Search

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

The survival rate of patients with lung adenocarcinoma (LUAD) is low. This study analyzed the correlation between the expression of long noncoding RNA (lncRNA) and epigenetic alterations along with the investigation of the prognostic value of these outcomes for LUAD. Differentially expressed lncRNAs were identified based on multiomic data and positively related genes using DESeq2 in R, differentially histone-modifying genes specific to LUAD based on histone modification data, gene enhancers from information collected from the FANTOM5 (Function Annotation Of The Mammalian Genome-5) (fantom.gsc.riken.jp/5) human enhancer database, gene promoters using the ChIPseeker and the human lincRNAs Transcripts database in R, and differentially methylated regions (DMRs) using Bumphunter in R. Overall survival was estimated by Kaplan-Meier, comparisons were performed among groups using log-rank tests to derive differences between sample subclasses, and epigenetic lncRNAs (epi-lncRNAs) potentially relevant to LUAD prognosis were identified. A total of seven dysregulated epi-lncRNAs in LUAD were identified by comparing histone modifications and alterations in histone methylation regions on lncRNA promoter and enhancer elements, including H3K4me2, H3K27me3, H3K4me1, H3K9me3, H4K20me1, H3K9ac, H3K79me2, H3K27ac, H3K4me3, and H3K36me3. Furthermore, 69 LUAD-specific dysregulated epi-lncRNAs were identified. Moreover, lncRNAs-based prognostic analysis of LUAD samples was performed and explored that seven of these lncRNAs, including A2M-AS1, AL161431.1, DDX11-AS1, FAM83A-AS1, MHENCR, MNX1-AS1, and NKILA (7-EpiLncRNA), showed the potential to serve as markers for LUAD prognosis. Additionally, patients having a high 7-EpiLncRNA score showed a generally more unfavorable prognosis compared with those which scored lower. Seven lncRNAs were identified as markers of prognosis in patients with LUAD. The outcomes of this research will help us understand epigenetically aberrant regulation of lncRNA expression in LUAD in a better way and have implications for research advances in the regulatory role of lncRNAs in LUAD.

To date, anticancer immunotherapy has presented some clinical benefits to most of advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC) patients. In addition to MSI status, we aimed to reveal the potential predictive value of adenomatous polyposis coli (APC) gene mutations in CRC patients. A total of 238 Chinese CRC patients was retrospectively identified and analyzed for clinical features and gene alternations in APC-mutant type (MT) and APC-wild-type (WT) groups. Clinical responses were then evaluated from the public TCGA database and MSKCC immunotherapy database. Although programmed cell death ligand 1 (PD-L1) level, MSI status, loss of heterogeneity at the human leukocyte antigen (HLA LOH), and tumor neoantigen burden (TNB) level were not statistically different between the APC-MT group and APC-WT group, tumor mutation burden (TMB) level was significantly higher in APC-MT patients ( P < 0.05 ). Furthermore, comutation analysis for APC mutations revealed co-occurring genomic alterations of PCDHB7 and exclusive mutations of CTNNB1, BRAF, AFF3, and SNX25 ( P < 0.05 ). Besides, overall survival from MSKCC-CRC cohort was longer in the APC-WT group than in the APC-MT group (HR 2.26 (95% CI 1.05–4.88), P < 0.05 ). Furthermore, most of patients in the APC-WT group were detected as high-grade immune subtypes (C2–C4) comparing with those in the APC-MT group. In addition, the percentages of NK T cells, Treg cells, and fibroblasts cells were higher in APC-WT patients than in APC-MT patients ( P < 0.05 ). In summary, APC mutations might be associated with poor outcomes for immunotherapy in CRC patients regardless of MSI status. This study suggested APC gene mutations might be a potential predictor for immunotherapy in CRC.

Background. Immunotherapy is a promising therapy for metastatic gastric cancer (GC) patients. However, the component of tumor microenvironment (TME) is a pivotal factor hindering immunotherapy outcome. CD8 T cells suppress tumor progression. This study developed an immune subtyping system and a prognostic model for guiding personalized therapy of GC patients. Methods. Marker genes related to CD8 T cells were identified by weighted correlation network analysis (WGCNA). Consensus clustering was used to develop immune subtypes. Univariate Cox regression analysis was performed to screen prognostic genes. Functional analysis (KEGG and GO annotation) and gene set enrichment analysis were applied. Results. Based on marker genes related to CD8 T cells, we identified three immune subtypes (IC1, IC2, and IC3) with distinct prognosis and differential TME. In IC3, CD8 T cell function was impaired by high activation of CXCR4/CXCL12 axis, and impaired T cell function predicted high response to immune checkpoint blockade. IC1 was sensitive to chemotherapeutic drugs but showed low response to immunotherapy. We also developed an 8-gene prognostic signature with robust performance to stratify GC patients into high-risk and low-risk groups. Conclusions. This study identified three immune subtypes and a prognostic signature, and both were effective in direct personalized therapy for GC patients. The correlation between TME and immunotherapy was further characterized from a new perspective.

Due to good maneuverability, UAVs and vehicles are often used for environment perception in smart cities. In order to improve the efficiency of sensor data sharing in UAV-assisted mmWave vehicular network (VN), this paper proposes a sensor data sharing method based on blockage effect identification and network coding. The concurrent sending vehicles selection method is proposed based on the availability of mmWave link, the number of target vehicles of sensor data packet, the distance between a sensor data packet and target vehicle, the number of concurrent sending vehicles, and the waiting time of sensor data packet. The construction method of the coded packet is put forward based on the status information about the existing packets of vehicles. Simulation results demonstrated that efficiency of the proposed method is superior to baseline solutions in terms of the packet loss ratio, transmission time, and packet dissemination ratio.

Effective emergency message dissemination is a great importance on a specific road in vehicular networks (VN). The existing methods are not most efficient solutions for message dissemination on the curve road, which primarily focus on highway and urban road. In order to improve the efficiency of message dissemination on the curved road, the paper proposed a message dissemination method based on bidirectional relay nodes. The message can be disseminated in two directions simultaneously. The paper designed a relay node selection method based on the neighbor nodes’ coverage length of the road. Different waiting delays are assigned to the neighbor nodes according to the cover capability of the road in which the message has not arrived. Simulation results demonstrated that the efficiency of the proposed method is superior to the common solutions in terms of the contention delay and the propagation velocity.

Due to the complex mechanisms affecting anti-tumor immune response, a single biomarker is insufficient to identify patients who will benefit from immune checkpoint inhibitors (ICIs) treatment. Therefore, a comprehensive predictive model is urgently required to predict the response to ICIs. A total of 162 non-small-cell lung cancer (NSCLC) patients undergoing ICIs treatment from three independent cohorts were enrolled and used as training and test cohorts (training cohort = 69, test cohort1 = 72, test cohort2 = 21). Eight genomic markers were extracted or calculated for each patient. Ten machine learning classifiers, such as the gaussian process classifier, random forest, and support vector machine (SVM), were evaluated. Three genomic biomarkers, namely tumor mutation burden, intratumoral heterogeneity, and loss of heterozygosity in human leukocyte antigen were screened out, and the SVM_poly method was adopted to construct a durable clinical benefit (DCB) prediction model. Compared with a single biomarker, the DCB multi-feature model exhibits better predictive value with the area under the curve values equal to 0.77 and 0.78 for test cohort1 and cohort2, respectively. The patients predicted to have DCB showed improved median progression-free survival (mPFS) and median overall survival (mOS) than those predicted to have non-durable clinical benefit.

Background. Glycolysis is closely associated with tumor progression, but the roles of lncRNAs in glycolysis have not been comprehensively investigated in lung adenocarcinoma (LUAD). This study is aimed at studying the possible mechanisms of glycolysis-related lncRNAs in tumor development and providing a guidance for targeted therapy. Methods. Unsupervised consensus clustering was used to identify molecular subtypes. Gene enrichment analysis was applied to screen important pathways involved in tumor progression. A series of immune analysis was performed to assess immune infiltration. Critical transcription factors (TFs) interacting with lncRNAs were selected by Pearson correlation analysis. A first-order partial correlation analysis was implemented to identify critical lncRNAs with prognostic significance. Results. Three molecular subtypes (C1, C2, and C3) were identified with distinct overall survival. Three subtypes showed differential immune infiltration, and C3 subtype was the optimal for immunotherapy treatment. Ten lncRNA-TF pairs among four glycolysis-related lncRNAs (FTX, LINC00472, PSMA3-AS1, and SNHG14) and six TFs (FOXP1, SP1, MYC, FOXM1, HIF1A, and FOS) were involved in tumor progression. We identified four critical glycolysis-related lncRNAs significantly associated with prognosis. Conclusions. This study identified three molecular subtypes that could guide personalized therapy. The four-lncRNA prognostic model can serve as an indicator for predicting prognosis or early screening of lung adenocarcinoma patients. The current results improve the understanding of the relation between lncRNAs and glycolysis.

Background Although PD-L1 expression is a crucial predictive biomarker for immunotherapy, it can be influenced by many factors. Methods A total of 248 Chinese patients with lung adenocarcinoma was retrospectively identified. Data for clinical features, gene alternations, signaling pathways and immune signatures was analyzed among negative expression group (TPS Results Firstly, high tumor mutation burden was significantly associated with high PD-L1 expression in these Chinese patients with lung adenocarcinoma. In addition, gene alternations including TP53, PRKDC, KMT2D, TET1 and SETD2 apparently occurred in high PD-L1 expression group. Moreover, pathway analysis showed that mutations involving in DDR pathway, TP53 pathway, cell-cycle pathway and NOTCH pathway were obviously varied among three PD-L1 expression groups. Besides, most of patients in high PD-L1 expression group from TCGA database were determined as high-grade immune subtypes (C2-C4), showing significant higher proportions of IFN-gamma, CD8+ T-cells, NK cells, NK CD56 dim cells, Th1 cells, Th2 cells (P SETD2 mutation slightly correlated with overall survival from MSKCC cohort (HR 1.92 [95%CI 0.90–4.10], P = 0.085), and the percentage of IFN-gamma was significantly higher in SETD2 mutant group than in wild-type group (P Conclusions This study illustrated in-depth genomic correlates of PD-L1 expression in Chinese lung adenocarcinoma patients and relevant immune signatures from public database, which might interpret more potential molecular mechanisms for immunotherapy in NSCLC.

Stiffness-changing materials (SCMs) have received lots of interests due to their reversible transition between their soft and rigid states for modern applications. However, the irreversible stiffness transition, slow response, and sustained external stimuli strictly hinder the broad utilizations of SCMs. Here, this work reports electrically driven SCMs based on supercooled liquid metals (LMs). A small voltage (5 V) can successfully initiate the stable and reversible stiffness change of the SCMs in electrolyte solution. Surprisingly, the LM-based SCMs (LM-SCMs) exhibited a significant change in 1000 times difference of moduli (65 kPa versus 79 MPa). Moreover, such a stiffness transition of the LM-SCM was ultrarapidly completed in a few seconds (

Immunotherapy alone or chemo-immunotherapy has recently been recommended for treating advanced lung carcinoma in patients without driver mutations. However, the efficacy of immunotherapy and molecular mechanism in large-cell lung cancer (LCLC) remains unclear. Here, we reported a rare case of multiple fulminant postoperative body and mouth metastases in LCLC treating with combination immunotherapy. Initially, the patient was diagnosed as early stage LCLC and underwent a radical resection of the right lower lobe. Just one month later, multiple fulminant body and mouth lesions appeared in the right upper arm, right elbow, right waist, and tongue root. Meanwhile, serum neuron specific enolase (NSE) concentration dramatically increased from 12.12 to 30.14 ng/ml. Immumohistochemistry findings demonstrated moderate PD-L1 expressions with tumor proportion score (TPS), while next-generation sequencing indicated moderate tumor mutational burden (TMB) levels and gene mutations in PBRM1 L1230P and TP53 L194R of both foci. Besides, loss of heterozygosity (LOH) at human leukocyte antigen (HLA) class I (HLA-A*02:03, HLA-B*55:02 and HLA-C*12:03) were detected in the right upper arm metastasis, which may facilitate malignant postoperative metastases in this case. Notably, this patient received combination therapy with anti-PD-1 antibody sintilimab plus anlotinib, and achieved a partial response for at least 12 months. Using an integrated computational method, the mutant peptide TEIPENDIPL derived from PBRM1 L1230P was predicted to be a specific neoantigen and could still be presented by HLA-B*40:01. This case suggests that immunotherapy plus antiangiogenic drug may provide an alternative therapeutic option for advanced LCLC patients without common gene mutations.

A detailed investigation was carried out to develop novel pore- and morphology-controllable ETS-10 zeolite. The XRD, N2 adsorption/desorption, SEM, TEM and 29Si NMR MAS results proved that a series of hierarchical ETS-10 zeolites was successfully synthesized and more importantly, their morphologies and pore sizes can be freely confined in the desired range under the mesoporogen, morphology- and structure-directing actions of different additives. What's more, the close relationship between various additives and raw materials especially titanium source was discussed, which played an active part in morphology change and hierarchical pores formation. This can be ascribed to the special reducibility of inorganic Ti source, system liquidity and pH, and the enhanced inorganic species dissolution. Finally, the synthesized hierarchical ETS-10 materials were used as heterogeneous catalysts for different biomass-derivatives hydrogenation. Remarkably catalytic performance can be attributed to the unique TiO6 octahedra carrying two negative charges that strengthens the interaction with active metal species, and thus improves their dispersion. Moreover, the inherent strong Lewis basicity and moderate Lewis acidity favor the oriented conversion of reactants. The controllably hierarchical structure and morphology benefit exposure of more highly dispersed active sites and prolong the catalyst life circle. Especially, an analogous molecular-recognition pattern was found by using sodium lignosulphonate, which is identified as the leading role in noticeably enhancing the catalytic activity and selectivity of the correspondingly ETS-10-based catalyst.

TiO2 nanotubes (TNTs) have been extensively applied in many fields owing to their excellent porous structure and surface properties. Herein, a series of CuO-ZnO-CeO2/TNTs catalysts are synthesized through a deposition-precipitation method. The effects of TNTs content and support morphology on the catalyst physicochemical properties and catalytic performance are investigated. The incorporation of TNTs support into CuO-ZnO-CeO2 catalysts not only promotes CuO reducibility and improves the metallic Cu dispersion and specific surface area, but also enhances CO2 adsorption and increases the proportion of basic sites γ, thereby resulting in high CO2 conversion and CH3OH selectivity. It is also shown that CO2 conversion is positively correlated with the Cu specific surface area and that CH3OH selectivity is related to the proportion of basic sites γ. Due to the excellent reducibility, high metallic Cu surface area, superior CO2 adsorption and large proportion of basic sites γ, CuO-ZnO-CeO2/10 wt.% TNTs gives excellent catalytic performance and possesses a great potential as catalyst for methanol synthesis.

The extrusion of hierarchically porous ZSM-5 zeolite was studied and three important process factors, i.e., the content of pseudo boehmite as binder, content of nitric acid as peptizer, and extrusion speed, were examined. The mechanical properties of the shaped ZSM-5 were investigated by Weibull statistics and the textural properties were studied by nitrogen adsorption/desorption. Results revealed that the extrusion speed affected the mechanical reliability but had less effect on the textural properties. However, the addition of pseudo boehmite and nitric acid not only improved the mechanical reliability but also brought better pore structure. There is, therefore, a great possibility of improving the mechanical reliability and pore structure by optimizing the extrusion conditions. It is shown that the optimal properties of the shaped ZSM-5 could be obtained when 33 wt% pseudo boehmite, 13 wt% nitric acid and 50 r/min extrusion speed were used. The optimized extrusion of hierarchically porous ZSM-5 zeolite might have true industrial potential in the near future.

Hierarchically porous SAPO-11 zeolite (M-SAPO-11) was synthesized and used as support to prepare a series of Cu or/and Ni catalysts. Hydrogenolysis of glycerol was then conducted over the prepared metal-acid bifunctional catalysts. An M-SAPO-11-supported bimetallic catalyst with the Cu/Ni ratio of 2/1 shows extraordinary catalytic activity. The mesopores generated in M-SAPO-11 alleviate the diffusion barriers of reactants that are present in conventional SAPO-11 microporous channels during the liquid-phase reaction. Besides, the added Ni promotes the formation of highly dispersed Cu active phase, which makes the bimetallic catalyst superior to monometallic one. Furthermore, temperature has a greater impact on glycerol conversion in various technological parameters.

Background: Immune checkpoint inhibitor (ICI) combined with chemotherapy as a neoadjuvant therapy has been applied to the treatment of ESCC. However, the optimal regimen needs to be further explored, and the mechanisms by which the ICI combined with chemotherapy modulates the evolution of ESCC are unknown. Methods: In this single-arm phase 2 trial, patients received nab-paclitaxel 260 mg/m2 for 2 cycles and oral S-1 (d1-14, bid) for two weeks, combined with 240 mg intravenous toripalimab for 2 cycles before surgery. The primary outcome was the major pathological response (MPR). Biopsies and plasma before and after neoadjuvant therapy were analyzed for whole-exome sequencing, transcriptome sequencing, PD-L1 expression and 92 proteins using proximity extension assay technology. Results: After neoadjuvant therapy, 26 patients (48.15%) achieved MPR, 16 (29.63%) achieved pCR. 18.3% of the patients experienced grade ≥3 AEs. Compared to patients PD-L1-low, patients with PD-L1-high had a significant higher ratio of PR. During therapy, TMB and TNB were significantly decreased in PR patients, and the ratio of gained and increased clones were significantly lower in MPR patients than nonMPR patients, while the lost and decreased clones were significantly higher in MPR patients than nonMPR patients. Transcriptome analyses before and during therapy revealed CD8 and CD4 T cells were increased in all patients, however, the exhausted cells, nTreg and iTreg were significantly increased in nonMPR patients. Proteins analyses revealed the levels of TRAIL and MUC16 were significantly increased in MPR and PR patients, respectively, while the levels of IFN-γ and IL18 were significantly decreased in MPR and PR patients, respectively. And the expression of ADA, ARG1, CD83, TNFRSF4 and VEGFR2 in plasma were found to be related with serious adverse events. Conclusion: In this study, neoadjuvant therapy with toripalimab, nab-paclitaxel and S-1 was well tolerated and showed promising antitumor activity in patients with resectable ESCC, and the changes of genomic, transcriptome, PD-L1 expression and proteins in plasma were comprehensively analyzed and correlated with clinical outcomes, which provided insight into the mechanism of action of Toripalimab combined with nab-Paclitaxel and S-1 in ESCC patients. Citation Format: Guoqing Zhang, Jing Yuan, Chaohu Pan, Qing Xu, Xiaoli Cui, Jing Zhang, Minglu Liu, Zhigang Song, Liangliang Wu, Dongfang Wu, Bo Yang, Haitao Luo, Yi Hu, Shunchang Jiao. Multi-omics analysis uncovers prognostic biomarkers and tumor ecosystem dynamics during toripalimab combined with nab-paclitaxel and s-1 as neoadjuvant therapy for esophageal squamous carcinoma: A single-center, open-label, single-arm phase 2 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT544.

Basic mesoporous zeolite ETS-10 (ETS-10-M) with high surface area (366 m2·g−1) and large mesopores volume (0.21 cm3·g−1) is synthesized by templated with an organosilan surfactant. After loading of Ni species and calcination, the obtained Ni/ETS-10-M as a bi-functional catalyst shows high activity and good product selectivity in the fluorination of N-aryl amides with N-fluorobenzenesulfonimide (NFSI). The Ni2+ species in Ni/ETS-10-M facilitate the formation of fluorine radical from NFSI, and the basic sites in Ni/ETS-10-M favour N-aryl amide transformation into corresponding carbon-radical, and reacted with fluorine radical to form the desired product. Ni/ETS-10-M catalyst exhibits good catalytic activity even it reused seven times.

Lysosomal acid lipase (LAL)-dependent lipolysis degrades cholesteryl ester (CE) and triglyceride in the lysosome. LAL deficiency in human and mice leads to hypercholesterolemia, hepatic CE deposition, and atherosclerosis. Despite its hepatocyte-specific deficiency leads to CE accumulation, the regulation of LAL in cholesterol metabolic disease remains elusive. For the in vitro study, the target gene Lipa was transfected with recombinant shRNA or lentiviral vector in Hepa1-6 cells. It was found that LAL silencing in cells affected lysosomal function by reducing LAL activity and proteolytic activity, and altered the expression of genes related to cholesterol metabolism and autophagy, leading to cholesterol accumulation; whereas LAL overexpression improved the above effects. To explore the impacts of hepatic LAL on cholesterol metabolic disease in vivo, apolipoprotein E deficient (ApoE−/−) mice were intravenously injected with lentivirus to achieve hepatic LAL overexpression and fed a Western diet for 16 weeks. The results showed that hepatic LAL overexpression significantly reduced plasma lipid levels, alleviated inflammation and oxidative status in plasma and liver, and attenuated hepatic steatosis and fibrosis in ApoE−/− mice. Mechanically, hepatic LAL promoted cholesterol transport and biliary excretion by increasing liver X receptor alpha (LXRα) and its downstream genes, and modulated the compliance of the autophagy-lysosomal pathway. Our data provide the original evidence of the validity of hepatic LAL in controlling cholesterol metabolism and liver homeostasis, suggesting that targeting hepatic LAL may provide a promising approach to rescue cholesterol metabolic disorders, such as hypercholesterolemia and liver disease.

Flexible electronic devices have penetrated into a variety of industry sectors (i.e., consumer electronics, automotive, and medical) in human life, and this calls for better properties of stretchable conductive composites as the crucial elements. Traditionally, conductive inorganic fillers are incorporated in flexible polymers to prepare conductive composites, which falls short of the required properties in more demanding devices nowadays due to limited deformation, low conductivity, and poor processability. Herein, liquid metals were successfully incorporated in microporous polymer matrixes using a simple codissolving and film casting/solvent evaporation approach. The microporous liquid metal-embedded polymer (LMEP) was insulative as fabricated due to discontinuous liquid metals (LMs), while it became conductive upon stretching. Interestingly, the LMEP films showed a reversible insulator-conductor transition due to the regenerated pores in polymer matrix under organic vapor. Negligible changes in the resistance value were seen even after 50 solvent exposure-tensile strain cycles, demonstrating the excellent stability of the electrical properties of these films. Furthermore, most of the commercially available soluble polymers including rigid plastics and soft elastomers are suitable for the fabrication of LMEP. With the ideal characteristics, they have been successfully exploited in model alarm systems to prevent temperature overloads and solvent leakage, showcasing the great potential in next generation sensors used in industry settings.

Background The coronavirus disease 2019 (COVID-19) epidemic has lasted for nearly 4 months by this study was conducted. We aimed to describe drug utilization, disease progression, and adverse drug events of COVID-19. Methods A retrospective, single-center case series study enrolled 165 consecutive hospitalized COVID-19 patients who were followed up until March 25, 2020, from a designated hospital in Wuhan. Patients were grouped by a baseline degree of severity: non-severe and severe. An analytical study of drug utilization, disease progression, and adverse events (AEs) of COVID-19 was conducted. Results Of the 165 COVID-19 cases, antivirals, antibacterials, glucocorticoids, and traditional Chinese medicine (TCM) were administered to 92.7%, 98.8%, 68.5%, and 55.2% of patients, respectively. The total kinds of drugs administered to the severe subgroup [26, interquartile range (IQR) 18-39] were 11 more than the non-severe subgroup (15, IQR 10-24), regardless of comorbidities. The 2 most common combinations of medications in the 165 cases were 'antiviral therapy + glucocorticoids + TCM' (81, 49.1%) and 'antiviral therapy + glucocorticoids' (23, 13.9%). Compared with non-severe cases, severe cases received more glucocorticoids (88.5% vs. 66.2%, P=0.02), but less TCM (50.0% vs. 63.3%, P=0.20), and suffered a higher percentage of death (34.6% vs. 7.2%, P=0.001). At the end of the follow-up, 130 (78.8%) patients had been discharged, and 24 (14.5%) died. There were 13 patients (7.9%) who had elevated liver enzymes, and 49 patients (29.7%) presented with worsening kidney function during the follow-up. Conclusions Of the 165 COVID-19 patients, the fatality rate remained high (14.5%). Drug utilization for COVID-19 was diverse and generally complied with the existing guidelines. Combination regimens containing antiviral drugs might be beneficial to assist COVID-19 recovery. Additionally, liver and kidney AEs should not be ignored.

Background Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease (IBD) with unknown etiology. The lack of specific clinical manifestations, standard diagnostic criteria, objective and accurate indicators to the severity of the disease and the efficacy of the treatment, often results in difficulties in diagnosis and timely treatment of UC. Therefore, there is a need to develop a clinically suitable serum biomarker assay with high specificity and sensitivity. Objective and methods To explore the significance of anti-neutrophil cytoplasmic antibodies (ANCA) and anti-saccharomyces cerevisiae antibodies (ASCA) in the diagnosis, differential diagnosis and treatment assessment in patients with ulcerative colitis (UC). Serum levels of ANCA-IgG, ASCA-IgA and ASCA-IgG were measured by an enzyme-linked immunosorbent assay (ELISA) in 105 UC patients, 52 non-UC patients and 100 healthy controls. Results (1) Both the ANCA-IgG level and its positive rate in UC patients were significantly higher than those in non-UC controls and healthy controls (p p > 0.05). (2) The sensitivity of ANCA+ and ANCA+/ASCA− in detecting UC patients was 61.90% and 55.24%, respectively, whereas the specificity was 91.45% and 94.08%, respectively. The sensitivity of ASCA+ and ASCA+/ANCA− in non-UC disease controls was 5.33% and 3.85%, respectively, and specificity was 83.9% and 88.78%, respectively. (3) When UC patients were grouped into mild, moderate or severe subtypes, the ANCA-IgG levels were correlated with the severity of UC, and the differences of the ANCA-IgG levels were statistically different among the three subtypes (p Conclusions (1) Serum levels of ANCA may be useful in the diagnosis of UC. (2) Dynamic quantitation of ANCA-IgG levels may be helpful in determining the severity of UC and therefore, may guide treatment of UC.

Background: The epidemic of coronavirus disease 2019 (COVID-19) has been lasting for nearly three months Although several treatments have been introduced to th

Hierarchically structured ETS-10-supported highly dispersed Co (Co/HMETS-10) is a promising catalyst to selectively catalyse hydrodeoxygenation (HDO) of lignin-derived phenolic compounds. It is shown that almost 100% guaiacol conversion and 96.9% cyclohexane yield are achieved under mild conditions. Co/HMETS-10 exhibits much higher activity and superior reusability due to the advantageous effects of its unique framework, hierarchical structure, Lewis acid sites and Co species. The hierarchically porous structure benefits mass transfer and facilitates the combination of the reacting substrate and acid, metal sites. The characteristic shape selectivity of ETS-10 structure and moderate amount of Lewis acid lead to the high HDO selectivity. In addition, compared with Ni and Fe, Co is more inclined to function in hydrogenolysis of Caryl–OMe bond, thereby improving the catalytic performance. Further HDO experiments indicate the excellent catalytic performance and extensive applicability in selectively deep deoxygenation of various lignin model compounds for production of cycloalkanes.

Combination of semiconductors is one of the most efficient ways to improve photocatalytic activities. Plate BiOBr loaded plate Bi2O2CO3 facet is fabricated via one-step hydrothermal process, where urea acts not only as carbon source but as capping agent. As-prepared Bi2O2CO3/BiOBr is of an irregular multi-plate shape, a desirable structure for improved photocatalytic properties. Bi2O2CO3/BiOBr nanoplates with exposed active {001} facet exhibit a ciprofloxacin degradation rate of 90% under visible-light for 4 h. The photodegradation mechanism is speculated. The high activity is attributed to the exposed {001} facet of Bi2O2CO3, formation of heterojunction, extended photoresponse range, and efficient charges carrier transfer.

A series of Cu-Ni/CeO2-nanotube catalysts is prepared by an impregnation method for CO2 hydrogenation to CH3OH. Regular CeO2 nanotubes are perfectly formed with a tube diameter of about 30-50 nm and Cu-Ni alloy is well dispersed on CeO2 nanotube without nanotube morphology change. There is a synergistic effect between Ni and Cu, promoting the bimetallic Cu-Ni dispersion, reducibility, CO adsorption and hydrogenation. Additionally, a strong interaction is observed between Cu-Ni alloy and CeO2, and it contributes to partial reduction of Ce4+ to Ce3+ and formation of oxygen vacancies which adsorb and activate CO2. It is shown that both CO2 conversion and CH3OH space-time yield increase at first, reach their maximum values at a Ni/(Cu+Ni) ratio of 2/3, and then decrease with increasing the Ni/(Cu+Ni) ratio. The CeO2-nanotube supported CuNi2 catalyst gives CO2 conversion of 17.8% and CH3OH space-time yield of 18.1 mmol/(gcat∙h) after preliminary optimization. Furthermore, it exhibits an excellent catalytic per...

The phase junction of BiOBr and Bi4O5Br2 nanoplates is constructed by controlling the basicity in one-pot hydrothermal process. The crystalline phase, morphology, optical property, chemical state of surface elements and photocatalytic performance of the obtained samples are investigated in detail. Results display that the stacked BiOBr particles are gradually transformed to Bi4O5Br2 with a multi-plate structure by increasing the pH value. The photocatalytic performance of the obtained samples is estimated by the degradation of ciprofloxacin solution under visible light. It is displayed that the photodegradation activity order is BiOBr/Bi4O5Br2 (pH = 7) > Bi4O5Br2 > BiOBr, which may be associated with the matching band structure and the efficient transfer and separation of charge. Moreover, a reasonable charge separation pathway is surveyed.

Nickel lysine salen complex was successfully synthesized via a stepwise procedure and applied as a heterogeneous catalyst for styrene epoxidation. For comparison, several other transition metal (Mn, Fe, Co, and Cu) lysine salen complexes were also synthesized. The prepared catalysts were characterized by Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX). Data obtained by FT-IR and Raman spectroscopy indicated the formation of C=N bonds and the complexation of these bonds with metal ions. SEM analysis revealed that the complexation of metal ions with the C=N involves the change in surface morphology of samples. In addition, atomic percent composition of samples was obtained from EDX spectra, which was the complementary evidence for the formation of complexes. Results of catalytic measurements showed that a high conversion of styrene (91.51%) and selectivity to styrene oxide (91.99%) could be achieved over the nickel lysine salen complex with tert-butyl hydroperoxide as the oxidant. When the catalyst was reused the conversion of styrene decreased but the selectivity to styrene oxide still remained high.

A highly selective morphology formation of Cu-Ni bimetallic nanocrystals is developed with a solvothermal method, using poly(vinylpyrrolidone) (PVP) as capping agent and aniline as reducing agent in benzyl alcohol. It is shown that temperature is crucial to the controlled synthesis of nanocrystals, and that Cu-Ni nanoparticles evolve from hexagonal nanoplates to nanowires with increasing the concentration of pyrrolidone unit. The synthetic Cu-Ni hexagonal nanoplates and nanowires are well dispersed and have high crystallinity, purity, uniformity of shape and size, and face-centered cubic lattice structure. Furthermore, a mechanism of the formation of Cu-Ni nanocrystals is proposed, and the functions of capping agent, reducing agent, solvent, etc. are discussed. It is also found that both nanoplates and nanowires show better catalytic activities in o-xylene combustion than the conventional catalyst. Especially, the Cu-Ni nanowire catalyst exhibits the most excellent catalytic performance due to the formation of durian-like surface structure.

Transition metal borates, attracting researchers to investigate whether they can exhibit Li cycling similar to the metal oxides, were criticized for their poor electrochemical reversibility. Herein, citric acid assisted sol-gel technique had been used to synthesize high-performance VBO3 anode for Li-ion batteries. High-purity and well-crystallized VBO3 particles covered with amorphous carbon layer (VBO3/carbon) were applied as electrodes for both rechargeable Li and Na batteries. In the Li system, the VBO3/carbon composite delivered a high reversible capacity of 859.5 mA h g−1 in the first cycle, and showed an outstanding rate ability of ∼720 mA h g−1 even at a current density of 200 mA g−1, which suggests both V and B in VBO3 had participated in the electrochemical redox reaction during the Li intercalation and extraction. However, the Na storage of VBO3/carbon after conversion reaction exhibited typical capacitance behavior but poor electrochemical reversibility.

Pei Hu,1,2 Bin Cheng,3 Yulin He,3 Zhiqiang Wei,3 Dongfang Wu,1 Zhongji Meng3,4 1Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, 2Department of Clinical Laboratory Medicine, 3Institute of Biomedical Research, 4Department of Infectious Disease, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China Introduction: Autophagy plays an important role in the growth and survival of hepatocellular carcinoma (HCC) cells through several target proteins or signaling pathways. Glypican-3 (GPC3) is a new reliable HCC marker, which is involved in tumor growth in HCC, primarily mediated by wnt/β-catenin signaling. Objective: The present study aimed to identify the role of autophagy in the proliferation of HepG2 cells through GPC3/wnt/β-catenin signaling. Results and discussion: Results demonstrated that induction of autophagy by nutrition starvation and rapamycin treatment led to the downregulation of GPC3 expression in HepG2 cells, accompanied by the decreased expression of wnt downstream target genes (β-catenin, c-myc and cyclin D1). On the other hand, inhibition of autophagy by 3-methyl adenine (3-MA) could rescue rapamycin-directed downregulation of GPC3 and wnt/β-catenin target genes and augment the proliferation of HepG2 cells. Furthermore, interference of GPC3 by siRNA suppressed wnt/β-catenin signaling and attenuated 3-MA stimulation of HepG2 cell proliferation. More interestingly, the mRNA of GPC3 remained unchanged when the protein levels of GPC3 were decreased by autophagy activation, suggesting that induction of autophagy may accelerate the degradation of GPC3. Conclusion: These results suggest that autophagy suppresses proliferation of HepG2 cells partially by inhibition of GPC3/wnt/β-catenin signaling. Keywords: hepatocellular carcinoma, glypican-3, autophagy, proliferation, wnt/β-catenin signaling

A transesterification reaction has been carried out over a transition metal modified hierarchical ETS-10 (METS-10) catalyst to synthesize glycerol carbonate (GC) from glycerol. The inherent Lewis basicity of ETS-10 favors oriented conversion of glycerol, and the hierarchical structure benefits exposure of more active sites, shortens the molecular diffusion path, suppresses the formation of coke in the micropores, and then enhances the catalytic reactivity and stability. Furthermore, the influence of transition metals (Fe, Co, Ni, Cu, Zn and Mn) on the basic sites of supports has been investigated in detail. It is found that basicity change of the catalyst depends on not only the cation size, nature and composition of the transition metal but also the zeolite structure and pore topology. Besides, the presence of a certain amount of Ni0 species from catalyst reduction has proved to play a critical role in strengthening the interaction of Lewis basic sites (TiO62−) with active glycerol hydroxyl groups. Finally, a 97.7% glycerol conversion and 97.1% GC yield have been obtained over Ni/METS-10, of which the high catalytic performance can be maintained after 8 runs.

Alumina-washcoated FeCrAl alloy sheets are prepared to investigate the effects of metallic substrate pretreatments on the mechanical stability of monolithic catalysts. It is shown that chemical and thermal pretreatments produce different effects on the metallic surface morphology and phase, and different mechanisms are involved in their ways of improving the washcoat adhesion. Combination of chemical and thermal pretreatments leads to the formation of α-alumina whiskers on corroded and rough metallic surface, thus giving the most satisfactory washcoat adhesion. It is also pointed out that not only mechanical shock resistance but also thermal shock resistance is crucial to metallic monolithic catalysts.

A series of composites containing hexagonal tungsten trioxide (h-WO3) and reduced graphene oxide (rGO) sheets are synthesized via a modified one-step hydrothermal route without assisted additive. The composites are characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and UV-vis absorption spectroscopy. The new procedure made it possible to increase the reduction degree of GO. Based on the evidence presented hexagonal WO3 grows on the surface of graphene through chemical interactions with the surface. The visible-light photocatalytic degradation of methylene blue shows that the h-WO3/rGO composites exhibit superior photocatalytic performance of 96% with a maximum degradation rate achieved under visible-light irradiation for 6 h. The speculations concerning the mechanism of photocatalytic reactions are discussed. The improved photocatalytic activity can be accounted for by the increased adsorption toward chemical species, the enhanced light absorption and an efficient separation of photogenerated electron-hole pairs and transfer of charge carriers.

BACKGROUND: High-density lipoprotein (HDL) plays an antiatherogenic role by mediating reverse cholesterol transport (RCT), antioxidation, anti-inflammation, and endothelial cell protection. Recently, series of evidence have shown that HDL can also convert to proatherogenic HDL under certain circumstances. Plasma paraoxonase 1 (PON1) as an HDL-bound esterase, is responsible for most of the antioxidant properties of HDL. However, whether PON1 can serve as a therapeutic target of dysfunctional HDL-related atherosclerosis remains unclear. METHODS: In this study, scavenger receptor class B type I deficient (Scarb1(−/−)) mice were used as the animal model with dysfunctional HDL and increased atherosclerotic susceptibility. Hepatic PON1 overexpression and secretion into circulation were achieved by lentivirus injection through the tail vein. We monitored plasma lipids levels and lipoprotein profiles in Scarb1(−/−) mice, and measured the levels and activities of proteins associated with HDL function. Meanwhile, lipid deposition in the liver and atherosclerotic lesions was quantified. Hepatic genes relevant to HDL metabolism and inflammation were analyzed. RESULTS: The results showed the relative levels of PON1 in liver and plasma were increased by 1.1-fold and 1.6-fold, respectively, and mean plasma PON1 activity was increased by 63%. High-level PON1 increased the antioxidative and anti-inflammatory properties, promoted HDL maturation and macrophage cholesterol efflux through increasing HDL functional proteins components apolipoprotein A1 (APOA1), apolipoprotein E (APOE), and lecithin-cholesterol acyltransferase (LCAT), while decreased inflammatory protein markers, such as serum amyloid A (SAA), apolipoprotein A4 (APOA4) and alpha 1 antitrypsin (A1AT). Furthermore, hepatic PON1 overexpression linked the effects of antioxidation and anti-inflammation with HDL metabolism regulation mainly through up-regulating liver X receptor alpha (LXRα) and its downstream genes. The pleiotropic effects involved promoting HDL biogenesis by raising the level of APOA1, increasing cholesterol uptake by the liver through the APOE-low density lipoprotein receptor (LDLR) pathway, and increasing cholesterol excretion into the bile, thereby reducing hepatic steatosis and aorta atherosclerosis in Western diet-fed mice. CONCLUSIONS: Our study reveals that high-level PON1 improved dysfunctional HDL and alleviated the development of atherosclerosis in Scarb1(−/−) mice. It is suggested that PON1 represents a promising target of HDL-based therapeutic strategy for HDL-related atherosclerotic cardiovascular disease.

Background: Immune checkpoint blockades have revolutionized anticancer treatments for lung cancers, and PD-L1 expression has been served as crucial predictive biomarkers for immunotherapies. However, PD-L1 expression has been found to be influenced by some extrinsic or intrinsic factors in vitro or to be associated with other biomarkers in vivo. Methods: A amount of tumor tissues was taken from a biopsy or surgery for PD-L1 expression assay and genomic profiling in Chinese lung adenocarcinoma patients. In-depth retrospective analyses of clinical features, gene alternations, singling pathways and immune signatures was conducted in negative group (TPS < 1%), intermediate group (1% ≤ TPS < 50%), and high group (TPS ≥ 50%). Clinical responses to selected mutation were also evaluated from public database such as TCGA and MSKCC.Results: A total of 248 Chinese patients with lung adenocarcinoma was retrospectively identified and included in this study, consisting of negative group (n=124, 50%), intermediate group (n=93, 38%), and high group (n=38, 12%). High tumor mutation burden was significantly as associated with high PD-L1 expression. In addition, PD-L1 expression was highly related with gene alternations such as PRKDC, KMT2D, ERBB2 and SETD2. Moreover, signaling pathways of DDR, TP53, cell cycles and NOTCH also obviously related with PD-L1 expression. Besides, most of patients in high PD-L1 group were determined as high-grade immune subtypes (C2-C4), showing significant higher levels of IFN-gamma, CD8+ T-cells, NK cells, NK CD56 dim cells, Th1 cells, Th2 cells (P < 0.0001). Moreover, the prognostic value of SETD2 mutation was slight positive with overall survival from MSKCC cohort (HR 1.92 [95%CI 0.90-4.10], P =0.085), and the percentage of IFN-gamma was significantly higher in SETD2 mutant group than in wild-type subgroup (P < 0.01).Conclusions: This study illustrated in-depth genomic profiles and immune signatures of PD-L1 expression in Chinese lung adenocarcinoma patients, which might interpret more potential molecular mechanisms for anti-cancer immunotherapy in NSCLC.

Developing highly active catalysts for bio-oil hydrodeoxygenation is of great importance in the low cost production of conventional transport alkane fuels. Toward this goal, a Ni catalyst supported on mesoporous ZSM-5 zeolite mixed with 25 wt% γ-Al2O3 (Ni/Al-HMZSM-5) was designed for hydrodeoxygenation of phenol as model compound. For comparison, the catalytic activities of Ni catalysts on conventional microporous ZSM-5, mesoporous ZSM-5 and γ-Al2O3 were also investigated. It was found that almost complete phenol conversion (99.6%) was achieved over the Ni/Al-HMZSM-5 catalyst along with a high cyclohexane selectivity (98.3%) under a relatively mild condition (170 °C, 4 MPa H2). The open mesopores, stronger acid sites and synergism effect of Bronsted and Lewis acidities are jointly responsible for the excellent hydrodeoxygenation performance. In addition, it was shown that the catalyst was recycled several times with little loss of activity and selectivity.

A hierarchically porous ETS-10-supported highly dispersed Ni catalyst was designed to selectively catalyze the conversion of cellulose to levulinic acid under mild reaction conditions. Full conversion of cellulose and remarkably high yield (91.0%) of levulinic acid are achieved due to the synergistic effect of the unique porous structures and Lewis acid sites in the presence of a hydrogen atmosphere. Moderate Lewis acidic centers of the heterogeneous catalyst are revealed to play a positive role in activating the reaction substrates and intermediates, resulting in prominently catalytic activity. Meanwhile, hierarchical pores centered at 16 nm in ETS-10 benefit the mass transfer and therefore further enhance its catalytic performance. Also, during the process of levulinic acid formation, introduction of hydrogen is responsible for converting cellulose thoroughly and keeping the metal Ni from oxidization by the oxy-compounds, which is distinctive from the widely reported pathway dominated only by cellulose ...

Ischemic preconditioning is an endogenous protective mechanism that may be triggered by exposure to hydrogen peroxide (H2O2). However, the exact mechanisms underlying preconditioning remain to be fully understood. Ataxia-telangiectasia mutated (ATM) is regarded as an essential endogenous protective protein against stress. The aim of the present study was therefore to investigate whether ATM mediates H2O2 preconditioning. Preconditioning of Neuro‑2a (N2a) cells with 100 µM H2O2 for 90 min resulted in protection from injury induced by a long period of exposure to 600 µM H2O2. In addition, preconditioning with 100 µM H2O2 activated ATM and increased ATM mRNA and protein expression levels in N2a cells. Furthermore, the protective effects induced by H2O2 preconditioning were attenuated by pretreatment with the ATM inhibitor, Ku55933, or ATM small interfering RNA. In conclusion, these findings suggested that ATM is involved in H2O2 preconditioning‑mediated protection against oxidative stress‑induced injury in N2a cells. To the best of our knowledge, the present study demonstrated, for the first time, that the ATM protein is a key mediator of H2O2 preconditioning.