Zinc oxide nanoparticles have biphasic roles on Mycobacterium-induced inflammation by activating autophagy and ferroptosis mechanisms in infected macrophages.

The ability of zinc oxide nanoparticles (ZnONPs) to induce bacteriostasis in Mycobacterium tuberculosis (M. tb) and their roles in regulating the pathogenic activities of immune cells have been reported previously, but the specific mechanisms underlying these regulatory functions remain unclear. This work aimed to determine how ZnONPs play the antibacterial role against M. tb. In vitro activity assays were employed to determine the minimum inhibitory concentrations (MICs) of the ZnONPs against various strains of M. tb (BCG, H37Rv, and clinical susceptible MDR and XDR strains). The ZnONPs had MICs of 0.5-2 mg/L against all tested isolates. In addition, changes in the expression levels of autophagy and ferroptosis-related markers in BCG-infected macrophages exposed to ZnONPs were measured. BCG-infected mice that were administered ZnONPs were used to determine the ZnONPs functions in vivo. ZnONPs decreased the number of bacteria engulfed by the macrophages in a dose-dependent manner, while different doses of ZnONPs also affected inflammation in different directions. Although ZnONPs enhanced the BCG-induced autophagy of macrophages in a dose-dependent manner, only low doses of ZnONPs activated autophagy mechanisms by increasing the levels of pro-inflammatory factors. The ZnONPs also enhanced BCG-induced ferroptosis of macrophages at high doses. Co-administration of a ferroptosis inhibitor with the ZnONPs improved the anti-Mycobacterium activity of ZnONPs in an in vivo mouse model and alleviated acute lung injury caused by ZnONPs. Based on the above findings, we conclude that ZnONPs may act as potential antibacterial agents in future animal and clinical studies.

Prognostic Assessment of COVID-19 in the Intensive Care Unit by Machine Learning Methods: Model Development and Validation.

BACKGROUND: Patients with COVID-19 in the intensive care unit (ICU) have a high mortality rate, and methods to assess patients' prognosis early and administer precise treatment are of great significance. OBJECTIVE: The aim of this study was to use machine learning to construct a model for the analysis of risk factors and prediction of mortality among ICU patients with COVID-19. METHODS: In this study, 123 patients with COVID-19 in the ICU of Vulcan Hill Hospital were retrospectively selected from the database, and the data were randomly divided into a training data set (n=98) and test data set (n=25) with a 4:1 ratio. Significance tests, correlation analysis, and factor analysis were used to screen 100 potential risk factors individually. Conventional logistic regression methods and four machine learning algorithms were used to construct the risk prediction model for the prognosis of patients with COVID-19 in the ICU. The performance of these machine learning models was measured by the area under the receiver operating characteristic curve (AUC). Interpretation and evaluation of the risk prediction model were performed using calibration curves, SHapley Additive exPlanations (SHAP), Local Interpretable Model-Agnostic Explanations (LIME), etc, to ensure its stability and reliability. The outcome was based on the ICU deaths recorded from the database. RESULTS: Layer-by-layer screening of 100 potential risk factors finally revealed 8 important risk factors that were included in the risk prediction model: lymphocyte percentage, prothrombin time, lactate dehydrogenase, total bilirubin, eosinophil percentage, creatinine, neutrophil percentage, and albumin level. Finally, an eXtreme Gradient Boosting (XGBoost) model established with the 8 important risk factors showed the best recognition ability in the training set of 5-fold cross validation (AUC=0.86) and the verification queue (AUC=0.92). The calibration curve showed that the risk predicted by the model was in good agreement with the actual risk. In addition, using the SHAP and LIME algorithms, feature interpretation and sample prediction interpretation algorithms of the XGBoost black box model were implemented. Additionally, the model was translated into a web-based risk calculator that is freely available for public usage. CONCLUSIONS: The 8-factor XGBoost model predicts risk of death in ICU patients with COVID-19 well; it initially demonstrates stability and can be used effectively to predict COVID-19 prognosis in ICU patients.

Oxygen and pH responsive theragnostic liposomes for early-stage diagnosis and photothermal therapy of solid tumours.

The development of cancer treatment is of great importance, especially in the early stage. In this work, we synthesized a pH-sensitive amphiphilic ruthenium complex containing two alkyl chains and two PEG chains, which was utilized as an oxygen sensitive fluorescent probe for co-assembly with lipids to harvest a liposomal delivery system (RuPC) for the encapsulation of a photothermal agent indocyanine green (ICG). The resultant ICG encapsulated liposome (RuPC@ICG) enabled the delivery of ICG into cells via a membrane fusion pathway, by which the ruthenium complex was localized in the cell membrane for better detection of the extracellular oxygen concentration. Such characteristics allowed ratiometric imaging to distinguish the tumour location from normal tissues just 3 days after cancer cells were implanted, by monitoring the hypoxia condition and tracing the metabolism. Moreover, the pH sensitivity of the liposomes favoured cell uptake, and improved the anti-tumour efficiency of the formulation in vivo under NIR irradiation. Assuming liposomal systems have fewer safety issues, our work not only provides a facile method for the construction of a theragnostic system by combining phototherapy with photoluminescence imaging, but hopefully paves the way for clinical translation from bench to bedside.

Effect of tocilizumab plus corticosteroid on clinical outcome in patients hospitalized with severe fever with thrombocytopenia syndrome: A randomized clinical trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.

Pyk2 regulates sepsis-induced lung injury via ferroptosis.

Objectives: The onset of sepsis represents a hyper-inflammatory condition that can lead to organ failure and mortality. Recent findings suggest a potential beneficial effect of protein tyrosine kinase Pyk2 inhibitor on sepsis in a mouse model. In this study, we investigated the regulatory role of Pyk2 inhibitor in ferroptosis and sepsis-associated acute lung injury (ALI). Materials and Methods: A Pyk2 inhibitor or a ferroptosis regulator were injected into mice sustaining sepsis-induced ALI and the effects on lung injury and pro-inflammatory response were evaluated. Clinically, Pyk2 expression was determined in serum samples of patients with sepsis. Further, the association between serum Pyk2 levels and clinical features was determined. Results: Experimental mouse models revealed that treatment with Pyk2 inhibitor TAE226 can significantly alleviate lung injury, downregulate pro-inflammatory responses and decrease markers of ferroptosis, which were induced by LPS. Both upregulation and downregulation of ferroptosis can lead to the loss of TAE226 function, indicating that Pyk2 promotes inflammation via ferroptosis induction. Analysis of clinical samples revealed that the serum Pyk2 levels were significantly increased in patients with sepsis. The serum Pyk2 levels were associated with APACHE2 scores and 30-day mortality. Further, we found a negative correlation between serum Pyk2 and Fe3+ levels, which was consistent with the mechanism identified in the mouse model. Conclusion: Pyk2 inhibitor of ferroptosis is a promising therapeutic candidate against sepsis-related ALI.

Constructing multifunctional Cu Single-Atom nanozyme for synergistic nanocatalytic Therapy-Mediated Multidrug-Resistant bacteria infected wound healing.

Developing an effective strategy to combat multi-drug-resistant (MDR) bacteria and promote wound healing without overuse of antibiotics remains an important and challenging goal. Herein, we established a synergistic reactive oxygen species (ROS) and reactive nitrogen species (RNS)-mediated nanocatalytic therapy, which was consisted of a multifunctional Cu single-atom nanozyme loaded with the l-arginine (l-Arg@Cu-SAzymes) and a low level of hydrogen peroxide (H2O2) as a trigger. l-Arg@Cu-SAzymes can possess excellent dual enzyme-like activities: catalase (CAT)-like activity that decompose H2O2 into O2, and subsequent oxidase (OXD)-like activity that convert O2 to cytotoxic superoxide anion radical (•O2-). Meanwhile, l-Arg@Cu-SAzymes can also be triggered by H2O2 to release nitric oxide (NO), which can continue to react with •O2- to generate more lethal peroxynitrite (ONOO-). Collectively, the synergistic ROS and RNS mediated by l-Arg@Cu-SAzymes endow the treatment system with an outstanding antibacterial ability against MDR bacteria and reduce the inflammation at the wound site. Furthermore, l-Arg@Cu-SAzymes-mediated NO and O2 release promote the cell proliferation, collagen synthesis, and the angiogenesis, as well as facilitate macrophage polarization to reparative M2 phenotype, thereby accelerating wound closure and tissue remodeling. Therefore, l-Arg@Cu-SAzymes-based synergistic nanocatalytic therapy can be regarded as a promising strategy for MDR bacterial infected wounds treatment, owing to their potent antibacterial efficacy and enhanced tissue remodeling effects.

Case report: Rare epithelioid hemangioendothelioma occurs in both main bronchus and lung.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor of endothelial origin with low- to intermediate-grade malignant potentials. Since there is no characteristic clinical or biological marker available for PEH, most cases require a surgical lung biopsy for diagnosis. To date, although some patients with PEH reported in the literature were diagnosed through bronchoscopic biopsy, most of the patients still underwent surgical lung biopsy for confirmation. In this case report, we present a rare case diagnosed as PEH through endobronchial biopsies due to the presence of an intraluminal mass that blocked the trachea and caused atelectasis in the right upper lobe. Moreover, since surgery was not appropriate for this patient with unresectable bilateral multiple nodules, we adopted genetic analysis using NGS to provide a guide for personalized treatment. Then, based on the NGS results, the patient was treated with anti-PD-1 mAb and sirolimus for 1 year and has been stable in a 1-year follow-up examination.

Human infection with a reassortment avian influenza A H3N8 virus: an epidemiological investigation study.

A four-year-old boy developed recurrent fever and severe pneumonia in April, 2022. High-throughput sequencing revealed a reassortant avian influenza A-H3N8 virus (A/Henan/ZMD-22-2/2022(H3N8) with avian-origin HA and NA genes. The six internal genes were acquired from Eurasian lineage H9N2 viruses. Molecular substitutions analysis revealed the haemagglutin retained avian-like receptor binding specificity but that PB2 genes possessed sequence changes (E627K) associated with increased virulence and transmissibility in mammalian animal models. The patient developed respiratory failure, liver, renal, coagulation dysfunction and sepsis. Endotracheal intubation and extracorporeal membrane oxygenation were administered. H3N8 RNA was detected from nasopharyngeal swab of a dog, anal swab of a cat, and environmental samples collected in the patient's house. The full-length HA sequences from the dog and cat were identical to the sequence from the patient. No influenza-like illness was developed and no H3N8 RNA was identified in family members. Serological testing revealed neutralizing antibody response against ZMD-22-2 virus in the patient and three family members. Our results suggest that a triple reassortant H3N8 caused severe human disease. There is some evidence of mammalian adaptation, possible via an intermediary mammalian species, but no evidence of person-to-person transmission. The potential threat from avian influenza viruses warrants continuous evaluation and mitigation.

Drug-Eluting Beads Bronchial Arterial Chemoembolization in Treating Relapsed/Refractory Small Cell Lung Cancer Patients: Results from a Pilot Study.

BACKGROUND: We aimed to explore the efficacy and tolerance of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) treatment in relapsed/refractory small cell lung cancer (SCLC) patients. METHODS: Eleven relapsed/refractory SCLC patients were enrolled and treated with DEB-BACE. Then, treatment response and tumor marker levels were assessed at the first, second and sixth month post treatment. Quality of life was assessed by the EORTC QLQ-C30 scale. Progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS: At the first, second and sixth month post treatment, the objective response rates were 63.6%, 54.5%, and 36.4%, respectively; and the disease control rates were 90.9%, 90.9% and 54.5%, respectively. In addition, the neuron-specific enolase (NSE) and progastrin-releasing peptide levels were reduced at the second and sixth month. Quality of life assessed by EORTC QLQ-C30 scale, which included subscales of general health status, functional domains, symptom domains, and single domains except for financial difficulty, was markedly improved at second month post treatment. Median values of PFS and OS were 5.1 (95% CI: 4.1-5.9) months and 9.0 (95% CI: 6.0-12.0) months, respectively. The ECOG score and preoperative NSE level were independent predictive factors for PFS, and age as well as lesion location were independent predictive factors for OS. Adverse events were all mild and manageable with chest pain and chest stuffiness the most common ones. CONCLUSION: DEB-BACE could be a therapeutic option for relapsed/refractory SCLC patients regarding its favorable treatment response, quality of life, survival benefit and safety profile.

The Pathogenesis of Eosinophilic Asthma: A Positive Feedback Mechanism That Promotes Th2 Immune Response via Filaggrin Deficiency.

Eosinophilic asthma (EA) is a common subtype of asthma and often progresses to severe disease. In order to understand its pathogenesis, targeted next-generation gene sequencing was performed on 77 Chinese EA patients and 431 Chinese healthy controls to obtain differential genomic variations. Among the 41 Single Nucleotide Polymorphisms (SNPs) screened for mutation sites in more than 3 patients, filaggrin gene FLG rs192116923 T>G and FLG rs75235053 C>G were newly found to be associated with EA patients with atopic dermatitis (AD) (P <0.001) and severe EA (P=0.032), respectively. Filaggrin has been shown to be mainly expressed in epithelial cells and plays an important role in formation of an effective skin barrier. Bioinformatic analysis indicated FLG rs192116923 T>G may increase the binding of Smad3 to transmit TGF-ß1 signaling, and thereby inhibit filaggrin expression, and FLG rs75235053 C>G may add new splicing sites to reduce filaggrin monomers. It has been known that the level of Th2 cytokine IL-4 is increased in EA patients, and IL-4 increases airway epithelial permeability and enhances inflammatory response through some unclear mechanisms. To figure out whether filaggrin is involved in immune responses in asthma, we have treated human respiratory epithelial cell line BEAS-2B cells with IL-4 and found that the expression levels of filaggrin and E-cadherin decreased significantly in a time and dose-dependent manner, suggesting that IL-4 increased airway epithelial permeability by reducing filaggrin and adhesion molecule. In addition, in our study, IL-4 increased the expression of epithel-derived inflammatory cytokines IL-33 and TSLP which further enhanced the Th2 inflammatory response. To investigate the role of filaggrin in development of EA, knockdown filaggrin with siRNA revealed a decrease in E-cadherin levels, which were further down-regulated by IL-4 stimulation. Knockdown of filaggrin alone did not affect the levels of IL-33 and TSLP, but further exacerbated the decrease of IL-33/TSLP caused by IL-4, suggesting that filaggrin may involve in IL-4R signaling pathway to regulate the level of IL-33/TSLP. In conclusion, in the Th2 cytokine milieu of asthma, FLG deficient mutation in airway epithelial cells may increase the epithelial permeability and the expression of IL-33/TSLP which positively feedback the Th2 inflammation response.

Drug-eluting beads bronchial arterial chemoembolization plus intercostals arterial infusion chemotherapy is effective and well-tolerated in treating non-small cell lung cancer patients with refractory malignant pleural effusion.

BACKGROUND: The study aimed to explore the efficacy and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) plus intercostals arterial infusion chemotherapy in non-small cell lung cancer (NSCLC) patients with refractory malignant pleural effusion (MPE). METHODS: 17 NSCLC patients with refractory MPE treated by DEB-BACE plus the intercostals arterial infusion chemotherapy (DEB-BACE group) were recruited. Their treatment response [complete remission (CR), partial remission (PR), overall efficacy, failure] for MPE was assessed at 1 month after therapy; adverse effects were recorded; MPE progression-free survival and overall survival (OS) were calculated. Moreover, 19 NSCLC patients with refractory MPE treated by conventional chemotherapy were reviewed as control (chemotherapy group), then their medical records were collected. RESULTS: With respect to MPE response, DEB-BACE group exhibited increased CR (82.4% vs. 10.5%, P<0.001) and overall efficacy (100.0% vs. 52.6%, P=0.001), similar PR (17.6% vs. 42.1%, P=0.112) while less failure (0.0% vs. 47.4%, P=0.001) compared to chemotherapy group. Furthermore, OS was prolonged in DEB-BACE group (median: 13.4; 95% CI: 11.0-15.8 months) than chemotherapy group (median: 7.0; 95% CI: 4.4-9.6 months) (P=0.002). Further analyses displayed that in DEB-BACE group, CR was associated with improved ECOG score and longer MPE progression-free survival, and adverse events mainly included fever, chest distress/pain, gastrointestinal side effects, myelosuppression, rash and hemoptysis, which were all mild and tolerable. CONCLUSIONS: DEB-BACE plus intercostals arterial infusion chemotherapy could serve as a salvage treatment option for NSCLC patients with refractory MPE.

MicroRNA-21 mediates bone marrow mesenchymal stem cells protection of radiation-induced lung injury during the acute phase by regulating polarization of alveolar macrophages.

BACKGROUND: Radiation-induced lung injury (RILI) often occurs in patients with non-small cell lung cancer (NSCLC) after radiotherapy, and the prognosis of patients with RILI is usually poor. This work plan to investigate the expression patterns of microRNA-21(miR-21) in NSCLC patients with RILI and the protective effects of miR-21 over-expressed bone marrow mesenchymal stem cells (BMSCs) against RILI in rat model. METHODS: MiR-21 expressions were determined in both serum samples and bronchoalveolar lavage fluid (BALF) samples from NSCLC patients after radiation therapy. The correlation between miR-21 expression and the follow-up clinical characterizations were determined. Further, miR-21 over-expressed BMSCs were transplanted into RILI rats and the protective effects were evaluated. BMSCs and alveolar macrophages (AMs) were co-cultured in vitro and the macrophage M1 polarization markers were determined by ELISA and qRT-PCR assays. RESULTS: Expression of miR-21 was significantly increased in NSCLC patients with RILI compared with control group, especially before or at 4 weeks after radiation therapy commenced. The miR-21 levels were highly correlated with IL-12, TNF-α, and IL-6 expressions and the severity of RILI. Animal based experiments demonstrated that BMSCs treatment had a remarkable effect on alleviating alveolitis in RILI rats, and miR-21 over-expression could enhance this effect significantly. Cell based experiments demonstrated that BMSCs notably inhibited M1 polarization of AMs and this inhibition is in a miR-21 dependent manner. CONCLUSIONS: These results indicated that BMSCs could blocked the proinflammatory pathway of macrophage through miR-21 over-expression, thus could be a potential therapeutic strategy for RILI.

Reduced Sleep in the Week Prior to Diagnosis of COVID-19 is Associated with the Severity of COVID-19.

BACKGROUND: The rapid outbreak of coronavirus disease 2019 (COVID-19) is a major health concern, in response to which widespread risk factor research is being carried out. OBJECTIVE: To discover how physical activity and lifestyle affect the epidemic as well as the disease severity and prognosis of COVID-19 patients. METHODS: This multicenter, retrospective cohort study included 203 adults infected with COVID-19 and 228 uninfected adults in three Chinese provinces, with 164 (80.7%) of the infected participants and 188 (82.5%) of the uninfected participants answering a doctor-administered telephone questionnaire on lifestyle. The binary logistic regression model and the ordinal logit model were used to observe relevance. RESULTS: Comparing sick and non-sick patients, we found that irregular exercise (P=0.004), sedentary lifestyle (P=0.010), and overexertion (P<0.001) may be associated with the susceptibility to COVID-19. In symptomatic patients, using the recommended status as a reference, risk of severe infection increased with decreased sleep status, being 6.729 (95% CI=2.138-21.181) times higher for potentially appropriate sleep (P=0.001) and peaking at 8.612 (95% CI=1.913-38.760) times higher for lack of sleep (P=0.005). Reduction in average daily sleep time significantly increased the likely severity (P=0.002). DISCUSSION: Through further examination of damage of external lung organs, we found that lack of sleep affected not only disease severity but also prognosis. Based on these findings, the public should prioritize a healthy lifestyle and get adequate sleep in response to the outbreak. The study of life habits may bring new ideas for the prevention and treatment of COVID-19.

The advantage of Sirolimus in amplifying regulatory B cells and regulatory T cells in liver transplant patients.

Sirolimus has been shown to ameliorate steroid-resistant rejection and induce long-term immune tolerance among liver transplant patients. However, the detailed mechanism of how Sirolimus achieve these advantages is still lacking. This study attempts to reveal some possible mechanisms by investigating regulatory B cells (Bregs), regulatory T cells (Tregs) and some cytokines in liver transplant recipients whose Tacrolimus was partially converted to Sirolimus. The results showed that CD19+CD24+CD38+Bregs and CD4+CD25+FoxP3+Tregs increased significantly during the first month after drug conversion (P < 0.01 and P < 0.05). The percentages of IL-10+Bregs and TGF-ß1+Bregs were also elevated (P < 0.05 and P < 0.01), and the same trend was observed in the levels of IL-10 and TGF-ß1 (P < 0.01 and P < 0.01). However, in the observation period, these investigated lymphocyte subsets and cytokines didn't change significantly in patients without Sirolimus usage. The incidence of biliary stenosis in the conversion group were significantly lower than that in the control group (P < 0.05). At the same time, in vitro experiments showed that Sirolimus could significantly amplify Bregs and Tregs (P < 0.01 and P < 0.01) while Tacrolimus did not show the amplifications effects. Sirolimus' function of amplifying Bregs was weakened, and its function of amplifying Tregs even disappeared after IL-10 and TGF-ß1 were neutralized. In conclusion, Sirolimus could amplify Bregs and Tregs among liver transplant recipient, which might be benefit to mitigate the immune response, decrease chances of rejection and alleviate biliary complication. IL-10 and TGF-ß1 may play important roles during this process.

Inhibition of proliferation and apoptosis induced by a Na+/H+ exchanger-1 (NHE-1) antisense gene on drug-resistant human small cell lung cancer cells.

The goal of this study was to evaluate the effect of the Na+/H+ exchanger-1 (NHE-1) antisense gene on drug-resistant human small cell lung cancer (SCLC) cell proliferation and apoptosis. A recombinant NHE-1 antisense gene was transfected into drug-resistant human SCLC H446/CDDP cells. Intracellular pH (pHi) was measured with fluorescence spectrophotometry. Cell proliferation was assayed cytometrically, and expression of the apoptosis gene caspase-3 was assayed using immunohistochemistry. Apoptosis and the cell cycles were imaged using a flow cytometer. pHi decreased significantly in transfected cells compared with control cells transfected with an empty vector (6.86+/-0.01 and 7.25+/-0.02, respectively, P<0.01). Cell proliferation began to decrease 48 h after antisense gene transfection, and the expression of the caspase-3 was stronger in transfected cells compared to the control group. The drug resistant exponent was significantly decreased (P<0.01), and there were more cells in G1 in the transfected group compared to the control group (70 and 57%, respectively, P<0.05). The rate of apoptosis in transfected cells was significantly higher than in the control group (12.18+/-1.86 and 2.37+/-0.33%, respectively, P<0.01). The NHE-1 antisense gene was able to induce drug-resistant human SCLC H446/CDDP cells to become acidified and apoptotic, which could provide a novel therapy for multidrug resistance SCLC.

Exploration of the involvement of LncRNA in HIV-associated encephalitis using bioinformatics.

BACKGROUND: HIV-associated encephalitis (HIVE) is one of the common complications of HIV infection, and the pathogenesis of HIVE remains unclear, while lncRNA might be involved it. In this study, we made re-annotation on the expression profiling from the HIVE study in the public database, identified the lncRNA that might be involved in HIVE, and explored the possible mechanism. METHODS: In the GEO public database, the microarray expression profile (GSE35864) of three regions of brain tissues (white matter, frontal cortex and basal ganglia brain tissues) was chosen, updated annotation was performed to construct the non-cording-RNA (ncRNA) microarray data. Morpheus was used to identify the differential expressed ncRNA, and Genbank of NCBI was used to identify lncRNAs. The StarBase, PITA and miRDB databases were used to predict the target miRNAs of lncRNA. The TargetScan, PicTar and MiRanda databases were used to predict the target genes of miRNAs. The GO and KEGG pathway analysis were used to make function analysis on the targets genes. RESULTS: Seventeen differentially expressed lncRNAs were observed in the white matter of brain tissues, for which 352 target miRNAs and 6,659 target genes were predicted. The GO function analysis indicated that the lncRNAs were mainly involved in the nuclear transcription and translation processes. The KEGG pathway analysis showed that the target genes were significantly enriched in 33 signal pathways, of which 11 were clearly related to the nervous system function. DISCUSSION: The brand-new and different microarray results can be obtained through the updated annotation of the chips, and it is feasible to identify lncRNAs from ordinary chips. The results suggest that lncRNA may be involved in the occurrence and development of HIVE, which provides a new direction for further research on the diagnosis and treatment of HIVE.

Evaluation of the Efficacy of Novel Oxazolidinone Analogues against Nontuberculous Mycobacteria In Vitro.

Nontuberculous mycobacteria (NTM) are associated with a number of clinical diseases and only a few antitubercular agents are active against them. Oxazolidinones comprise a novel class of antimicrobials that inhibit bacterial protein synthesis at the ribosome. Linezolid, the first oxazolidinone antibacterial agent approved for clinical use, has excellent activity against some NTM but is ineffective against others. Sy142 and sy144 are novel oxazolidinones with demonstrated activties against Mycobacterium tuberculosis and Staphylococcus aureus. In this work, we compared the susceptibilities of key NTM species to linezolid, sy142, and sy144. The organisms included 21 isolates of Mycobacterium abscessus, 31 of Mycobacterium avium, 11 of Mycobacterium chelonae, 24 of Mycobacterium fortuitum, 26 of Mycobacterium kansasii, and 17 of Mycobacterium intracellulare. For M. kansasii and M. fortuitum, linezolid showed excellent antimicrobial activity, and an equal MIC range was found in sy142 and sy144. For the species that linezolid was less active against, sy142 and sy144 showed greater antimicrobial activities or exhibited equal compared to linezolid. Particularly, for M. avium and M. intracellulare, the in vitro antimicrobial activity of sy142 was 4-fold higher than that of linezolid. These results demonstrate the potential of these compounds to treat NTM infections.