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As one of the largest and most representative families of natural medicines harvested from plants, the mass production of opioids legitimately occupies large, worldwide farmland cultivation of opiu...

As of August 27, 2021, the ongoing pandemic of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has spread to over 220 countries, areas, and territories. Thus far, 214,468,601 confirmed cases, including 4,470,969 deaths, have been reported to the World Health Organization. To combat the COVID‐19 pandemic, multiomics‐based strategies, including genomics, transcriptomics, proteomics, and metabolomics, have been used to study the diagnosis methods, pathogenesis, prognosis, and potential drug targets of COVID‐19. In order to help researchers and clinicians to keep up with the knowledge of COVID‐19, we summarized the most recent progresses reported in omics‐based research papers. This review discusses omics‐based approaches for studying COVID‐19, summarizing newly emerged SARS‐CoV‐2 variants as well as potential diagnostic methods, risk factors, and pathological features of COVID‐19. This review can help researchers and clinicians gain insight into COVID‐19 features, providing direction for future drug development and guidance for clinical treatment, so that patients can receive appropriate treatment as soon as possible to reduce the risk of disease progression., In the global COVID‐19 pandemic, multiomics‐based strategies have been applied into the surveillance of newly emerged SARS‐CoV‐2 variants and the study of diagnostic methods, risk factors, and pathological features of COVID‐19, which will contribute to the prevention and control of this pandemic.

An outbreak of COVID-19 that began in late 2019 was caused by a novel coronavirus(SARS-CoV-2). It has become a global pandemic. As of June 9, 2020, it has infected nearly 7 million people and killed more than 400,000, but there is no specific drug. Therefore, there is an urgent need to find or develop more drugs to suppress the virus. Here, we propose a new nonlinear end-to-end model called LUNAR. It uses graph convolutional neural networks to automatically learn the neighborhood information of complex heterogeneous relational networks and combines the attention mechanism to reflect the importance of the sum of different types of neighborhood information to obtain the representation characteristics of each node. Finally, through the topology reconstruction process, the feature representations of drugs and targets are forcibly extracted to match the observed network as much as possible. Through this reconstruction process, we obtain the strength of the relationship between different nodes and predict drug candidates that may affect the treatment of COVID-19 based on the known targets of COVID-19. These selected candidate drugs can be used as a reference for experimental scientists and accelerate the speed of drug development. LUNAR can well integrate various topological structure information in heterogeneous networks, and skillfully combine attention mechanisms to reflect the importance of neighborhood information of different types of nodes, improving the interpretability of the model. The area under the curve(AUC) of the model is 0.949 and the accurate recall curve (AUPR) is 0.866 using 10-fold cross-validation. These two performance indexes show that the model has superior predictive performance. Besides, some of the drugs screened out by our model have appeared in some clinical studies to further illustrate the effectiveness of the model.

Inorganic cesium lead halide perovskites offer a pathway towards thermally stable photovoltaics. However, moisture-induced phase degradation restricts the application of hole transport layers (HTLs) with hygroscopic dopants. Dopant-free HTLs fail to realize efficient photovoltaics due to severe electrical loss. Herein, we developed an electrical loss management strategy by manipulating poly(3-hexylthiophene) with a small molecule, i.e., SMe-TATPyr. The developed P3HT/SMe-TATPyr HTL shows a three-time increase of carrier mobility owing to breaking the long-range ordering of "edge-on" P3HT and inducing the formation of "face-on" clusters, over 50 % decrease of the perovskite surface defect density, and a reduced voltage loss at the perovskite/HTL interface because of favorable energy level alignment. The CsPbI2 Br perovskite solar cell demonstrates a record-high efficiency of 16.93 % for dopant-free HTL, and superior moisture and thermal stability by maintaining 96 % efficiency at low-humidity condition (10-25 % R. H.) for 1500 hours and over 95 % efficiency after annealing at 85 °C for 1000 hours.

In this work, a new small molecular material, 9,9'-(pyrene-1,6-diyldimethylylidene)bis[N,N,N′,N′-tetrakis(4-methoxyphenyl)-9H-fluorene-2,7-diamine] (PFD), as a hole-transporting layer was designed for perovskite solar cells (PSCs). PFD has a rigid and flat pyrene unit as the central building block and a symmetric structure to increase the conjugation degree for better carrier conductivity. A power conversion efficiency (PCE) of 18.6% was achieved for PSC based on undoped PFD. When spiro-OMeTAD is further introduced on the top of PFD (PFD/spiro-OMeTAD), a PCE of 21.02% was achieved with a steady-state efficiency of 19.92%, revealing that PFD as an interfacial layer could restrain carrier recombination. Unencapsulated devices based on PFD or PFD/spiro-OMeTAD exhibit excellent stability including long-term stability for over 1400 h under ambient condition, and moisture stability under the “Double 60 program” test simultaneously at 60% RH and 60 °C in air. Besides, no obvious degradation was found for the PFD/spiro-OMeTAD device over 200 h under continuous illumination at the maximum power point tracking (MPPT) in N2 atmosphere. It is thus suggested that PFD could be a promising dopant-free HTM for PSCs, and also acts as an interface layer to suppress the carrier recombination to further improve the device performance.

The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism, blood coagulation, immune response, angiogenesis, and cell microenvironment regulation. Several inflammatory factors were upregulated, which was possibly caused by the activation of NF-κB signaling. Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered. Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection, and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.

There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes has been named coronavirus disease 2019 (COVID-19). More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was 1%–2%. No specific treatment has been reported. Herein, we examined the effects of favipiravir (FPV) versus lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million international unit (IU) twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million IU twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance median time was found for the FPV arm versus the control arm (4 d (interquartile range (IQR): 2.5–9) versus 11 d (IQR: 8–13), P < 0.001). The FPV arm also showed significant improvement in chest CT compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest CT. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.

The recent outbreak of novel coronavirus pneumonia (COVID-19) caused by a new coronavirus has posed a great threat to public health. Identifying safe and effective antivirals is of urgent demand to cure the huge number of patients. Virus-encoded proteases are considered potential drug targets. The human immunodeficiency virus protease inhibitors (lopinavir/ritonavir) has been recommended in the global Solidarity Trial in March launched by World Health Organization. However, there is currently no experimental evidence to support or against its clinical use. We evaluated the antiviral efficacy of lopinavir/ritonavir along with other two viral protease inhibitors in vitro, and discussed the possible inhibitory mechanism in silico. The in vitro to in vivo extrapolation was carried out to assess whether lopinavir/ritonavir could be effective in clinical. Among the four tested compounds, lopinavir showed the best inhibitory effect against the novel coronavirus infection. However, further in vitro to in vivo extrapolation of pharmacokinetics suggested that lopinavir/ritonavir could not reach effective concentration under standard dosing regimen [marketed as Kaletra®, contained lopinavir/ritonavir (200 mg/50 mg) tablets, recommended dosage is 400 mg/10 mg (2 tablets) twice daily]. This research concluded that lopinavir/ritonavir should be stopped for clinical use due to the huge gap between in vitro IC50 and free plasma concentration. Nevertheless, the structure–activity relationship analysis of the four inhibitors provided further information for de novel design of future viral protease inhibitors of SARS-CoV-2.

SARS-CoV-2 has been widely spread around the world and COVID-19 was declared a global pandemic by the World Health Organization. Limited clinically effective antiviral drugs are available now. The development of anti-SARS-CoV-2 drugs has become an urgent work worldwide. At present, potential therapeutic targets and drugs for SARS-CoV-2 are continuously reported, and many repositioning drugs are undergoing extensive clinical research, including remdesivir and chloroquine. On the other hand, structures of many important viral target proteins and host target proteins, including that of RdRp and Mpro were constantly reported, which greatly promoted structure-based drug design. This paper summarizes the current research progress and challenges in the development of anti-SARS-CoV-2 drugs, and proposes novel short-term and long-term drug research strategies.

Clinically diagnosing low-grade gliomas and microscopic metastatic tumors in the spinal cord using magnetic resonance imaging (MRI) is challenging, as the blood-brain barrier (BBB) almost completely excludes the MRI contrast agent gadopentetate dimeglumine, GdDTPA (Magnevist), from the brain. The development of a more efficient, safe, and broad-spectrum glioma diagnosis and treatment would therefore have a great clinical value. Based on the high expression levels of both transferrin receptor 1 (TfR1) and low-density lipoprotein receptor-related protein 1 (LRP1) in BBB-related cells and glioma cells, we designed a novel protein nanoparticle, ferritin-HREV107-Angiopep-2 (Fn-Rev-Ang). We found that Fn-Rev-Ang rapidly crossed the BBB in mice and had drug-loading properties. Moreover, the brain MRI signal intensity ratio associated with Fn-Rev-Ang-GdDTPA was higher than that associated with Fn-GdDTPA alone. Importantly, gliomas with diameters below 1 mm and microscopic metastatic tumors in the spinal cord were successfully detected in mice by MRI with Fn-Rev-Ang-GdDTPA, which is not possible using the current clinical MRI technology. In addition, Fn-Rev-Ang-loaded doxorubicin had a strong inhibitory effect on mouse brain gliomas and their metastasis, which significantly prolonged the animal survival time. Thus, our newly constructed Fn-Rev-Ang nanodelivery carrier may help expand the use of MRI to the early diagnosis and treatment of microscopic tumors, thereby offering a possible basis for improving the survival rate of patients with gliomas and microscopic spinal metastatic tumors.

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.

Currently, there is an urgent need to develop low-cost hole-transporting materials (HTMs) for inverted perovskite solar cells (PSCs), whose power conversion efficiency (PCE) is still inferior to th...

AIM: To evaluate the anatomic and visual outcomes of 25-gauge vitrectomy combined with air tamponade for the treatment of idiopathic macular hole (IMH). METHODS: Thirty eyes of 27 patients with IMH were included in this prospective interventional study. All patients underwent 25-gauge pars plana vitrectomy (PPV) combined with phacoemulsification and air tamponade. Best corrected visual acuity [BCVA; logarithm of the minimum angle of resolution (logMAR)], perimetry and multifocal electroretinography (mfERG) were conducted before and after the operation. Anatomical changes were evaluated with optical coherence tomography (OCT). RESULTS: The macular holes closed successfully in 28 eyes after the primary vitrectomy. The mean BCVA improved from 0.72±0.22 logMAR preoperatively to 0.29±0.18 logMAR postoperatively (P

The electrochromic property and device construction of a triphenylamine-based oriented two-dimensional covalent organic framework (2D COF) film on indium tin oxide (ITO) coated glass was reported. The characterization of the 2D COF3PA-TT film revealed that the film was uniform, with good crystallinity, and oriented with its 2D plane parallel to the substrate. For the first time, the electrochromic properties of 2D COF3PA-TT film were studied. 2D COF3PA-TT film on ITO exhibited reversible color transition between deep red and dark brown during redox process. Spectroelectrochemical experiments revealed color changes in the absorption spectra of 2D COF3PA-TT film in the visible and near-infrared regions and showed the characteristics of intervalence charge transfer. The quasi-solid-state electrochromic device was prepared based on the COF3PA-TT film, and it exhibited moderate performance and stability in the near-infrared region.

Background Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Acupotomy may be effective for KOA, but the evidence is limited. This trial aims to determine the effectiveness and safety of acupotomy for KOA. Methods/design This is a parallel-group, assessor-blinded randomized controlled trial. Two hundred patients with KOA will be recruited and randomly assigned to two groups (group A or group D) in a 1:1 ratio. Patients in group A will receive acupotomy and topical diclofenac diethylamine for 4 weeks, while patients in group D will receive topical diclofenac diethylamine alone for 4 weeks. The primary outcome will be the response rate—the proportion of patients who achieve the minimal clinically important improvement in pain and function at week 4 compared with baseline. Secondary outcomes will include pain, function, quality of life, the use of rescue medicine (loxoprofen sodium), and adverse events at weeks 4, 8, and 24 after randomization. Besides, joint fluid and serum will be collected to assess the level of inflammatory cytokines, like TNF-α, IL-1β, and MMP-3. Discussion This study will contribute to a better understanding of the effectiveness and safety of acupotomy in combination with topical nonsteroidal anti-inflammatory drugs. If the hypothesis is confirmed, acupotomy may be recommended as adjunctive therapy for patients with KOA. Results of the study will be of great importance for the guidelines of clinical therapy. Trial registration Chinese Clinical Trial Registry ChiCTR2100043005 Registered on 4 February 2021.

PURPOSE The aim of this study was to analyze the application effect of medical adhesive in emergency surgical scalp and facial skin treatment. To explore the better application of medical adhesive in emergency work. METHODS A total of 180 patients with scalp and facial skin laceration admitted to the emergency department of the Affiliated Hospital of Southwest Medical University from August 2018 to August 2019 were selected. The patients were divided into the control group (n = 70) and the treatment group (n = 110) using the random number table method. The control group was treated with debridement, local anesthesia, and suture technique without medical adhesive, whereas the treatment group was treated with medical adhesive after debridement without local anesthesia. The operation time, pain degree, total cost, and satisfaction of the 2 groups were compared. RESULTS The operation time in treatment group was shorter than that in control group (12.0 ± 2.6 minutes versus 17.7 ± 2.5 minutes, P

Background Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel. Methods and design A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3–4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session. Discussion This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial. Trial registration Chinese Clinical Trial Registry ChiCTR1800014400. Registered on 10 January 2018

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92–0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis., The systemic immune features that distinguish COVID-19 from common infections remain incompletely elucidated. Here McClain et al. compare RNA sequencing in peripheral blood between subjects with SARS-CoV-2 and other respiratory infections and demonstrate dysregulated immune responses in COVID-19 with both heterogeneous and conserved components.

Information encryption and decryption have attracted particular attention; however, the applications are frequently restricted by limited coding capacity due to the indistinguishable broad photoluminescence band of conventional stimuli-responsive fluorescent materials. Here, we present a concept of confidential information encryption with photoresponsive liquid crystal (LC) lasing materials, which were used to fabricate ordered microlaser arrays through a microtemplate-assisted inkjet printing method. LC microlasers exhibit narrow-bandwidth single-mode emissions, and the wavelength of LC microlasers was reversibly modulated based on the optical isomerization of the chiral dopant in LCs. On this basis, we demonstrate phototunable information authentication on LC microlaser arrays using the wavelength of LC microlasers as primary codes. These results provide enlightenment for the implementation of microlaser-based cryptographic primitives for information encryption and anticounterfeiting applications.

BackgroundSubstantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. Methods: Rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified published and unpublished RCTs by September 14, 2020 (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, PubMed, Cochrane COVID-19 registry). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine/chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status.ResultsSixty-two trials were potentially eligible. We included 16 unpublished trials (1596 patients) and 10 publications/preprints (6317 patients). The combined summary OR on all-cause mortality for hydroxychloroquine was 1.08 (95%CI: 0.99, 1.18; I2=0%; 24 trials; 7659 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2=0%; 4 trials; 307 patients). We identified no subgroup effects.ConclusionsWe found no benefit of hydroxychloroquine or chloroquine on the survival of COVID-19 patients. For hydroxychloroquine, the confidence interval is compatible with increased mortality (OR 1.18) or negligibly reduced mortality (OR 0.99). Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Background: The pharmacokinetics and appropriate dose regimens of favipiravir are unknown in hospitalized influenza patients; such data are also needed to determine dosage selection for favipiravir trials in COVID-19. Methods: In this dose-escalating study, favipiravir pharmacokinetics and tolerability were assessed in critically ill influenza patients. Participants received one of two dosing regimens; Japan licensed dose (1600 mg BID on day 1 and 600 mg BID on the following days) and the higher dose (1800 mg/800 mg BID) trialed in uncomplicated influenza. The primary pharmacokinetic endpoint was the proportion of patients with a minimum observed plasma trough concentration (Ctrough) ≥20 mg/L at all measured time points after the second dose. Results: Sixteen patients were enrolled into the low dose group and 19 patients into the high dose group of the study. Favipiravir Ctrough decreased significantly over time in both groups (p 80% of the duration of treatment of the two dose regimens evaluated (18.8% and 42.1% of patients for low and high dose regimen, respectively). Increasing the favipravir dosage predicted a higher proportion of patients reaching this threshold of 20 mg/L, suggesting that dosing regimens of ≥3600/2600 mg might be required for adequate concentrations. The two dosing regimens were well-tolerated in critical ill patients with influenza. Conclusion: The two dosing regimens proposed for uncomplicated influenza did not achieve our pre-defined treatment threshold.

Recent studies have been demonstrated that host immune imbalance is an important factors leading to acute respiratory distress syndrome (ARDS) in COVID-19 patients. Therefore, discovery of potential drugs and identification of their mechanisms of action for the prevention of immune imbalance in COVID-19 patients are urgently needed. In this study, we proposed a network representation learning-based methodology, termed AIdrug2cov, to discover drug mechanism and anti-inflammatory response for patients with COVID19. In AIdrug2cov, a deep bidirectional Transformer encoder network representation approach is developed to automatically learn lowdimensional vector of heterogeneous network. Using the representation vectors, AIdrug2cov identifies 40 potential targets and 24 high-confidence drugs that bind to tumor necrosis factor(TNF)-α or interleukin(IL)-6 to prevent excessive inflammatory responses in COVID-19 patients. In particular, AIdrug2cov indicated that chloroquine and hydroxychloroquine are able to reduce fatality of COVID-19 patients, and that their mechanisms of action are likely mediated through their inhibition of inflammatory cytokines on top of their antiviral ability, consistent with the findings of clinical studies. In addition, the results in 5 pharmacological application suggested that AIdrug2cov significantly outperforms 5 other state-of-the-art network representation approaches, future demonstrating the availability of AIdrug2cov in drug development field. In summary, AIdrug2cov is practically useful for accelerating COVID-19 therapeutic development. The source code and data can be downloaded from https://github.com/pengsl-lab/AIdrug2cov.git

The outbreak of coronavirus disease 2019 (COVID-19) has caused more than 80 813 confirmed cases in all provinces of China, and 21 110 cases reported in 93 countries of six continents as of 7 March 2020 since middle December 2019. Due to biological nature of the novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with faster spreading and unknown transmission pattern, it makes us in a difficulty position to contain the disease transmission globally. To date, we have found it is one of the greatest challenges to human beings in fighting against COVID-19 in the history, because SARS-CoV-2 is different from SARS-CoV and MERS-CoV in terms of biological features and transmissibility, and also found the containment strategies including the non-pharmaceutical public health measures implemented in China are effective and successful. In order to prevent a potential pandemic-level outbreak of COVID-19, we, as a community of shared future for mankind, recommend for all international leaders to support preparedness in low and middle income countries especially, take strong global interventions by using old approaches or new tools, mobilize global resources to equip hospital facilities and supplies to protect noisome infections and to provide personal protective tools such as facemask to general population, and quickly initiate research projects on drug and vaccine development. We also recommend for the international community to develop better coordination, cooperation, and strong solidarity in the joint efforts of fighting against COVID-19 spreading recommended by the joint mission report of the WHO-China experts, against violating the International Health Regulation (WHO, 2005), and against stigmatization, in order to eventually win the battle against our common enemy — COVID-19.

Molecular docking, as one of the widely used virtual screening methods, aims to predict the binding-conformations of small molecule ligands to the appropriate target binding site. Because of the computational complexity and the arrival of the big data era, molecular docking requests High- Performance Computing (HPC) to improve its performance and accuracy. We discuss, in detail, the advances in accelerating molecular docking software in parallel, based on the different common HPC platforms, respectively. Not only the existing suitable programs have been optimized and ported to HPC platforms, but also many novel parallel algorithms have been designed and implemented. This review focuses on the techniques and methods adopted in parallelizing docking software. Where appropriate, we refer readers to exemplary case studies.

As a pump for extracting carriers from the absorber to the cathode, hole transporting materials (HTMs) play indispensable roles in promoting the power conversion efficiencies (PCE) of perovskite solar cells (PSCs). In this context, we present two simple HTMs using 2,2′-(1,2-phenylene) bisthiophene or naphtho[1,2-b:4,3-b′]dithiophene as a π-bridge to link two electron-donor units (4′,4′′-dimethoxytriphenylamine): PBT and NDT. Their frontier molecular orbital energies match well with those of perovskites as is consistent with the DFT calculation results. The PCE measured under mimetic solar illumination (AM 1.5, 100 mW cm−2) increases from 13.6% (PBT) to 18.8% (NDT), which surpass that of the spiro-OMeTAD (18.1%) reference. The modified annulated core in NDT makes it perform better in photovoltaic conversion than PBT. The reason for this is discussed from aspects of hole mobility, charge collection probability (Pc) and recombination kinetics.

Perovskite solar cells represent one of the most exciting developments in photovoltaics in the past decade, with the power conversion efficiencies of over 25% being achieved to date. In high-performance perovskite solar cells, hole-transporting materials are generally employed to extract and transport holes from perovskite. Among them, small molecular hole transporting materials have attracted intense interest due to their tunable energy levels, structural variety, and simple synthesis. The commonly used hole-transporting material is 2,2′,7,7′-tetrakis(N,N-di-p-methoxyphenyl amino)-9,9′-spirobifluorene (spiro-OMeTAD). Considering the high synthetic cost of spiro-OMeTAD and the device stability issue associated with the use of dopants, much research has been focused on the development of alternative high-performance hole-transporting materials. Herein, this review summarizes the recent developments in highly efficient small molecular hole-transporting materials with a power conversion efficiency close to or over 20%. On the basis of their structural features, three categories of small molecules are identified and discussed as highly efficient hole-transporting materials: spiro molecules with new terminal groups or a new spiro skeleton, star-shaped small molecular hole-transporting materials with three or four branches, and linear hole-transporting materials with a D-A, D-π-D, D-A-D, or D-A-π-A-D structure. The relationships of the optoelectronic properties of these hole-transporting materials and the device performance are discussed, with a comparison to those of model compounds in some cases. Finally, an outlook is addressed on the future development of hole-transporting materials for high-performance perovskite solar cells. We hope that this review can provide important guidance for the design and synthesis of new hole-transporting materials and finally help to promote the commercialization of perovskite solar cells.

Cerebral hemorrhage (ICH) is a common cerebrovascular condition with high mortality, disability and recurrence rates. TLR4-mediated acute inflammatory injury plays a pivotal role in ICH. Verbascoside (VB) is an active component of multiple medicinal plants, and exerts neuroprotective effects in ischemic stroke by targeting the inflammatory response. However, the effects of VB on ICH and the underlying mechanisms remain unclear. In this study, we analyzed the therapeutic effects of VB on acute ICH, and the possible involvement of TLR4-mediated inflammation. VB improved the behavioral score and reduced the hematoma volume, brain edema and neuronal apoptosis in a murine model of acute ICH. Mechanistically, VB attenuated macroglia activation and decreased inflammatory factor levels, which in turn protected the neurons. Furthermore, TLR4 knockout abolished the effects of VB both in vivo and in vitro. Taken together, VB attenuates the symptoms of ICH by targeting the TLR4-mediated acute inflammatory response.

Background: Sepsis is a serious clinical condition with a poor prognosis, despite improvements in diagnosis and treatment.Therefore, novel biomarkers are necessary that can help with estimating prognosis and improving clinical outcomes of patients with sepsis. Methods: The gene expression profiles GSE54514 and GSE63042 were downloaded from the GEO database. DEGs were screened by t test after logarithmization of raw data; then, the common DEGs between the 2 gene expression profiles were identified by up-regulation and down-regulation intersection. The DEGs were analyzed using bioinformatics, and a protein-protein interaction (PPI) survival network was constructed using STRING. Survival curves were constructed to explore the relationship between core genes and the prognosis of sepsis patients based on GSE54514 data. Results: A total of 688 common DEGs were identified between survivors and non-survivors of sepsis, and 96 genes were involved in survival networks. The crucial genes Signal transducer and activator of transcription 5A (STAT5A), CCAAT/enhancer-binding protein beta (CEBPB), Myc proto-oncogene protein (MYC), and REL-associated protein (RELA) were identified and showed increased expression in sepsis survivors. These crucial genes had a positive correlation with patients’ survival time according to the survival analysis. Conclusions: Our findings indicate that the genes STAT5A, CEBPB, MYC, and RELA may be important in predicting the prognosis of sepsis patients.

Recently both N-acetylcysteine (NAC) and Dexmedetomidine (DEX) have shown emerging roles in protection of acute lung injury (ALI). However, how their protective roles work and whether they can provide synergistic effects in ALI remain unknown. Here we explored it from the hot research viewpoint of Th1/Th2/Th17 cytokines balance. Lipopolysaccharide (LPS)-induced ALI was established and treated with NAC and/or DEX. Mice were divided into Sham group, ALI group, NAC group, DEX group and NAC+DEX group. Mice were sampled at 6, 12 and 24 hours after the model construction. Histopathology, wet to dry ratio and myeloperoxidase (MPO) activity were assessed in lung tissues. Protein concentration and cell count were assessed in bronchoalveolar lavage fluid (BALF). Th1/Th2/Th17 cytokines were assessed in plasma, BALF and lung homogenate. ALI-induced lung morphological damage, edema and aberrant MPO activity can be attenuated by NAC or DEX and mostly by NAC+DEX. NAC with DEX significantly reduced ALI-induced protein leakage and cell infiltration in BALF. Th1/Th2/Th17 cytokines imbalance aggravated with ALI progression. NAC, DEX and especially NAC+DEX can effectively correct these unbalanced cytokines. Galectin-9 and Tim-3 were transcriptionally up-regulated in ALI. Combination of NAC with DEX obtained a maximum effect on decreasing Galectin-9/Tim-3 expression. In summary, Th1/Th2/Th17 cytokines imbalance is newly found to participate in LPS-induced ALI. NAC or DEX administration can attenuate ALI by rebalancing Th1/Th2/Th17 cytokines. Their protective roles can be enhanced when co-administration, because DEX may relieve the Galectin-9/Tim-3 axis-mediated immune suppression.

By introducing six triarylamine groups to a hexaphenylbenzene (HPB) or a hexakis(2-thienyl)benzene (HTB) core, two propeller-shaped, triarylamine-rich, and low-cost hole-transporting materials (HTMs), which are termed as HPB-OMe and HTB-OMe, respectively, with considerable hole mobility, were obtained by easy synthetic routes. Solid-state planar perovskite CH3NH3PbI3 solar cells (PSCs) with two new HTMs showed high power conversion efficiencies (12.9% for HPB-OMe and 17.3% for HTB-OMe in forward scans) under standard 100 mW cm–2 AM 1.5G illumination without doping. A comparison of matched-degree of energy levels, hole-transporting ability, photovoltaic conversion efficiencies, and recombination of the two HTMs indicated that developing multi-triarylamine- and thiophene-rich molecules provides candidate and efficient dopant-free HTMs for PSCs.

The aim of this study was to investigate the expression of phosphatase of regenerating live-3 (PRL-3) in human stage III colorectal cancer (CRC) and to evaluate its correlation with metachronous liver metastasis (MLM) and prognosis. The retrospective cohort study included 116 stage III CRC primary tumors and 60 normal colorectal tissues. PRL-3 expression was measured by immunohistochemistry. We investigated the correlation of PRL-3 with clinicopathologic features by the chi-square test. The association of PRL-3 expression with MLM was assessed by binary logistic regression. Overall survival (OS) and disease-free survival (DFS) between patients with positive PRL-3 expression and those with negative PRL-3 expression were compared by the Kaplan–Meier method and Cox proportional hazards regression model. We found that 32.8% of stage III CRC primary tumors were PRL-3 positive, and 15.0% of normal colorectal epithelia showed high PRL-3 expression (P = .012). Seventeen tumors (47.2%) among 36 cases that developed MLM were PRL-3 positive, and only 21 tumors (26.3%) in the 80 cases that did not develop MLM had positive PRL-3 expression (P = .026). PRL-3 expression was associated with MLM (P = .028). Patients with positive expression of PRL-3 showed a significantly shorter OS (40.32 ± 3.97 vs 53.96 ± 2.77 months, P = .009) and DFS (34.97 ± 4.30 vs 44.48 ± 2.89 months, P = .036). A multivariate analysis indicated that PRL-3 expression was an independent unfavorable prognostic factor for OS (P = .007). Our study suggested that high PRL-3 expression is an independent risk factor for MLM and poor prognosis. PRL-3 is expected to be a promising biomarker for predicting the incidence of MLM and prognosis in patients with stage III CRC.

Aiming at the chaotic behavior of PMSG under certain parameters, a method based on ADHDP is proposed to track the maximum wind power point, which can make the system out of chaos and track the maximum power point stably, and the optimal control problems of the complex nonlinear system can be solved effectively.Cloud RBF neural network is adopted as the function approximation structure of ADHDP. Cloud model introduces the randomness and fuzziness into new algorithm, at the same time, the new algorithm retains the learning ability and topological relation of RBF neural network.This method is realized by using the optimal power-speed curve and the vector control principle, adjusting the stator output voltage to control the electromagnetic and then the wind turbine rotor speed can be operated at the optimal speed that corresponds to the maximum power point, meanwhile, the measurement of wind speed also can be avoided. Aiming at the chaotic behavior of PMSG under certain parameters, the new ADHDP method based on Cloud RBF neural network is proposed to track the point of maximum wind power, which can make the system out of chaos and track the point of maximum power stably, and the optimal control problems of the complex nonlinear system can be solved effectively. This method is realized by using the optimal power-speed curve and the vector control principle, and by adjusting the stator output voltage to control the electromagnetic torque, then the rotor speed of wind turbine can operate at the optimal speed that corresponds to the point of maximum power, meanwhile, the measure of wind speed also can be avoided. The simulation results show the effectiveness of the proposed method.

In gob-side entry driving, the coal pillar width determines the stability of the surrounding rock and the pillar itself. Thus, to improve the stability of gas outburst coal seams, the reasonably narrow width of the coal pillars of the 40403 working face of the Shengyuan coal mine 4# was theoretically determined. Through two-dimensional simulations, the surrounding rock stability for a roadway with different coal pillar widths was evaluated. The mechanism of the surrounding rock displacement and stress distribution with the increase of the coal pillar width was also defined; for pillar widths of 2–4, 4–6, and 6–10 m, the vertical stress distribution was approximately triangular, trapezoidal, and parabolic, respectively. The coal pillar displacement was significantly greater on the goaf side than on to the roadway side. As the width of the coal pillar was incremented, its displacement on the goaf side increased, while that on the roadway side remained relatively small. The combination of the simulation results with on-site measurements finally revealed that 5 m is a reasonably narrow coal pillar width. Then, the findings were successfully applied to the 40403 working face of the Shengyuan coal mine 4#, achieving good outburst prevention and cost reduction.

Background: The aim of this study was to evaluate the clinical efficacy of Xuanfei Baidu Decoction (XBD) combined with conventional drug therapy compared with conventional medicine alone in patients with coronavirus disease 2019 (COVID-19). Methods: Forty-two patients with COVID-19 were randomly assigned to XBD plus conventional medicine (n = 22) and conventional medicine alone (n = 20). Both groups were treated for 1 week. The primary endpoint was the disappearance rate of main symptoms (fever, cough, and fatigue). Results: Compared with the conventional medicine, the disappearance rate of clinical symptoms such as fever, cough, fatigue and loss of appetite in the experimental group were significantly reduced (P

Real-time visualization of assembly processes and sophisticated signal processing at the nanoscale are two challenging topics in photonic nanomaterials. Here, high-quality light-harvesting crystalline nanorods were developed by the coassembly of two polypyridyl Ir(III) and Ru(II) metallophosphors, behaving as the antenna chromophore and energy acceptor, respectively. By using a one-pot or stepwise growth condition, homogeneous and multiblock heterojunction nanorods were prepared, respectively. These nanostructures display multicolor phosphorescence from green to red due to the efficient triplet energy transfer and light-harvesting capability at low acceptor doping ratios. Heterojunction nanorods show gradient emission-color switches during different growth stages, in which the real-time stepwise assembly can be vividly visualized using fluorescence microscopy techniques. Triplet excitons were successfully manipulated in both homogeneous and heterojunction nanorods to realize waveguided green, orange, and red emissions and advanced photonic signal logics and encoding/decoding on single multiblock heterojunction nanorod.

Closed vascular injuries have danger of developing critical tissue ischemia with a high risk of amputation and limb loss. However, limited effective strategies exist at present. In this study, we investigate the role of hepatocyte growth factor (HGF) on apoptosis of vascular endothelial cells (VECs). First, apoptosis of VECs was induced by hypoxia treatment with or without HGF. Annexin V-7AAD apoptosis assay revealed that HGF overexpression significantly reduced VEC apoptosis. Then a closed peripheral vascular injury animal model was created by balloon catheter in female New Zealand rabbit. The VECs overexpressing HGF were injected into balloon injury rabbit. TUNEL and caspase 3 staining assays revealed that balloon catheter-treated artery showed severe intimal hyperplasia, with a 70% apoptosis rate (P < 0.05, vs. sham group), while HGF-overexpressing group showed a significant reduction of apoptosis. Furthermore, the expressions of Fas/FasL and their downstream apoptosis-related proteins were significantly decreased in HGF-overexpressing group when compared with those in balloon injury group as detected by western blot analysis. All these data indicated that HGF exhibited anti-apoptotic effects during VEC apoptosis, which might be mediated by the inhibition of Fas/FasL pathway. Our study provides a theoretic basis for the application of HGF in the gene therapy of closed peripheral vascular injury.

Two new hole transporting materials (HTMs) based on triphenylamine and carbazole core moieties are designed and applied in planar perovskite solar cells. 18.2% power conversion efficiency (PCE) has been achieved, and 84% of the initial performance can be retained after 50 days.

Purpose: To probe the effective treatment for patients with Begin Prostate Hyperplasia (BPH) along with bladder stones with Plasmakinetic Resection of Prostate combining with Transurethral Nephrolithotripsy by Pneumatic and Ultrasound Lithotripsy． Methods: Twenty five cases of patients of BPH combined with bladder stones were chosen. Plasmakinetic Resection of Prostate Combining with Transurethral Nephrolithotripsy by Pneumatic and Ultrasound Lithotripsy was used to compare the maximal urinary flow rate (Qmax), residual urine and other index in those patients before and after operations. Results: All operations in 25 cases were successful, without any complications. Three months after operations, Qmax, and residual urine were significantly improved in patients. Conclusions: Simultaneous transurethral bladder calculi lithotripsy combined with PKRP is considered as the safe, effective and minimal invasive surgical method to cure BPH along with bladder stones, also obviously improving the symptoms of obstruction, effectively removing calculus and improving the quality of life.

Rationale: Abdominal pain is one of the most common complaints for patients in emergency department. It's difficult to make an accurate diagnosis by emergency physician in time, especially in patients with situs inversus totalis. Patient concerns: A patient with acute exacerbation of chronic left upper quadrant abdominal pain. Diagnoses: cholangiolithiasis with situs inversus totalis. Interventions: laparoscopic cholecystectomy and laparoscopic exploration of common bile duct. Outcomes: The patient had an uneventful recovery. Lessons: High suspicion and adequate evaluation are important for diagnosis in patients with abdominal pain and situs inversus totalis in emergency department, and physical examination, electrocardiogrphy and radiological investigations are necessary.

Currently, the planning of electric vehicle(EV) charging piles usually adopts the analogy methods, which would bring great deviations due to the lack of considering the influence of regional driving characteristics and the scale of electric vehicles. In this paper, a three-state probability model with four parameters was proposed. The number of fast charging piles was calculated based on various regional driving characteristics. Calculation results of the fast charging pile in typical areas are also calculated which can provide reference for the planning department.

In this paper, we presented an algorithm for NLOS error mitigation based on adaptive Kalman filter with colored measurement noise. To eliminate NLOS error which induced by TOF-based distance measurements, a colored noise model is firstly established according to measurement noise and the filter parameters are adjusted dynamically based on the severity of NLOS environment. Then combined with adaptive Kalman filtering algorithm, the NLOS error mitigation process is adjusted in real time in order to obtain optimal estimation. The simulation experiments show that the algorithm has small error and high precision and is suitable for real-time dynamic location systems.

PP1-12, a new protein phosphatase-1 inhibitor, is designed and synthesized to modulate the endoplasmic reticulum (ER) stress apoptotic pathway, which is involved in various cardiovascular diseases. In this study, we examined the effect of PP1-12 on ventricular remodeling and heart function after myocardial infarction. Rats that survived within 24 hours after coronary ligation were randomly divided into 6 groups and treated with normal saline, vehicle, PP1-12 at 1, 3, and 10 mg·kg·d and perindopril at 2 mg·kg·d for 4 weeks, respectively. At the end of the follow-up point, we evaluated echocardiographic and hemodynamic parameters, myocardial pathomorphology, apoptosis, and interstitial fibrosis, as well as the expression levels of important proteins involved in ER stress and apoptosis. Left ventricular geometry and function were ameliorated by PP1-12. PP1-12 inhibited interstitial fibrosis and reduced apoptosis of cardiomyocytes in a dose-dependent manner. PP1-12 decreased GRP78 and caspase-12 expression and increased p-eIF2α and Bcl-2/Bax expression. These results suggest that PP1-12 efficiently inhibits left ventricular remodeling and improves heart function. The mechanism involved may be associated with the ability of PP1-12 to depress myocardial apoptosis induced by ER stress.