Cissus antractica -ZnO NPs Induce Apoptosis in A549 Cells through ROS-Mediated p53/Bcl-2/Bax Signaling Pathways and Inhibit Inflammatory Cytokines (preprint)

Green products have excellent potential for discovering and producing new medicinal products. In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants sources. This eco-friendly approach was used in the recent research to biosynthesize zinc oxide nanoparticles (ZnO NPs) from Cissus antractica plant. The present study aims to examine the cell cytotoxicity, cell death, and pathways of apoptosis in lung cancer cells (A549) and inflammation properties treated with biosynthesized ZnO NPs. Additionally, synthe-sized ZnO nanoparticles were characterized using UV–vis spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The XRD and TEM analyses exhibited 31 nm as the size of synthesized nanoparticles, the pure crystal form of ZnO NPs, and the shape of the NPs as nearly spherical and hexagonal quartzite. The MTT assay used for cytotoxicity evaluation de-picted the significant toxic effect of CA-ZnONPs against the A549 lung cancer cells at concentra-tions up to 20 µg/mL than non-cancerous cells. Furthermore, we observed an elevated ROS level in cancer cells. These NPs also demonstrated dose-dependent ability to suppress colony for-mation and cell migration, which increases their potential as a lung cancer treatment. Further-more, The NPs formulation's ability to induce apoptosis in cancer cells was further supported by Hoechst and propidium iodide dye. Further, CA ZnO NPs increased the gene expression of BAX, Cyto-c, Caspase 3 and 9, but decreased the expression of Bcl-2, indicating that the nanoformulation triggered mitochondrial-mediated apoptosis. Besides, this study showed that NPs suppressed in-flammatory responses by subsequently decreasing reactive oxygen species (ROS) generation, downregulating the expression of the pro-inflammatory cytokines TNF-α, iNOS, COX-2, IL-6, IL-8, and NO. Moreover, the study's findings imply that Cissus antractica are a potential source with biosynthesize nanoparticles that can might be further investigated for the progress of an-ti-inflammatory and anti-cancer drugs with further study.

Recent advances in the effect of ultrasound on the binding of protein−polyphenol complexes in foodstuff

Foodstuff is a complex system that consists of a variety of nutrients. Protein is the basis of human life and health, which is made up of amino acids combined in different proportional orders. Polyphenols are a class of small molecule active substances with strong pro-life health effects. It has been found that protein and polyphenols can be combined by covalent and non-covalent interactions to form complex delivery carriers. The interaction between the two can effectively improve the physiological activities of proteins and enhance the bio-accessibility of polyphenols. With the maturation of ultrasound technology, several studies have shown that ultrasound can promote the production of protein−polyphenol complexes. To promote the study of protein–polyphenol interactions in foodstuff by ultrasound technology, the preparation methods of protein−polyphenol complexes, the effects of ultrasound on complex generation, and analytical methods were systematically summarized based on an extensive literature review, and further research directions were proposed. It provides the reference for the ultrasound study of protein−polyphenol complexes.

Social anxiety and depression symptoms in Chinese left-behind children after the lifting of COVID-19 lockdown: A network analysis.

BACKGROUND: Returning to social life after the lifting of COVID-19 lockdown may increase risk of social anxiety, which is highly co-morbid with depression. However, few studies have reported the association between them. AIMS: To explore the complex relationship between social anxiety and depression symptoms in left-behind children after the lifting of the COVID-19 lockdown. METHODS: A cross-sectional survey was conducted 6 months after the lockdown removal. A total of 3,107 left-behind children completed the survey with a mean age of 13.33 and a response rate of 87.77%. Depression and social anxiety severity were assessed by the DSM-5 Patient Health Questionnaire for Adolescents and the DSM-5 Social Anxiety Disorder Questionnaire, respectively. The symptom-level association between the two disorders was examined using network analysis. RESULTS: After the lifting of COVID-19 lockdown, the prevalence of depression and social anxiety in left-behind children was 19.57% and 12.36%, respectively, with a co-morbidity rate of 8.98%. Network analysis showed that "Social tension" and "Social avoidance" had the greatest expected influence; "Humiliation" and "Motor" were bridge symptom nodes in the network. The directed acyclic graph indicated that "Social fright" was at the upstream of all symptoms. CONCLUSION: Attention should be paid to social anxiety symptoms in left-behind children after the lifting of COVID-19 lockdown. Prevention and intervention measures should be taken promptly to reduce the comorbidity of social anxiety and depression symptoms in the left-behind children after the lifting of lockdown.

Complement and complement regulatory proteins are upregulated in lungs of COVID-19 patients.

We explored the pathological changes and the activation of local complement system in COVID-19 pneumonia. Lung paraffin sections of COVID-19 infected patients were analyzed by HE (hematoxylin-eosin) staining. The deposition of complement C3, the deposition of C3b/iC3b/C3d and C5b-9, and the expression of complement regulatory proteins, CD59, CD46 and CD55 were detected by immunohistochemistry. In COVID-19 patients' lung tissues, fibrin exudation, mixed with erythrocyte, alveolar macrophage and shed pneumocyte are usually observed in the alveoli. The formation of an "alveolar emboli" structure may contribute to thrombosis and consolidation in lung tissue. In addition, we also found that compared to normal tissue, the lung tissues of COVID-19 patients displayed the hyper-activation of complement that is represented by extensive deposition of C3, C3b/iC3b/C3d and C5b-9, and the increased expression level of complement regulatory proteins CD55, and especially CD59 but not CD46. The thrombosis and consolidation in lung tissues may contribute to the pathogenesis of COVID-19. The increased expression of CD55 and CD59 may reflect a feedback of self-protection on the complement hyper-activation. Further, the increased C3 deposition and the strongly activated complement system in lung tissues may suggest the rationale of complement-targeted therapeutics in conquering COVID-19.

Neutralization effect of plasma from vaccinated COVID-19 convalescents on SARS-CoV-2 Omicron variants.

Background: COVID-19 has caused a global pandemic and the death toll is increasing. With the coronavirus continuously mutating, Omicron has replaced Delta as the most widely reported variant in the world. Studies have shown that the plasma of some vaccinated people does not neutralize the Omicron variant. However, further studies are needed to determine whether plasma neutralizes Omicron after one- or two-dose vaccine in patients who have recovered from infection with the original strain. Methods: The pseudovirus neutralization assays were performed on 64 plasma samples of convalescent COVID-19 patients, which were divided into pre-vaccination group, one-dose vaccinated group and two-dose vaccinated group. Results: In the three groups, there were significant reductions of sera neutralizing activity from WT to Delta variant (B.1.617.2), and from WT to Omicron variant (B.1.1.529) (ps<0.001), but the difference between Delta and Omicron variants were not significant (p>0.05). The average neutralization of the Omicron variant showed a significant difference between pre-vaccination and two-dose vaccinated convalescent individuals (p<0.01). Conclusions: Among the 64 plasma samples of COVID-19 convalescents, whether vaccinated or not, Omicron (B.1.1.529) escaped the neutralizing antibodies, with a significantly decreased neutralization activity compared to WT. And two-dose of vaccine could significantly raise the average neutralization of Omicron in convalescent individuals.

Synthesis and anti-SARS-CoV-2 evaluation of lipid prodrugs of ß-D-N4-hydroxycytidine (NHC) and a 3'-fluoro-substituted analogue of NHC.

ß-D-N4-hydroxycytidine (NHC, EIDD-1931) is a nucleoside analogue that exhibits broad spectrum antiviral activity against a variety of RNA viruses. Herein, we report the synthesis of a series of lipid prodrugs of NHC and a novel 3'-fluoro modified NHC analogue, and evaluation of their antiviral activity against five variants of SARS-CoV-2. All lipid prodrugs showed potent antiviral activity against the tested SARS-CoV-2 variants with EC50 values in the range of 0.31-3.51 µM, which were comparable to those of NHC or higher than those of remdesivir and molnupiravir. An increase in the cytostatic activity of the lipid prodrugs was found, but prodrug 2d proved equally selective as molnupinavir. The 3'-F analogue of NHC (6) only displayed minor antiviral activity against the SARS-CoV-2 Omicron variant (EC50 = 29.91 µM), while no activity was found for other variants at the highest concentration tested. The promising antiviral data of the lipid prodrugs of NHC suggest that they deserve further investigation as new anti-SARS-CoV-2 drugs.

Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases.

Human diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security and the global economy. The development and distribution of novel prophylactic and therapeutic vaccines are the prioritized countermeasures of human disease. Among all vaccine platforms, viral vector vaccines offer distinguished advantages and represent prominent choices for pathogens that have hampered control efforts based on conventional vaccine approaches. Currently, viral vector vaccines remain one of the best strategies for induction of robust humoral and cellular immunity against human diseases. Numerous viruses of different families and origins, including vesicular stomatitis virus, rabies virus, parainfluenza virus, measles virus, Newcastle disease virus, influenza virus, adenovirus and poxvirus, are deemed to be prominent viral vectors that differ in structural characteristics, design strategy, antigen presentation capability, immunogenicity and protective efficacy. This review summarized the overall profile of the design strategies, progress in advance and steps taken to address barriers to the deployment of these viral vector vaccines, simultaneously highlighting their potential for mucosal delivery, therapeutic application in cancer as well as other key aspects concerning the rational application of these viral vector vaccines. Appropriate and accurate technological advances in viral vector vaccines would consolidate their position as a leading approach to accelerate breakthroughs in novel vaccines and facilitate a rapid response to public health emergencies.

Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.

OBJECTIVE: To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms. DESIGN: Prospective, open-label, multicentre, stratified, randomised clinical trial. SETTING: Five hospitals in UK and India, from September 2020 to May 2021. PARTICIPANTS: Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset. INTERVENTION: Leflunomide 100 mg/day (3 days) followed by 10-20 mg/day (7 days) added to standard care. PRIMARY OUTCOMES: The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days. RESULTS: Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4-8) compared with 7 days (IQR 5-10) in SOC group (p=0.047). CONCLUSION: Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients. TRIAL REGISTRATION NUMBERS: EudraCT Number: 2020-002952-18, NCT05007678.

The care status and factors affecting antiretroviral therapy timing for people living with HIV: a retrospective cohort study in Shandong Province, China.

This study described the care status of People Living with HIV (PLWH) including antiretroviral therapy (ART) and viral suppression from 2018 to 2020. We recognized that immediate ART was associated with improved viral suppression. Therefore, we also aimed to explore the factors affecting the early initiation of ART. We initiated a retrospective cohort study to evaluate the care status of people living with HIV in Shandong Province. From 2018 to 2020, patients infected by homosexual transmission in particular had a higher ART rate (78.82%, 79.69%, and 87.72%, respectively). Of PLWH who received ART, 79.57%, 77.63%, and 67.71% achieved viral suppression, respectively. However, COVID-19 may affect the rate of ART and viral suppression, which we need to explore in our research. From 2018 to 2020, the proportion of immediate antiretroviral therapy within 30 days of diagnosis increased from 48.12% to 65.42%. Multivariate logistic regression demonstrated that patients with junior college degree or above (OR, 1.39 [95%CI, 1.12-1.73]) and key population or medical institutions (OR, 3.62 [95%CI, 2.18-6.16]; OR, 3.88 [95%CI, 2.33-6.59]) were substantially likely to receive ART immediately, while patients outside the province (OR, 0.60 [95%CI, 0.50-0.73]) were less likely to receive ART immediately.

The Effect of Intolerance of Uncertainty on State Anxiety in the Regular Epidemic Prevention and Control Phase in the Context of Informatization: A Moderated Chain Mediation Model.

The COVID-19 pandemic has led to a generally high level of state anxiety resulting from the high contagiousness of the disease and strict prevention and control policies. The present study mainly focused on the relationship between the individual intolerance of uncertainty and state anxiety in the regular epidemic prevention and control phase in China, and aimed to investigate the mediating role of information overload and rumination, as well as the moderating role of self-compassion. A total of 992 Chinese residents from 31 provinces participated in this study, and completed questionnaires regarding intolerance of uncertainty, information overload, self-compassion, rumination, and state anxiety. Descriptive statistics and correlation analyses, as well as tests for mediating effects and moderated chain mediating effects, were performed on the data using SPSS 26.0 and Process 3.5 macro program. The findings indicated that intolerance of uncertainty significantly predicted individual state anxiety. Information overload mediates the effects of intolerance of uncertainty and state anxiety. Rumination also mediates the effect of uncertainty intolerance on state anxiety. Information overload and rumination have a chain mediation effect on the link between intolerance of uncertainty and state anxiety. Self-compassion mediates the effect of information overload on rumination. The results illuminate theoretical and practical implications in the regular epidemic prevention and control phases and reveal the protective role of self-compassion.

Orthokeratology compliance, digital device use, and myopia control among children with myopia during COVID-19 home confinement in Taiwan.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic profoundly impacts lifestyle habits and myopia control in children worldwide. This study investigated the changes in eyecare habits, orthokeratology compliance, axial length, and time interval of follow-up visits during home confinement in the COVID-19 pandemic in Taiwan. Methods: This investigation was part of a prospective study undertaken to evaluate the effectiveness of a mobile application. A semi-structured telephone interview was conducted with parents retrospectively to document eyecare habits and myopia control during the COVID-19 home confinement. Results: Thirty-three children with myopia participated in the follow-up of orthokeratology lenses for 2 years. The children's time viewing digital devices such as tablets and televisions significantly increased during the COVID-19 pandemic (P < 0.05). An analysis using McNemar's test found that the proportional growth of axial length <0.2 mm in 2021 was significantly higher than that in 2020 (77.42% vs. 58.06%, P < 0.05). In the multivariate logistic regression analysis, onset <10 years of age (P = 0.001) and parents with high myopia (P < 0.001) were independent risk factors for the growth of axial length ≥0.2 mm in 2021. Conclusion: The suspension of face-to-face classes and after-school tutorials benefited myopic axial elongation in children during COVID-19 home confinement. The use of digital devices and staying indoors may not be the exclusive reasons for myopia progression. Educating parents about the influence of extra learning classes after school on myopia progression would be prudent.

Advances And Challenges In Using Nirmatrelvir And Its Derivatives Against Sars-Cov-2 Infection.

On 22 December 2021, the United States Food and Drug Administration (FDA) approved the first Mpro inhibitor, i.e., oral antiviral nirmatrelvir (PF-07321332)/ritonavir (Paxlovid), for the treatment of early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nirmatrelvir inhibits SARS-CoV-2 infection, but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression. The chiral structure of nirmatrelvir plays a key role in its antiviral activity. Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P450 3A4 (CYP3A4) expression and occupying the plasma protein binding sites. Multidrug resistance protein 1 (MDR1) inhibitors may increase the efficacy of nirmatrelvir. However, paxlovid has many contraindications. Some patients treated with paxlovid experience a second round of coronavirus disease 2019 (COVID-19) symptoms soon after recovery. Interestingly, the antiviral activity of nirmatrelvir metabolites, such as compounds 12-18, is similar to or higher than that of nirmatrelvir. Herein, we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge to drug developers and physicians in the fight against COVID-19.

Artificial intelligence-based internet hospital pharmacy services in China: Perspective based on a case study.

Background: Recently, internet hospitals have been emerging in China, saving patients time and money during the COVID-19 pandemic. In addition, pharmacy services that link doctors and patients are becoming essential in improving patient satisfaction. However, the existing internet hospital pharmacy service mode relies primarily on manual operations, making it cumbersome, inefficient, and high-risk. Objective: To establish an internet hospital pharmacy service mode based on artificial intelligence (AI) and provide new insights into pharmacy services in internet hospitals during the COVID-19 pandemic. Methods: An AI-based internet hospital pharmacy service mode was established. Initially, prescription rules were formulated and embedded into the internet hospital system to review the prescriptions using AI. Then, the "medicine pick-up code," which is a Quick Response (QR) code that represents a specific offline self-pick-up order, was created. Patients or volunteers could pick up medications at an offline hospital or drugstore by scanning the QR code through the window and wait for the dispensing machine or pharmacist to dispense the drugs. Moreover, the medication consultation function was also operational. Results: The established internet pharmacy service mode had four major functional segments: online drug catalog search, prescription preview by AI, drug dispensing and distribution, and AI-based medication consultation response. The qualified rate of AI preview was 83.65%. Among the 16.35% inappropriate prescriptions, 49% were accepted and modified by physicians proactively and 51.00% were passed after pharmacists intervened. The "offline self-pick-up" mode was preferred by 86% of the patients for collecting their medication in the internet hospital, which made the QR code to be fully applied. A total of 426 medication consultants were served, and 48.83% of them consulted outside working hours. The most frequently asked questions during consultations were about the internet hospital dispensing process, followed by disease diagnosis, and patient education. Therefore, an AI-based medication consultation was proposed to respond immediately when pharmacists were unavailable. Conclusion: The established AI-based internet hospital pharmacy service mode could provide references for pharmacy departments during the COVID-19 pandemic. The significance of this study lies in ensuring safe/rational use of medicines and raising pharmacists' working efficiency.

Metagenomic insights into the effects of benzyl dodecyl dimethyl ammonium bromide (BDAB) shock on bacteria-driven nitrogen removal in a moving-bed biofilm reactor (MBBR).

The use of disinfectants made from quaternary ammonium compounds (QACs) has greatly increased since the outbreak of SARS-CoV-2. However, the effect of QACs on wastewater treatment performance is still unclear. In this study, a commonly used QAC, i.e., benzyl dodecyl dimethyl ammonium bromide (BDAB), was added to a moving-bed biofilm reactor (MBBR) to investigate BDAB's effect on nutrient removal. When the BDAB concentration was increased to 50 mg L-1, the ammonia removal efficiency (ARE) greatly decreased, as did the nitrate production rate constants (NPR). This inhibition was partly recovered by decreasing the BDAB concentration to 30 mg L-1. Metagenomic sequencing revealed the functional genera present during different stages of the control (Rc) and BDAB-added reactors (Re). The enriched genera (Rudaea, Nitrosospira, Sphingomonas, and Rhodanobacter) in Rc mainly related to the nitrogen metabolism, while the enriched genera in Re was BDAB-concentration dependent. Functional genes analysis suggested that a lack of ammonia oxidase-encoding genes (amoABC) may have caused a decrease in ARE in Re, while the efflux pump-encoding genes emrE, mdfA, and oprM and a gene encoding BAC oxygenase (oxyBAC) were responsible for BDAB resistance. The increase in the total abundance of antibiotic resistance genes (ARGs) in Re revealed a potential risk arising from BDAB. Overall, this study revealed the potential effect and ecological risks of BDAB introduction in WWTPs.

Mental Health of Healthcare Workers during COVID-19 Pandemic in Taiwan: The First Wave Outbreak Occurred 1 Year Later Than in Other Countries.

We probed the psychological influence exerted on traumatic stress endured by healthcare workers (HCWs) and the coping behaviors adopted during the first wave of COVID-19 in Taiwan, which occurred one year later than in other countries. Clinical HCWs from two branches of a hospital network in Taichung, Taiwan, were recruited for this cross-sectional study. The participants were administered a questionnaire on sociodemographic and work-related characteristics, perceived influence exerted by COVID-19, coping behaviors in relation to COVID-19, and Impact of Event Scale-Revised scores. We obtained 769 valid questionnaires. A chi-square test, generalized linear modeling, and multivariate stepwise regression analyses were performed. Although the first wave of COVID-19 occurred one year later in Taiwan than in other countries, the traumatic stress experienced by Taiwanese HCWs was noted to be comparable to that of those in other countries. Factors for increased traumatic stress included caring for more patients with COVID-19, fair or poor self-rated mental health, higher perceived influence of COVID-19, vulnerable household income, and more negative coping behaviors. Positive coping behaviors such as exposure reduction and protection measures decreased traumatic stress. Accordingly, managers should strengthen protective measures, enhance COVID-19-related training, and provide psychological support and counseling for high-risk employees.

Burnout and Mental Health and Well-Being of School Nurses After the First Wave of the COVID-19 Pandemic: A National Cross-Sectional Survey.

The aim of this study was to examine the associations between job stressors, COVID-19-related concerns, burnout, and mental health and well-being among school nurses, and whether any of these associations are mediated by burnout. Based on stratified proportional sampling, data collection was conducted by an online questionnaire distributed to 600 school nurses in Taiwan. A total of 256 participants aged between 27 and 62 years (mean = 47.08; standard deviation = 7.28) returned questionnaires. Results showed that burnout was the main mediating variable that fully mediated the relationship between COVID-19-related concerns and mental health and well-being. The effects of job stressors on mental health and well-being included direct negative effects (ß = -.29) and indirect negative effects (ß = -.67) through mediating factors. School health managers should be more aware of burnout and mental health and well-being among school nurses under the impact of COVID-19.

Adjusting intervention strategies for mental health of COVID-19 patients: A network analysis based on a survey in Omicron-infected patients.

Background: The COVID-19 pandemic had a major impact on people's mental health. As the SAS-Cov-2 evolves to become less virulent, the number of asymptomatic patients increases. It remains unclear if the mild symptoms are associated with mild perceived stress and mental illness, and the interventions to improve the mental health of the patients are rarely reported. Methods: This cross-sectional study investigated the level of depression, anxiety and perceived stress of 1,305 COVID-19 patients who received treatment in the Fangcang shelter hospitals in Shanghai, China. Network analysis was used to explore the relationship among depression, anxiety and perceived stress. Results: The prevalence of depression, anxiety and perceived stress in the patients with Omicron infection were 9.03, 4.60, and 17.03%, respectively, lower than the prevalence reported during the initial outbreak of COVID-19. "Restlessness (A5)," "Uncontrollable worry (A2)," "Trouble relaxing (A4)" and "Fatigue (D4)" had the highest expected influence values. "Irritability (A6)" and "Uncontrollable (S1)" were bridge symptoms in the network. Comparative analysis of the network identified differences in the network structures between symptomatic and asymptomatic patients. Conclusion: This study investigated the prevalence of depression, anxiety and perceived stress and the correlation among them in Omicron-infected patients in Fangcang shelter hospital, in Shanghai, China. The core symptoms identified in the study provide insight into targeted clinical prevention and intervention of mental health in non-severe Omicron-infected patients.

A Study on the Economic Resilience of Industrial Parks

The development of globalization has brought about obvious differences in the resilience of different regions against economic crises. Regional economic resilience refers to the ability of a region's economy to resist shocks when faced with external disturbances or to break away from its existing growth model in favor of a better path, Resilience represents the region's adaptability, innovation, and sustainability. This paper describes an empirical analysis on the 60 designated industrial park developments under the Industrial Development Bureau in Taiwan. Over a period of short-term disturbances, the industrial parks are analyzed from four aspects: industrial structure, regional development foundation, enterprise competitiveness and labor conditions, and government governance and policy systems. Through discriminant analysis, we analyze the characteristics of factors that mainly affect the economic resilience of 60 industrial parks faced with shocks such as the subprime mortgage crisis in 2008, the five-day work week in 2016, and the COVID-19 outbreak in 2019. We found that industrial structure, specifically diversified industrial structure, is the major factor behind enhanced regional economic resilience. If the scale of specialized industries is large enough, they can form sufficient capacity to resist external changes and also be economically resilient. Under the negative impact, the amount of innovation can be an important part of post-disaster recovery, and stable innovation input will become a main factor for the sustainable development of industrial parks. The pressure of the uncertainty of global economic development and the transformation and upgrading of the domestic economy underscore that enterprises urgently need automation and digital transformation to enhance their competitiveness. In order to enhance economic resilience to adapt to changes in the overall environment, the industrial parks need to adjust adaptively, improve their industrial structure, and promote innovation, hoping that the regional economy will move towards a more stable and sustainable development path.

Molecular characteristics of ambient organic aerosols in Shanghai winter before and after the COVID-19 outbreak.

During the global pandemic of COVID-19, the world adopted different strategies to avoid the human and economic loss, and so does China. The reduction of human activities during this time period caused reduction in PM emissions. This study adopted a HPLC-Q-TOF-MS to compare the chemical compositions of ambient aerosol samples collected in Shanghai winter before (2018, 2019) and after (2021) the COVID-19 outbreak. The identified compositions were classified into subgroups of CHO, CHN, CHON, CHONS, CHOS and CHN compounds. Results showed that CHO compounds and CHON compounds were dominating the organic compounds in ESI- and ESI+, respectively. The average percentages of CHO- compounds were 57.97 % in 2018, 58.98 % in 2019, and 43.93 % in 2021, respectively. The average percentages of CHON+ compounds were 52.74 % in 2018, 50.34 % in 2019, and 52.02 % in 2021, respectively. The proportion of aliphatic compounds increased gradually during the three years, especially in 2021, indicating that CHO compounds were less affected by aromatic precursors after the COVID-19 outbreak. The contribution of anthropogenic emissions in Shanghai was weakened compared with the previous years. In addition, there was an enhanced emission source containing hydroxyl for CHOS compound formation in 2021. The variations of atmospheric oxidation degree among the three years were not significant.

Efficient Targeted Delivery of Bifunctional Circular Aptamer-ASO Chimera to Suppress the SARS-CoV-2 Proliferation and Inflammation.

Inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and excessive inflammation is the current task in the prevention and treatment of corona vireus disease 2019 (COVID-19). Here, a dual-function circular aptamer-ASO chimera (circSApt-NASO) is designed to suppress SARS-CoV-2 replication and inflammation. The chemically unmodified circSApt-NASO exhibits high serum stability by artificial cyclization. It is also demonstrated that the SApt binding to spike protein enables the chimera to be efficiently delivered into the host cells expressing ACE2 along with the infection of SARS-CoV-2. Among them, the SApt potently inhibits spike-induced inflammation. The NASO targeting to silence N genes not only display robust anti-N-induced inflammatory activity, but also achieve efficient inhibition of SARS-CoV-2 replication. Overall, benefiting from the high stability of the cyclization, antispike aptamer-dependent, and viral infection-mediate targeted delivery, the circSApt-NASO displays robust potential against authentic SARS-CoV-2 and Omicron, providing a promising specific anti-inflammatory and antiproliferative reagent for therapeutic COVID-19.