Identification and quantitative analysis of bioactive components from Potentilla kleiniana Wight et Arn with anti HIV-1 proteases activity.

Potentilla kleiniana Wight et Arn（PK, 'Wu Pi Feng' in Chinese） was recorded as Miao ethnic medicine for treatment of fever, cough, ulcer, and erysipelas for thousands years. This study aimed to evaluate the antiviral activity of four PK extracts and seven compounds by using HIV-1 protease (HIV-1 PR). In addition, Ultra-High Performance Liquid Chromatography and High Resolution Mass Spectrometry (UPLC-HRMS) was employed to identify the bioactive components. The toxicity assessment of the extracts was done before antiviral screening using a highly specific human aspartyl protease, renin protease by fluorimetric method. As a result, seven compounds and four extracts of PK inhibited HIV-1 PR with IC50 range from 0.009 to 0.36 mg/mL, and did not appreciably inhibit the general human protease renin. This study first demonstrated that four PK extracts, ellagic acid and ursolic acid potent inhibit HIV-1 protease, could be used as an efficacious drug candidate to treat SARS-CoV-2 infection.

Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Pathogen spectrum analysis of acute respiratory infection among inpatients before and after the outbreak of COVID-19 pandemic in Huairou district of Beijing

Objective To analyze the composition and epidemiological characteristics of respiratory pathogens in hospitalized patients with respiratory tract infections in Huairou district before and after the outbreak of corona virus disease 2019（COVID-19）. Methods Respiratory specimens were collected from hospitalized patients who met the case definition in Huairou district during the period of January 2018 and December 2021. The samples were tested for influenza virus, respiratory syncytial virus, adenovirus, parainfluenza virus, metapneumovirus, coronavirus, rhinovirus, bocavirus, enterovirus, mycoplasma pneumoniae, chlamydophila pneumoniae and other respiratory pathogens by using ABI 7500 real-time fluorescent quantitative PCR assay. Results From January 2018 to December 2021, a total of 1 148 samples were tested and the overall positive rate was 24. 65%（283cases）. The positive detection rate after the outbreak of COVID-19 in 2020-2021（79/522） was significantly lower than that before the outbreak of COVID-19 in 2018-2019（204/626）（15. 13% vs 32. 59%, χ~2=46. 683, P＜0. 01）. The positive rates in children aged 0-＜2 years and 2-＜5 years after the outbreak of COVID-19were 46. 15% and 45. 45% respectively, were significantly higher than those in other age groups （χ~2=73. 053,P＜0. 01）. Mycoplasma pneumoniae（12. 75%）, enterovirus（10. 29%） and adenovirus（10. 29%） were the top three pathogens before the outbreak, while, after the outbreak, the top three pathogens were syncytial virus（21. 52%）, parainfluenza（17. 72%） and rhinovirus（17. 72%）. In Huairou district, the detection rate of respiratory pathogens peaked in winter, there was also a small peak in summer. Conclusion After the outbreak of COVID-19, children under 5 years old are still the main population for respiratory infection control. The change of pathogen spectrum before and after the outbreak of covid-19 is helpful for clinician to recognize and diagnose the disease.

Mediating effect of mindfulness level on the relationship between marital quality and postpartum depression among primiparas.

BACKGROUND: Postpartum depression refers to a depressive episode or depressive symptoms up to 12 mo after delivery. Trait mindfulness has presented a protective factor for postpartum depressive symptoms and proved efficient in improving relationship satisfaction among couples. AIM: To investigate the correlations among mindfulness, marital quality, anxiety, and depression in a large city in western China during the post-corona virus infectious disease-2019 era and determine whether trait mindfulness mediates the relationship between marital quality and postpartum anxiety and depression among primiparas. METHODS: A cross-sectional study was conducted. The self-administered questionnaire was submitted online through smartphones. The levels of mindfulness, anxiety, depression, and marital quality were respectively investigated by the mindful attention awareness scale (MAAS), the self-rating anxiety scale (SAS), the self-rating depression scale (SDS), and the marriage perception scale (MPS) in these enrolled Han and Tujia primiparas. RESULTS: No statistical significance was observed in the prevalence of postpartum anxiety and depression, nor scores of MAAS and MPS-Total in different regions or ethnicities (P > 0.05). However, MPS-Marital interaction (P < 0.05), MPS-Family relationship (MPS-FR) (P < 0.01), and MPS-Marital conflict (MPS-MC) (P < 0.01) scores of urban primiparas were higher than those of rural primiparas. The MPS-MC score of Han primiparas was higher than that of Tujia primiparas (P < 0.05). Negative correlations were observed between MAAS and SAS (r = -0.457, P < 0.01), and MAAS and SDS (r = -0.439, P < 0.01). SAS has revealed a highly positive correlation with SDS (r = 0.720, P < 0.01) and a weak negative correlation with MPS (r = -0.200, P < 0.05). Besides, a weak negative correlation was observed between MAAS and MPS-MC (r = -0.184, P < 0.05), and a weak positive correlation was noticed between SAS and MPS-MC (r = -0.225, P < 0.01). Mediation analysis demonstrated a full mediation effect of mindfulness level on the relationship between MPS-FR and postpartum anxiety (P < 0.05, 95%CI: -0.384 to 0.033), MPS-MC and postpartum anxiety (P < 0.01, 95%CI: 0.027-0.193), MPS-FR and postpartum depression (P < 0.05, 95%CI: -0.365 to 0.031), and MPS-MC and postpartum depression (P < 0.01, 95%CI: 0.022-0.206). CONCLUSION: Mindfulness demonstrates negative correlations with marital conflict, postpartum anxiety and depression, and it may have cross-ethnic and trans-regional characteristics. Although the mindfulness levels have revealed no significant mediating effect between the total score of marital quality and postpartum depression in this study, it demonstrates a full mediation effect on the relationships between family relationships, marital conflict, and postpartum anxiety and depression.

Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study

Various undesirable side effects are frequently associated with isomers of chiral clinical agents. The separation of chiral medicines remains a challenging issue in the medicines research. In this work, we employed cyclic decapeptide as the host molecule and the M06-2X theoretical computational method for chiral recognition of four clinical candidate guests and their isomers, including bucillamine, molnupiravir, azvudine, and VV116, which are relevant for the treatment of COVID-19. The obtained results indicated that bucillamine and molnupiravir and their respective isomers may be distinguished by cyclic decapeptide and that some of the isomers of Azvudine and VV116 may be discriminated by cyclic decapeptide. The inclusion conformation, deformation analysis, and electrostatic potential analysis also visualized the binding modes and binding sites between cyclic peptides and medicine candidates. A series of weak interaction analyses suggest that hydrogen bonding and dispersion interactions may be the primary factors for the recognition and separation of the clinical candidates by cyclic decapeptides. Visualized analyses of noncovalent interaction, hydrogen bond interaction, and NBO, AIM topological demonstrated that the difference of dispersion interaction is not obvious between the complexes, while the type and number of hydrogen bonds are very different, hinting that hydrogen bonds might be crucial for the differentiation of molnupiravir and its isomers. These findings might provide a theoretical reference for the identification and separation of chiral compounds in host–guest interaction. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-023-02149-5.

Ultraefficiently Calming Cytokine Storm Using Ti3C2T x MXene.

During the global outbreak of COVID-19 pandemic, "cytokine storm" conditions are regarded as the fatal step resulting in most mortality. Hemoperfusion is widely used to remove cytokines from the blood of severely ill patients to prevent uncontrolled inflammation induced by a cytokine storm. This article discoveres, for the first time, that 2D Ti3C2T x MXene sheet demonstrates an ultrahigh removal capability for typical cytokine interleukin-6. In particular, MXene shows a 13.4 times higher removal efficiency over traditional activated carbon absorbents. Molecular-level investigations reveal that MXene exhibits a strong chemisorption mechanism for immobilizing cytokine interleukin-6 molecules, which is different from activated carbon absorbents. MXene sheet also demonstrates excellent blood compatibility without any deleterious side influence on the composition of human blood. This work can open a new avenue to use MXene sheets as an ultraefficient hemoperfusion absorbent to eliminate the cytokine storm syndrome in treatment of severe COVID-19 patients.

Potential treatment of COVID-19 with traditional chinese medicine: What herbs can help win the battle with SARS-CoV-2?

Traditional Chinese medicine (TCM) has been successfully applied worldwide in the treatment of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacological mechanisms underlying this success remain unclear. Hence, the aim of this review is to combine pharmacological assays based on the theory of TCM in order to elucidate the potential signaling pathways, targets, active compounds, and formulas of herbs that are involved in the TCM treatment of COVID-19, which exhibits combatting viral infections, immune regulation, and amelioration of lung injury and fibrosis. Extensive reports on target screening are elucidated using virtual prediction via docking analysis or network pharmacology based on existing data. The results of these reports indicate that an intricate regulatory mechanism is involved in the pathogenesis of COVID-19. Therefore, more pharmacological research on the natural herbs used in TCM should be conducted in order to determine the association between TCM and COVID-19 and account for the observed therapeutic effects of TCM against COVID-19.

Xuanfei Baidu Decoction regulates NETs formation via CXCL2/CXCR2 signaling pathway that is involved in acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening symptoms in Coronavirus Disease 2019 (COVID-19) patients. Xuanfei Baidu Decoction (XFBD) is a recommend first-line traditional Chinese medicine (TCM) formula therapeutic strategy for COVID-19 patients. Prior studies demonstrated the pharmacological roles and mechanisms of XFBD and its derived effective components against inflammation and infections through multiple model systems, which provided the biological explanations for its clinical use. Our previous work revealed that XFBD inhibited macrophages and neutrophils infiltration via PD-1/IL17A signaling pathway. However, the subsequent biological processes are not well elucidated. Here, we proposed a hypothesis that XFBD can regulate the neutrophils-mediated immune responses, including neutrophil extracellular traps (NETs) formation and the generation of platelet-neutrophil aggregates (PNAs) after XFBD administration in lipopolysaccharide (LPS)-induced ALI mice. The mechanism behind it was also firstly explained, that is XFBD regulated NETs formation via CXCL2/CXCR2 axis. Altogether, our findings demonstrated the sequential immune responses of XFBD after inhibiting neutrophils infiltration, as well as shedding light on exploiting the therapy of XFBD targeting neutrophils to ameliorate ALI during the clinical course.

Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study.

Various undesirable side effects are frequently associated with isomers of chiral clinical agents. The separation of chiral medicines remains a challenging issue in the medicines research. In this work, we employed cyclic decapeptide as the host molecule and the M06-2X theoretical computational method for chiral recognition of four clinical candidate guests and their isomers, including bucillamine, molnupiravir, azvudine, and VV116, which are relevant for the treatment of COVID-19. The obtained results indicated that bucillamine and molnupiravir and their respective isomers may be distinguished by cyclic decapeptide and that some of the isomers of Azvudine and VV116 may be discriminated by cyclic decapeptide. The inclusion conformation, deformation analysis, and electrostatic potential analysis also visualized the binding modes and binding sites between cyclic peptides and medicine candidates. A series of weak interaction analyses suggest that hydrogen bonding and dispersion interactions may be the primary factors for the recognition and separation of the clinical candidates by cyclic decapeptides. Visualized analyses of noncovalent interaction, hydrogen bond interaction, and NBO, AIM topological demonstrated that the difference of dispersion interaction is not obvious between the complexes, while the type and number of hydrogen bonds are very different, hinting that hydrogen bonds might be crucial for the differentiation of molnupiravir and its isomers. These findings might provide a theoretical reference for the identification and separation of chiral compounds in host-guest interaction. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-023-02149-5.

Comment on "Crosstalk between gut microbiota and COVID-19 impacts pancreatic cancer progression".

The coronavirus disease 2019 (COVID-19) pandemic has become a global burden, further exacerbating the occurrence of risk events in cancer patients. The high risk of death from pancreatic cancer makes it one of the most lethal malignancies. Recently, it was reported in the World Journal of Gastrointestinal Oncology that COVID-19 influences pancreatic cancer progression via the lung-gut-pancreatic axis, and the authors provided insights into the intrinsic crosstalk mechanisms in which the gut microbiota is involved, the characteristics and effects of inflammatory factors, and immunotherapeutic strategies for treating both diseases. Here, we review the latest cutting-edge researches in the field of the lung-gut-pancreatic axis and discuss future perspectives to address the severe survival challenges posed by the COVID-19 pandemic in patients with pancreatic cancer.

Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura: a case report and review of the literature.

BACKGROUND: Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently. CASE PRESENTATION: We report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up. CONCLUSIONS: Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.

Association between psychological capital and depressive symptoms during COVID-19: The mediating role of perceived social support and the moderating effect of employment pressure.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic affects individuals' mental health that can result in fear of getting COVID-19 infection and depression. Prior research has demonstrated that both psychological capital and perceived social support are related to the severity of depression. Yet no study explored the direction of associations between these factors. This undermines the validity of psychological capital as a basis for health interventions. Methods: This study aimed to explore the association between psychological capital, perceived social support, employment pressure, and depressive symptoms during COVID-19. A cross-sectional design was employed in a sample of 708 Chinese senior medical students who were asked to complete an online questionnaire survey. Results: Results indicated that psychological capital negatively predicts depressive symptoms (ß = -0.55, p < 0.001); perceived social support plays a mediating role in the impact of psychological capital on depressive symptoms (indirect = -0.11, SE = 0.02, p < 0.001, 95%CI [-0.16, -0.07]), and these associations were moderated by employment pressure. Medical students with high employment pressure, the negative impact of psychological capital on depressive symptoms was statistically significant (ß = -0.37, SE = 0.05, p < 0.001, 95% CI [-0.046, -0.27]); when the perceived employment pressure was low, the negative effect of psychological capital on depressive symptoms, although significant, was stronger (ß = -0.49, SE = 0.04, p < 0.001, 95% CI [-0.57, -0.40]). Discussion: The current study highlights that it is of great significance to address Chinese medical students' employment pressure and improve their mental health during the COVID-19 epidemic.

Drug-induced liver injury in COVID-19 patients during hospitalization.

Since coronavirus disease 2019 (COVID-19) outbreaks in December 2019 in Wuhan, almost no studies have systematically described drug-induced liver injury (DILI) in COVID-19 patients. This study aimed to assess the characteristics of liver test abnormality or liver injury in patients with COVID-19, and further to explore DILI in COVID-19 patients during hospitalization. It was a single-center retrospective analysis of confirmed severe acute respiratory syndrome coronavirus 2 infected patients in the hospital from January 2020 to March 2020. Univariate and multivariate logistic regression analysis were used to assess the risk factors associated with liver test abnormality or liver injury. At admission, 148 (48.8%, 148/303) patients had abnormal liver test results and 7 (2.4%, 7/303) had liver injury, while 195 (64.4%, 195/303) had abnormal liver test results and 17 (5.6%, 17/303) had liver injury during hospitalization. After excluding these patients with liver disease and liver function abnormalities or liver injury at admission, 15 (11.1%, 15/135) patients developed DILI during hospitalization. Further regression analysis indicated that methylprednisolone (odds ratio = 4.177, 95% confidence interval [1.106-15.771], P = .035), but not Chinese herbal medicine or other used drug, was associated with DILI in patients during hospitalization. Abnormal liver function results were in more than half of patients with COVID-19, and the incidence of DILI in COVID-19 patients was 11.1% during hospitalization. Liver test abnormality or liver injury in patients might be directly caused by the viral infection at admission, but the detrimental effects on liver injury mainly related to certain medications used during hospitalization, particularly methylprednisolone. Severe COVID-19 could increase the occurrence of liver injury (P = .007) during hospitalization, but not a risk factor of liver injury. However, Chinese herbal medicine was a protective factor for liver injury.

Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D.

The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation.

Price discovery in China's crude oil futures markets: An emerging Asian benchmark?

We examine the price discovery performance of China's crude oil futures traded on the Shanghai International Energy Exchange (INE) for the spot prices of 19 types of deliverable and nondeliverable Asian crude oil. We find evidence for the INE crude oil futures price discovery function even at the early stage for almost all the deliverable crudes and some nondeliverable crudes. Both the INE crude oil futures price and the spot price significantly contribute to the price discovery process, with substantially time‐varying informational roles. While the price discovery performance was severely damaged around the period of COVID‐19 pandemic shock intensification in China with the temporary cancellation of nighttime trading, it improved to some extent after China started the recovery from the shock. But such improvement deteriorated drastically and disappeared since early 2021. Further analysis reveals that both economic fundamentals (e.g., the warehouse inventory) and trading‐related characteristics of the futures market are significant determinants of the price discovery performance. The overall findings imply that the INE crude oil futures market has evolved into a useful and important information source in pricing Asian crudes, and is on the path to emerge as an Asian benchmark.

Thorectidiol A Isolated from the Marine Sponge Dactylospongia elegans Disrupts Interactions of the SARS-CoV-2 Spike Receptor Binding Domain with the Host ACE2 Receptor.

Thorectidiols isolated from the marine sponge Dactylospongia elegans (family Thorectidae, order Dictyoceratida) collected in Papua New Guinea are a family of symmetrical and unsymmetrical dimeric biphenyl meroterpenoid stereoisomers presumed to be products of oxidative phenol coupling of a co-occurring racemic monomer, thorectidol (3). One member of the family, thorectidiol A (1), has been isolated in its natural form, and its structure has been elucidated by analysis of NMR, MS, and ECD data. Acetylation of the sponge extract facilitated isolation of additional thorectidiol diacetate stereoisomers and the isolation of the racemic monomer thorectidol acetate (6). Racemic thorectidiol A (1) showed selective inhibition of the SARS-CoV-2 spike receptor binding domain (RBD) interaction with the host ACE2 receptor with an IC50 = 1.0 ± 0.7 µM.

Exploring pharmacological active ingredients of traditional Chinese medicine by pharmacotranscriptomic map in ITCM.

With the emergence of high-throughput technologies, computational screening based on gene expression profiles has become one of the most effective methods for drug discovery. More importantly, profile-based approaches remarkably enhance novel drug-disease pair discovery without relying on drug- or disease-specific prior knowledge, which has been widely used in modern medicine. However, profile-based systematic screening of active ingredients of traditional Chinese medicine (TCM) has been scarcely performed due to inadequate pharmacotranscriptomic data. Here, we develop the largest-to-date online TCM active ingredients-based pharmacotranscriptomic platform integrated traditional Chinese medicine (ITCM) for the effective screening of active ingredients. First, we performed unified high-throughput experiments and constructed the largest data repository of 496 representative active ingredients, which was five times larger than the previous one built by our team. The transcriptome-based multi-scale analysis was also performed to elucidate their mechanism. Then, we developed six state-of-art signature search methods to screen active ingredients and determine the optimal signature size for all methods. Moreover, we integrated them into a screening strategy, TCM-Query, to identify the potential active ingredients for the special disease. In addition, we also comprehensively collected the TCM-related resource by literature mining. Finally, we applied ITCM to an active ingredient bavachinin, and two diseases, including prostate cancer and COVID-19, to demonstrate the power of drug discovery. ITCM was aimed to comprehensively explore the active ingredients of TCM and boost studies of pharmacological action and drug discovery. ITCM is available at http://itcm.biotcm.net.

Interleukin-18-primed human umbilical cord-mesenchymal stem cells achieve superior therapeutic efficacy for severe viral pneumonia via enhancing T-cell immunosuppression.

Coronavirus disease 2019 (COVID-19) treatments are still urgently needed for critically and severely ill patients. Human umbilical cord-mesenchymal stem cells (hUC-MSCs) infusion has therapeutic benefits in COVID-19 patients; however, uncertain therapeutic efficacy has been reported in severe patients. In this study, we selected an appropriate cytokine, IL-18, based on the special cytokine expression profile in severe pneumonia of mice induced by H1N1virus to prime hUC-MSCs in vitro and improve the therapeutic effect of hUC-MSCs in vivo. In vitro, we demonstrated that IL-18-primed hUC-MSCs (IL18-hUCMSC) have higher proliferative ability than non-primed hUC-MSCs (hUCMSCcon). In addition, VCAM-1, MMP-1, TGF-ß1, and some chemokines (CCL2 and CXCL12 cytokines) are more highly expressed in IL18-hUCMSCs. We found that IL18-hUCMSC significantly enhanced the immunosuppressive effect on CD3+ T-cells. In vivo, we demonstrated that IL18-hUCMSC infusion could reduce the body weight loss caused by a viral infection and significantly improve the survival rate. Of note, IL18-hUCMSC can also significantly attenuate certain clinical symptoms, including reduced activity, ruffled fur, hunched backs, and lung injuries. Pathologically, IL18-hUCMSC transplantation significantly enhanced the inhibition of inflammation, viral load, fibrosis, and cell apoptosis in acute lung injuries. Notably, IL18-hUCMSC treatment has a superior inhibitory effect on T-cell exudation and proinflammatory cytokine secretion in bronchoalveolar lavage fluid (BALF). Altogether, IL-18 is a promising cytokine that can prime hUC-MSCs to improve the efficacy of precision therapy against viral-induced pneumonia, such as COVID-19.

Dynamic Group Difference Coding Based on Thermal Infrared Face Image for Fever Screening

Recently, noncontact temperature measurement methods based on infrared face perception have received widely attentions since fever screening plays an important role in the early prediction of respiratory infections, such as SARS, H1N1, and COVID-19. However, the performance of these methods always significantly degrades when facing the changes of environment. Thus, the majority of these methods leverage the block-body and sensors to reduce the influence of environment changes. It is a pity that the increased instrument complexity leads to higher costs and failure rate. To address the aforementioned issues, this article presents a novel fever screening method, named dynamic group difference coding (DGDC), which is based on the analysis about the influencing factors. The key idea of DGDC is to compute the temperature differences between the target person and the recently passed crowd (dynamic group). Specifically, we develop the face temperature encoder (FTE) to describe the face temperature and thus construct the difference matrix of the embedding feature between the target person and the dynamic group. Multilayer perceptions (MLP) are employed to capture the intrinsic information by characterizing the difference matrix in vertical and horizontal directions, respectively. Finally, we provide a dataset of thermal infrared face (TIF) images and conduct extensive experiments to demonstrate the advantages of the proposed method over the competing methods.