The histopathological changes of piglets intestinal tissues and the effection of pathogenicity-associated factors induced by porcine deltacoronavirus

For exploring the histopathological changes of intestinal tissues and the mechanism of porcine deltacoronavirus(PDCo V) replication and leading to inflammatory lesions of piglets intestine which induced by PDCo V infection, 10-day-old piglets were infected by PDCo V strain TJ1 which isolated from Tianjin through oral route in this study. The piglets were necropsied at 4 days post-infection. Through histopathological observation, the main lesions of jejunum, ileum, colon and cecum were investigated. The diffuse inflammatory cell infiltration was found in mesenchyme, lamina propria and submucosa of intestinal mucosa, and the mucosal villi atrophy occurred in response to local tissues. The m RNA expression level of PDCo V M gene, innate immune genes including IFN-a, IFN-beta, DDX58 and STAT2 as well as the inflammatory cytoines including TNF-a and IL-6 in intestinal tissues were examined. The results showed that PDCo V replication was achieved by inhibiting host cell innate immune response, and the occurrence of inflammatory lesions in jejunum, ileum and colon were promoted through the enhancement of TNF-a and IL-6 expression. This study can provide a theoretical basis for the pathogenic mechanism study of porcine deltacoronavirus.

The Analysis of Causality and Risk Spillover between Crude Oil and China's Agricultural Futures.

This paper aims to apply the time-varying Granger causality test (TVGC) and the DY Spillover Index (Diebold and Yilmaz, 2012) to measure the Granger causality and dynamic risk spillover effects of the international crude oil futures market on China's agricultural commodity futures market from the perspectives of return and volatility spillovers. Empirical evidence relating to the TVGC test suggests the existence of unidirectional Granger causality between crude oil futures and agricultural product futures. This relationship shows a strong time-varying property, in particular for sudden or extreme events such as financial crises and natural disasters. On the other hand, the volatility spillover in crude oil and agricultural product futures markets responds asymmetrically and bidirectionally according to the result of the DY Spillover index, and the periodicity of total volatility spillover correlates closely with the occurrence of global economic events, which indicates that the spillover effect between crude oil and agricultural commodity futures markets will be exacerbated in turbulent financial and economic times. Such findings are expected to help in formulating policy recommendations, portfolio design, and risk-management decisions.

Identification and integrated analysis of lncRNAs and miRNAs in IPEC-J2 cells provide novel insight into the regulation of the innate immune response by PDCoV infection.

BACKGROUND: Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are pivotal regulators involved in the pathogenic mechanism of multiple coronaviruses. Porcine deltacoronavirus (PDCoV) has evolved multiple strategies to escape the innate immune response of host cells, but whether ncRNAs are involved in this process during PDCoV infection is still unknown. RESULTS: In this study, the expression profiles of miRNAs, lncRNAs and mRNAs in IPEC-J2 cells infected with PDCoV at 0, 12 and 24 hours postinfection (hpi) were identified through small RNA and RNA sequencing. The differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were screened from the comparison group of IPEC-J2 cells at 0 and 12 hpi as well as the comparison group of IPEC-J2 cells at 12 and 24 hpi. The target genes of these DEncRNAs were predicted. The bioinformatics analysis of the target genes revealed multiple significantly enriched functions and pathways. Among them, the genes that were associated with innate immunity were specifically screened. The expression of innate immunity-related ncRNAs and mRNAs was validated by RT-qPCR. Competing endogenous RNA (ceRNA) regulatory networks among innate immunity-related ncRNAs and their target mRNAs were established. Moreover, we found that the replication of PDCoV was significantly inhibited by two innate immunity-related miRNAs, ssc-miR-30c-3p and ssc-miR-374b-3p, in IPEC-J2 cells. CONCLUSIONS: This study provides a data platform to conduct studies of the pathogenic mechanism of PDCoV from a new perspective and will be helpful for further elucidation of the functional role of ncRNAs involved in PDCoV escaping the innate immune response.

Design and Development of Nanomaterial-Based Drug Carriers to Overcome the Blood-Brain Barrier by Using Different Transport Mechanisms.

Central nervous system (CNS) diseases are the leading causes of death and disabilities in the world. It is quite challenging to treat CNS diseases efficiently because of the blood-brain barrier (BBB). It is a physical barrier with tight junction proteins and high selectivity to limit the substance transportation between the blood and neural tissues. Thus, it is important to understand BBB transport mechanisms for developing novel drug carriers to overcome the BBB. This paper introduces the structure of the BBB and its physiological transport mechanisms. Meanwhile, different strategies for crossing the BBB by using nanomaterial-based drug carriers are reviewed, including carrier-mediated, adsorptive-mediated, and receptor-mediated transcytosis. Since the viral-induced CNS diseases are associated with BBB breakdown, various neurotropic viruses and their mechanisms on BBB disruption are reviewed and discussed, which are considered as an alternative solution to overcome the BBB. Therefore, most recent studies on virus-mimicking nanocarriers for drug delivery to cross the BBB are also reviewed and discussed. On the other hand, the routes of administration of drug-loaded nanocarriers to the CNS have been reviewed. In sum, this paper reviews and discusses various strategies and routes of nano-formulated drug delivery systems across the BBB to the brain, which will contribute to the advanced diagnosis and treatment of CNS diseases.

Efficacy of Acupuncture in Post-partum With Diastasis Recti Abdominis: A Randomized Controlled Clinical Trial Study Protocol.

Background: Diastasis rectus abdominis (DRA) is one of the common complications during pregnancy and post-partum, which has psychological and physical effects on post-partum women. Acupuncture, a worldwide alternative therapy, has attracted wide attention in preventing and treating diseases related to pregnancy and childbirth. This study aims to evaluate the efficacy of acupuncture combined with physical training in treating post-partum rectus muscle dissociation. Methods: This is a randomized, controlled trial of DRA in post-partum conducted at Hangzhou Hospital of Traditional Chinese Medicine Affiliated with Zhejiang University of Chinese Medicine. The primary purpose is to evaluate the effectiveness of acupuncture and physical training on DRA in post-partum women. The study will be conducted from March 2022 to March 2023. The acupuncture group received acupuncture and physical training (n = 48), the sham acupuncture group received sham acupuncture and physical training (n = 48), and the physical training group received physical training (n = 48). These experiments perform once/day, five times a week for 2 weeks, followed up for half a year after the end of the course of treatment. Our tests perform a course of treatment, which includes a total of 10 consecutive treatments. Furthermore, the patient will be followed up for half a year after the treatment. Primary and secondary indicators, including inter recti distance (IRD), linea alba (LA) tension, the MOS item short-form health survey (SF-36), short-form McGill pain questionnaire-2 (SF-MPQ-2), body mass index (BMI), waist-to-hip ratio (WHR), leeds dyspepsia questionnaire (LDQ), menstrual distress questionnaire (MDQ), 10 items of edinburgh post-natal depression scale (EPDS-10), the modified body self-image scale (MBIS), international consultation incontinence questionnaire short-form (ICIQ-SF) and hernia-related quality-of-life survey (HerQles), which will be evaluated before and after treatment and half a year after treatment. Adverse events and side effects during each treatment will be collected and recorded. Discussion: There is evidence that acupuncture and physical training can treat DRA in post-partum. In this study, we evaluate the effectiveness of acupuncture in post-partum with DRA.

Impact of the COVID-19 on the vertical distributions of major pollutants from a tower in the Pearl River Delta.

The outbreak of the 2019 novel coronavirus (COVID-19) had a large impact on human health and socio-economics worldwide. The lockdown implemented in China beginning from January 23, 2020 led to sharp reductions in human activities and associated emissions. The declines in primary pollution provided a unique opportunity to examine the relationship between anthropogenic emissions and air quality. This study reports on air pollutant and meteorological measurements at different heights from a tall tower in the Pearl River Delta. These measurements were used to investigate the vertical scale response of pollutants to understand reductions in human activities. Compared to that in the pre-lockdown period (from December 16, 2019), the concentrations of surface layer nitric oxide (NOx), fine particulate matter (PM2.5), and daily maximum 8 h average ozone (MDA8O3) declined significantly during the lockdown by 76.8%, 49.4%, and 18.6%, respectively. Although the vertical profiles of NOx and O3 changed during the lockdown period, those of PM2.5 remained the same. During the lockdown period, there were statistically significant correlations between PM2.5 and O3 but not between PM2.5 and NOx at four heights, indicating that the main composition of PM2.5 have dramatically changed, during which the impact of NOx on PM2.5 became insignificant. Additionally, O3 concentrations were also insensitive to NOx concentrations during the lockdown, implying that O3 levels were more of a representative of regional background level. In this case, local photochemical formation is no longer a significant ozone source. This evidence suggests that it is possible to mitigation of PM2.5 and O3 levels simultaneously by significant reductions in anthropogenic emissions.

A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Clinical Trial to Assess Safety, Tolerability, and Pharmacokinetics of LY-CovMab, a Potent Human Neutralizing Antibody Against SARS-CoV-2.

INTRODUCTION: We aimed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of a single dose of LY-CovMab in Chinese healthy adults. METHODS: We conducted a phase 1, randomized, dose-escalation, placebo-controlled trial in 42 volunteers, 18-45 years of age, and 40 out of 42 received a single dose of LY-CovMab or placebo with LY-CovMab at a dose of 30 mg, 150 mg, 600 mg, 1200 mg, and 2400 mg. There were ten subjects in each group receiving LY-CovMab or placebo in a 4:1 ratio with the exception that the 30 mg group had two subjects both receiving LY-CovMab. RESULTS: Among the 42 randomized participants, 40 received an injection with 32 administered LY-CovMab and 8 administered placebo. A total of 18 drug-related treatment-emergent adverse events (TEAEs) were reported in 12 subjects (30.0%), including protein urine present (25%, 10/40) and blood creatinine increased (7.5%, 3/40). The incidence of drug-related TEAE in each dosage group was as follows: 150 mg (28.6%, 2/7), 600 mg (25%, 2/8), 1200 mg (14.3%, 1/7), 2400 mg (50%, 4/8), and placebo (37.5%, 3/8). All drug-related TEAEs were grade 1, and most of them were recovering/resolving or recovered/resolved without taking action. The serum exposure of LY-CovMab (Cmax, AUC0-last, AUC0-inf) after intravenous infusion increased in an approximately proportional manner as the dose increased from 150 to 2400 mg. The elimination half-life (t1/2) value did not differ among different dose cohorts and was estimated to be around 28.5 days. CONCLUSIONS: A single dose of LY-CovMab was shown to be safe and well tolerated in Chinese healthy adults. The pharmacokinetic (PK) profiles of LY-CovMab in healthy adults showed typical monoclonal antibody distribution and elimination characteristics. LY-CovMab demonstrated dose proportionality. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT04973735.

An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens with pandemic potential requires safe, protective, inexpensive, and easily accessible vaccines that can be developed and manufactured rapidly at a large scale. DNA vaccines can achieve these criteria, but induction of strong immune responses has often required bulky, expensive electroporation devices. Here, we report an ultra-low-cost (<1 USD), handheld (<50 g) electroporation system utilizing a microneedle electrode array ("ePatch") for DNA vaccination against SARS-CoV-2. The low cost and small size are achieved by combining a thumb-operated piezoelectric pulser derived from a common household stove lighter that emits microsecond, bipolar, oscillatory electric pulses and a microneedle electrode array that targets delivery of high electric field strength pulses to the skin's epidermis. Antibody responses against SARS-CoV-2 induced by this electroporation system in mice were strong and enabled at least 10-fold dose sparing compared to conventional intramuscular or intradermal injection of the DNA vaccine. Vaccination was well tolerated with mild, transient effects on the skin. This ePatch system is easily portable, without any battery or other power source supply, offering an attractive, inexpensive approach for rapid and accessible DNA vaccination to combat COVID-19, as well as other epidemics.

Analyzing knowledge entities about COVID-19 using entitymetrics.

COVID-19 cases have surpassed the 109 + million markers, with deaths tallying up to 2.4 million. Tens of thousands of papers regarding COVID-19 have been published along with countless bibliometric analyses done on COVID-19 literature. Despite this, none of the analyses have focused on domain entities occurring in scientific publications. However, analysis of these bio-entities and the relations among them, a strategy called entity metrics, could offer more insights into knowledge usage and diffusion in specific cases. Thus, this paper presents an entitymetric analysis on COVID-19 literature. We construct an entity-entity co-occurrence network and employ network indicators to analyze the extracted entities. We find that ACE-2 and C-reactive protein are two very important genes and that lopinavir and ritonavir are two very important chemicals, regardless of the results from either ranking.

Virus-inspired surface-nanoengineered antimicrobial liposome: A potential system to simultaneously achieve high activity and selectivity.

Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local "burst" release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6-6.3 µg mL-1), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.

Investigation on the mental health status of pregnant women in China during the Pandemic of COVID-19.

PURPOSE: To evaluate the anxiety and depression in pregnant women in China, and its influencing factors during the corona virus disease 2019 (COVID-19) pandemic. METHODS: From February 22 to February 27, a questionnaire survey was conducted on 156 pregnant women, including demographic characteristics, a self-rating anxiety scale (SAS), and a self-depression rating scale (SDS). RESULTS: A total of 13 non-homologous end-joining (8.3%, 13/156) patients were anxious, 79 patients (50.6%, 79/156) were depressed, and 13 patients (8.3%, 13/156) suffered from both anxiety and depression. The SAS score of pregnant women was 40.55 ± 6.09, and the SDS score was 50.42 ± 11.64. For the SAS score, only 8.3% of all patients (13/156) were in a light anxiety state. For the SDS score, 46.79% (73/156) of patients was normal, 23.72% of patients (37/156) showed mild depression, 22.44% (35/156) showed moderate depression, and 4.49% (7/156) showed severe depression. No significant changes were observed in SAS and SDS scores between patients from different regions within China, health state, gestational week, educational background, and living condition (P > 0.05). Moreover, no significant differences were observed between diagnosed/suspected patients and the normal control group (P > 0.05), and between pregnant women in Wuhan compared to other regions (P > 0.05). CONCLUSION: During the COVID-19 epidemic, the anxiety level of pregnant women was the same as that before the epidemic, while the level of depression was significantly higher. Pregnant women who lived in Wuhan, the epicenter of the epidemic, were not more anxious or depressed compared to pregnant women in other regions during the COVID-19 epidemic. Furthermore, the mental health status of pregnant women with COVID-19 was not more severe.

Update on recommendations for the diagnosis and treatment of SARS-CoV-2 infection in children.

Since the outbreak of novel coronavirus infection pneumonia in Wuhan City, China, in late 2019, such cases have been gradually reported in other parts of China and abroad. Children have become susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their immature immune function. As the outbreak has progressed, more cases of novel coronavirus infection/pneumonia in children have been reported. Compared with adults, the impact of SARS-CoV-2 infection in children is less severe, with a lower incidence and susceptibility in children, which results in fewer children being tested, thereby underestimating the actual number of infections. Therefore, strengthening the diagnosis of the disease is particularly important for children, and early and clear diagnosis can determine treatment strategies and reduce the harm caused by the disease to children. According to the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (trial version 7) issued by National Health Committee and the latest diagnosis and treatment strategies for novel coronavirus infection pneumonia in children, this review summarizes current strategies on diagnosis and treatment of SARS-CoV-2 infection in children.