Efficacy of low-intensity pulsed ultrasound for the treatment of viral pneumonia: study protocol for a randomized controlled trial.

BACKGROUND: Viral pneumonia has always been a problem faced by clinicians because of its insidious onset, strong infectivity, and lack of effective drugs. Patients with advanced age or underlying diseases may experience more severe symptoms and are prone to severe ventilation dysfunction. Reducing pulmonary inflammation and improving clinical symptoms is the focus of current treatment. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of therapeutic LIPUS in improving lung inflammation in hospitalized patients with viral pneumonia. METHODS: Sixty eligible participants with clinically confirmed viral pneumonia will be assigned to either (1) intervention group (LIPUS stimulus), (2) control group (null stimulus), or (3) self-control group (LIPUS stimulated areas versus non-stimulated areas). The primary outcome will be the difference in the extent of absorption and dissipation of lung inflammation on computed tomography. Secondary outcomes include changes in lung inflammation on ultrasonography images, pulmonary function, blood gas analysis, fingertip arterial oxygen saturation, serum inflammatory factor levels, the sputum excretion volume, time to the disappearance of pulmonary rales, pneumonia status score, and course of pneumonia. Adverse events will be recorded. DISCUSSION: This study is the first clinical study of the efficacy of therapeutic LIPUS in the treatment of viral pneumonia. Given that the current clinical recovery mainly depends on the body's self-limiting and conventional symptomatic treatment, LIPUS, as a new therapy method, might be a major advance in the treatment of viral pneumonia. TRIAL REGISTRATION: ChiCTR2200059550 Chinese Clinical Trial Registry, May 3, 2022.

Smartphone integrated handheld (SPEED) digital polymerase chain reaction device.

We demonstrate a smartphone integrated handheld (SPEED) digital polymerase chain reaction (dPCR) device for point-of-care application. The device has dimensions of ≈100 × 200 × 35 mm3 and a weight of ≈400 g. It can perform 45 PCR cycles in ≈49 min. The device also features integrated, miniaturized modules for thermal cycling, image taking, and wireless data communication. These functions are controlled by self-developed Android-based applications. The only consumable is the developed silicon-based dPCR chip, which has the potential to be recycled. The device's precision and accuracy are comparable with commercial dPCR machines. We have verified the SPEED dPCR prototype's utility in the testing of severe acute respiratory syndrome coronavirus 2, the detection of cancer-associated gene sequences, and the confirmations of Down syndrome diagnoses. Due to its low upfront capital investment, as well as its nominal running cost, we envision that the SPEED dPCR device will help to perform cancer screenings and non-invasive prenatal tests for the general population. It will also aid in the timely identification and monitoring of infectious disease testing, thereby expediting alerts with respect to potential emerging pandemics.

Case report: Anti-CNTN1 antibody-associated nodopathies disease with asymmetric onset.

Anti-contactin-1 (CNTN1) IgG4 antibody-associated nodopathies is an autoimmune antibody-mediated peripheral neuropathy with a unique clinical presentation, pathophysiology, electrophysiology, and therapeutic response. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. Here, a 62-year-old male patient presented with subacute unilateral limb onset, progressive exacerbation, marked weakness of the extremities, cranial, and autonomic nerve involvement. Neurophysiology showed slowed motor nerve conduction velocity (MCV), prolonged distal motor delay (DML), slowed sensory nerve conduction velocity (SCV), decreased sensory nerve activity potential (SNAP) amplitude, decreased amplitude of bilateral neuromotor conduction, abnormal cutaneous sympathetic response (SSR) in both lower extremities, axonal damage, prolonged F-wave latency, and discrete waves. In the initial phase, there was a response to intravenous immunoglobulin (IVIG), and corticosteroids and rituximab were also effective. After 1 year follow-up, the patient improved significantly. This article reports on a patient with nodular disease with anti-contactin-1 (CNTN1) IgG4 antibodies and reviews the literature to improve clinicians' understanding of the disease.

Preclinical evaluation of ISH0339, a tetravalent broadly neutralizing bispecific antibody against SARS-CoV-2 with long-term protection.

BACKGROUND: Ending the global COVID-19 pandemic requires efficacious therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, the emerging Omicron sublineages largely escaped the neutralization of current authorized monoclonal antibody therapies. Here we report a tetravalent bispecific antibody ISH0339, as a potential candidate for long-term and broad protection against COVID-19. METHODS: We report here the making of ISH0339, a novel tetravalent bispecific antibody composed of a pair of non-competing neutralizing antibodies that binds specifically to two different neutralizing epitopes of SARS-CoV-2 receptor-binding domain (RBD) and contains an engineered Fc region for prolonged antibody half-life. We describe the preclinical characterization of ISH0339 and discuss its potential as a novel agent for both prophylactic and therapeutic purposes against SARS-CoV-2 infection. RESULTS: ISH0339 bound to SARS-CoV-2 RBD specifically with high affinity and potently blocked the binding of RBD to the host receptor hACE2. ISH0339 demonstrated greater binding, blocking and neutralizing efficiency than its parental monoclonal antibodies, and retained neutralizing ability to all tested SARS-CoV-2 variants of concern. Single dosing of ISH0339 showed potent neutralizing activity for treatment via intravenous injection and for prophylaxis via nasal spray. Preclinical studies following single dosing of ISH0339 showed favorable pharmacokinetics and well-tolerated toxicology profile. CONCLUSION: ISH0339 has demonstrated a favorable safety profile and potent anti-SARS-CoV-2 activities against all current variants of concern. Furthermore, prophylactic and therapeutic application of ISH0339 significantly reduced the viral titer in lungs. Investigational New Drug studies to evaluate the safety, tolerability and preliminary efficacy of ISH0339 for both prophylactic and therapeutic purposes against SARS-CoV-2 infection have been filed.

Delivery of Anti-microRNA-21 by Lung-Targeted Liposomes for Pulmonary Fibrosis Treatment

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder with a low survival rate. Pulmonary fibrosis is one of the complications of COVID-19 and has a high prevalence in COVID-19 patients. Currently, no effective therapies other than lung transplantation are available to cure IPF and post-COVID-19 pulmonary fibrosis. MicroRNAs are small non-coding RNAs that mediate the development and progression of pulmonary fibrosis, thus making them potent drug candidates for this serious disease. MicroRNA-21 (miR-21) promotes not only the differentiation of fibroblasts to myofibroblasts but also epithelial-mesenchymal transition, both of which have been proposed as fundamental processes in pulmonary fibrosis development. Delivery of anti-miR-21 to block the miR-21-associated fibrogenic pathways represents a promising therapy for pulmonary fibrosis. However, microRNA treatment is challenged by quick degradation of RNA in blood, poor cellular uptake and off-target effects. To overcome these challenges, we developed a lung-targeted, cationic liposome formulation to encapsulate anti-miR-21, enhance its delivery efficiency and improve the therapeutic efficacy. We optimized the liposome formulation and demonstrated the anti-fibrotic effects using both in vitro and in vivo lung fibrosis models. Our results showed that anti-miR-21 delivered by cationic liposomes suppressed myofibroblast differentiation, reduced the synthesis of extracellular matrix and inhibited fibrosis progression. Graphical abstract Wu and colleagues developed a new lipid nanodrug for post-COVID-19 pulmonary fibrosis and idiopathic pulmonary fibrosis, which lack effective therapy except lung transplantation. This new lipid nanodrug enabled lung targeted delivery of RNA therapeutics (anti-microRNA-21) and showed strong anti-fibrotic effects, representing a potent treatment for pulmonary fibrosis.

Delivery of anti-microRNA-21 by lung-targeted liposomes for pulmonary fibrosis treatment.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder with a low survival rate. Pulmonary fibrosis is one of the complications of COVID-19 and has a high prevalence in COVID-19 patients. Currently, no effective therapies other than lung transplantation are available to cure IPF and post-COVID-19 pulmonary fibrosis. MicroRNAs are small non-coding RNAs that mediate the development and progression of pulmonary fibrosis, thus making them potent drug candidates for this serious disease. MicroRNA-21 (miR-21) promotes not only the differentiation of fibroblasts to myofibroblasts but also epithelial-mesenchymal transition, both of which have been proposed as fundamental processes in pulmonary fibrosis development. Delivery of anti-miR-21 to block the miR-21-associated fibrogenic pathways represents a promising therapy for pulmonary fibrosis. However, microRNA treatment is challenged by quick degradation of RNA in blood, poor cellular uptake, and off-target effects. To overcome these challenges, we developed a lung-targeted, cationic liposome formulation to encapsulate anti-miR-21, enhance its delivery efficiency, and improve the therapeutic efficacy. We optimized the liposome formulation and demonstrated the anti-fibrotic effects using both in vitro and in vivo lung fibrosis models. Our results showed that anti-miR-21 delivered by cationic liposomes suppressed myofibroblast differentiation, reduced the synthesis of extracellular matrix, and inhibited fibrosis progression.

Effects of coping on nurses' mental health during the COVID-19 pandemic: Mediating role of social support and psychological resilience.

BACKGROUND: Fighting against the COVID-19 pandemic, front-line nurses were under unprecedented psychological pressure. Therefore, it is necessary to promptly evaluate the psychological status of nurses during the COVID-19 epidemic period. AIM: To investigate nurses' mental health during the COVID-19 pandemic, and to test the mediating role of social support and psychological resilience between coping and mental health. DESIGN: This was a descriptive, cross-sectional survey which used a structural equation model. METHOD: In total, 711 registered nurses were included. All participants were invited to complete a socio-demographic questionnaire, the general health questionnaire, the trait coping style questionnaire, the perceived social support scale and the Conner-Davidson Resilience scale. RESULTS: In total, 50.1% nurses had high risk of mental health. Positive coping positively affected social support and psychological resilience, while it negatively affected mental health. Negative coping negatively affected social support and psychological resilience, while it positively affected mental health. Social support positively affected psychological resilience, while it negatively affected mental health. In addition, social support mediated coping and psychological resilience, and coping and mental health. Moreover, psychological resilience negatively affected mental health, and it mediated coping and mental health.

Research Progress of Raman Spectroscopy and Raman Imaging in Pharmaceutical Analysis.

The analytical investigation of the pharmaceutical process monitors the critical process parameters of the drug, beginning from its development until marketing and post-marketing, and appropriate corrective action can be taken to change the pharmaceutical design at any stage of the process. Advanced analytical methods, such as Raman spectroscopy, are particularly suitable for use in the field of drug analysis, especially for qualitative and quantitative work, due to the advantages of simple sample preparation, fast, non-destructive analysis speed and effective avoidance of moisture interference. Advanced Raman imaging techniques have gradually become a powerful alternative method for monitoring changes in polymorph distribution and active pharmaceutical ingredient distribution in drug processing and pharmacokinetics. Surface-enhanced Raman spectroscopy (SERS) has also solved the inherent insensitivity and fluorescence problems of Raman, which has made good progress in the field of illegal drug analysis. This review summarizes the application of Raman spectroscopy and imaging technology, which are used in the qualitative and quantitative analysis of solid tablets, quality control of the production process, drug crystal analysis, illegal drug analysis, and monitoring of drug dissolution and release in the field of drug analysis in recent years.

Anti-SARS-CoV-2 spike immunoglobulin G and immunoglobulin M titers decline as interval from the second inactivated vaccine dose to the onset of illness is prolonged in breakthrough infection patients.

BACKGROUND: Understanding of the early immune response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections is limited. METHODS: Ninety-eight patients with coronavirus disease 2019 (COVID-19) breakthrough infections were divided into two groups, with intervals from receiving the second dose of inactivated vaccine to the onset of illness <60 or ≥60 days. RESULTS: The median lymphocyte count and the median anti-SARS-CoV-2 spike immunoglobulin G (IgG) and immunoglobulin M (IgM) titers were higher in the <60-day interval group compared with the corresponding medians in the ≥60-day interval group (p = 0.005, p = 0.001, and p = 0.001, respectively). The median interleukin-6 (IL-6) level in the <60-day interval group was significantly lower than the median IL-6 level in the ≥60-day interval group (p < 0.001). CONCLUSIONS: Our results highlight the different anti-SARS-CoV-2 spike IgG and IgM antibody titers among patients with different intervals from receiving the second dose of inactivated vaccine to the onset of illness.

Effects of physical activity and use of digital devices on visual acuity in children and adolescents during the COVID-19 pandemic: A cross-sectional study.

Purpose: To determine the association between poor visual acuity, the use of digital devices and physical activity (PA) during the COVID-19 pandemic. Methods: A total of 327,646 Chinese children and adolescents were included in the analysis using a cluster random sampling method; this is a case-control study, of those 144,708 children and adolescents with poor visual acuity were included in the case group, while 182,938 who did not have poor visual acuity were included in the control group. A logistic regression model was used to assess the contribution of PA and the use of digital devices to poor visual acuity. Results: A total of 144,708 children and adolescents experienced poor visual acuity during the COVID-19 pandemic; 54.8% were male, and 55.2% live in rural areas. Compared to controls, children and adolescents with poor visual acuity exhibited more time for the use of digital devices (4.51 ± 2.44 vs. 3.79 ± 2.34 for cases and controls, respectively; P < 0.001) and PA (3.07 ± 0.92 vs. 2.85 ± 1.00 for cases and controls, respectively; P < 0.001). During the COVID-19 pandemic, risk factors related to poor visual acuity among children and adolescents included the use of digital devices (OR 1.135; 95% CI 1.132-1.139), and PA (OR 1.269; 95%CI 1.259-1.278). The results of interaction analysis show that for children and adolescents aged 12 to 17, the positive association between the use of digital devices and poor visual acuity decreased. The interaction effect between PA and digital devices is 0.987. Conclusions: Children and adolescents were at risk of poor visual acuity during the COVID-19 pandemic. Extended use of the digital devices increased the risk of poor visual acuity, especially for children aged 6-11 years. But the risk of poor visual acuity among children and adolescents decreases as the time spent on PA increases.

Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice.

The ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals is an important part of pandemic preparedness. Here, we have engineer a series of designer cells which we term autonomous, intelligent, virus-inducible immune-like (ALICE) cells as sense-and-destroy antiviral system. After developing a destabilized STING-based sensor to detect viruses from seven different genera, we have used a synthetic signal transduction system to link viral detection to the expression of multiple antiviral effector molecules, including antiviral cytokines, a CRISPR-Cas9 module for viral degradation and the secretion of a neutralizing antibody. We perform a proof-of-concept study using multiple iterations of our ALICE system in vitro, followed by in vivo functionality testing in mice. We show that dual output ALICESaCas9+Ab system delivered by an AAV-vector inhibited viral infection in herpetic simplex keratitis (HSK) mouse model. Our work demonstrates that viral detection and antiviral countermeasures can be paired for intelligent sense-and-destroy applications as a flexible and innovative method against virus infection.

Comparison of the duration of viral RNA shedding and anti-SARS-CoV-2 spike IgG and IgM antibody titers in COVID-19 patients who were vaccinated with inactivated vaccines or not: a retrospective study.

BACKGROUND: At present, the role of inactivated vaccines in viral RNA shedding among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) breakthrough infections is still unknown. METHODS: We collected data of 147 coronavirus disease 2019 (COVID-19) patients with mild-to-moderate illness who were hospitalized in the Third People's Hospital of Yangzhou from 7 to 20 August 2021 and analyzed the differences in symptoms and laboratory tests among fully vaccinated (FV), partially vaccinated (PV) and unvaccinated (UV) patients. RESULTS: The median duration of viral RNA shedding was shorter in the FV (12 [IQR, 9.5-14] days) and PV (13 [IQR, 9-16.75] days) groups than in the UV group (15 [IQR, 11.75-17.25] days) (adjusted P < 0.001 and adjusted P = 0.23, respectively). The median titers of SARS-CoV-2-specific IgG and IgM were significantly higher in the FV (12.29 S/co [IQR, 2.08-63.59] and 0.3 S/co [IQR, 0.05-2.29], respectively) and PV (0.68 S/co [IQR, 0.14-28.69] and 0.12 S/co [0.03-5.23], respectively) groups than in the UV group (0.06 S/co [IQR, 0.03-0.47] and 0.04 S/co [IQR, 0.02-0.07]) (adjusted P < 0.001 and adjusted P = 0.008, respectively). CONCLUSIONS: Inactivated vaccines may shorten viral RNA shedding in breakthrough infected patients who have mild-to-moderate illness and may improve the ability of the host to generate specific antibodies to infection.

Aptamer-Gated Mesoporous Silica Nanoparticles for N Protein Triggered Release of Remdesivir and Treatment of Novel Coronavirus (2019-nCoV).

Since the 2019-nCoV outbreak was first reported, hundreds of millions of people all over the world have been infected. There is no doubt that improving the cure rate of 2019-nCoV is one of the most effective means to deal with the current serious epidemic. At present, Remdesivir (RDV) has been clinically proven to be effective in the treatment of SARS-CoV-2. However, the uncertain side effects make it important to reduce the use of drugs while ensuring the self-healing effect. We report an approach here with targeted therapy for the treatment of SARS-CoV-2 and other coronaviruses illness. In this study, mesoporous silica was used as the carrier of RDV, the nucleocapsid protein (N protein) aptamer was hybridized with the complementary chain, and the double-stranded DNA was combined with gold nanoparticles as the gates of mesoporous silica pores. When the RDV-loaded mesoporous silica is incubated with the N protein, aptamer with gold nanoparticles dissociate from the complementary DNA oligonucleotide on the mesoporous silica surface and bind to the N protein. The releasing of RDV was determined by detecting the UV-vis absorption peak of RDV in the solution. These results show that the RDV delivery system designed in this work has potential clinical application for the treatment of 2019-nCoV.

Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity.

The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naïve SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.

The lending risk predicting of the folk informal financial organization from big data using the deep learning hybrid model

ABSTACT This article is first to predict and earlier warning folk lending risk used deep learning hybrid model, we find that the LSTM hybrid model has a higher predict accuracy on lending risk forecasting and earlier warning of the FIFO, with an obviously improvement of the average value of forecasting accuracy. The predict accuracy of LSTM-GRU and LSTM-CNN models on lending risk forecasting of the FIFO is higher than others during COVID-19 pandemic. Therefore, we believe that the LSTM hybrid model, especially the LSTM-GRU model can better predict and early warn lending risk of the FIFO on big data.

Prevalence of Sarcopenia in Patients With COVID-19: A Systematic Review and Meta-Analysis

Background It has been speculated that patients with sarcopenia are aggravated by the current novel coronavirus disease 2019 (COVID-19) epidemic. However, there is substantial uncertainty regarding the prevalence of sarcopenia in patients with COVID-19. Objectives The purpose of the study was to systematically evaluate the prevalence of sarcopenia in patients with COVID-19, including stratification by gender, study location, study population, study design, and diagnostic criteria. Design This is the systematic literature review and meta-analysis. Methods An electronic search was performed in MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science and Scopus to identify observational studies reporting a prevalence estimate for sarcopenia in patients with COVID-19. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and a meta-analysis was performed. Risk of bias (RoB) was assessed using the Newcastle–Ottawa Scale (NOS) for cohort studies and Joanna Briggs Institute (JBI) manual for cross-sectional studies, and Stata 14.0 was used to perform meta-analyses. Results A total of 4,639 studies were initially identified. After removing the duplicates and applying the selection criteria, we reviewed 151 full-text studies. A total of 21 studies, including 5,407 patients, were eligible for inclusion in this review finally. The prevalence of sarcopenia in patients with COVID-19 in individual studies varied from 0.8 to 90.2%. The pooled prevalence of sarcopenia in COVID-19 was 48.0% (95% confidence interval, CI: 30.8 to 65.1%, I2 = 99.68%, p = 0.000). We did not find any significant differences in the prevalence estimates between gender specificity (OR = 1.34;95% CI = 0.80–2.26;p = 0.001). By sex, the prevalence was 42.5% (95% CI: 31.7 to 53.4%) in men and 35.7% (95% CI: 24.2 to 47.2%) in women. The prevalence estimates significantly varied based on population settings and different diagnostic criteria of sarcopenia. ICU patients (69.7, 95% CI: 51.7 to 85.2%) were more likely to suffer from sarcopenia compared to other population settings. Conclusion To our knowledge, this is the first meta-analysis reporting on the prevalence of sarcopenia in patients with COVID-19. Sarcopenia is frequently observed in patients with COVID-19, with varying prevalence across population settings. This study would be useful for clinicians to prompt the increasing awareness of identifying sarcopenia and developing interventions at patients with COVID-19 with high risk of sarcopenia. Further prospective longitudinal studies to define the association of sarcopenia and its prognostic outcomes in COVID-19 survivors are urgently needed to propose the most appropriate treatment strategies during their admission and discharge. Systematic Review Registration [www.crd.york.ac.uk/prospero/], identifier [CRD42022300431].

Vaccination with Omicron Inactivated Vaccine in Pre-vaccinated Mice Protects against SARS-CoV-2 Prototype and Omicron Variants.

In response to the fast-waning immune response and the great threat of the Omicron variant of concern (VOC) to the public, we report the pilot-scale production of an inactivated Omicron vaccine candidate that induces high levels of neutralizing antibody titers to protect against the Omicron virus. Here, we demonstrate that the inactivated Omicron vaccine is safe and effective in recalling immune responses to the HB02, Omicron, and Delta viruses after one or two doses of BBIBP-CorV. In addition, the efficient productivity and good genetic stability of the manufactured inactivated vaccine is proved. These results support the further evaluation of the Omicron vaccine in a clinical trial.

Studies in the antiviral molecular mechanisms of 25-hydroxycholesterol: Disturbing cholesterol homeostasis and post-translational modification of proteins.

Efficient antiviral drug discovery has been a pressing issue of global public health concern since the outbreak of coronavirus disease 2019. In recent years, numerous in vitro and in vivo studies have shown that 25-hydroxycholesterol (25HC), a reactive oxysterol catalyzed by cholesterol-25-hydroxylase, exerts broad-spectrum antiviral activity with high efficiency and low toxicity. 25HC restricts viral internalization and disturbs the maturity of viral proteins using multiple mechanisms. First, 25HC reduces lipid rafts and cholesterol in the cytomembrane by inhibiting sterol-regulatory element binding proteins-2, stimulating liver X receptor, and activating Acyl-coenzyme A: cholesterol acyl-transferase. Second, 25HC impairs endosomal pathways by restricting the function of oxysterol-binding protein or Niemann-pick protein C1, causing the virus to fail to release nucleic acid. Third, 25HC disturbs the prenylation of viral proteins by suppressing the sterol-regulatory element binding protein pathway and glycosylation by increasing the sensitivity of glycans to endoglycosidase. This paper reviews previous studies on the antiviral activity of 25HC in order to fully understand its role in innate immunity and how it may contribute to the development of urgently needed broad-spectrum antiviral drugs.

Developing a Health-Spatial Indicator System for a Healthy City in Small and Midsized Cities.

A recent examination of the significant role of public health has prompted calls to re-investigate how the urban environment affects public health. A vital part of the solution includes Healthy City initiatives that have been the subject of extensive policies, implications, and practices globally. However, the existing literature mainly focuses on big cities and metropolitan areas, while investigations into small and midsized cities (SMCs) are lacking, and thus reflect the underlying issues of health inequity. This study develops an indicator system for evaluating Healthy City initiatives in SMCs, linking urban design and public health, supported by the analyzed opinions from experts collected using both questionnaires and interviews. The indicator system includes six primary dimensions and 37 variables: urban form and transportation (UFT); health-friendly service (HFS); environmental quality and governance (EQG); community and facility (CF); green and open space (GOS); and ecological construction and biodiversity (ECB). A fuzzy synthetic evaluation technique was used to assess the relative importance of factors, emphasizing the importance of UFT, HFS, and EQG, with importance indexes of 0.175, 0.174, and 0.174, respectively. This indicator system is helpful for SMCs seeking to construct a Healthy City in the future, and is based on urban design and governance inputs and for enhancing the Healthy City knowledge base of cities of varied scales.