Social carrying capacity and emotion dynamics in urban national parks during the COVID-19 pandemic. (Special Issue: Covid-19 and outdoor recreation.)

The COVID-19 pandemic has changed the mobility, accessibility, and behaviors of visitors dramatically. Under the impact of COVID-19, the social carrying capacity and emotion dynamics in parks and recreation areas are expected to change due to the uncertainty of health risks associated with visitors' behaviors. This study conducted an on-site visitor survey at Leiqiong Global Geological Park, a national park located in urban-proximate areas in Haikou, China. This study aims to examine factors impacting visitors' perceived crowding and emotions under varying levels of visitor use in urban national parks in the context of COVID-19. Study results suggest that visitors have the highest level of motivation for scenery and culture viewing and are generally satisfied with the environmental quality and design and COVID-19 prevention strategies and implementation efforts within the park. Moreover, this study suggests that the level of crowding and COVID-19 prevention strategies and implementation can affect visitors' emotions in urban natioanl parks significantly. These findings highlight the importance of enforcing the social carrying capacity limits and COVID-19 prevention strategies for urban parks and protected areas to mitigate physical and mental health risks during the COVID-19 pandemic.

Attenuation of a Highly Pathogenic Porcine Deltacoronavirus Strain CZ2020 by a Serial Passage In Vitro

Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that causes severe diarrhea to pigs of all ages, especially the suckling piglets under one-week-old. We previously isolated a highly pathogenic PDCoV strain, CZ2020, from a diarrheal piglet and have passaged it for over 100 passages. The adaptability of the CZ2020 increased gradually in vitro as the passage increased. Amino acid mutations were observed in pp1a, pp1ab, spike, envelop, and membrane proteins, and the spike protein accounts for 66.7% of all amino acid mutations. Then, the high passage strains, CZ2020-F80 and CZ2020-F100, were selected for evaluation of the pathogenicity in three-day-old piglets to examine whether these amino acid changes affected their virulence. At 2 days postchallenge (DPC), 2/5 piglets started to show typical diarrhea, and at 4 DPC, severe diarrhea was observed in the CZ2020-challenged piglets. Viral RNA could be detected at 1 DPC in rectal swabs and reached its highest at 4 DPC in the CZ2020-challenged group. CZ2020-F80- and CZ2020-F100-challenged groups have one piglet exhibiting mild diarrhea at 4 and 6 DPC, respectively. Compared with the CZ2020-challenged group, the piglets in CZ2020-F80- and F100-challenged groups had lower viral loads in rectal swabs, intestines, and other organs. No obvious histopathological lesions were observed in the intestines of CZ2020-F80- and F100-challenged piglets. Virulent PDCoV infection could also induce strong interferons and proinflammatory cytokines in vitro and in vivo. These data indicate that the strains, CZ2020-F80 and CZ2020-F100, were significantly attenuated via serial passaging in vitro and have the potential for developing attenuated vaccine candidates.

Transcriptomic and antiviral analyses of PoIFN-Delta5 against porcine enteric viruses in porcine intestinal epithelial cells.

The interferon-delta family was first reported in domestic pigs and belongs to the type I interferon (IFN-I) family. The enteric viruses could cause diarrhea in newborn piglets with high morbidity and mortality. We researched the function of the porcine IFN-delta (PoIFN-δ) family in the porcine intestinal epithelial cells (IPEC-J2) cells infected with porcine epidemic diarrhea virus (PEDV). Our study found that all PoIFN-δs shared a typical IFN-I signature and could be divided into five branches in the phylogenic tree. Different strains of PEDV could induce typical IFN transitorily, and the virulent strain AH2012/12 had the strongest induction of porcine IFN-δ and IFN-alpha (PoIFN-α) in the early stage of infection. In addition, it was found that PoIFN-δ5/6/9/11 and PoIFN-δ1/2 were highly expressed in the intestine. PoIFN-δ5 had a better antiviral effect on PEDV compared to PoIFN-δ1 due to its higher induction of ISGs. PoIFN-δ1 and PoIFN-δ5 also activated JAK-STAT and IRS signaling. For other enteric viruses, transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and porcine rotavirus (PoRV), PoIFN-δ1 and PoIFN-δ5 both showed an excellent antiviral effect. Transcriptome analyses uncovered the differences in host responses to PoIFN-α and PoIFN-δ5 and revealed thousands of differentially expressed genes were mainly enriched in the inflammatory response, antigen processing and presentation, and other immune-related pathways. PoIFN-δ5 would be a potential antiviral drug, especially against porcine enteric viruses. These studies were the first to report the antiviral function against porcine enteric viruses and broaden the new acquaintances of this type of interferon though not novelly discovered.

Occupation burnout and influencing factors of community medical staff in Shanghai central urban area during epidemic prevention and control

Objective: To understand the occupation burnout of community medical staff during epidemic and explore the influencing factors, so as to improve the mental health level of medical staff. Methods: Totally 843 community medical staff in the central urban area were studied. They were surveyed by a face-to-face with the questionnaire of JCQ, ERI and MBI. Results: Totally 835 valid questionnaires were recovered with an effective response rate of 99.1%. JCQ mode showed that the detection rate of occupational stress was 42.5%. The ERI mode showed the detection rate of occupational stress was 34.0%. The incidence of job burnout was 50.8%, of which the incidence of mild and moderate job burnout was 42.2% and the incidence of severe job burnout was 8.6%. The logistic regression analysis showed that the risk of job burnout of community medical staff was increased (P < 0.05), OR = 1.546 (aged 40 to < 50 years vs. aged < 30 years), OR = 1.506 to 1.707 (working time more than 10 years vs. less than 10 years), OR = 2.085 (working in public health departments vs. in clinical departments), OR = 2.408 (working more than 50 hours per week vs. less than 40 hours per week), and OR = 1.811 (working with night shift vs. without night shift). Compared with those with monthly income < 3 000 yuan, exercise frequency < 1 time per week and sleep time < 6 h per day, those with monthly income > 3 000 yuan (OR = 0.098 - 0.133), exercise frequency 1 time per week(OR = 0.308 - 0.603) and sleep time 6 h per day(OR = 0.300 - 0.334) had a lower risk of job burnout (P < 0.05). The higher the scores of social support (OR = 0.667) and return(OR = 0.605), the lower the risk of burnout of community medical personnel(P < 0.05);the higher the scores of giving (OR = 2.468)and intrinsic input (OR = 1.549), the greater the risk of burnout of community medical personnel(P < 0.05). Conclusions: During the epidemic prevention and control period, there was a certain degree of job burnout among community medical personnel. We can strengthen the intervention from individuals, organizations and society aspects and reduce the job burnout of community medical personnel by improving the level of professional skills, reasonable scheduling, appropriate exercise, and strengthening psychological counseling.

BIS-guided sedation prevents the cough reaction of patients under general anaesthesia caused by extubation: a randomized controlled trial.

BACKGROUND: The multiple modes of SARS-CoV-2 transmission including airborne, droplet, contact and faecal-oral transmissions that cause coronavirus disease 2019 (COVID-19) contribute to a public threat to the lives of people worldwide. Heavy aerosol production by coughing and the big peak expiratory flow in patients with respiratory infections (especially SARS-CoV-2) during recovery from general anaesthesia are the highest risk factors for infection in healthcare workers. To perform sedation before extubation significantly reduced the incidence of coughing during recovery from general anaesthesia. However, there are few studies on endotracheal tube removal under BIS-guided sedation in postanaesthesia care unit (PACU). We speculated that the BIS-guided sedation with dexmedetomidine and propofol would better prevent coughing caused by tracheal extubation and reducing peak expiratory flow. METHODS: Patients with general anaesthesia were randomly assigned to Group S (dexmedetomidine was infused in the operating room for 30 min, and the bispectral index (BIS) value was maintained 60-70 by infusion propofol at 0.5~1.5 µg/ml in the PACU until the endotracheal tubes were pulled out) and Group C (no dexmedetomidine and propofol treatment, replaced with the saline treatment). The incidence of coughing, agitation and active extubation, endotracheal tube tolerance and the peak expiratory flow at spontaneous breathing and at extubation were assessed. RESULTS: A total of 101 patients were randomly assigned to Group S (51 cases) and Group C (50 cases). The incidence of coughing, agitation and active extubation was significantly lower (1(51), 0(51) and 0(51), respectively) in Group S than (11(50), 8(50) and 5(50), respectively) in Group C (p < 0.05 or p < 0.01, respectively); the scores of cough were significantly reduced (1(1, 1)) in Group S than (1(1, 2)) in Group C (p < 0.01); and the endotracheal tube tolerance was significantly improved (0(0, 1)) in Group S than (1(1, 3)) in Group C (p < 0.001). The peak expiratory flow at spontaneous breathing and at extubation was significantly reduced (5(5, 7) and 6.5(6, 8), respectively) in Group S than (8(5, 10) and 21(9, 32)) in Group C (p < 0.001). CONCLUSIONS: BIS-guided sedation with dexmedetomidine and propofol significantly prevented coughing and reduced peak expiratory flow during recovery from general anaesthesia, which may play an important role in preventing medical staff from contracting COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200058429 (registration date: 09-04-2022) "retrospectively registered".

GRAMD4 regulates PEDV-induced cell apoptosis inhibiting virus replication via the endoplasmic reticulum stress pathway.

Porcine epidemic diarrhea (PED) caused by the porcine epidemic diarrhea virus (PEDV) has caused huge losses in the swine industry worldwide. Glucosyltransferase Rab-like GTPase activator and myotubularin domain containing 4 (GRAMD4) is a proapoptotic protein, which replaced p53 inducing mitochondrial apoptosis. However, the relationship between GRAMD4 and PEDV has not been reported. Here, we aimed to investigate the potential role of GRAMD4 during PEDV infection. In this study, we used co-immunoprecipitation (co-IP) and mass spectrometry to identify GRAMD4 interaction with PEDV non-structural protein 6 (NSP6). Immunoprecipitation and laser confocal microscopy were utilized to demonstrate that GRAMD4 interacts with NSP6. NSP6 reduces GRAMD4 production through PERK and IRE1 pathway-mediated apoptosis. We demonstrated that overexpression of GRAMD4 effectively impaired the replication of PEDV, whereas knockdown of GRAMD4 facilitated the replication of PEDV. Overexpression of GRAMD4 increased GRP78, phosphorylated PERK (p-PERK), phosphorylated IRE1(p-IRE1) levels, promoted CHOP, phosphorylated JNK (p-JNK), Bax expression, caspase 9 and caspase 3 cleavage, and inhibited Bcl-2 production. Knockdown of GRAMD4 has the opposite effect. Finally, deletion of the GRAM domain of GRAMD4 cannot cause endoplasmic reticulum stress (ER stress)-mediated apoptosis and inhibit virus replication. In conclusion, these studies revealed the mechanism by which GRAMD4 was associated with ER stress and apoptosis regulating PEDV replication. NSP6 acted as a potential down-regulator of GRAMD4 and promoted the degradation of GRAMD4. GRAMD4 played a role in facilitating apoptosis and restricting virus replication, and the GRAM domain was required. These findings provided a reference for host-PEDV interactions and offered the possibility for PEDV decontamination and prevention.

Children and young people's perspectives on and experiences of COVID‐19 in global contexts

An introduction is presented in which the author discusses articles within the issue on topics including children's perspectives and experiences during the COVID-19 pandemic in various aspects such as education, health and child care, challenges facing children and their families across different cultural and geographical contexts, and empowerment of children and young people through innovative methods.

Heterogeneous Nuclear Protein U Degraded the m6A Methylated TRAF3 Transcript by YTHDF2 To Promote Porcine Epidemic Diarrhea Virus Replication.

Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the Coronaviridae family and can cause fatal watery diarrhea in piglets, causing significant economic losses. Heterogeneous nuclear protein U (HNRNPU) is a novel RNA sensor involved in sensing viral RNA in the nucleus and mediating antiviral immunity. However, it remains elusive whether and how cytoplasmic PEDV can be sensed by the RNA sensor HNRNPU. In this study we determined that HNRNPU was the binding partner of Nsp13 by immunoprecipitation-liquid chromatography-tandem mass spectrometry (IP/LC-MS/MS) analysis. The interaction between Nsp13 and HNRNPU was demonstrated by using coimmunoprecipitation and confocal immunofluorescence. Next, we identified that HNRNPU expression is significantly increased during PEDV infection, whereas the transcription factor hepatocyte nuclear factor 1α (HNF1A) could negatively regulate HNRNPU expression. HNRNPU was retained in the cytoplasm by interaction with PEDV Nsp13. We found that HNRNPU overexpression effectively facilitated PEDV replication, while knockdown of HNRNPU impaired viral replication, suggesting a promoting function of HNRNPU to PEDV infection. Additionally, HNRNPU was found to promote PEDV replication by affecting TRAF3 degradation at the transcriptional level to inhibit PEDV-induced beta interferon (IFN-ß) production. Mechanistically, HNRNPU downregulates TRAF3 mRNA levels via the METTL3-METTL14/YTHDF2 axis and regulates immune responses through YTHDF2-dependent mRNA decay. Together, our findings reveal that HNRNPU serves as a negative regulator of innate immunity by degrading TRAF3 mRNA in a YTHDF2-dependent manner and consequently facilitating PEDV propagation. Our findings provide new insights into the immune escape of PEDV. IMPORTANCE PEDV, a highly infectious enteric coronavirus, has spread rapidly worldwide and caused severe economic losses. During virus infection, the host regulates innate immunity to inhibit virus infection. However, PEDV has evolved a variety of different strategies to suppress host IFN-mediated antiviral responses. Here, we identified that HNRNPU interacted with viral protein Nsp13. HNRNPU protein expression was upregulated, and the transcription factor HNF1A could negatively regulate HNRNPU expression during PEDV infection. HNRNPU also downregulated TRAF3 mRNA through the METTL3-METTL14/YTHDF2 axis to inhibit the production of IFN-ß and downstream antiviral genes in PEDV-infected cells, thereby promoting viral replication. Our findings reveal a new mechanism with which PEDV suppresses the host antiviral response.

Analysis on SARS-CoV-2 contamination in the environment exposure to the SARS-CoV-2 cases in Huangpu District of Shanghai in 2022

Objective: To analyze the detection of SARS-CoV-2 in household environment and public place environment of Huangpu District, and describe the feature of SARS-CoV-2 contamination in the environment exposure to the infected cases, so as to support the control strategies such as disinfection and health communication.

Compound lidocaine/prilocaine cream combined with tetracaine prevents cough caused by extubation after general anaesthesia: a randomised controlled trial.

BACKGROUND: Coughing caused by tracheal extubation is common following general anaesthesia. Heavy aerosol production by coughing during recovery from general anaesthesia in patients with respiratory infections (especially COVID-19) may be one of the highest risk factors for infection in healthcare workers. The application of local anaesthetics to the endotracheal tube is an effective method to reduce coughing. The most commonly used anaesthetics are compound lidocaine/prilocaine cream and tetracaine spray. However, coughing still occurs when the two anaesthetics are used alone. We speculated that the application of compound lidocaine/prilocaine combined with tetracaine spray would better prevent coughing caused by tracheal extubation. METHODS: Patients scheduled for laparoscopic cholecystectomy or cholecystectomy combined with common bile duct exploration under general anaesthesia were randomly assigned to Group C (saline spray), Group L (2 g compound lidocaine/prilocaine cream contains 5 mg of lidocaine and 5 mg prilocaine)), Group T (tetracaine) and Group F (compound lidocaine/prilocaine cream combined with tetracaine). The incidence of coughing, the endotracheal tube tolerance assessment, the incidence of agitation, the active extubation rate, the incidence of postoperative pharyngeal pain and the incidence of postoperative cough were recorded and analysed. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and the plasma concentrations of epinephrine and norepinephrine were measured immediately before extubation and 1 min after extubation. RESULTS: A total of 211 patients were randomly assigned to Group C (53 cases), Group L (52 cases), Group T (52 cases) and Group F (54 cases). The primary result is assessment of the incidence of cough. The patients emerged from general anaesthesia, 96% of Group C had cough, which was significantly reduced in Group L (61.5%, P < 0.001), Group T (75%, P < 0.05) and Group F (22.2%, P < 0.001). Group F had a significantly reduced incidence of cough compared to Group L and Group T (P < 0.05 or P < 0.01, respectively). The secondary results were assessed. The endotracheal tube tolerance score in Group C ((1, 3) 4, P < 0.001) was higher than Group L ((0, 1) 2), Group T ((0, 1.25) 3) and Group F ((0, 0) 1). Group F had a significantly lower score than Group L and Group T (P < 0.05, P < 0.01, respectively). The incidence of agitation and the active extubation rate were also higher in Group C (96.2% and 71.7%, respectively, P < 0.001) than Group L (48.1% and 15.4%, respectively), Group T (61.5% and 26.9%, respectively) and Group F (17.3% and 7.7%, respectively). Blood pressure, HR and plasma concentrations of epinephrine and norepinephrine were significantly higher in Group C than in all other groups at the time of extubation and 1 min after extubation (P < 0.001). Group F exhibited significantly reduced blood pressure, heart rate and plasma concentrations of epinephrine and norepinephrine compared to Group L and Group T (P < 0.05, P < 0.01 or P < 0.001, respectively). The incidence of postoperative pharyngeal pain and the incidence of postoperative cough were not significantly different among the groups. CONCLUSIONS: Compound lidocaine/prilocaine cream combined with tetracaine may be a more effective approach for preventing coughing and stabilising circulation during extubation following general anaesthesia. This may play an important role in preventing medical staff from contracting respiratory infectious diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200058429 (registration date: 09-04-2022) "retrospectively registered".

Comparative Study on International Research Hotspots and National-Level Policy Keywords of Dynamic Disaster Monitoring and Early Warning in China (2000-2021).

For more than 20 years, disaster dynamic monitoring and early warning have achieved orderly and sustainable development in China, forming a systematic academic research system and top-down policy design, which are inseparable from the research of China's scientific community and the promotion of government departments. In the past, most of the research on dynamic disaster monitoring and early warning focused on specific research in a certain field, scene, and discipline, while a few studies focused on research review or policy analysis, and few studies combined macro and meso research reviews in academia with national policy analysis for comparative analysis. It is necessary and urgent to explore the interaction between scholars' research and policy deployment, which can bring theoretical contributions and policy references to the top-down design, implementation promotion, and academic research of China's dynamic disaster monitoring and early warning. Based on 608 international research articles on dynamic disaster monitoring and early warning published by Chinese scholars from 2000-2021 and 187 national policy documents published during this period, this paper conducts a comparative analysis between the knowledge maps of international research hotspots and the co-occurrence maps of policy keywords on dynamic disaster monitoring and early warning. The research shows that in the stage of initial development (2000-2007), international research articles are few and focused, and research hotspots are somewhat alienated from policy keywords. In the stage of rising development (2008-2015), after the Wenchuan earthquake, research hotspots are closely related to policy keywords, mainly in the fields of geology, engineering disasters, meteorological disasters, natural disasters, etc. Meanwhile, research hotspots also focus on cutting-edge technologies and theories, while national-level policy keywords focus more on overall governance and macro promotion, but the two are gradually closely integrated. In the stage of rapid development (2016-2021), with the continuous attention and policy promotion of the national government, the establishment of the Ministry of Emergency Management, and the gradual establishment and improvement of the disaster early warning and monitoring system, research hotspots and policy keywords are integrated and overlapped with each other, realizing the organic linkage and mutual promotion between academic research and political deployment. The motivation, innovation, integration, and transformation of dynamic disaster monitoring and early warning are promoted by both policy and academic research. The institutions that issue policies at the national level include the State Council and relevant departments, the Ministry of Emergency Management, the Ministry of Water Resources, and other national ministries and commissions. The leading affiliated institutions of scholars' international research include China University of Mining and Technology, Chinese Academy of Sciences, Wuhan University, Shandong University of Science and Technology, and other institutions. The disciplines involved are mainly multidisciplinary geosciences, environmental sciences, electrical and electronic engineering, remote sensing, etc. It is worth noting that in the past two to three years, research and policies focusing on COVID-19, public health, epidemic prevention, environmental governance, and emergency management have gradually increased.

Impact of the COVID-19 pandemic on visual outcomes of diabetic macular edema patients at a tertiary care veterans affairs center.

Purpose: There are limited studies on factors that impacted retina clinic patient outcomes during the COVID-19 pandemic. We aimed to evaluate visual and anatomic outcomes in patients with diabetic macular edema (DME) requiring anti-VEGF injections at the veterans' affairs tertiary care eye clinic in Houston, TX. Methods: Patient volume from April 2020 was compared to that of April 2019 to determine attendance changes. To evaluate outcomes, we reviewed patients with DME who had scheduled appointments during April 2020. We tracked changes in central foveal thickness (CFT) and Snellen visual acuity (VA) measurements. Patient outcomes were classified as poor (defined as worsening VA or CFT at follow-up) or good (no worsening of either at follow-up). Regression analysis identified characteristics associated with poor outcomes. Results: To prevent the spread of COVID-19, patients were called to reschedule clinic appointments. Attendance frequency decreased from 523 patients in April 2019 to 246 patients in April 2020. 134 patients met inclusion criteria (mean age of 64.7 ± 8.8 years). 19/134 of patients were seen on schedule, 89/134 had delayed appointments (average follow-up interval of 115.2 ± 50.0 days), and 26/134 were lost to follow-up. Patients with delayed appointments had higher odds of poor outcome at follow-up compared to patients seen on schedule (OR = 4.03, 95% CI: 1.14-16.92, p = 0.04). Patient's baseline visual acuity, macular thickness, comorbidities, and diabetic retinopathy severity, and demographics did not affect visual outcome at follow-up. Conclusions: On average, patients were rescheduled to a visit 2.4 months later than their usual visit. Over half these patients experienced worsening of vision or edema. This demonstrates that lapses in care result in worsening of DME. However, there is no clear association between baseline characteristics and risk of disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01049-5.

Identifying Japanese Encephalitis Virus Using Metatranscriptomic Sequencing, Xinjiang, China.

The treat of infectious disease epidemics has increased the critical need for continuous broad-ranging surveillance of pathogens with outbreak potential. Using metatranscriptomic sequencing of blood samples, we identified several cases of Japanese encephalitis virus infection from Xinjiang Uyghur Autonomous Region, China. This discovery highlights the risk for known viral diseases even in nonendemic areas.

Impact of the COVID-19 pandemic on visual outcomes of diabetic macular edema patients at a tertiary care veterans affairs center

Purpose There are limited studies on factors that impacted retina clinic patient outcomes during the COVID-19 pandemic. We aimed to evaluate visual and anatomic outcomes in patients with diabetic macular edema (DME) requiring anti-VEGF injections at the veterans’ affairs tertiary care eye clinic in Houston, TX. Methods Patient volume from April 2020 was compared to that of April 2019 to determine attendance changes. To evaluate outcomes, we reviewed patients with DME who had scheduled appointments during April 2020. We tracked changes in central foveal thickness (CFT) and Snellen visual acuity (VA) measurements. Patient outcomes were classified as poor (defined as worsening VA or CFT at follow-up) or good (no worsening of either at follow-up). Regression analysis identified characteristics associated with poor outcomes. Results To prevent the spread of COVID-19, patients were called to reschedule clinic appointments. Attendance frequency decreased from 523 patients in April 2019 to 246 patients in April 2020. 134 patients met inclusion criteria (mean age of 64.7 ± 8.8 years). 19/134 of patients were seen on schedule, 89/134 had delayed appointments (average follow-up interval of 115.2 ± 50.0 days), and 26/134 were lost to follow-up. Patients with delayed appointments had higher odds of poor outcome at follow-up compared to patients seen on schedule (OR = 4.03, 95% CI: 1.14–16.92, p = 0.04). Patient’s baseline visual acuity, macular thickness, comorbidities, and diabetic retinopathy severity, and demographics did not affect visual outcome at follow-up. Conclusions On average, patients were rescheduled to a visit 2.4 months later than their usual visit. Over half these patients experienced worsening of vision or edema. This demonstrates that lapses in care result in worsening of DME. However, there is no clear association between baseline characteristics and risk of disease progression. Supplementary Information The online version contains supplementary material available at 10.1007/s40200-022-01049-5.

Detections of major respiratory pathogens in pneumonia patients in early phase of COVID-19 epidemic in Tongzhou, Beijing

Objective: To understand the infection status of major respiratory pathogens in pneumonia patients in the early phase of coronavirus disease 2019 (COVID-19) epidemic (January-March, 2020) in Tongzhou district of Beijing.

Global Burden of Respiratory Diseases Attributable to Ambient Particulate Matter Pollution: Findings From the Global Burden of Disease Study 2019.

Background: Exposure to ambient particulate matter pollution (APMP) is a global health issue that directly affects the human respiratory system. Thus, we estimated the spatiotemporal trends in the burden of APMP-related respiratory diseases from 1990 to 2019. Methods: Based on the Global Burden of Disease Study 2019, data on the burden of APMP-related respiratory diseases were analyzed by age, sex, cause, and location. Joinpoint regression analysis was used to analyze the temporal trends in the burden of different respiratory diseases over the 30 years. Results: Globally, in 2019, APMP contributed the most to chronic obstructive pulmonary disease (COPD), with 695.1 thousand deaths and 15.4 million disability-adjusted life years (DALYs); however, the corresponding age-standardized death and DALY rates declined from 1990 to 2019. Similarly, although age-standardized death and DALY rates since 1990 decreased by 24% and 40%, respectively, lower respiratory infections (LRIs) still had the second highest number of deaths and DALYs attributable to APMP. This was followed by tracheal, bronchus, and lung (TBL) cancer, which showed increased age-standardized death and DALY rates during the past 30 years and reached 3.78 deaths per 100,000 persons and 84.22 DALYs per 100,000 persons in 2019. Among children aged < 5 years, LRIs had a huge burden attributable to APMP, whereas for older people, COPD was the leading cause of death and DALYs attributable to APMP. The APMP-related burdens of LRIs and COPD were relatively higher among countries with low and low-middle socio-demographic index (SDI), while countries with high-middle SDI showed the highest burden of TBL cancer attributable to APMP. Conclusions: APMP contributed substantially to the global burden of respiratory diseases, posing a significant threat to human health. Effective actions aimed at air pollution can potentially avoid an increase in the PM2.5-associated disease burden, especially in highly polluted areas.

Dynamic Uncertainty Study of Multi-Center Location and Route Optimization for Medicine Logistics Company

Multi-center location of pharmaceutical logistics is the focus of pharmaceutical logistics research, and the dynamic uncertainty of pharmaceutical logistics multi-center location is a difficult point of research. In order to reduce the risk and cost of multi-enterprise, multi-category, large-volume, high-efficiency, and nationwide centralized medicine distribution, this study explores the best solution for planning medicine delivery for the medicine logistics. In this paper, based on the idea of big data, comprehensive consideration is given to uncertainties in center location, medicine type, medicine chemical characteristics, cost of medicine quality control (refrigeration and monitoring costs), delivery timeliness, and other factors. On this basis, a multi-center location- and route-optimization model for a medicine logistics company under dynamic uncertainty is constructed. The accuracy of the algorithm is improved by hybridizing the fuzzy C-means algorithm, sequential quadratic programming algorithm, and variable neighborhood search algorithm to combine the advantages of each. Finally, the model and the algorithm are verified through multi-enterprise, multi-category, high-volume, high-efficiency, and nationwide centralized medicine distribution cases, and various combinations of the three algorithms and several rival algorithms are compared and analyzed. Compared with rival algorithms, this hybrid algorithm has higher accuracy in solving multi-center location path optimization problem under the dynamic uncertainty in pharmaceutical logistics.

When Poly(A) Binding Proteins Meet Viral Infections, Including SARS-CoV-2.

Viruses have evolved diverse strategies to hijack the cellular gene expression system for their replication. The poly(A) binding proteins (PABPs), a family of critical gene expression factors, are viruses' common targets. PABPs act not only as a translation factor but also as a key factor of mRNA metabolism. During viral infections, the activities of PABPs are manipulated by various viruses, subverting the host translation machinery or evading the cellular antiviral defense mechanism. Viruses harness PABPs by modifying their stability, complex formation with other translation initiation factors, or subcellular localization to promote viral mRNAs translation while shutting off or competing with host protein synthesis. For the past decade, many studies have demonstrated the PABPs' roles during viral infection. This review summarizes a comprehensive perspective of PABPs' roles during viral infection and how viruses evade host antiviral defense through the manipulations of PABPs.

Aromatic Cadinane Sesquiterpenoids from the Fruiting Bodies of Phellinus pini Block SARS-CoV-2 Spike-ACE2 Interaction.

The ongoing COVID-19 global pandemic caused by SARS-CoV-2 inspires the development of effective inhibitors to block the SARS-CoV-2 spike-ACE2 interaction. A chemical investigation on the fruiting bodies of Phellinus pini led to the isolation of five aromatic cadinane sesquiterpenoids including four new ones, named piniterpenoids A-D (1-4), as well as three known lignans. Their structures were determined by extensive spectroscopic analysis including HRMS and 1D and 2D NMR. All of the aromatic cadinane sesquiterpenoids inhibited the SARS-CoV-2 spike-ACE2 interaction, with IC50 values ranging from 64.5 to 99.1 µM. A molecular docking study showed the disruption of the interaction of compound 1 via hydrogen interactions with Arg403, Asp405, and Arg408 of SARS-CoV-2 RBD and Arg393 and His34 residues of ACE2. These results suggested that aromatic cadinane sesquiterpenoids might be useful in developing agents for COVID-19.