. Nevertheless, MCMV-encoded p31 protein directly targets ZmPAO1 and enhances the enzyme activity to counteract Zma-miR167-mediated defense to some degree. We uncovered a role of the Zma-miR167-ZmARF3/30 module for restricting MCMV infection by regulating ZmPAO1 expression, while MCMV employs p31 to counteract this defense.

MicroRNA PC-3p-2869 Regulates Antler Growth and Inhibits Proliferation and Migration of Human Osteosarcoma and Chondrosarcoma Cells by Targeting CDK8, EEF1A1, and NTN1.

MicroRNAs (miRNAs) play a crucial role in maintaining the balance between the rapid growth and suppression of tumorigenesis during antler regeneration. This study investigated the role of a novel miRNA, PC-3p-2869 (miR-PC-2869), in antler growth and its therapeutic potential in human osteosarcoma and chondrosarcoma. Stem-loop RT-qPCR showed that miR-PC-2869 was expressed extensively in diverse layers of antler tissues. Overexpression of miR-PC-2869 suppressed the proliferation and migration of antler cartilage cells. Similarly, heterologous expression of miR-PC-2869 reduced the proliferation, colony formation, and migration of osteosarcoma cell line MG63 and U2OS and chondrosarcoma cell line SW1353. Moreover, 18 functional target genes of miR-PC-2869 in humans were identified based on the screening of the reporter library. Among them, 15 target genes, including CDK8, EEF1A1, and NTN1, possess conserved miR-PC-2869-binding sites between humans and red deer (Cervus elaphus). In line with this, miR-PC-2869 overexpression decreased the expression levels of CDK8, EEF1A1, and NTN1 in MG63, SW1353, and antler cartilage cells. As expected, the knockdown of CDK8, EEF1A1, or NTN1 inhibited the proliferation and migration of MG63, SW1353, and antler cartilage cells, demonstrating similar suppressive effects as miR-PC-2869 overexpression. Furthermore, we observed that CDK8, EEF1A1, and NTN1 mediated the regulation of c-myc and cyclin D1 by miR-PC-2869 in MG63, SW1353, and antler cartilage cells. Overall, our work uncovered the cellular functions and underlying molecular mechanism of antler-derived miR-PC-2869, highlighting its potential as a therapeutic candidate for bone cancer.

Effect of covalent photoconjugation of affibodies to epidermal growth factor receptor (EGFR) on cellular quiescence.

Cellular quiescence is a reversible state of cell cycle arrest whereby cells are temporarily maintained in the nondividing phase. Inducing quiescence in cancer cells by targeting growth receptors is a treatment strategy to slow cell growth in certain aggressive tumors, which in turn increases the efficacy of treatments such as surgery or systemic chemotherapy. However, ligand interactions with cell receptors induce receptor-mediated endocytosis followed by proteolytic degradation, which limits the duration of cellular quiescence. Here, we report the effects of targeted covalent affibody photoconjugation to epidermal growth factor receptors (EGFR) on EGFR-positive MDA-MB-468 breast cancer cells. First, covalently conjugating affibodies to cells increased doubling time two-fold and reduced ERK activity by 30% as compared to cells treated with an FDA-approved anti-EGFR antibody Cetuximab, which binds to EGFR noncovalently. The distribution of cells in each phase of the cell cycle was determined, and cells conjugated with the affibody demonstrated an accumulation in the G1 phase, indicative of G1 cell cycle arrest. Finally, the proliferative capacity of the cells was determined by the incorporation of 5-ethynyl-2-deoxyuridine and Ki67 Elisa assay, which showed that the percentage of proliferative cells with photoconjugated affibody was half of that found for the untreated control.

Tomato chlorosis virus-encoded p22 suppresses auxin signalling to promote infection via interference with SKP1-Cullin-F-boxTIR1 complex assembly.

Phytohormone auxin plays a fundamental role in plant growth and defense against pathogens. However, how auxin signalling is regulated during virus infection in plants remains largely unknown. Auxin/indole-3-acetic acid (Aux/IAA) is the repressor of auxin signalling and can be recognized by an F-box protein transport inhibitor response 1 (TIR1). Ubiquitination and degradation of Aux/IAA by SKP1-Cullin-F-boxTIR1 (SCFTIR1 ) complex can trigger auxin signalling. Here, with an emerging important plant virus worldwide, we showed that tomato chlorosis virus (ToCV) infection or stable transgenic overexpression of its p22 protein does not alter auxin accumulation level but significantly decreases the expression of auxin signalling-responsive genes, suggesting that p22 can attenuate host auxin signalling. Further, p22 could bind the C-terminal of SKP1.1 and compete with TIR1 to interfere with the SCFTIR1 complex assembly, leading to a suppression of Aux/IAA degradation. Silencing and over-expression assays suggested that both NbSKP1.1 and NbTIR1 suppress ToCV accumulation and disease symptoms. Altogether, ToCV p22 disrupts the auxin signalling through destabilizing SCFTIR1 by interacting with the C-terminal of NbSKP1.1 to promote ToCV infection. Our findings uncovered a previously unknown molecular mechanism employed by a plant virus to manipulate SCF complex-mediated ubiquitin pathway and to reprogram auxin signalling for efficient infection.

Bronchial angiofibroma in tuberous sclerosis complex: A case report and literature review.

Cutaneous angiofibroma is part of the classic triad of tuberous sclerosis complex (TSC). Angiofibroma is rarely reported to affect the mucous membranes of the trachea and bronchus. Tracheobronchial angiofibroma is also a hamartomatous manifestation of TSC. Considering the paucity of literature describing tracheal lesions in TSC, more case reports are needed to guide treatment planning. This case report adds to the existing clinical literature and provides a reference for clinical diagnosis.

Structural basis of the phosphorylation-independent recognition of cyclin D1 by the SCFFBXO31 ubiquitin ligase.

Ubiquitin-dependent proteolysis of cyclin D1 is associated with normal and tumor cell proliferation and survival. The SCFFBXO31 (Skp1-Cul1-Rbx1-FBXO31) ubiquitin ligase complex mediates genotoxic stress-induced cyclin D1 degradation. Previous studies have suggested that cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm. Here we present the crystal structures of the Skp1-FBXO31 complex alone and bound to a phosphorylated cyclin D1 C-terminal peptide. FBXO31 possesses a unique substrate-binding domain consisting of two ß-barrel motifs, whereas cyclin D1 binds to FBXO31 by tucking its free C-terminal carboxylate tail into an open cavity of the C-terminal FBXO31 ß-barrel. Biophysical and functional studies demonstrate that SCFFBXO31 is capable of recruiting and ubiquitinating cyclin D1 in a phosphorylation-independent manner. Our findings provide a conceptual framework for understanding the substrate specificity of the F-box protein FBXO31 and the mechanism of FBXO31-regulated cyclin D1 protein turnover.

The plant triterpenoid celastrol blocks PINK1-dependent mitophagy by disrupting PINK1's association with the mitochondrial protein TOM20.

A critical function of the PTEN-induced kinase 1 (PINK1)-Parkin pathway is to mediate the clearing of unhealthy or damaged mitochondria via mitophagy. Loss of either PINK1 or Parkin protein expression is associated with Parkinson's disease. Here, using a high-throughput screening approach along with recombinant protein expression and kinase, immunoblotting, and immunofluorescence live-cell imaging assays, we report that celastrol, a pentacyclic triterpenoid isolated from extracts of the medicinal plant Tripterygium wilfordii, blocks recruitment pof Parkin to mitochondria, preventing mitophagy in response to mitochondrial depolarization induced by carbonyl cyanide m-chlorophenylhydrazone or to gamitrinib-induced inhibition of mitochondrial heat shock protein 90 (HSP90). Celastrol's effect on mitophagy was independent of its known role in microtubule disruption. Instead, we show that celastrol suppresses Parkin recruitment by inactivating PINK1 and preventing it from phosphorylating Parkin and also ubiquitin. We also observed that PINK1 directly and strongly associates with TOM20, a component of the translocase of outer mitochondrial membrane (TOM) machinery and relatively weak binding to another TOM subunit, TOM70. Moreover, celastrol disrupted binding between PINK1 and TOM20 both in vitro and in vivo but did not affect binding between TOM20 and TOM70. Using native gel analysis, we also show that celastrol disrupts PINK1 complex formation upon mitochondrial depolarization and sequesters PINK1 to high-molecular-weight protein aggregates. These results reveal that celastrol regulates the mitochondrial quality control pathway by interfering with PINK1-TOM20 binding.

Enzymes Photo-Cross-Linked to Live Cell Receptors Retain Activity and EGFR Inhibition after Both Internalization and Recycling.

In this work, we show that a prodrug enzyme covalently photoconjugated to live cell receptors survives endosomal proteolysis and retains its catalytic activity over multiple days. Here, a fusion protein was designed with both an antiepidermal growth factor receptor (EGFR) affibody and the prodrug enzyme cytosine deaminase, which can convert prodrug 5-fluorocytosine to the anticancer drug 5-fluorouracil. A benzophenone group was added at a site-specific mutation within the affibody, and the fusion protein was selectively photoconjugated to EGFR receptors expressed on membranes of MDA-MB-468 breast cancer cells. The fusion protein was next labeled with two dyes for tracking uptake: AlexaFluor 488 and pH-sensitive pHAb. Flow cytometry showed that fusion proteins photo-cross-linked to EGFR first underwent receptor-mediated endocytosis within 12 h, followed by recycling back to the cell membrane within 24 h. These findings were also confirmed by confocal microscopy. The unique cross-linking of the affibody-enzyme fusion proteins was utilized for two anticancer treatments. First, the covalent linking of the protein to the EGFR led to inhibition of ERK signaling over a two-day period, whereas conventional antibody therapy only led to 6 h of inhibition. Second, when the affibody-CodA fusion proteins were photo-cross-linked to EGFR overexpressed on MDA-MB-468 breast cancer cells, prodrug conversion was found even 48 h postincubation without any apparent decrease in cell killing, while without photo-cross-linking no cell killing was observed 8 h postincubation. These studies show that affinity-mediated covalent conjugation of the affibody-enzymes to cell receptors allows for prolonged expression on membranes and retained enzymatic activity without genetic engineering.

Disease burden and prognostic factors for clinical failure in elderly community acquired pneumonia patients.

BACKGROUND: The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP). METHODS: 3011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis. RESULTS: The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH < 7.3, PaO2/FiO2 < 200 mmHg, sodium < 130 mmol/L, healthcare-associated pneumonia, white blood cells > 10,000/mm3, pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors. CONCLUSIONS: Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP. TRIAL REGISTRATION: A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb.

Genome-wide dose-dependent inhibition of histone deacetylases studies reveal their roles in enhancer remodeling and suppression of oncogenic super-enhancers.

Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line. Exposure to low nanomolar largazole concentrations (

Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network.

Although broad knowledge of influenza viral pneumonia has been established, the significance of non-influenza respiratory viruses in community-acquired pneumonia (CAP) and their impact on clinical outcomes remains unclear, especially in the non-immunocompromised adult population.Hospitalised immunocompetent patients with CAP were prospectively recruited from 34 hospitals in mainland China. Respiratory viruses were detected by molecular methods. Comparisons were conducted between influenza and non-influenza viral infection groups.In total, 915 out of 2336 adult patients with viral infection were enrolled in the analysis, with influenza virus (28.4%) the most frequently detected virus, followed by respiratory syncytial virus (3.6%), adenovirus (3.3%), human coronavirus (3.0%), parainfluenza virus (2.2%), human rhinovirus (1.8%) and human metapneumovirus (1.5%). Non-influenza viral infections accounted for 27.4% of viral pneumonia. Consolidation was more frequently observed in patients with adenovirus infection. The occurrence of complications such as sepsis (40.1% versus 39.6%; p=0.890) and hypoxaemia (40.1% versus 37.2%; p=0.449) during hospitalisation in the influenza viral infection group did not differ from that of the non-influenza viral infection group. Compared with influenza virus infection, the multivariable adjusted odds ratios of CURB-65 (confusion, urea >7 mmol·L-1, respiratory rate ≥30 breaths·min-1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) ≥3, arterial oxygen tension/inspiratory oxygen fraction <200 mmHg, and occurrence of sepsis and hypoxaemia for non-influenza respiratory virus infection were 0.87 (95% CI 0.26-2.84), 0.72 (95% CI 0.26-1.98), 1.00 (95% CI 0.63-1.58) and 1.05 (95% CI 0.66-1.65), respectively. The hazard ratio of 90-day mortality was 0.51 (95% CI 0.13-1.91).The high incidence of complications in non-influenza viral pneumonia and similar impact of non-influenza respiratory viruses relative to influenza virus on disease severity and outcomes suggest more attention should be given to CAP caused by non-influenza respiratory viruses.

A successful bronchial thermoplasty procedure in a "very severe" asthma patient with rare complications: a case report.

Introduction: Bronchial thermoplasty (BT) is a unique bronchoscopic treatment for severe asthma that utilizes radiofrequency ablation to reduce smooth muscle in the bronchial walls. Current studies mainly focused on uncontrolled severe asthma with a forced expiratory volume in 1 second (FEV1) above 60% and associated complications, no human studies have performed on "very severe" asthma as well as its complications. Case study: We present a 60-year-old male with more than 15 years history of very severe asthma, who underwent BT. His FEV1 was only 20.4% predicted, which would have excluded him from all prior clinical trials of BT. The first BT procedure occurred without an issue. After the second BT procedure, he experienced severe dyspnea due to an infection with a non-flu respiratory virus. This illness was complicated by the formation of a pulmonary cyst. During recovering from the third procedure, he developed stomach stones. This is mainly related with taking large amounts of hawthorn previously, also cannot exclude the role of thermal energy injury on gastrointestinal nerve function. Results: Despite these unexpected complications, his quality of life greatly improved after BT, yet his lung function did not improve. Conclusion: This case is the first to describe BT procedures in patient with this level of lung function compromise, although accompanied with rare complications; our report indicates BT may be an opportunity and choice for the "very severe" asthma patients.