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Previous reports on daptomycin's adverse drug reactions (ADRs) have been insufficient, often because of limited data. Pharmacovigilance risk signal detection is innovative and has been applied to the safety monitoring and reevaluation of drugs post-marketing.The study aimed to promote safe daptomycin prescribing by mining and evaluating the daptomycin ADR signals from the US Food and Drug Administration Adverse Event Reporting System (FAERS).A disproportionality analysis (reporting odds ratio ROR and proportional reporting ratio PRR) was utilized for FAERS data mining from the first quarter of 2004 to the second quarter of 2021 (the most recent quarterly data at the time of the study). Preferred Terms of ADR reports were categorized by System Organ Class (SOC) based on the Medical Dictionary for Regulatory Activities.This study retrieved 12,221 cases within the reporting period. A total of 140 repetitive signals were obtained by ROR and PRR, of which 53 new ADR signals were not recorded in the drug labels/datasheets. The top three ADR reports were "blood creatine phosphokinase elevation" (ROR, 56.66, 95% confidence interval (CI) 51.07-62.87, PRR 51.94), "eosinophilic pneumonia" (ROR 696.71, 95%CI 603.21-804.70, PRR 657.57), and "rhabdomyolysis" (ROR 22.85, 95%CI 19.94-26.18, PRR 21.83). The highest ROR of "antimicrobial susceptibility test resistant" was found at 9808.14. Reports of rare adverse events, such as "necrotizing fasciitis and compartment syndrome," have emerged. The significant SOCs were "Infections and Infestations" and "Investigations."New daptomycin ADR signals were detected. Clinicians should monitor these potential ADRs in patients receiving daptomycin.

Background and aim: Competing endogenous RNA (ceRNA) is believed to play vital roles in tumorigenesis. The goal of this study was to screen prognostic biomarkers in lung adenocarcinoma (LUAD). Methods: Common differentially expressed genes (DEGs) were collected from Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas databases (TCGA) using GEO2R and “limma” package in R, respectively. Overlapping DEGs were conducted using enrichment of functions and protein-protein interaction (PPI) network to discover significant candidate genes. By using a comprehensive analysis, we constructed an mRNA mediated ceRNA network. Survival rates were used Kaplan-Meier analysis. Statistical analysis was used to further identify the prognosis of studied genes. Results: Integrated analysis of GSE32863 and TCGA databases, a total of 886 overlapping DEGs, including 279 up-regulated and 607 down-regulated genes were identified. Considering the highest term of candidate genes in PPI, we identified TPX2, which was enriched in cell division signaling pathway. Besides, 35 differentially expressed miRNAs (DEmiRNAs) were predicted to target TPX2 and only 7 DEmiRNAs were identified to be prognostic biomarkers in LUAD. Then, 30 differentially expressed lncRNAs (DElncRNAs) were predicted to bind these 7 DEmiRNAs. Finally, we found that 7 DElncRNAs were correlated with the overall survival (all p

Additional file 7: Table S1. Clinical characteristic data of patients and normal controls.

Additional file 8: Table S2. Summary of standard products for lipid.

The integration of an Energy Storage System (ESS) is difficult to commercialize within the current Chinese market mainly because of the lacking of supporting policy and breakthrough technologies. However, it is considered an appropriate approach in a certain circumstance, for instance, in a remote rural area. This work presents a power-balanced ESS integration model and its control method. By using a rural distributed network in southern China, the results show that the proposed model is able to improve the three-phase power imbalance issue.

Background: Autophagy plays an important role in lung adenocarcinoma (LUAD). In this study, we aimed to explore the autophagy-related gene (ARG) expression pattern and to identify promising autophagy-related biomarkers to improve the prognosis of LUAD.Methods: The gene expression profiles and clinical information of LUAD patients were downloaded from the Cancer Genome Atlas (TCGA), and validation cohort information was extracted from the Gene Expression Omnibus database. The Human Autophagy Database (HADb) was used to extract ARGs. Gene expression data were analyzed using the limma package and visualized using the ggplot2 package as well as the pheatmap package in R software. Functional enrichment analysis was also performed for the differentially expressed ARGs (DEARGs). Then, consensus clustering revealed autophagy-related tumor subtypes, and differentially expressed genes (DEGs) were screened according to the subtypes. Next, the univariate Cox and multivariate Cox regression analyses were used to identify independent prognostic ARGs. After overlapping DEGs and the independent prognostic ARGs, the predictive risk model was established and validated. Correlation analyses between ARGs and clinicopathological variables were also explored. Finally, the TIMER and TISIDB databases were used to further explore the correlation analysis between immune cell infiltration levels and the risk score as well as clinicopathological variables in the predictive risk model.Results: A total of 222 genes from the HADb were identified as ARGs, and 28 of the 222 genes were pooled as DEARGs. The most significant GO term was autophagy (p = 3.05E-07), and KEGG analysis results indicated that 28 DEARGs were significantly enriched in the ErbB signaling pathway (p < 0.001). Then, consensus clustering analysis divided the LUAD into two clusters, and a total of 168 DEGs were identified according to cluster subtypes. Then univariate and multivariate Cox regression analyses were used to identify 12 genes that could serve as independent prognostic indicators. After overlapping 168 DEGs and 12 genes, 10 genes (ATG4A, BAK1, CAPNS1, CCR2, CTSD, EIF2AK3, ITGB1, MBTPS2, SPHK1, ST13) were selected for the further exploration of the prognostic pattern. Survival analysis results indicated that this risk model identified the prognosis (p = 4.379E-10). Combined with the correlation analysis results between ARGs and clinicopathological variables, five ARGs were screened as prognostic genes. Among them, SPHK1 expression levels were positively correlated with CD4+ T cells and dendritic cell infiltration levels.Conclusions: In this study, we constructed a predictive risk model and identified a five autophagy subtype-related gene expression pattern to improve the prognosis of LUAD. Understanding the subtypes of LUAD is helpful to accurately characterize the LUAD and develop personalized treatment.

We successfully synthesized the Bi2WO6 (BWO) with gradient concentration of oxygen vacancies and exhibited the excellent photocatalytic NO oxidation activity. And the oxygen vacancy introduced in photocatalyst is a popular method to enhance the photocatalytic performance. The formation of oxygen vacancy defects in BWO is responsible for the tuning band structure and modifying surface chemical state to improve carriers separation efficiency, enlarge visible light absorption range and facilitate reactant activation, which is unambiguously verified by the UV–vis DRS, XPS, EPR and DFT calculations. Moreover, the role of surface oxygen vacancy defects and reaction mechanism of photocatalytic NO oxidation were discussed in detail by combing the in situ DRIFT and theoretical calculations. This work could be broadly used to the design and synthesize high efficient photocatalysts and pave a way to understand the reaction mechanism of NO oxidization.

Improving the rate capability of transition metal oxides is of great important for the development of high-performance electrodes for supercapacitors. Here, a novel strategy of hydrogenation to enhance the electron transfer rate of manganese dioxide (MnO2) is proposed. Detailed preparative parameters (i.e. hydrogenation temperature and time) are systematically investigated. The hydrogenated MnO2 (H-MnOx) exhibits modified crystal phase/surface structures and increased electrical conductivity. The prepared H-MnOx exhibits high specific capacitance (640 mF cm−2 at current density of 1 mA cm−2), good rate capability (89.6% of capacitance retained from 1 to 10 mA cm−2), and good cycling stability (84.6% retention after 1000 cycles). The high specific capacitance is ascribed to the unique interconnected ultrathin nanosheets structure, which could not only provide porous channels for electrolyte infiltration to offer sufficient electrode/electrolyte interface, but also shorten the ions diffusion distance inside the active material. The good rate capability could be attributed to the good conductivity of the H-MnOx nanosheets, which was confirmed by the DFT calculation. These results highlight the importance of hydrogenation as a facile yet effective strategy to improve the rate capability of transition metal oxides for supercapacitors.

In this work, a series of MnO2 nanostructures with different crystallographic structures, including δ-MnO2 nanotubes and α-MnO2 nanorods, were prepared using polycarbonate membrane as a template. The crystallographic structure and morphology were controlled by adjusting the pH of the KMnO4 solutions via a one-step hydrothermal method. The crystal form of the samples changed from birnessite to α-MnO2 with the decrease in the applied pH values and a precise pH value for the critical point was found. When used as positive electrode materials in the supercapacitor, the structure prepared in the higher pH value solutions (MnO2-12, pH = 12) with a δ-type crystallographic structure gave an ideal specific capacitance of 364.1 F g−1 at a current density of 0.5 A g−1, a good rate capability, and a favorable cycling stability. An asymmetric supercapacitor assembled with MnO2-12 as the positive electrode and activated graphene (AG) as the negative electrode produced an energy density of 29.4 W h kg−1 at a power density of 248.9 W kg−1. The excellent electrochemical properties were attributed to the novel tubular structure composed of poor crystalline δ-MnO2 nanosheets, resulting in a high ionic conductivity and two-sided reaction surfaces.

The Λ b → Λ c ℓ − ν ¯ ℓ process has been discussed in the literatures as a probe for new physics. This process receives contributions in new physics models from scalar, vector, and tensor hadronic currents. The form factors of these currents can be obtained from the quark model or the lattice QCD. In this work, we present a c-code to read the scalar, vector, and tensor lattice QCD form factors. The code is published on github (https://github.com/darkfiresmith96/Lattice_QCD). A Mathematica code was used in reference Datta et al (2017 J. High Energy Phys. 8 131) to read the form factors. Our c-code is much faster than the Mathematica code where the ratio of the wall clock time for the c-code compared to the Mathematica code is 1:64.2 per data point. A web interface for user inputs is introduced.

Bronchopulmonary dysplasia (BPD) is a frequent complication characterized by accelerated lung alveolarization in newborns. Long non-coding RNAs (lncRNAs) and microRNAs (miRs) are regarded as essential regulators in various diseases, including BPD. However, the detailed mechanism of the functions of RNA imprinted and accumulated in nucleus (Rian) lncRNA in the progression of BPD have remained elusive. The aim of the present study was to illustrate the interaction between miR-421 and Rian in BPD models and MLE-12 cells. The ability of Rian to protect neonatal lungs from hyperoxia-induced lung damage was examined. A mouse model of BPD and a hyperoxia-stimulated MLE-12 cell damage model were generated and treated with specific plasmid/mimics for the overexpression of Rian/miR-421. The interaction between miR-421 and Rian was predicted and verified using StarBase and a dual-luciferase reporter assay, respectively. The expression levels of miR-421 or Rian in both tissues and the MLE-12 alveolar epithelial cell line were assessed using reverse transcription-quantitative (RT-q)PCR. As parameters of alveolarization, the mean linear intercept (MLI), radial alveolar count (RAC) and the lung weight/body weight (LW/BW) ratio were measured. Furthermore, RT-qPCR was used to measure mRNA levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the lung tissue of mice, and ELISAs were performed to determine the levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the supernatant of MLE-12 cells. Cell growth and apoptosis were evaluated using an MTT assay and flow cytometry, respectively. Furthermore, caspase-3 activity was assessed using a caspase-3 activity detection kit. Prediction with StarBase and the dual-luciferase reporter assay revealed that miR-421 directly targeted Rian. RT-qPCR analysis confirmed that Rian was downregulated and miR-421 was upregulated in lung tissues of the mouse model of BPD and in hyperoxia-induced MLE-12 cells. However, the expression of miR-421 was decreased by Rian-overexpression, an effect that was reversed by miR-421 mimics. In addition, BPD was alleviated by Rian-plasmid, as confirmed by the enhanced RAC and reduced MLI and LW/BW ratio. The present results also indicated that Rian-plasmid inhibited the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) in BPD mouse serum and hyperoxia-induced MLE-12 cells. In addition, Rian-plasmid eliminated the effect of hyperoxia to inhibit cell viability and induce apoptosis in MLE-12 cells. However, all of these effects of Rian were markedly reversed by miR-421 mimics. The present results indicated that Rian may attenuate hyperoxic damage in neonatal lungs and may serve as a novel molecular target for BPD treatment.

Background. Acute lung injury (ALI) is a fatal syndrome frequently induced by lipopolysaccharide (LPS) released from the bacterial cell wall. LPS could also trigger autophagy of lung bronchial epithelial cell to relieve the inflammation, while the overwhelming LPS would impair the balance of autophagy consequently inducing serious lung injury. Methods. We observed the autophagy variation of 16HBE, human bronchial epithelial cell, under exposure to different concentrations of LPS through western blot, immunofluorescence staining, and electron microscopy. Eight strands of 16HBE were divided into two groups upon 1000 ng/ml LPS stimulation or not, which were sent to be sequenced at whole transcriptome. Subsequently, we analyzed the sequencing data in functional enrichment, pathway analysis, and candidate gene selection and constructed a hsa-miR-663b-related competing endogenous RNA (ceRNA) network. Results. We set a series of concentrations of LPS to stimulate 16HBE and observed the variation of autophagy in related protein expression and autophagosome count. We found that the effective concentration of LPS was 1000 ng/ml at 12 hours of exposure and sequenced the 1000 ng/ml LPS-stimulated 16HBE. As a result, a total of 750 differentially expressed genes (DEGs), 449 differentially expressed lncRNAs (DElncRNAs), 76 differentially expressed circRNAs (DEcircRNAs), and 127 differentially expressed miRNAs (DEmiRNAs) were identified. We constructed the protein-protein interaction (PPI) network to visualize the interaction between DEGs and located 36 genes to comprehend the core discrepancy between LPS-stimulated 16HBE and the negative control group. In combined analysis of differentially expressed RNAs (DERNAs), we analyzed all the targeted relationships of ceRNA in DERNAs and figured hsa-miR-663b as a central mediator in the ceRNA network to play when LPS induced the variation of autophagy in 16HBE. Conclusion. Our research indicated that the hsa-miR-663b-related ceRNA network may contribute to the key regulatory mechanism in LPS-induced changes of autophagy and ALI.

Yakuchinone A (1) is a bioactive diarylheptanoid isolated from the dried fruits of Alpinia oxyphylla. Microbial transformation has been recognized as an efficient method to produce new biologically active derivatives from natural products. In the present study, microbial transformation of yakuchinone A was performed with the fungus Mucor hiemalis KCTC 26779, which led to the isolation of nine new metabolites (2, 3a, 3b, and 4–9). Their structures were elucidated as (3S)-oxyphyllacinol (2), (3S,7R)- and (3S,7S)-7-hydroxyoxyphyllacinol (3a and 3b), (3S)-oxyphyllacinol-4′-O-β-d-glucopyranoside (4), (3S)-4″-hydroxyoxyphyllacinol (5), (3S)-3″-hydroxyoxyphyllacinol (6), (3S)-2″-hydroxyoxyphyllacinol (7), (3S)-2″-hydroxyoxyphyllacinol-2″-O-β-d-glucopyranoside (8), and (3S)-oxyphyllacinol-3-O-β-d-glucopyranoside (9) based on the comprehensive spectroscopic analyses and the application of modified Mosher’s method. All compounds were evaluated for their cytotoxic activities against melanoma, as well as breast, lung, and colorectal cancer cell lines. Compound 9, which was O-glucosylated on the diarylheptanoid alkyl chain, exhibited the most selective cytotoxic activities against melanoma cell lines with the IC50 values ranging from 6.09 to 9.74 μM, indicating that it might be considered as a possible anti-cancer lead compound.

Aims Pyroptosis and inflammation are involved in the development of chronic obstructive pulmonary disease (COPD). However, the cigarette smoke-mediated mechanism of COPD remains unclear. In this study, we aimed to investigate the role of nucleotide-binding domain-like receptor protein-3 (NLRP3) inflammasome-mediated pyroptosis in the death of human bronchial epithelial (HBE) cells after cigarette smoke extract (CSE) exposure. Main methods The protein level of NLRP3 in lung tissue was measured after cigarette smoke exposure in vivo. In vitro, HBE cells were treated with CSE. Subsequently, the activity of caspase-1, lactate dehydrogenase (LDH) release, release of interleukin (IL)-1β and NLRP3 expression levels were measured. The involvement of reactive oxygen species (ROS) was also explored. Key findings After exposure to CSE, increased release of LDH, the transcriptional and translational upregulation of NLRP3, the caspase-1 activity levels, and enhanced IL-1β and IL-18 release were observed in 16HBE cells. In addition, NLRP3 was required to activate the caspase-1. Our results suggested that pre-stimulated of 16HBE with a caspase-1 inhibitor, or using NLRP3 siRNA to silence NLRP3 expression, also caused the decrease of IL-1β release and pyroptosis. Significances. CSE induced inflammation and contributed to pyroptosis through the ROS/NLRP3/caspase-1 pathway in 16HBE cells. The NLRP3 inflammasome participates in CSE-induced HBE cell damage and pyroptosis, which could provide new insights into COPD.

Lung adenocarcinoma (LUAD) has become the main histologic type, which account for nearly 40% of lung cancer. The present study aimed to investigate the gene expression signature in smoking related LUAD. A total of 45 smoking related DEGs in LUAD were identified and functional enrichment analysis was also performed. Then Cox's regression model and Kaplan-Meier analysis were used to screen potential prognostic genes. Finally, AURKA and FAM83A were left for further immune-related mechanism exploration. Kaplan-Meier analysis indicated survival rates are related to different immune cell (B cell and Dendritic cell) infiltration levels. Mechanistically, we further explore the correlation between AURKA and FAM83A gene expression levels and tumor-infiltrating lymphocytes (TILs) level as well as their response to immunomodulators. The results suggested that AURKA and FAM83A are highly expressed in smoking related LUAD, and negatively correlated to B cell and Dendritic cell infiltration levels. At the same time, B cell and Dendritic cell infiltration levels also related to the prognosis of LUAD. We further revealed AURKA and FAM83A could be novel targets to improve the prognosis of LUAD through regulated the response to immunomodulators.

Abnormal glycolysis is one of the hallmarks of cancer and plays an important role in its development. This study was devoted to identify glycolysis related genes as prognostic biomarkers for non-small cell lung cancer (NSCLC). The mRNA expression profile and clinical follow-up data were obtained using The Cancer Genome Atlas (TCGA) database. The validation set was obtained by bootstrap method of random repeated sampling. A total of 200 glycolysis-related genes were obtained from Gene Set Enrichment Analysis (GSEA) and 46 genes were significantly associated with overall survival (OS). Five genes (PKP2, LDHA, HMMR, COL5A1 and B3GNT3) were eventually identified to calculate risk score of NSCLC patients. The univariate and multivariate Cox regression analysis indicated that the risk score was an independent prognostic factor (training set: HR=2.126, 95% CI [1.605, 2.815], p

Background: In recent years, LncRNA acts as a member of competing endogenous RNA (ceRNA), playing an important role in drug resistance of lung cancer. The aim of this study was to identify potential biomarkers about cisplatin resistant lung cancer cells using a comprehensive ceRNA network.Methods: GSE6410 (GPL-201) analyzed gene expression changes about cispaltin resistance in A549 NSCLC cells. GSE43249 (GPL-14613) included noncoding RNA expression profiling derived from the cisplatin resistant A549 lung cells. GEO2R, an online analysis tool, analyzed the differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs). To explore the functional enrichment implication of differentially expressed mRNAs, we used the GO and KEGG pathway analysis. Through miRDB、Targetscan、Starbase、miRWalk, we found targeted miRNAs. The Kaplan-Meier curve method was used to show clinical survival analysis of targeted RNAs (P). The Starbase database predicted potential lncRNAs mediated targeted miRNAs. Eventually, the novel ceRNA network of lncRNAs, miRNAs, mRNA was constructed by cytoscape3.7.2.Results:118 differentially expressed mRNAs were the basis of the mediated ceRNA network. DAVID and Kaplan-Meier picked out BAX, an apoptosis regulator. Venn Diagram demonstrated 8 miRNAs commomly regulating Bax. Starbase predicted lncRNA XIST mediated miRNAs. Finally, lncRNA XIST maybe a useful biomarker regulating cisplatin resistance in lung cancer cells.Conclusions: LncRNA XIST competitively bound to miRNA 520 in the regulation of cisplatin resistance by BAX , participating apoptosis in the p53 signaling pathway.

Composting of cattle manure was conducted under four ventilation strategies, i.e., no-aeration (A-00), continuous aeration (B-44), non-aeration for 14 d and then aeration for 42 d (C-04), aeration for 14 d and then no-aeration for 42 d (D-40). Physicochemical parameters and potential ammonia oxidation (PAO) indicated that continuous and intermittent ventilation provide favourable conditions for ammonia-oxidizing bacteria (AOB) and archaea (AOA) to oxidize ammonia. Quantitative PCR (qPCR) analysis showed AOB amoA gene abundance of all treatments on every sampling day ranged from 2.25 × 105 to 2.76 × 109copies/g, was significantly lower than that of archaeal amoA gene from 2.71 × 108 to 9.05 × 1011copies/g. There was also a significantly positive relationship between PAO rates and AOB (r2 ≥ 0.066, p < 0.05) and AOA (r2 ≥ 0.300, p < 0.05) abundance. These data suggested that ammonia oxidation is driven by both AOA and AOB in cattle manure composting.

Advanced protection and operation of power systems, especially microgrids, requires rapid detection and estimation of system states. Microgrids, however, are a challenge due to the high variability of distributed generation and modern load profiles. Setting of relays and establishing Remedial Action Schemes on these systems requires rapid detection and state estimation and modeling of complex loads. This work demonstrates the design and operation of a high-speed method for estimating states and load composition across a 286-bus campus test-bed utilizing only a few PMUs. The method is based on training data that is analyzed offline via Singular Value Decomposition to determine clustering vectors that can be utilized for state estimation in real-time. This is combined with a priori bus studies to estimate load composition in terms of residential, industrial, and commercial in real-time. A case-study using the Oregon State University campus grid is presented, and it is shown that the estimation method is accurate (to within 1% in the test shown) while requiring less than 0.2 ms computation time.

Composting is a controlled biological process used to stabilize and transform waste into a soil treatment. Aeration rate is one factor that controls the process of composting, as it ensures the growth of adequate aerobic microbe populations. To investigate the effect of aeration rates on the physicochemical indexes of compost and the loss of nitrogen content during composting, aerobic composting processes with different aeration rates (A: 0.2 L/min/kg TS, B: 0.05 L/min/kg TS and C: 0 L/min/kg TS) were studied. Ammonium-nitrogen, nitrate nitrogen, total nitrogen and other factors in compost samples from different periods were measured. The results showed that aeration rate significantly affected O 2 content under different conditions. The aeration rate also significantly affected water content, nitrate nitrogen, and nitrogen loss. NH3 emissions increased as aeration rates increased at high temperatures owing to nitrogen loss. These results showed that aeration rate had a significant effect on total nitrogen and ammonia emissions (p < 0.05). Thus, optimization of the ventilation method could significantly increase seed germination rate.