Immunomodulatory effects of complex probiotics on the immuno-suppressed mice induced by cyclophosphamide.

Introduction: Previous studies have reported the beneficial effects of Bifidobacterium animalis subsp. lactis XLTG11, Lacticaseibacillus casei Zhang, and Lactiplantibacillus plantarum P8, respectively. However, studies on the immunomodulatory enhancing effects of three complex probiotics have not been conducted. The aim of our study is to investigate the immunomodulatory effects of complex probiotics effect on the immunosuppressed mice induced by cyclophosphamide (CTX). Methods: An immunocompromised mouse model was established by intraperitoneal injection of cyclophosphamide, which was gavage of different doses of complex probiotics and levamisole hydrochloride. The splenic and thymic indices, intestinal barrier, leukocyte and lymphocyte counts, percentage of splenic lymphocyte subpopulations, cytokine levels, and gut microbiota were determined. Results: Results showed that the complex probiotics significantly elevated the spleen and thymus indices, increased the villi and crypt depth and the goblet cells. The leukocyte and lymphocyte counts and the percentage of splenic lymphocyte subpopulations in the CTX-treated mice were significantly elevated by the complex probiotics. In addition, the cytokines (IL-6, IL-10, IL-1ß, and IFN-γ) were significantly increased after complex probiotic treatment. The complex probiotics restored the gut microbiota structure to the pattern of the control group by reducing the ratio of Firmicutes/Bacteroidetes and enhancing the relative abundances of specific microbiota that produced short-chain fatty acids. Discussion: This study provides theoretical support for the immunity-enhancing function of the complex probiotics as well as a pharmacological basis for its further development and utilization.

College Students' Degree of Support for Online Learning during the COVID-19 Pandemic and Associated Factors: A Cross-Sectional Study.

BACKGROUND: Educational institutions worldwide have experienced the suspension of offline teaching activities in favor of online teaching due to the outbreak of the COVID-19 pandemic. However, few studies have focused on the degree of support for online learning among college students in mainland China. Therefore, the aim of this study was to investigate the degree of support for online learning among Chinese college students during the epidemic and whether depression, loneliness, family communication, and social support were associated factors. METHODS: A questionnaire was used to collect cross-sectional data from 9319 college students in mainland China, and a structural equation model was analyzed. RESULTS: The results of the study showed high degrees of support for online learning among Chinese college students during the COVID-19 pandemic, with more than half expressing support. The SEM (Structural Equation Modeling) results showed that depression had a negative and significant effect on college students' support for online learning (ß = -0.07; p < 0.001); family communication had a positive and significant effect on college students' support for online learning (ß = 0.09; p < 0.001); social support had a positive and significant effect on college students' support for online learning (ß = 0.11; p < 0.001). CONCLUSIONS: Social support and family communication can alleviate the negative psychological status of college students, and depression plays a mediating role in the effect of social support and family communication on college students' degree of support for online learning. In addition, a significant chain-mediating effect was found of family communication, loneliness, and depression between social support and college students' degree of support for online learning. Government and education institutions must focus on college students' mental health issues and consider family interventions and general support that college students require.

An Optimization Method for Distributing Emergency Materials Which Balances Multiple Decision Criteria

In emergency rescue operations, it is very important for emergency management to arrange emergency materials scientifically and reasonably according to emergency needs. However, the decision criteria for emergency material distribution are often diverse, coupled with the lack of information acquisition due to the suddenness and development complexity of disasters, which makes the scientific decisions about emergency material distribution face great challenges. This paper proposes a multi-criteria decision optimization model of emergency material distribution under uncertainty that combines the 4E criteria of performance evaluation (economic criterion, efficiency criterion, effectiveness criterion and equity criterion). Then, the solution method of the multiple decision criteria model is designed. Finally, a case study of emergency medical material distribution during COVID-19 in China was conducted for model verification. The results show that different decision criteria have an important impact on the distribution of emergency materials, and the proposed model has significant advantages in the allocation of large-scale disaster relief materials, which can provide a useful reference for emergency material distribution under uncertain information conditions.

Anti-fatigue effect from Ginseng Radix et Rhizoma: a suggestive and promising treatment for long COVID

Two years after the coronavirus disease 2019 (COVID-19) outbreak, an increasing number of patients continue to suffer from long COVID (LC), persistent symptoms, and/or delayed or long-term complications beyond the initial 4 weeks from the onset of symptoms. Constant fatigue is one of the most common LC symptoms, leading to severely reduced quality of life among patients. Ginseng Radix et Rhizoma—known as the King of Herbs in traditional Chinese medicine—has shown clinical anti-fatigue effects. In this review, we summarize the underlying anti-fatigue mechanisms of Ginseng Radix et Rhizoma extracts and their bioactive compounds, with a special focus on anti-viral, immune remodeling, endocrine system regulation, and metabolism, suggesting that Ginseng Radix et Rhizoma is a potentially promising treatment for LC, especially in regard to targeting fatigue.

A Multi-Regional Collaborative Optimization Model of Emergency Medical Materials for Responding to COVID-19

Medical materials are the most important, fundamental resources necessary for emergency relief of major infectious disease disasters. The scientific and optimal allocation of emergency medical materials is the key to reducing casualties and losses in epidemic regions, and to improving the effectiveness and efficiency of rescue operations. In response to the cross-border characteristics of major infectious diseases, the imbalance of material storage, and the differences of supply across regions, a multi-objective optimization model for a multi-regional collaborative allocation of emergency medical materials was developed. Then, an improved adaptive genetic algorithm (IAGA) was designed and applied to solve the proposed model. Finally, a case study of the collaborative response to the COVID-19 epidemic in the Yangtze River Delta of China was conducted for model verification. The results show that collaborative allocation can improve the material satisfaction rate at demand points, especially under peak demand pressure during the early stage of the response, and can meet all material needs at all demand points in the shortest possible amount of time. The proposed model can achieve the effective integration and mutual sharing of emergency materials across regions, and improve the efficiency of emergency material utilization and rescue efforts. The material allocation scheme considers the difference coefficients in different regions, which is conducive to enhancing the flexibility of decision-making and the practical applicability of collaborative allocation operations. A comparative analysis of the algorithms shows that the proposed IAGA is an effective method for managing large-scale multi-regional emergency material allocation optimization problems, as it has higher solving efficiency, better convergence, and stronger stability.

Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody.

An essential step for SARS-CoV-2 infection is the attachment to the host cell receptor by its Spike receptor-binding domain (RBD). Most of the existing RBD-targeting neutralizing antibodies block the receptor-binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non-RBM-targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages the RBD at an epitope distal to the RBM with a KD of 5.6 nM, neutralizes SARS-CoV-2 including the current Variants of Concern such as B.1.1.7, B.1.351, P.1, and B.1.617.2 (Delta), displays modest cross-reactivity against SARS-CoV, and reduces viral replication in hamsters. The epitope coincides with a predicted "ideal" vulnerability site with high functional and structural constraints. Mutation of the residues of the conserved epitope variably affects FD20-binding but confers little or no resistance to neutralization. Finally, in vitro mode-of-action characterization and negative-stain electron microscopy suggest a neutralization mechanism by which FD20 destructs the Spike. Our results reveal a conserved vulnerability site in the SARS-CoV-2 Spike for the development of potential antiviral drugs.

RNA-dependent RNA polymerase of SARS-CoV-2 as a therapeutic target.

The global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), named coronavirus disease 2019, has infected more than 8.9 million people worldwide. This calls for urgent effective therapeutic measures. RNA-dependent RNA polymerase (RdRp) activity in viral transcription and replication has been recognized as an attractive target to design novel antiviral strategies. Although SARS-CoV-2 shares less genetic similarity with SARS-CoV (~79%) and Middle East respiratory syndrome coronavirus (~50%), the respective RdRps of the three coronaviruses are highly conserved, suggesting that RdRp is a good broad-spectrum antiviral target for coronaviruses. In this review, we discuss the antiviral potential of RdRp inhibitors (mainly nucleoside analogs) with an aim to provide a comprehensive account of drug discovery on SARS-CoV-2.

Ginkgolic acid and anacardic acid are specific covalent inhibitors of SARS-CoV-2 cysteine proteases.

BACKGROUND: In the urgent campaign to develop therapeutics against SARS-CoV-2, natural products have been an important source of new lead compounds. RESULTS: We herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PLpro). Moreover, our study demonstrated that the two hit compounds are dual inhibitors targeting the SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) in addition to PLpro. A mechanism of action study using enzyme kinetics further characterized the two compounds as irreversible inhibitors against both 3CLpro and PLpro. Significantly, both identified compounds inhibit SARS-CoV-2 replication in vitro at nontoxic concentrations. CONCLUSIONS: Our finding provides two novel natural products as promising SARS-CoV-2 antivirals.

Unfolding the Determinants of COVID-19 Vaccine Acceptance in China.

BACKGROUND: China is at the forefront of global efforts to develop COVID-19 vaccines and has five fast-tracked candidates at the final-stage, large-scale human clinical trials testing phase. Vaccine-promoting policymaking for public engagement is a prerequisite for social mobilization. However, making an informed and judicious choice is a dilemma for the Chinese government in the vaccine promotion context. OBJECTIVE: In this study, public opinions in China were analyzed via dialogues on Chinese social media, based on which Chinese netizens' views on COVID-19 vaccines and vaccination were investigated. We also aimed to develop strategies for promoting vaccination programs in China based on an in-depth understanding of the challenges in risk communication and social mobilization. METHODS: We proposed a novel behavioral dynamics model, SRS/I (susceptible-reading-susceptible/immune), to analyze opinion transmission paradigms on Chinese social media. Coupled with a meta-analysis and natural language processing techniques, the emotion polarity of individual opinions was examined in their given context. RESULTS: We collected more than 1.75 million Weibo messages about COVID-19 vaccines from January to October 2020. According to the public opinion reproduction ratio (R0), the dynamic propagation of those messages can be classified into three periods: the ferment period (R01=1.1360), the revolution period (R02=2.8278), and the transmission period (R03=3.0729). Topics on COVID-19 vaccine acceptance in China include price and side effects. From September to October, Weibo users claimed that the vaccine was overpriced, making up 18.3% (n=899) of messages; 38.1% (n=81,909) of relevant topics on Weibo received likes. On the contrary, the number of messages that considered the vaccine to be reasonably priced was twice as high but received fewer likes, accounting for 25.0% (n=53,693). In addition, we obtained 441 (47.7%) positive and 295 (31.9%) negative Weibo messages about side effects. Interestingly, inactivated vaccines instigated more heated discussions than any other vaccine type. The discussions, forwards, comments, and likes associated with topics related to inactivated vaccines accounted for 53% (n=588), 42% (n=3072), 56% (n=3671), and 49% (n=17,940), respectively, of the total activity associated with the five types of vaccines in China. CONCLUSIONS: Most Chinese netizens believe that the vaccine is less expensive than previously thought, while some claim they cannot afford it for their entire family. The findings demonstrate that Chinese individuals are inclined to be positive about side effects over time and are proud of China's involvement with vaccine development. Nevertheless, they have a collective misunderstanding about inactivated vaccines, insisting that inactivated vaccines are safer than other vaccines. Reflecting on netizens' collective responses, the unfolding determinants of COVID-19 vaccine acceptance provide illuminating benchmarks for vaccine-promoting policies.

Screening for Anti-Influenza Actives of Prefractionated Traditional Chinese Medicines.

Traditional Chinese medicines (TCMs) have proven to possess advantages in counteracting virus infections according to clinical practices. It's therefore of great value to discover novel antivirals from TCMs. In this paper, One hundred medicinal plants which have been included in TCM prescriptions for antiviral treatment were selected and prefractionated into 5 fractions each by sequentially using cyclohexane, dichloromethane, ethyl acetate, n-butanol, and water. 500 TCM-simplified extracts were then subjected to a phenotypic screening using a recombinant IAV expressing Gaussia luciferase. Ten TCM fractions were identified to possess antiviral activities against influenza virus. The IC50's of the hit fractions range from 1.08 to 6.45 µg/mL, while the SIs, from 7.52 to 98.40. Furthermore, all the ten hit fractions inhibited the propagation of progeny influenza virus significantly at 20 µg/mL. The hit TCM fractions deserve further isolation for responsible constituents leading towards anti-influenza drugs. Moreover, a library consisting of 500 simplified TCM extracts was established, facilitating antiviral screening in quick response to emerging and re-emerging viruses such as Ebola virus and current SARS-CoV-2 pandemic.