A retrospective analysis of first-line PD-1 monoclonal antibodies treatment in patients with leptomeningeal metastasis from solid tumors.

INTRODUCTION: Patients whose solid tumors (ST) show leptomeningeal metastasis (LM) have very poor prognosis and short overall survival. The aim of this study was to evaluate the efficacy of first-line programed death-1(PD-1) monoclonal antibody (mAb) treatment in these patients. METHODS: We retrospectively evaluated patients diagnosed with LM from ST who were treated with first-line PD-1 mAb at our hospital between April 1 and November 30, 2019. We analyzed their clinicopathological characteristics and response to the treatment. RESULTS: We collected and analyzed data from 6 patients with different primary ST. 5 patients received PD-1 mAb combined with chemotherapy and/or anti-angiogenic drugs, while one received only PD-1 mAb. The median (range) number of treatment cycles was 5.5 (1-21). PD-1 mAb treatment did not cause neurotoxicity. The time period of first assessment varied from 21 to 65 days after treatment. Among 5 patients who got obvious symptoms relief, 4 patients persisted for > 3 months and even showed a reduction in the number of tumor cells in cerebrosprinal fluid. Ventriculoperitoneal (VP) shunt was used to treat hydrocephalus observed beneficial in 3 patients: 2 before and 1 after PD-1 mAb treatment. The median (range) follow-up time was 214 (57-460) days. 4 patients died. The overall survival ranged from 57 days to at least 460 days. 1 of the two alive patients continued to show no worsening of symptoms after 457 days. CONCLUSIONS: Patients with LM from ST can benefit from first-line PD-1 mAb combined treatment without additional neurotoxicity. Further research is required to validate the safety and efficacy.

A spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo.

Neutralizing antibodies exert a potent inhibitory effect on viral entry; however, they are less effective in therapeutic models than in prophylactic models, presumably because of their limited efficacy in eliminating virus-producing cells via Fc-mediated cytotoxicity. Herein, we present a SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy for controlling SARS-CoV-2 infection. This approach blocks the entry of free virus into permissive cells by competing with membrane receptors and eliminates virus-infected cells via powerful T cell-mediated cytotoxicity. S-BiTE is effective against both the original and Delta variant of SARS-CoV2 with similar efficacy, suggesting its potential application against immune-escaping variants. In addition, in humanized mouse model with live SARS-COV-2 infection, S-BiTE treated mice showed significantly less viral load than neutralization only treated group. The S-BiTE strategy may have broad applications in combating other coronavirus infections.

Psychological status of infertile men during the Coronavirus Disease 2019 Pandemic in China: a cross-sectional investigation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has had a widespread and profound impact on people's mental health. The factors associated with mental symptoms among men diagnosed with infertility, a disease closely related to psychological conditions, remain unclear. The aim of this study is to investigate the risk factors associated with mental symptoms among infertile Chinese men during the pandemic. RESULTS: A total of 4,098 eligible participants were recruited in this cross-sectional, nationwide study, including 2,034 (49.6%) with primary infertility and 2,064 (50.4%) with secondary infertility. The prevalence of mental health conditions was 36.3%, 39.6%, and 6.7% for anxiety, depression, and post-pandemic stress, respectively. Sexual dysfunction is associated with a higher risk with adjusted odds ratios (ORs) of 1.40 for anxiety, 1.38 for depression, and 2.32 for stress. Men receiving infertility drug therapy displayed a higher risk for anxiety (adjusted OR, 1.31) and depression (adjusted OR, 1.28) symptoms, while those receiving intrauterine insemination had a lower risk of anxiety (adjusted OR, 0.56) and depression (adjusted OR, 0.55) symptoms. CONCLUSION: The COVID-19 pandemic has had a significant psychological impact on infertile men. Several psychologically vulnerable populations were identified, including individuals with sexual dysfunction, respondents receiving infertility drug therapy, and those experiencing control measures for COVID-19. The findings provide a comprehensive profile of the mental health status of infertile Chinese men during the COVID-19 outbreak and provide potential psychological intervention strategies.

RéSUMé: CONTEXTE: L'épidémie de maladie à coronavirus 2019 (COVID-19) a eu un impact étendu et profond sur la santé mentale des gens. Les facteurs associés aux symptômes mentaux chez les hommes diagnostiqués comme infertiles, une maladie étroitement liée aux conditions psychologiques, restent flous. L'objectif de cette étude est d'étudier les facteurs de risque associés aux symptômes mentaux chez les hommes chinois infertiles pendant la pandémie. RéSULTATS: Au total, 4 098 participants admissibles ont été recrutés dans cette étude transversale à l'échelle nationale, dont 2 034 (49,6%) présentaient une infertilité primaire et 2 064 (50,4%) une infertilité secondaire. La prévalence des problèmes de santé mentale était respectivement de 36,3 %, 39,6 % et 6,7 % pour l'anxiété, la dépression, et le stress postpandémique. La dysfonction sexuelle est associée à un risque plus élevé avec des odds ratios ajustés (OR) de 1,40 pour l'anxiété, 1,38 pour la dépression et 2,32 pour le stress. Les hommes recevant un traitement médicamenteux contre l'infertilité présentaient un risque plus élevé de symptômes d'anxiété (OR ajusté, 1,31) et de dépression (OR ajusté, 1,28), alors que ceux dont le traitement consistait à faire des inséminations intra-utérines présentaient un risque plus faible de symptômes d'anxiété (OR ajusté, 0,56) et de dépression (OR ajusté, 0,55). CONCLUSIONS: La pandémie de COVID-19 a eu un impact psychologique important sur les hommes infertiles. Plusieurs populations psychologiquement vulnérables ont été identifiées, notamment les personnes souffrant de dysfonction sexuelle, les hommes recevant un traitement médicamenteux contre l'infertilité, et ceux subissant des mesures de contrôle de la COVID-19. Les résultats fournissent un profil complet de l'état de santé mentale des hommes Chinois infertiles pendant l'épidémie de COVID-19 et fournissent des stratégies potentielles d'intervention psychologique.

A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

Mental health and self-management in glaucoma patients during the COVID-19 pandemic: a cross-sectional study in China.

PURPOSE: To investigate mental health and self-management in glaucoma patients during the COVID-19 pandemic in China and to describe the correlation between anxiety, depression, glaucoma, and self-management. METHODS: This cross-sectional study included glaucoma patients who enrolled in the case management platform and completed an online survey. The survey included the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and Glaucoma Self-Management Questionnaire (GSMQ). RESULTS: Among 109 glaucoma patients enrolled in this study, the proportions of patients suffering from depression and anxiety during the COVID-19 pandemic were 26.6% and 20.2%, respectively. A statistical association was found between depression and self-management behaviour in these glaucoma patients (r = -0.247, P = 0.010). The self-management scores in patients less than 35 years were lower than those in patients aged 35-60 years (P = 0.046). The scores of body function promotion in men were lower than those in women (P = 0.048). Patients with primary school education and below had lower scores in the medical management of disease than those with either middle school education (P = 0.032) or community college education or higher (P = 0.022). CONCLUSION: A high proportion of anxiety and depression was found in glaucoma patients during the COVID-19 pandemic. Better self-management behaviour was associated with stronger mental health regulation. It is important to help glaucoma patients improve their self-management behaviours, especially for young men with low educational levels.

Effect of Antidiabetic Therapy on Clinical Outcomes of COVID-19 Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: No study has yet systematically evaluated the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with type 2 diabetes (T2D). OBJECTIVE: We aimed to evaluate the effect of different antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. METHODS: We comprehensively retrieved the published research which examined the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. The odds ratio (OR) and its 95% confidence interval (95% CI) for clinical outcomes were calculated using the random-effects model, and meta-regression was adopted to evaluate the potential sources of heterogeneity between studies. RESULTS: A total of 54 studies were included in this study. We found that the use of metformin (OR = 0.66, 95% CI: 0.58-0.75), SGLT-2i (OR = 0.80, 95% CI: 0.73-0.88), and GLP-1ra (OR = 0.83, 95% CI: 0.70-0.98) were significantly associated with lower mortality risk in COVID-19 patients with T2D, while insulin use might unexpectedly increase the ICU admission rate (OR = 2.32, 95% CI: 1.34-4.01) and risk of death (OR = 1.52, 95% CI: 1.32-1.75). No statistically significant associations were identified for DPP-4i, SUs, AGIs, and TZDs. CONCLUSION AND RELEVANCE: We demonstrated that the usage of metformin, SGLT-2i, and GLP-1ra could significantly decrease mortality in COVID-19 patients with T2D. The heterogeneity across the studies, baseline characteristics of the included patients, shortage of dosage and the duration of antidiabetic drugs and autonomy of drug selection might limit the objectivity and accuracy of results. Further adequately powered and high-quality randomized controlled trials are warranted for conclusive findings.

Using a telemedicine-assisted airway model to improve the communication and teamwork of tracheal intubation during the coronavirus disease 2019 pandemic.

INTRODUCTION: Isolated spaces impair communication and teamwork during tracheal intubation (TI) in suspected coronavirus disease 2019 patients. We thus aimed to evaluate the telemedicine-assisted airway model (TAM) to improve communication and teamwork during the pandemic. METHODS: This two-stage prospective study included adult patients intubated in the emergency department of the National Taiwan University Hospital between 1 August 2020 and 31 July 2021. First, we randomised patients receiving TI in the standard setting into the conventional group (Con-G) and the isolation area into the isolation group (Iso-G). We evaluated the obstacles to communication and teamwork in an isolation scenario. Second, we developed the TAM to facilitate communication and teamwork between staff in separate spaces during TI and assigned patients to the TAM group (TAM-G). Communication and teamwork were evaluated using the Team Emergency Assessment Measure (TEAM). Subjective evaluations were conducted using a questionnaire administered to medical staff. RESULTS: Eighty-nine patients were enrolled: 17, 34, and 38 in the Con-G, Iso-G, and TAM-G, respectively. The communication frequency (CF) of the Con-G and Iso-G was the highest and lowest, respectively. The CF of the TAM-G increased and approached that of the Con-G. The overall TEAM score was the highest in the Con-G and the lowest in the Iso-G, while the overall score in the TAM-G was comparable to that of the Con-G. DISCUSSION: The TAM may improve communication and teamwork for TIs without compromising efficacy during the pandemic. This study was registered at ClinicalTrials.gov; registration numbers: NCT04479332 and NCT04591873.

Use of Latent Dirichlet Allocation and Structural Equation Modeling in Determining the Factors for Continuance Intention of Knowledge Payment Platform

Knowledge payment is a new type of E-learning that has developed in the era of social media. With the influence of the COVID-19 epidemic, the knowledge payment market is developing rapidly. Exploring the influencing factors of users' continuance intention is beneficial for the sustainable development of knowledge payment platforms. Our study took 'Himalayan FM';as an example and included two studies: Study 1 used latent dirichlet allocation (LDA) to explore the main factors affecting the users' willingness to continue use, through mining user comment data on the knowledge payment platform;Study 2 constructed the conceptual model by integrating the technology acceptance model (TAM) and IS success model (IS) and carried out empirical analysis by SPSS and AMOS using the data that were collected through the questionnaire. The results show that: (1) perceived usefulness, user satisfaction, and spokesperson identity have a direct positive impact on users' willingness to continuous use, while perceived cost has a direct negative impact on users' willingness to continue use;(2) perceived ease of use, content quality, and system quality of knowledge payment platforms impacted user satisfaction directly, then affected users' willingness to continue use indirectly;(3) users' perceived enjoyment, membership experience, auditory experience, and other factors also directly impacted user satisfaction, affecting users' willingness to continue use indirectly. This study effectively expands the factors influencing knowledge payment users' willingness to continue use and provides a useful reference for the sustainable development of knowledge payment platforms.

The Influence of Affective Feedback Adaptive Learning System on Learning Engagement and Self-Directed Learning.

The outbreak of the two-year corona virus has made a great difference on existing methods of learning and instruction. Online education has become a crucial role to maintain non-stop learning after the post-epidemic period. The advanced technologies and growing popularity of network equipment have made it easy to deploy remote connections. However, teachers still face challenges when they actually implement distance courses. During the learning process, the quality of learning can be improved if the researchers consider multiple factors, including emotions, attitudes, engagement, cognition, neuroscientific and cultural psychology. After analyzing these factors, instructors can have better understanding of students' mental building and cognitive understanding in their process of learning, and be familiar with the way of interaction with students and appropriately adjust their teaching. Therefore, the current study established a learning system that aimed to understand learners' emotional signals during learning by applying the adaptive-feedback emotional computing technology. The purpose of the system was to allow learners to (1) self-examine their learning condition, (2) enhance their self-directed learning, (3) help learners who are in negative learning emotions or settings to lower anxieties, and (4) promote their learning attitudes and engagement. Result showed that the system with the adaptive-feedback emotional computing technology has significantly improved the learning effectiveness, lowered learning anxieties and increased students' self-directed learning.

The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint.

The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to other members of the Coronaviridae family. We also show that these spike NTD (S-NTD) proteins adhere to Calu3 cells, a human lung cell line, although the biological relevance of this is unclear. In contrast to what has been shown for Middle East respiratory syndrome coronavirus (MERS-CoV), which attaches sialic acids during cell entry, sialic acids present on Calu3 cells inhibited sarbecovirus infection. Therefore, while sarbecoviruses can interact with cell surface glycans similarly to other coronaviruses, their reliance on glycans for entry is different from that of other respiratory coronaviruses, suggesting sarbecoviruses and MERS-CoV have adapted to different cell types, tissues, or hosts during their divergent evolution. Our findings provide important clues for further exploring the biological functions of sarbecovirus glycan binding and adds to our growing understanding of the complex forces that shape coronavirus spike evolution. IMPORTANCE Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. We also show that, unlike some coronaviruses, including MERS-CoV, sialic acids present on the surface of Calu3, a human lung cell culture, inhibit SARS-CoV-2 and other sarbecoviruses. These results suggest that while glycan binding might be an ancestral trait conserved across different coronavirus families, the functional outcome during infection can vary, reflecting divergent viral evolution. Our results expand our knowledge on the biological functions of the S-NTD across diverse sarbecoviruses and provide insight on the evolutionary history of coronavirus spike.

An adjusted ELISpot-based immunoassay for evaluation of SARS-CoV-2-specific T-cell responses.

Like antibody evaluation, using an effective antigen-specific T-cell immunity assessment method in coronavirus disease 2019 (COVID-19) patients, survivors and vaccinees is crucial for understanding the immune persistence, prognosis assessment, and vaccine development for COVID-19. This study evaluated an empirically adjusted enzyme-linked immunospot assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell immunity in 175 peripheral blood samples from COVID-19 convalescents and healthy individuals. Results of viral nucleic acid were used as the gold standard of infection confirmation. The SARS-CoV-2M peptide pool had higher sensitivity of 85% and specificity of 71% for the single peptide pool. For combined peptide pools, the parallel evaluation (at least one of the peptide pools is positive) of total peptide pools (S1&S2&M&N) had higher sensitivity (up to 93%), and the serial evaluation (all peptide pools are positive) of total peptide pools had higher specificity (up to 100%). The result of the serial evaluation was better than that of the parallel evaluation as a whole. The detection efficiency of M and N peptide pool serial evaluation appeared the highest, with a sensitivity of 80% and specificity of 93%. This T-cell immunity detection assay introduced in this report can achieve high operability and applicability. Therefore, it can be an effective SARS-CoV-2-specific cellular immune function evaluation method.

One-Year Sustained Cellular and Humoral Immunities in Coronavirus Disease 2019 (COVID-19) Convalescents.

BACKGROUND: The longitudinal antigen-specific immunity in COVID-19 convalescents is crucial for long-term protection upon individual re-exposure to SARS-CoV-2, and even more pivotal for ultimately achieving population-level immunity. We conducted this cohort study to better understand the features of immune memory in individuals with different disease severities at 1 year post-disease onset. METHODS: We conducted a systematic antigen-specific immune evaluation in 101 COVID-19 convalescents, who had asymptomatic, mild, moderate, or severe disease, through 2 visits at months 6 and 12 after disease onset. The SARS-CoV-2-specific antibodies, comprising neutralizing antibody (NAb), immunoglobulin (Ig) G, and IgM, were assessed by mutually corroborated assays (ie, neutralization, enzyme-linked immunosorbent assay [ELISA], and microparticle chemiluminescence immunoassay [MCLIA]). Meanwhile, T-cell memory against SARS-CoV-2 spike, membrane, and nucleocapsid proteins was tested through enzyme-linked immunospot assay (ELISpot), intracellular cytokine staining, and tetramer staining-based flow cytometry, respectively. RESULTS: SARS-CoV-2-specific IgG antibodies, and NAb, can persist among >95% of COVID-19 convalescents from 6 to 12 months after disease onset. At least 19/71 (26%) of COVID-19 convalescents (double positive in ELISA and MCLIA) had detectable circulating IgM antibody against SARS-CoV-2 at 12 months post-disease onset. Notably, numbers of convalescents with positive SARS-CoV-2-specific T-cell responses (≥1 of the SARS-CoV-2 antigen S1, S2, M, and N proteins) were 71/76 (93%) and 67/73 (92%) at 6 and 12 months, respectively. Furthermore, both antibody and T-cell memory levels in the convalescents were positively associated with disease severity. CONCLUSIONS: SARS-CoV-2-specific cellular and humoral immunities are durable at least until 1 year after disease onset.

Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice.

Severe acute respiratory syndrome coronavirus (SARS-CoV-1) and SARS-CoV-2 are highly pathogenic to humans and have caused pandemics in 2003 and 2019, respectively. Genetically diverse SARS-related coronaviruses (SARSr-CoVs) have been detected or isolated from bats, and some of these viruses have been demonstrated to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor and to have the potential to spill over to humans. A pan-sarbecovirus vaccine that provides protection against SARSr-CoV infection is urgently needed. In this study, we evaluated the protective efficacy of an inactivated SARS-CoV-2 vaccine against recombinant SARSr-CoVs carrying two different spike proteins (named rWIV1 and rRsSHC014S, respectively). Although serum neutralizing assays showed limited cross-reactivity between the three viruses, the inactivated SARS-CoV-2 vaccine provided full protection against SARS-CoV-2 and rWIV1 and partial protection against rRsSHC014S infection in human ACE2 transgenic mice. Passive transfer of SARS-CoV-2-vaccinated mouse sera provided low protection for rWIV1 but not for rRsSHC014S infection in human ACE2 mice. A specific cellular immune response induced by WIV1 membrane protein peptides was detected in the vaccinated animals, which may explain the cross-protection of the inactivated vaccine. This study shows the possibility of developing a pan-sarbecovirus vaccine against SARSr-CoVs for future preparedness. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlight the necessity of developing wide-spectrum vaccines against infection of various SARSr-CoVs. In this study, we tested the protective efficacy of the SARS-CoV-2 inactivated vaccine (IAV) against two SARSr-CoVs with different spike proteins in human ACE2 transgenic mice. We demonstrate that the SARS-CoV-2 IAV provides full protection against rWIV1 and partial protection against rRsSHC014S. The T-cell response stimulated by the M protein may account for the cross protection against heterogeneous SARSr-CoVs. Our findings suggest the feasibility of the development of pan-sarbecovirus vaccines, which can be a strategy of preparedness for future outbreaks caused by novel SARSr-CoVs from wildlife.

SARS-CoV-2 Entry Inhibitors Targeting Virus-ACE2 or Virus-TMPRSS2 Interactions.

COVID-19 is an infectious disease caused by SARS-CoV-2. The life cycle of SARS-CoV-2 includes the entry into the target cells, replicase translation, replicating and transcribing genomes, translating structural proteins, assembling and releasing new virions. Entering host cells is a crucial stage in the early life cycle of the virus, and blocking this stage can effectively prevent virus infection. SARS enters the target cells mediated by the interaction between the viral S protein and the target cell surface receptor angiotensin- converting enzyme 2 (ACE2), as well as the cleavage effect of a type-II transmembrane serine protease (TMPRSS2) on the S protein. Therefore, the ACE2 receptor and TMPRSS2 are important targets for SARS-CoV-2 entry inhibitors. Herein, we provide a concise report/information on drugs with potential therapeutic value targeting virus-ACE2 or virus-TMPRSS2 interactions to provide a reference for the design and discovery of potential entry inhibitors against SARS-CoV-2.

Pollution characteristics and sources of environmentally persistent free radicals and oxidation potential in fine particulate matter related to city lockdown (CLD) in Xi'an, China.

The impact of COVID-19 control on air quality have been prevalent for the past two years, however few studies have explored the toxicity of atmospheric particulate matter during the epidemic control. Therefore, this research highlights the characteristics and sources of oxidative potential (OP) and the new health risk substances environmentally persistent free radicals (EPFRs) in comparison to city lockdown (CLD) with early days of 2019-2020. Daily particulate matter (PM2.5) samples were collected from January 14 to February 3, 2020, with the same period during 2019 in Xi'an city. The results indicated that the average concentration of PM2.5 decreased by 48% during CLD. Concentrations of other air pollutants and components, such as PM10, NO2, SO2, WSIs, OC and EC were also decreased by 22%, 19%, 2%, 17%, 6%, and 4% respectively during the CLD, compared to the same period in 2019. Whereas only O3 increased by 30% during CLD. The concentrations of EPFRs in PM2.5 was considerably lower than in 2019, which decreased by 12% during CLD. However, the OP level was increased slightly during CLD. Moreover, both EPFRs/PM and DTTv/PM did not decrease or even increase significantly, manifesting that the toxicity of particulate matter has not been reduced by more gains during the CLD. Based on PMF analysis, during the epidemic period, the contribution of traffic emission is significantly reduced, while EPFRs and DTTv increased, which consist of significant O3 and secondary aerosols. This research leads to able future research on human health effect of EPFRs and oxidative potential and can be also used to formulate the majors to control EPFRs and OP emissions, suggest the need for further studies on the secondary processing of EPFRs and OP during the lockdown period in Xi'an. .The COVID-19 lockdown had a significant impact on both social and economic aspects. The city lockdown, however, had a positive impact on the environment and improved air quality, however, no significant health benefits were observed in Xi'an, China.

Post-sequelae one year after hospital discharge among older COVID-19 patients: A multi-center prospective cohort study.

BACKGROUND: To systematically evaluate the prevalence of post-sequelae and chronic obstructive pulmonary disease assessment test (CAT) scoring one year after hospital discharge among older COVID-19 patients, as well as potential risk factors. METHODS: A multi-center prospective cohort study involving 1,233 eligible older COVID-19 patients was conducted. All patients were followed-up between Mar 1, 2021 and Mar 20, 2021. CAT scoring was adopted to measure symptom burden in COVID-19 patients. RESULTS: Of the 1233 eligible cases, 630 (51.1%) reported at least one sequelae. The top six post-sequelae included fatigue (32.4%), sweating (20.0%), chest tightness (15.8%), anxiety (11.4%), myalgia (9.0%), and cough (5.8%). Severe patients had significantly higher percentage of fatigue, sweating, chest tightness, myalgia, and cough (P<0.05), while anxiety was universal in all subjects. Sweating, anxiety, palpitation, edema of lower limbs, smell reduction, and taste change were emerging sequelae. Disease severity during hospitalization (OR: 1.46, 95% CI: 1.15-1.84, P = 0.002), and follow-up time (OR: 0.71, 95% CI: 0.50-0.99, P = 0.043) were independently associated with risk of post-sequelae, while disease severity during hospitalization was significantly associated with increased risk of emerging sequelae (OR: 1.33, 95% CI: 1.03-1.71, P = 0.029). The median of CAT score was 2 (0-5) in all patients, and a total of 120 patients (9.7%) had CAT scores ≥10. Disease severity during hospitalization (OR: 1.81, 95% CI: 1.23-2.67, P = 0.003) and age (OR: 1.07, 95% CI: 1.04-1.09, P<0.001) were significantly associated with increased risk of CAT scores ≥10. CONCLUSIONS: While the dramatic decline in the prevalence rate of persistent symptoms is reassuring, new sequelae among older COVID-19 patients cannot be ignored. Disease severity during hospitalization, age, and follow-up time contributed to the risk of post-sequelae and CAT scoring one year after hospital discharge among older COVID-19 patients. Our study provides valuable clues for long-term post-sequelae of the older COVID-19 patients, as well as their risk factors.

Novel suction-based in vivo cutaneous DNA transfection platform.

This work reports a suction-based cutaneous delivery method for in vivo DNA transfection. Following intradermal Mantoux injection of plasmid DNA in a rat model, a moderate negative pressure is applied to the injection site, a technique similar to Chinese báguàn and Middle Eastern hijama cupping therapies. Strong GFP expression was demonstrated with pEGFP-N1 plasmids where fluorescence was observed as early as 1 hour after dosing. Modeling indicates a strong correlation between focal strain/stress and expression patterns. The absence of visible and/or histological tissue injury contrasts with current in vivo transfection systems such as electroporation. Specific utility was demonstrated with a synthetic SARS-CoV-2 DNA vaccine, which generated host humoral immune response in rats with notable antibody production. This method enables an easy-to-use, cost-effective, and highly scalable platform for both laboratorial transfection needs and clinical applications for nucleic acid­based therapeutics and vaccines.