A droplet digital PCR chip with passive bubble removal for absolute nucleic acid quantification

Droplet digital polymerase chain reaction (ddPCR) is an extremely sensitive method for the precisely determining the concentration of target nucleic acids. However, air bubbles between droplets during amplification can cause significant droplet loss and decreased accuracy in results. In the present study, an all-in-one microfluidic chip that integrates emulsification, passive bubble removal, droplet monolayer storage, on-chip nucleic acid amplification, and droplet fluorescence signal readout is proposed. The integrated passive bubble removal structures automatically complete the trapping and guiding of the bubbles, ensuring that the droplets do not touch the bubbles during amplification and thus is not lost. The ddPCR device with optimized key parameters proved to be effective and efficient by completely removing bubbles between droplets and having a dead volume of less than 1 %. The ability of the ddPCR chip to accurately quantify nucleic acids was evaluated by measuring plasmids with the SARS-CoV-2N gene at concentrations ranging from 10 to 50 000 copies/μL. The innovative ddPCR device satisfies the requirement for accurate nucleic acid quantification and is expected to accelerate the popularity of dPCR due to its low processing difficulty, ease of use and high robustness.

The impact of COVID-19 on economy, air pollution and income: evidence from China.

The global pandemic caused by the outbreak of COVID-19 has posed significant risks to our health. Preventive measures such as closed management have greatly affected the economies, environments and societies of various countries. Economy, air pollution and income are three important interconnected aspects of sustainable development. However, current research lacks systematic quantitative analysis of their relationships. To fill the gap, this study adopts monthly data from January 2016 to April 2022 and constructs both a Simultaneous Equation Model (SEM) and a Time Varying Parameter Stochastic Volatility Vector Autoregressive (TVP-SV-VAR) model to empirically analyze the impact of COVID-19 on China's economy, air pollution and income. This study finds that the COVID-19 has a negative impact on China's economy and income, and a positive impact on air pollution, and the impact of the COVID-19 is systematic. In addition, there is an inverted-U shaped relationship between air pollution and economics, and a positive correlation between economic and income. The impact of COVID-19 on the economy, air pollution and income show a process of sharp fluctuations to gradual stabilization that gradually stabilized over time. This process is time-varying in the short-term, medium-term and long-term. The impacts are persistent at three different time points (before, during and after the outbreak of COVID-19), but the negative impact on the economy and income is persistent, while the positive impact on air pollution is limited. This study provides a more systematic and dynamic understanding of the COVID-19 preventive and mitigation measures in China and even the world, which helps to provide insights into the formulation of more comprehensive planning strategies in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s00477-023-02450-z.

Effectiveness of Chinese medicine formula Huashibaidu granule on mild COVID-19 patients: A prospective, non-randomized, controlled trial

Background The effectiveness and safety of Huashibaidu granule (HSBD) in treating mild Corona Virus Disease 2019 (COVID-19) patients infected with SARS-CoV-2 remain to be identified. We aimed to evaluate the effectiveness of HSBD in mild COVID-19 patients. Methods A prospective, non-randomized, controlled study in mild COVID-19 patients was conducted in Shanghai, from April 8 to May 6, 2022. The enrolled patients were diagnosed as mild COVID-19. Finally, 360 patients received HSBD, and 368 patients received TCM placebo (administered orally 20g twice daily for 7 days). The primary endpoints were the negative conversion rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the negative conversion time. Secondary endpoints included the hospitalized days and the improvement in the clinical condition. Results The negative conversion rate of SARS-CoV-2 at 7 days posttreatment in the HSBD group was higher than that in the control group (95.28% vs. 82.61%, P < 0.001). The median negative conversion time in the HSBD group was markedly decreased by 2 days compared with the control group (3 [3-6] vs. 5 [4-7], P < 0.001). In addition, the median hospitalized day was shortened in the HSBD group by 1 day compared with the control group (6 [4-7] vs. 7 [5-9], P < 0.001). The clinical improvement rate (275/360 [76.39%]) in the HSBD group within 7 days was significantly higher than that (203/368 [55.16%]) in the control group (P < 0.001). The improvement of symptom scores in the HSBD group was higher than that in the control group (2 [1-4] vs. 1 [1-2], P < 0.001). No severe adverse events occurred. Conclusions Our study suggested that HSBD effectively increased the negative conversion rate of SARS-CoV-2 and shortened the negative conversion time and hospitalized days in mild COVID-19 patients. Clinical trial registration Chinese Clinical Trial Registry, ChiCTR2200058668

Analysis and simulation of a stochastic COVID-19 model with large-scale nucleic acid detection and isolation measures: A case study of the outbreak in Urumqi, China in August 2022.

In this paper, a stochastic COVID-19 model with large-scale nucleic acid detection and isolation measures is proposed. Firstly, the existence and uniqueness of the global positive solution is obtained. Secondly, threshold criteria for the stochastic extinction and persistence in the mean with probability one are established. Moreover, a sufficient condition for the existence of unique ergodic stationary distribution for any positive solution is also established. Finally, numerical simulations are carried out in combination with real COVID-19 data from Urumqi, China and the theoretical results are verified.

Crystal structure of the membrane (M) protein from a bat betacoronavirus.

The membrane (M) protein is the most abundant structural protein of coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2, and plays a central role in virus assembly through its interaction with various partner proteins. However, mechanistic details about how M protein interacts with others remain elusive due to lack of high-resolution structures. Here, we present the first crystal structure of a betacoronavirus M protein from Pipistrellus bat coronavirus HKU5 (batCOV5-M), which is closely related to MERS-CoV, SARS-CoV, and SARS-CoV-2 M proteins. Furthermore, an interaction analysis indicates that the carboxy-terminus of the batCOV5 nucleocapsid (N) protein mediates its interaction with batCOV5-M. Combined with a computational docking analysis an M-N interaction model is proposed, providing insight into the mechanism of M protein-mediated protein interactions.

A robust defect detection method for syringe scale without positive samples.

With the worldwide spread of the COVID-19 pandemic, the demand for medical syringes has increased dramatically. Scale defect, one of the most common defects on syringes, has become a major barrier to boosting syringe production. Existing methods for scale defect detection suffer from large volumes of data requirements and the inability to handle diverse and uncertain defects. In this paper, we propose a robust scale defects detection method with only negative samples and favorable detection performance to solve this problem. Different from conventional methods that work in a batch-mode defects detection manner, we propose to locate the defects on syringes with a two-stage framework, which consists of two components, that is, the scale extraction network and the scale defect discriminator. Concretely, the SeNet is first built to utilize the convolutional neural network to extract the main structure of the scale. After that, the scale defect discriminator is designed to detect and label the scale defects. To evaluate the performance of our method, we conduct experiments on one real-world syringe dataset. The competitive results, that is, 99.7% on F1, prove the effectiveness of our method.

Safety and immunogenicity of COVID-19 vaccination in patients with hepatocellular carcinoma (CHESS-NMCID 2101): A multicenter prospective study.

Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole-virion COVID-19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP-CorV, and WIBP-CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9-23.2) AU/ml at 45 (IQR: 19-72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ-glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003-1.049], p = 0.049). In conclusion, this study found that inactivated COVID-19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID-19. Future validation studies are warranted.

Gender Differences in the Associations Between Physical Activity, Smartphone Use, and Weight Stigma

Background Physical activity (PA) is important for health. However, there is little evidence on how weight stigma, time spent on sedentary activities (including smartphone, social media, online learning), time spent on outdoor activity, and nomophobia associate with PA among Chinese individuals with consideration of gender. The present study examined the aforementioned associations in the COVID-19 pandemic era. Methods University students (N = 3,135;1,798 females, 1,337 males) with a mean age of 19.65 years (SD = 2.38) years completed an online survey from November to December, 2021. The online survey assessed weight stigma (using the Perceived Weight Stigma Scale and Weight Bias Internalization Scale), PA (using the International Physical Activity Questionnaire Short Form), time spent on different activities (using self-designed items for time on smartphone, outdoor activity, social media, and online learning), and nomophobia (using the Nomophobia Questionnaire). Parallel mediation models were constructed (dependent variable: PA;mediators: perceived weight stigma, weight-related self-stigma, time spent on smartphone, time spent on outdoor activity, time spent on social media, and time spent online learning;independent variable: nomophobia) and evaluated using Hayes' Process Macro Model 4 (IBM SPSS 20.0). Results Weight-related self-stigma (β = −0.06;p = 0.03), time spent on outdoor activity (β = 0.21;p < 0.001), time spent on social media (β = 0.07;p = 0.02), time spent on online learning (β = 0.06;p = 0.03), and nomophobia (β = −0.07;p = 0.01) were all significant factors explaining the PA among female participants. Perceived weight stigma (β = −0.07;p = 0.01), time spent on outdoor activity (β = 0.27;p < 0.001), and time spent on online learning (β = 0.10;p = 0.002) were all significant factors explaining PA among male participants. Conclusion Chinese healthcare providers should design programs on weight stigma reduction and outdoor activity improvement to enhance PA among university students.

Safety and immunogenicity of SARS-CoV-2 vaccines in Chinese patients with cirrhosis: a prospective multicenter study.

BACKGROUND: Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. METHODS: In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. RESULTS: In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child-Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. CONCLUSIONS: Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child-Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination.

Investigation of the psychological status of suspected patients during the Coronavirus disease 2019 epidemic.

We explored the psychological changes in suspected patients during the coronavirus disease 2019 (COVID-19) epidemic and obtained evidence for early psychological guidance and intervention in this group. A total of 31 inpatients with suspected COVID-19 were identified at our hospital. The depression module of the Patient Health Questionnaire (PHQ-9), the General Anxiety Disorder (GAD)-7 scale, and the Self-Reporting Questionnaire (SRQ-20) mental health self-assessment questionnaire were used to assess depression, anxiety, and overall mental health. Among the patients, 32.3% had symptoms of depression and 19.4% had symptoms of anxiety. Levels of anxiety and fear varied. In comparing the PHQ-9 and 7-item Generalized Anxiety Disorder Scale scores of suspected and confirmed patients, there was no significant difference in the distribution of severity of anxiety or depression in the 2 groups. The PHQ-9 scores indicated mild depression symptoms in 25.8% of suspected patients, moderate symptoms in 0%, and severe symptoms in 6.5%. Overall, 50% of confirmed patients had symptoms, with 30.8% classified as mild, 15.4% classified as moderate, and 3.8% classified as severe. The 7-item Generalized Anxiety Disorder Scale scores in the group of suspected patients showed that 9.7% had mild symptoms, 0% had moderate symptoms, and 9.7% had severe symptoms. In the group of confirmed patients, 38.4% had symptoms (34.6% mild, 0% moderate, and 3.8% severe). Diagnosed patients had more visible symptoms of depression and different total PHQ-9 scores. During the COVID-19 epidemic, suspected and diagnosed patients had different levels of mental health problems. Diagnosed patients had more visible symptoms. The performance of suspected patients was higher, but their mental state was more polarized. It may thus be important to monitor the psychological state of suspected patients as early as possible to enable timely interventions that promote psychological rehabilitation.

Linking aerosol characteristics of size distributions, core potential pathogens and toxic metal(loid)s to wastewater treatment process.

Wastewater treatment plants (WWTPs) play important roles in water purification but are also important source of aerosols. However, the relationship between aerosol characteristics and wastewater treatment process remains poorly understood. In this study, aerosols were collected over a 24-month period from a WWTP using a modified anaerobic-anoxic-oxic process. The aerated tank (AerT) was characterized by the highest respiratory fraction (RF) concentrations (861-1525 CFU/m3) and proportions (50.76%-65.96%) of aerosol particles. Fourteen core potential pathogens and 15 toxic metal(loid)s were identified in aerosols. Mycobacterium was the genus that aerosolized most easily in fine grid, pre-anoxic tank, and AerT. High wastewater treatment efficiency may increase the emission of RF and core potential pathogens. The median size of activated sludge, richness of core potential pathogens in wastewater, and total suspended particulates were the most influential factors directly related to the RF proportions, core community of potential pathogens, and composition of toxic metal(loid)s in WWTP aerosols, respectively. Relative humidity, temperature, input and removal of biochemical oxygen demand, dissolved oxygen, and mixed liquor suspended solids could also directly or indirectly affect the aerosol characteristics. This study enhances the mechanistic understanding of linking aerosol characteristics to treatment processes and has important implications for targeted manipulation.