Assessment of the excretion of oxidative stress biomarkers and anabolic steroids based on sewage: A case study of college students and the general population.

The use of wastewater-based epidemiology to evaluate the health and lifestyle of the population is a novel research interest. However, studies concerning the excretion of endogenous metabolites due to oxidative stress and the consumption of anabolic steroids have rarely been involved. In this study, we compared the effects of events such as final examination and sports meeting on the levels of four oxidative stress biomarkers (8-isoPGF2α, HNE-MA, 8-OHdG, and HCY) and four prohibited anabolic steroids (Testosterone, Androstenedione, Boldenone, and Metandienone) in sewage, using university students and urban populations as studying target. It was found that the per capita mass load of the four oxidative stress biomarkers 8-isoPGF2α, HNE-MA, 8-OHdG, and HCY in the sewage of Guangzhou urban area and university town were 256.6 ± 76.1, 9.4 ± 3.8, 1.1 ± 0.5, and 0.9 ± 0.4 mg/d/1000, respectively. The mean mass load of 8-isoPGF2α was significantly higher than that before the COVID-19 pandemic (74.9 ± 29.6 mg/d/1000 people, P < 0.05). The per capita load levels of oxidative stress biomarkers were significantly higher (P < 0.05) during the 2022 exam week relative to the pre-exam period, indicating that the exams caused transient stress to students. The per capita mass load of androgenic steroids was 77.7 mg/d/1000 people. There was an increase in the per capita load level of androgenic steroids during the provincial sports meeting. In this study, we quantified the concentration of oxidative stress biomarkers and androgenic steroids in the sewage and better realized the application of WBE on the health level and lifestyle of the population during special events.

Trends in the availability of community-based psychological counselling services for oldest-old in China, 2005 to 2018.

BACKGROUND: Community-based psychological counselling services (CPCS) is crucial for the oldest-old who often faces challenges or are reluctant to seek care at the healthcare settings. This study aims to examine trends in availability of CPCS over time and rural-urban disparities in service availability among nationwide oldest-old in China. METHODS: Multiple cross-sectional data were derived from the 2005-2018 Chinese Longitudinal Health Longevity Survey. Service availability was reported by each oldest-old participant or their next-of-kins as having CPCS in one's neighborhood. We used Cochran-Armitage tests to estimate service availability trends and applied sample-weighted logistic regression models to examine its rural-urban disparities. RESULTS: Of 38,032 oldest-old, CPCS availability decreased from 6.7 % in 2005 to 4.8 % in 2008/2009, followed by continual increases to 13.6 % in 2017/2018. In 2017/2018, rural oldest-old's neighborhoods had no greater service availability. Oldest-old residing in the Central (6.7 %), Western (13.4 %) and Northeast China (8.1 %) were less likely to report having services locally than their Eastern counterparts (17.8 %). Oldest-old having any disability or living in the nursing homes reported having greater service availability than those without disability or living at home. LIMITATION: Service availability might have been disrupted during the COVID-19 pandemic. CONCLUSIONS: Despite the increasing service availability, as of 2017/2018, only 13.6 % oldest-old in China had reported CPCS availability. It raises concerns on the disproportionate access to and continuity of mental health care, especially for those living the Central, Western China and those living at home. Policy efforts are needed to incentivize service expansion and eliminate disparities in the service availability.

Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.

SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

Mechanism and potential treatments for gastrointestinal dysfunction in patients with COVID-19.

The global coronavirus disease 2019 (COVID-19) has become one of the biggest threats to the world since 2019. The respiratory and gastrointestinal tracts are the main targets for severe acute respiratory syndrome coronavirus 2 infection for they highly express angiotensin-converting enzyme-2 and transmembrane protease serine 2. In patients suffering from COVID-19, gastrointestinal symptoms have ranged from 12% to 61%. Anorexia, nausea and/or vomiting, diarrhea, and abdominal pain are considered to be the main gastrointestinal symptoms of COVID-19. It has been reported that the direct damage of intestinal mucosal epithelial cells, malnutrition, and intestinal flora disorders are involved in COVID-19. However, the underlying mechanisms remain unclear. Thus, in this study, we reviewed and discussed the correlated mechanisms that cause gastrointestinal symptoms in order to help to develop the treatment strategy and build an appropriate guideline for medical workers.

Ephedrae Herba: A Review of Its Phytochemistry, Pharmacology, Clinical Application, and Alkaloid Toxicity.

Ephedrae Herba (Ephedra), known as "MaHuang" in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.

Seroepidemiology of pertussis in the east of China: Estimates of incidence of infection in adolescents and adults pre- and post-COVID-19.

Introduction: The dramatic decrease in the number of reported cases of pertussis during COVID-19 pandemic has been underestimated. The objective was to compare the estimated incidence rate of pertussis in populations pre- and post-COVID-19 pandemic by analyzing the anti-pertussis toxin (anti-PT) IgG and anti-filamentous hemagglutininant (anti-FHA) IgG antibodies in healthy Chinese population from 2018 to 2021. Methods: All serum samples (N = 1,000) were collected from healthy population (aged ≥ 15 years) who attended an annual monitoring project of antibody levels in Jiangsu province in 2018-2021 were measured by ELISA. Results: The positive rates of anti-PT IgG and anti-FHA IgG antibodies were 11.4% (114/1,000) and 20.2% (202/1,000) (≥40 IU/ml), the GMC were 17.25 (95% CI: 15.49-19.03) IU/mL and 24.94 (95% CI: 22.73-27.16) IU/mL in the study population, respectively. The percentage of participants with anti-PT IgG antibodies higher than 40 IU/mL was 5.20% (11/212) in 2018, 5.5% (19/348) in 2019, 21.2% (46/217) in 2020 and 17.0% (38/223) in 2021, respectively. The non-detectable rate (<5 IU/mL) of anti-PT IgG antibodies was 16.9, 17.7, 28.1, and 37.3% in 2018, 2019, 2020, and 2021, respectively. We assumed that the infection occurred within 58.6 days, and based on the overall proportion (2.9%) of individuals with anti-PT IgG antibody ≥100 IU/ml, the incidence rate (/100) was estimated by the formula to be 18.08 (95% CI: 12.40-26.11). In addition, the estimated incidence of Post-COVID-19 was higher than that of Pre-COVID-19 (36.33/100 vs. 12.84/100), and the difference was statistically significant (p < 0.05). Conclusions: Our results suggest a high rate of under-reporting of pertussis in Jiangsu Province both pre- and post-COVID-19 pandemic, and there are a large number of adults of childbearing age who are susceptible to pertussis. It seems imperative that vaccination of adolescents and adults should be considered for inclusion in vaccination programs.

A trial of arbidol hydrochloride in adults with COVID-19.

BACKGROUND: To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19. METHODS: This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable. RESULTS: A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P  = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. CONCLUSIONS: SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week anas, accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1.

Characterization and immunogenicity of SARS-CoV-2 spike proteins with varied glycosylation.

The ongoing coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drastically changed our way of life and continues to have an unmitigated socioeconomic impact across the globe. Research into potential vaccine design and production is focused on the spike (S) protein of the virus, which is critical for virus entry into host cells. Yet, whether the degree of glycosylation in the S protein is associated with vaccine efficacy remains unclear. Here, we first optimized the expression of the S protein in mammalian cells. While we found no significant discrepancy in purity, homogeneity, or receptor binding ability among S proteins derived from 293F cells (referred to as 293F S-2P), 293S GnTI- cells (defective in N-acetylglucosaminyl transferase I enzyme; 293S S-2P), or TN-5B1-4 insect cells (Bac S-2P), there was significant variation in the glycosylation patterns and thermal stability of the proteins. Compared with the partially glycosylated 293S S-2P or Bac S-2P, the fully glycosylated 293F S-2P exhibited higher binding reactivity to convalescent sera. In addition, 293F S-2P induced higher IgG and neutralizing antibody titres than 293S or Bac S-2P in mice. Furthermore, a prime-boost-boost regimen, using a combined immunization of S-2P proteins with various degrees of glycosylation, elicited a more robust neutralizing antibody response than a single S-2P alone. Collectively, this study provides insight into ways to design a more effective SARS-CoV-2 immunogen.

The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.

Case fatality rate of the adult in-patients with COVID-19 and digestive system tumors: A systematic review and meta-analysis.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, endoscopic screening for gastrointestinal tumors was suspended or delayed in most countries. Thus, our study aimed to quantify the impact of COVID-19 on the clinical outcomes of patients with digestive system tumors through a systematic review and meta-analysis. METHODS: We systematically searched the PubMed, Web of Science, Cochrane Library, and Embase databases as of March 7, 2021 to identify the case fatality rate (CFR) of COVID-19 patients diagnosed with digestive system tumors. A random-effects model was used for meta-analysis, I2 was used to assess heterogeneity, and funnel plot was used to assess publication bias. RESULTS: A total of 13 studies were included, involving 2943 tumor patients with COVID-19, of which 871 were digestive system tumors, and the CFR was 24% (95% CI, 18%-30%; I2 = 55.7%). The mortality rate of colorectal cancer was 21% (95% CI, 14%-27%; I2 = 0.0%), gastric cancer was 25% (95% CI, 6%-45%; I2 = 0.0%), and hepatobiliary cancer was 29%. In general, there was no significant difference in the CFR of digestive system tumors. CONCLUSION: The combined CFR of digestive system tumors and COVID-19 patients was 24%, which is much higher than that of the general population. Under the premise of fully complying with the international guidelines to limit the spread of COVID-19, we call for the resumption of endoscopic screening programs and selective surgery as soon as possible. REGISTRATION INFORMATION: PROSPERO registration no. CRD42021248194.

Learning COVID-19 Pneumonia Lesion Segmentation From Imperfect Annotations via Divergence-Aware Selective Training.

Automatic segmentation of COVID-19 pneumonia lesions is critical for quantitative measurement for diagnosis and treatment management. For this task, deep learning is the state-of-the-art method while requires a large set of accurately annotated images for training, which is difficult to obtain due to limited access to experts and the time-consuming annotation process. To address this problem, we aim to train the segmentation network from imperfect annotations, where the training set consists of a small clean set of accurately annotated images by experts and a large noisy set of inaccurate annotations by non-experts. To avoid the labels with different qualities corrupting the segmentation model, we propose a new approach to train segmentation networks to deal with noisy labels. We introduce a dual-branch network to separately learn from the accurate and noisy annotations. To fully exploit the imperfect annotations as well as suppressing the noise, we design a Divergence-Aware Selective Training (DAST) strategy, where a divergence-aware noisiness score is used to identify severely noisy annotations and slightly noisy annotations. For severely noisy samples we use an regularization through dual-branch consistency between predictions from the two branches. We also refine slightly noisy samples and use them as supplementary data for the clean branch to avoid overfitting. Experimental results show that our method achieves a higher performance than standard training process for COVID-19 pneumonia lesion segmentation when learning from imperfect labels, and our framework outperforms the state-of-the-art noise-tolerate methods significantly with various clean label percentages.

Three SARS-CoV-2 antibodies provide broad and synergistic neutralization against variants of concern, including Omicron.

The rapidly spreading Omicron variant is highly resistant to vaccines, convalescent sera, and neutralizing antibodies (nAbs), highlighting the urgent need for potent therapeutic nAbs. Here, a panel of human nAbs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent patients show diverse neutralization against Omicron, of which XMA01 and XMA04 maintain nanomolar affinities and excellent neutralization (half maximal inhibitory concentration [IC50]: ∼20 ng/mL). nAb XMA09 shows weak but unattenuated neutralization against all variants of concern (VOCs) as well as SARS-CoV. Structural analysis reveals that the above three antibodies could synergistically bind to the receptor-binding domains (RBDs) of both wild-type and Omicron spikes and defines the critical determinants for nAb-mediated broad neutralizations. Three nAbs confer synergistic neutralization against Omicron, resulting from the inter-antibody interaction between XMA04 and XMA01(or XMA09). Furthermore, the XMA01/XMA04 cocktail provides synergistic protection against Beta and Omicron variant infections in hamsters. In summary, our results provide insights for the rational design of antibody cocktail therapeutics or universal vaccines against Omicron.

Public opinion and attitude towards COVID-19 vaccination among parents of middle school students

Objective: To explore the impact of public opinion on the attitude towards COVID-19 vaccination among parents of middle school students aged 12 to 17 years. Methods A total of 477 parents of middle school students were recruited online and offline. News reports and virtual online comments on the vaccination of children aged 12 to 17 were provided for them to read, after which all the parents reported their attitude towards COVID-19 vaccination for their child. Results Totally 73.55% of parents were willing to vaccinate their child. In addition, public opinion showed significant impacts on parental attitude towards COVID-19 vaccination (F=67.89, P < 0.01). After reading positive opinions (4.02..0.91), parental willingness to vaccinate was significantly higher than other comment conditions;Under the influence of negative opinions (2.56..0.88), parents' willingness to child vaccination was significantly lower than other opinion groups;There was no significant difference (P=0.77) between the neutral opinion group (3.71..0.79) and the control group (3.68..0.81). Conclusion The attitude towards child COVID-19 vaccination among parents of middle school students might be influenced by public opinions. Guidance on public opinion is key for child COVID-19 vaccination improvement.

Response time analysis of a manufacturing supply chain with performance evaluation process algebra

The supply and demand shocks brought on by the Covid-19 crisis are forcing manufacturers everywhere to reassess or even reorganise their supply chains. This paper proposes a general framework that can achieve fast compositional modelling with stochastic performance evaluation process algebra (PEPA) for supply chain systems. The key feature of such a framework is the PEPA-based quantitative analysis approach which includes a new method for calculating response time based on compositional PEPA models. The framework aims to provide an efficient modelling prototype for supply chain systems while supporting accurate response time-based quantitative analysis. To our knowledge, this is the first work using process algebra-based compositional modelling to quantitatively analyse supply chain systems.

Broken-Edge Decision-Making Strategy for COVID-19 over Air Railway Composite Network.

In order to control the spread of the COVID-19 virus, this study proposes an ARCN-SUTS (air railway composite network susceptible-untested-tested-susceptible) model based on the correlation characteristics of the air railway composite network in mainland China. Furthermore, this study also puts forward a broken-edge decision-making strategy for the purpose of making decision about the edge efficiently broken and avoiding the second outbreak of the virus spread to minimize the economic losses for railway and civil aviation companies. Finally, simulation results demonstrate that the proposed strategy can effectively control the spread of the virus with minimal economic losses.

Persistent white matter changes in recovered COVID-19 patients at the 1-year follow-up.

There is growing evidence that severe acute respiratory syndrome coronavirus 2 can affect the CNS. However, data on white matter and cognitive sequelae at the 1-year follow-up are lacking. Therefore, we explored these characteristics in this study. We investigated 22 recovered coronavirus disease 2019 (COVID-19) patients and 21 matched healthy controls. Diffusion tensor imaging, diffusion kurtosis imaging and neurite orientation dispersion and density imaging were performed to identify white matter changes, and the subscales of the Wechsler Intelligence scale were used to assess cognitive function. Correlations between diffusion metrics, cognitive function and other clinical characteristics were then examined. We also conducted subgroup analysis based on patient admission to the intensive care unit. The corona radiata, corpus callosum and superior longitudinal fasciculus had a lower volume fraction of intracellular water in the recovered COVID-19 group than in the healthy control group. Patients who had been admitted to the intensive care unit had lower fractional anisotropy in the body of the corpus callosum than those who had not. Compared with the healthy controls, the recovered COVID-19 patients demonstrated no significant decline in cognitive function. White matter tended to present with fewer abnormalities for shorter hospital stays and longer follow-up times. Lower axonal density was detected in clinically recovered COVID-19 patients after 1 year. Patients who had been admitted to the intensive care unit had slightly more white matter abnormalities. No significant decline in cognitive function was found in recovered COVID-19 patients. The duration of hospital stay may be a predictor for white matter changes at the 1-year follow-up.

Survivors of COVID-19 exhibit altered amplitudes of low frequency fluctuation in the brain: a resting-state functional magnetic resonance imaging study at 1-year follow-up.

Although some short-term follow-up studies have found that individuals recovering from coronavirus disease 2019 (COVID-19) exhibit anxiety, depression, and altered brain microstructure, their long-term physical problems, neuropsychiatric sequelae, and changes in brain function remain unknown. This observational cohort study collected 1-year follow-up data from 22 patients who had been hospitalized with COVID-19 (8 males and 11 females, aged 54.2 ± 8.7 years). Fatigue and myalgia were persistent symptoms at the 1-year follow-up. The resting state functional magnetic resonance imaging revealed that compared with 29 healthy controls (7 males and 18 females, aged 50.5 ± 11.6 years), COVID-19 survivors had greatly increased amplitude of low-frequency fluctuation (ALFF) values in the left precentral gyrus, middle frontal gyrus, inferior frontal gyrus of operculum, inferior frontal gyrus of triangle, insula, hippocampus, parahippocampal gyrus, fusiform gyrus, postcentral gyrus, inferior parietal angular gyrus, supramarginal gyrus, angular gyrus, thalamus, middle temporal gyrus, inferior temporal gyrus, caudate, and putamen. ALFF values in the left caudate of the COVID-19 survivors were positively correlated with their Athens Insomnia Scale scores, and those in the left precentral gyrus were positively correlated with neutrophil count during hospitalization. The long-term follow-up results suggest that the ALFF in brain regions related to mood and sleep regulation were altered in COVID-19 survivors. This can help us understand the neurobiological mechanisms of COVID-19-related neuropsychiatric sequelae. This study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University (approval No. 2020S004) on March 19, 2020.

Spatio-Temporal Evolution and Spatial Heterogeneity of Influencing Factors of SO2 Emissions in Chinese Cities: Fresh Evidence from MGWR

In this study, based on the multi-source nature and humanities data of 270 Chinese cities from 2007 to2018, the spatio-temporal evolution characteristics of SO2 emissions are revealed by using Moran’s I, a hot spot analysis, kernel density, and standard deviation ellipse models. The spatial scale heterogeneity of influencing factors is explored by using the multiscale geographically weighted regression model to make the regression results more accurate and reliable. The results show that (1) SO2 emissions showed spatial clustering characteristics during the study period, decreased by 85.12% through pollution governance, and exhibited spatial heterogeneity of differentiation. (2) The spatial distribution direction of SO2 emissions’ standard deviation ellipse in cities was “northeast–southwest”. The gravity center of the SO2 emissions shifted to the northeast, from Zhumadian City to Zhoukou City in Henan Province. The results of hot spots showed a polarization trend of “clustering hot spots in the north and dispersing cold spots in the south”. (3) The MGWR model is more accurate than the OLS and classical GWR regressions. The different spatial bandwidths have a different effect on the identification of influencing factors. There were several main influencing factors on urban SO2 emissions: the regional innovation and entrepreneurship level, government intervention, and urban precipitation;important factors: population intensity, financial development, and foreign direct investment;secondary factors: industrial structure upgrading and road construction. Based on the above conclusions, this paper explores the spatial heterogeneity of urban SO2 emissions and their influencing factors, and provides empirical evidence and reference for the precise management of SO2 emission reduction in “one city, one policy”.