Evaluating the synergistic effect of digitalization and industrialization on total factor carbon emission performance.

Combating climate change and reducing carbon dioxide emissions are serious challenges shared by countries around the world. In the current era, digitalization has a significant impact on CO2 emissions. However, prior studies have not assessed the synergy between digitalization and industrialization on carbon emission performance. The principal component analysis and non-radial directional distance function (NDDF) are used to measure the digitalization and total factor carbon emission performance of Chinese 245 prefecture-level cities from 2003 to 2019. This study establishes a fixed effects model to study the panel data. The findings are as follows: (1) Digitalization can significantly promote Chinese cities' CO2 emission reduction. This result still holds after several robustness checks. (2) The heterogeneity results indicate that digitalization mainly improves central cities' carbon emission performance. Meanwhile, the impact of digitalization is more obvious after 2011. (3) Digitalization improves urban carbon emission performance through energy efficiency, industrial transformation, and technological innovation. (4) It is worth noting that digitalization synergizes with industrialization to improve carbon emission performance in Chinese cities. This study provides empirical evidence and some constructive policy recommendations for the government to push the collaborative development of the digitalization and low-carbon economy.

Cross-influence of information and risk effects on the IPO market: exploring risk disclosure with a machine learning approach.

The paper examines whether the structure of the risk factor disclosure in an IPO prospectus helps explain the cross-section of first-day returns in a sample of Chinese initial public offerings. This paper analyzes the semantics and content of risk disclosure based on an unsupervised machine learning algorithm. From both long-term and short-term perspectives, this paper explores how the information effect and risk effect of risk disclosure play their respective roles. The results show that risk disclosure has a stronger risk effect at the semantic novelty level and a more substantial information effect at the risk content level. A novel aspect of the paper lies in the use of text analysis (semantic novelty and content richness) to characterize the structure of the risk factor disclosure. The study shows that initial IPO returns negatively correlate with semantic novelty and content richness. We show the interaction between risk effect and information effect on risk disclosure under the nature of the same stock plate. When enterprise information transparency is low, the impact of semantic novelty and content richness on the IPO market is respectively enhanced.

Outlier knowledge management for extreme public health events: Understanding public opinions about COVID-19 based on microblog data.

Based on complex adaptive system theory and information theory for investigating heterogeneous situations, this paper develops an outlier knowledge management framework based on three aspects-dimension, object, and situation-for dealing with extreme public health events. In the context of the COVID-19 pandemic, we apply advanced natural language processing (NLP) technology to conduct data mining and feature extraction on the microblog data from the Wuhan area and the imported case province (Henan Province) during the high and median operating periods of the epidemic. Our experiment indicates that the semantic and sentiment vocabulary of words, the sentiment curve, and the portrait of patients seeking help were all heterogeneous in the context of COVID-19. We extract and acquire the outlier knowledge of COVID-19 and incorporate it into the outlier knowledge base of extreme public health events for knowledge sharing and transformation. The knowledge base serves as a think tank for public opinion guidance and platform suggestions for dealing with extreme public health events. This paper provides novel ideas and methods for outlier knowledge management in healthcare contexts.

Synthesis, Molecular Docking Analysis, and Biological Evaluations of Saccharide-Modified Sulfonamides as Carbonic Anhydrase IX Inhibitors.

Based on the strategy of the "tail approach", 15 novel saccharide-modified sulfonamides were designed and synthesised. The novel compounds were evaluated as inhibitors of three human carbonic anhydrase (CA) isoforms, namely cytoplasmic CA II, transmembrane CA IX, and XII. Most of these compounds showed good activity against CAs and high topological polar surface area (TPSA) values, which had a positive effect on the selective inhibition of transmembrane isoforms CA IX and XII. In the in vitro activity studies, compounds 16a, 16b, and 16e reduced the viability of HT-29 and MDA-MB-231 cells with a high expression of CA IX under hypoxia. The inhibitory activity of compound 16e on the human osteosarcoma cell line MG-63 with a high expression of CA IX and XII was better than that of AZM. Moreover, high concentrations of compounds 16a and 16b reversed the acidification of the tumour microenvironment. In addition, compound 16a had a certain inhibitory effect on the migration of MDA-MB-231 cells. All the above results indicate that the saccharide-modified sulfonamide has further research value for the development of CA IX inhibitors.

Infrared Thermal Imaging of Patients With Acute Upper Respiratory Tract Infection: Mixed Methods Analysis.

BACKGROUND: Upper respiratory tract infection is a common disease of the respiratory system. Its incidence is very high, and it can even cause pandemics. Infrared thermal imaging (IRTI) can provide an objective and quantifiable reference for the visual diagnosis of people with acute respiratory tract infection, and it can function as an effective indicator of clinical diagnosis. OBJECTIVE: The aims of this study are to observe and analyze the infrared expression location and characteristics of patients with acute upper respiratory tract infection through IRTI technology and to clearly express the quantification of temperature, analyze the role of IRTI in acute upper respiratory tract diagnostic research, and understand the impact of IRTI in qualitative and quantitative research. METHODS: From December 2018 to February 2019, 154 patients with acute upper respiratory tract infection were randomly selected from the emergency department of the First Affiliated Hospital of Guangzhou Medical University. Among these patients, 73 were men and 81 were women. The subjects were divided into two groups according to the presence of fever, namely, fever and nonfever groups. Qualitative and quantitative analyses of the infrared thermal images were performed to compare the results before and after application of the technology. RESULTS: Using the method described in this paper, through the analysis of experimental data, we elucidated the role of IRTI in the diagnosis of acute upper respiratory tract infection, and we found that qualitative and quantitative IRTI analyses play important roles. Through the combination of theory and experimental data, the IRTI analysis showed good results in identifying acute upper respiratory tract infection. CONCLUSIONS: IRTI technology plays an important role in identifying the infrared expression location and characteristics of patients with acute upper respiratory tract infection as well as in the quantification of clear expression of body temperature, and it provides an objective and quantifiable reference basis for elucidating the pathogenesis of these patients.

Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives.

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the "tail approach" and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.

Global analysis of HBV-mediated host proteome and ubiquitylome change in HepG2.2.15 human hepatoblastoma cell line.

Hepatitis B virus (HBV) infection remains a major health issue worldwide and the leading cause of cirrhosis and hepatocellular carcinoma (HCC). It has been reported previously that HBV invasion can extensively alter transcriptome, the proteome of exosomes and host cell lipid rafts. The impact of HBV on host proteins through regulating their global post-translational modifications (PTMs), however, is not well studied. Viruses have been reported to exploit cellular processes by enhancing or inhibiting the ubiquitination of specific substrates. Nevertheless, host cell physiology in terms of global proteome and ubiquitylome has not been addressed yet. Here by using HBV-integrated HepG2.2.15 model cell line we first report that HBV significantly modify the host global ubiquitylome. As currently the most widely used HBV cell culture model, HepG2.2.15 can be cultivated for multiple generations for protein labeling, and can replicate HBV, express HBV proteins and secrete complete HBV Dane particles, which makes it a suitable cell line for ubiquitylome analysis to study HBV replication, hepatocyte immune response and HBV-related HCC progression. Our previous experimental results showed that the total ubiquitination level of HepG2.2.15 cell line was significantly higher than that of the corresponding parental HepG2 cell line. By performing a Ubiscan quantification analysis based on stable isotope labeling of amino acids in cell culture (SILAC) of HepG2.2.15 and HepG2 cell lines, we identified a total of 7188 proteins and the protein levels of nearly 19% of them were changed over 2-folds. We further identified 3798 ubiquitinated Lys sites in 1476 host proteins with altered ubiquitination in response to HBV. Our results also showed that the global proteome and ubiquitylome were negatively correlated, indicating that ubiquitination might be involved in the degradation of host proteins upon HBV integration. We first demonstrated the ubiquitination change of VAMP3, VAMP8, DNAJB6, RAB8A, LYN, VDAC2, OTULIN, SLC1A4, SLC1A5, HGS and TOLLIP. In addition, we described 5 novel host factors SLC1A4, SLC1A5, EIF4A1, TOLLIP and BRCC36 that efficiently reduced the amounts of secreted HBsAg and HBeAg. Overall, the HBV-mediated host proteome and ubiquitylome change we reported will provide a valuable resource for further investigation of HBV pathogenesis and host-virus interaction networks.

FRET imaging revealed that nanocrystals enhanced drug oral absorption by dissolution rather than endocytosis: A case study of coumarin 6.

Nanocrystals (NCs) exhibit potential in improving oral bioavailability for poorly water-soluble drugs. However, whether NCs improve oral absorption by quick dissolution or by endocytosis remains inconclusive because tracking of dissolved drugs and NCs particles cannot occur simultaneously. In this study, we aim to elucidate how NCs improve oral absorption by using coumarin 6 (C6), an aggregation-caused quenching fluorophore, and 2-((5-(4-(dip-tolylamino)phenyl)thiophen-2-yl)methylene)malononitrile (MeTTMN), an aggregation-induced emission fluorophore. C6 was used as a model drug to prepare NCs and MeTTMN was incorporated to construct fluorescence resonance energy transfer (FRET) pairs. Thus, the molecular absorption can be detected using the fluorescence signal of dissolved C6 and the NCs particles can be tracked simultaneously by monitoring FRET signals. The reliability of this tracking method was validated. Accordingly, in vitro dissolution, gastrointestinal traffic, and biodistribution studies were conducted. The results showed that dissolved C6 molecules were the main absorption mode of C6 NCs. Identification of such pathways bears considerable significance for the broad application of drug NCs in improving the druggability of insoluble drugs.

Suppression of HIV-1 Integration by Targeting HIV-1 Integrase for Degradation with A Chimeric Ubiquitin Ligase.

Human immunodeficiency virus (HIV) attacks human immune system and causes life-threatening acquired immune deficiency syndrome (AIDS). Treatment with combination antiretroviral therapy (cART) could inhibit virus growth and slow progression of the disease, however, at the same time posing various adverse effects. Host ubiquitin-proteasome pathway (UPP) plays important roles in host immunity against pathogens including viruses by inducing degradation of viral proteins. Previously a series of methods for retargeting substrates for ubiquitin-proteasome degradation have been successfully established. In this study, we attempted to design and construct artificial chimeric ubiquitin ligases (E3s) based on known human E3s in order to manually target HIV-1 integrase for ubiquitin proteasome pathway-mediated degradation. Herein, a series of prototypical chimeric E3s have been designed and constructed, and original substrate-binding domains of these E3s were replaced with host protein domains which interacted with viral proteins. After functional assessment screening, 146LI was identified as a functional chimeric E3 for HIV-1 NL4-3 integrase. 146LI was then further optimized to generate 146LIS (146LI short) which has been shown to induce Lys48-specific polyubiquitination and reduce protein level of HIV-1 NL4-3 integrase more effectively in cells. Lymphocyte cells with 146LIS knock-in generated by CRISPR/Cas-mediated homology-directed repair (HDR) showed remarkably decreased integration of HIV-1 NL4-3 viral DNAs and reduced viral replication without obvious cell cytotoxicity. Our study successfully obtained an artificial chimeric E3 which can induce Lys48-specific polyubiquitination and proteasome-mediated degradation of HIV-1 NL4-3 integrase, thus effectively inhibiting viral DNA integration and viral replication upon virus infection.

Information technology solutions, challenges, and suggestions for tackling the COVID-19 pandemic.

Various technology innovations and applications have been developed to fight the coronavirus pandemic. The pandemic also has implications for the design, development, and use of technologies. There is an urgent need for a greater understanding of what roles information systems and technology researchers can play in this global pandemic. This paper examines emerging technologies used to mitigate the threats of COVID-19 and relevant challenges related to technology design, development, and use. It also provides insights and suggestions into how information systems and technology scholars can help fight the COVID-19 pandemic. This paper helps promote future research and technology development to produce better solutions for tackling the COVID-19 pandemic and future pandemics.

Prone versus Supine Position Ventilation in Adult Patients with Acute Respiratory Distress Syndrome: A Meta-Analysis of Randomized Controlled Trials.

The purpose of this meta-analysis was to compare the efficacy and safety of prone versus supine position ventilation for adult acute respiratory distress syndrome (ARDS) patients. The electronic databases of PubMed, Embase, and the Cochrane Library were systematically searched from their inception up to September 2020. The relative risks (RRs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were employed to calculate pooled outcomes using the random-effects models. Twelve randomized controlled trials that had recruited a total of 2264 adults with ARDS were selected for the final meta-analysis. The risk of mortality in patients who received prone position ventilation was 13% lower than for those who received supine ventilation, but this effect was not statistically significant (RR: 0.87; 95% CI: 0.75-1.00; P = 0.055). There were no significant differences between prone and supine position ventilation on the duration of mechanical ventilation (WMD: -0.22; P = 0.883) or ICU stays (WMD: -0.39; P = 0.738). The pooled RRs indicate that patients who received prone position ventilation had increased incidence of pressure scores (RR: 1.23; P = 0.003), displacement of a thoracotomy tube (RR: 3.14; P = 0.047), and endotracheal tube obstruction (RR: 2.45; P = 0.001). The results indicated that prone positioning during ventilation might have a beneficial effect on mortality, though incidence of several adverse events was significantly increased for these patients.

miR-let-7a suppresses α-Synuclein-induced microglia inflammation through targeting STAT3 in Parkinson's disease.

Microglia-mediated neuroinflammation is critical for the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). microRNA-let-7a (miR-let-7a) targets the signal transducer and activator of transcription-3 (STAT3) and regulates microglia function. However, less is known about whether it plays a functional role in PD. In this report, by utilizing a mouse PD model induced by the overexpression of α-Synuclein (α-Syn), a pathological hallmark of PD, we found that miR-let-7a expression was downregulated, while STAT3 was synchronously activated in the substantia nigra pars compacta (SNpc). Similar results were obtained in α-Syn-treated BV-2 microglia cells cultured in vitro. Additionally, STAT3 was proven to be a direct target of miR-let-7a in BV-2 microglia cells, suggesting that miR-let-7a downregulation may contribute to STAT3 activation in α-Syn-induced mouse PD. Moreover, miR-let-7a overexpression suppressed α-Syn-induced BV-2 microglia cell activation and pro-inflammatory cytokine production, and these effects were abrogated by restoring STAT3 protein, hence establishing that miR-let-7a suppresses microglia-mediated inflammation through targeting STAT3. Lastly, miR-let-7a overexpression via injection of miR-7 mimics into mouse striatum suppressed microglia activation and reduced pro-inflammatory cytokine production, which were accompanied by relieved movement disorder and improved spatial memory deficits in α-Syn-induced PD mice. Altogether, these results may identify miR-let-7a as a negative regulator of microglia-elicited neuroinflammation, at least partially explaining its alleviating effects on PD symptoms.

Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase Inhibitory Evaluations of Benzenesulfonamide Derivatives Containing Thiazolidinone.

To find novel human carbonic anhydrase (hCA) inhibitors, we synthesized thirteen compounds by combining thiazolidinone with benzenesulfonamide. The result of the X-ray single-crystal diffraction experiment confirmed the configuration of this class of compounds. The enzyme inhibition assays against hCA II and IX showed desirable potency profiles, as effective as the positive controls. The docking studies revealed that compounds (2) and (7) efficiently bound in the active site cavity of hCA IX by forming sufficient interactions with active site residues. The fragment of thiazolidinone played an important role in the binding of the molecules to the active site.

Exploring Risks Transferred from Cloud-Based Information Systems: A Quantitative and Longitudinal Model.

With the growing popularity of Internet of Things (IoT) and Cyber-Physical Systems (CPS), cloud- based systems have assumed a greater important role. However, there lacks formal approaches to modeling the risks transferred through information systems implemented in a cloud-based environment. This paper explores formal methods to quantify the risks associated with an information system and evaluate its variation throughout its implementation. Specifically, we study the risk variation through a quantitative and longitudinal model spanning from the launch of a cloud-based information systems project to its completion. In addition, we propose to redefine the risk estimation method to differentiate a mitigated risk from an unmitigated risk. This research makes valuable contributions by helping practitioners understand whether cloud computing presents a competitive advantage or a threat to the sustainability of a company.

Expression profiles of long noncoding RNAs and mRNAs in post-cardiac arrest rat brains.

To investigate long noncoding (lnc)-RNA and mRNA expression profiles in post­cardiac arrest (CA) brains, an external transthoracic electrical current was applied for 8 min to induce CA (the CA group). A total of 4 rats received sham-operations and served as the blank control (BC) group. Upon return of spontaneous circulation (ROSC), lncRNA and mRNA expression in the rat cerebral cortex was assayed with high­throughput Agilent lncRNA and mRNA microarrays. In total, 37 lncRNAs were upregulated and 21 lncRNAs were downregulated in the CA group, and 258 mRNA transcripts were differentially expressed with 177 mRNAs upregulated and 81 mRNAs downregulated in the CA group. The differentially expressed lncRNAs in the CA group were co­expressed with thousands of mRNAs. The differentially expressed lncRNAs could be clustered into >100 signaling pathways and processes according to Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. The most common predicted functions involved metabolic pathways, protein synthesis, transport and degradation during CA­ROSC. CA­ROSC led to significant alterations in cerebral lncRNA and mRNA expression profiles. Thus, lncRNA­mRNA network interactions have the potential to regulate vital metabolic pathways and processes involved in CA-ROSC.

Synthesis, biological evaluation and structure-activity relationship studies of hederacolchiside E and its derivatives as potential anti-Alzheimer agents.

Inspired by the previously reported neuroprotective activity of hederacolchiside E (1), we synthesized hederacolchiside E for the first time along with eleven of its derivatives. The neuroprotective effects of these compounds were further evaluated against H2O2- and Aß1-42-induced injury using cell-based assays. The derivatives showed obvious differences in activity due to structural variations, and two of them exhibited better neuroprotective effects than 1 in the Aß1-42-induced injury model. Compound 7 was the most active derivative and had a relatively simple chemical structure. Moreover, 1 and 7 can significantly reduce the release of lactate dehydrogenase (LDH), level of intracellular reactive oxygen species (ROS) and extent of malondialdehyde (MDA) increase resulting from Aß1-42 treatment, which demonstrated that these kinds of compounds show neuroprotective effects in Alzheimer's disease (AD) models via modulating oxidative stress. Compound 7 could be used as promising lead for the development of a new type of neuroprotective agent against AD.

Impact of pneumonia and lung cancer on mortality of women with hypertension.

Essential hypertension is one of the most severe women's health problems. Modern life brings more chances of pulmonary diseases to human. The purpose of the study is to investigate weather pneumonia and lung cancer are associated with the mortality of women with hypertension in different age. A cross-sectional retrospective study was conducted in women with hypertension, who were admitted into our hospital in 2004-2013. 14219 women were enrolled and 68.8 ± 12.2 year old (y). Isolated hypertension was 14.7%. The age of death was 78.1 ± 9.8 y. The mortality was 4.4% for average and 0.2%, 1.1%, 2.4%, 4.8%, 10.4% and 15.8% in group age ≦49, 50-59, 60-69, 70-79, 80-89 and ≧90 y separately. This mortality increased with age was positively significantly correlated with the increased incidences of pneumonia (P < 0.05, r = 0.77). Pneumonia was a significant risk associated with the mortality in age 55-89 y (OR = 6.4-22.5; 95% CI = 3.06-51.12). While, lung cancer was the significant risk in 70-79 y. These observations indicate that pneumonia and lung cancer are significant risk factors associated with the mortality of certain age women with hypertension, and bring an alert that pneumonia and lung cancer should be prevented and treated intensively in modern life in order to reduce the mortality.