Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

The Association of School Learning Environment With Adolescent Health Behaviors.

BACKGROUND: In 2020, schools shifted to remote learning in response to mitigating COVID-19. Since then, students have fluctuated between in-person and remote learning environments. Changes to instructional models raise questions about the impact on health. METHODS: This study leveraged a statewide surveillance system (Healthy Kids Colorado Survey) to examine the relationship between learning environment and adolescent health. The survey was administered in Fall 2020 to 26 high schools, resulting in 4564 respondents. RESULTS: Overall, results suggested positive and negative associations between the 3 learning environments. Notably, as compared to in-person students, hybrid and remote students reported more stress (OR = 1.82, p < .001; OR = 1.41, p = .001), less school connectedness (OR = 0.71 and 0.61, p < .001); remote students reported more parental abuse (OR = 1.33, p = .010) and less alcohol consumption (OR = 0.61, p < .001). CONCLUSION: This study may be used to better understand risk and protective factors experienced by youth at school and home with the goal of improving prevention strategies.

Longitudinal neutralization activities on authentic Omicron variant provided by three doses of BBIBP-CorV vaccination during one year.

The majority of people in China have been immunized with the inactivated viral vaccine BBIBP-CorV. The emergence of the Omicron variant raised the concerns about protection efficacy of the inactivated viral vaccine in China. However, longitudinal neutralization data describing protection efficacy against Omicron variant is still lacking. Here we present one-year longitudinal neutralization data of BBIBP-CorV on authentic Omicron, Delta, and wild-type strains using 224 sera collected from 14 volunteers who have finished three doses BBIBP-CorV. The sera were also subjected for monitoring the SARS-CoV-2 specific IgG, IgA, and IgM responses on protein and peptide microarrays. The neutralization titers showed different protection efficacies against the three strains. By incorporating IgG and IgA signals of proteins and Spike protein derived peptide on microarray, panels as potential surrogate biomarkers for rapid estimation of neutralization titers were established. These data support the necessity of the 3rd dose of BBIBP-CorV vaccination. After further validation and assay development, the panels could be used for reliable, convenient and fast evaluation of the efficacy of vaccination.

Is Household Unemployment Associated With Increased Verbal and Physical Child Abuse During the COVID Pandemic?

PURPOSE: The economic downturn due to the Coronavirus Disease 2019 (COVID-19) pandemic initially led to a large increase in the US unemployment rate. Being laid-off or losing a job could cause financial stress and have an impact on the relationship between parents or other adults in the home and children. We aimed to assess the effect of household unemployment on child physical and emotional abuse during the early part of the COVID-19 pandemic, with an older population of children. METHODS: Data were from a sample of 7,555 students from 51 schools that participated in a survey administered from October to December 2020. We conducted weighted multivariable logistic regression models and report adjusted odds ratio to estimate associations between recent household unemployment and emotional and physical abuse. RESULTS: Having a parent or other adult in the home with a job loss was associated with higher odds of emotional or physical abuse. CONCLUSIONS: The findings are consistent with child maltreatment prevention strategies focused on alleviating economic hardship.

A Bayesian analysis based on multivariate stochastic volatility model: evidence from green stocks.

Green stocks are companies environmental protective and friendly. We test Green stock index in Shanghai Stock Exchange and China Securities Index as safe-havens for global investors. Suitable multivariate-SV model and Bayesian method are used to estimate the spillover effect between different assets among local and global markets. We choose multivariate volatility model because it can efficiently simulate the spillover effect by using machine learning MCMC method. The results show that the Environmental Protection Index (EPI) of Shanghai Stock Exchange (SSE) and China Securities Index (CSI) have no significant volatility spillover from Shanghai Stock index, S &P index, gold price, oil future prices of USA and China. During COVID-19 pandemic, we find Green stock index is a suitable safe-haven with low volatility spillover. Green stock indexes has a strongly one-way spillover to the crude oil future price. Environmentally friendly investor can use diversity green assets to provide a low risk investment portfolio in EPI stock market. The DCGCt-MSV model using machine learning of MCMC method is accurate and outperform others in Bayes parameter estimation.

A Bayesian analysis based on multivariate stochastic volatility model: evidence from green stocks

Green stocks are companies environmental protective and friendly. We test Green stock index in Shanghai Stock Exchange and China Securities Index as safe-havens for global investors. Suitable multivariate-SV model and Bayesian method are used to estimate the spillover effect between different assets among local and global markets. We choose multivariate volatility model because it can efficiently simulate the spillover effect by using machine learning MCMC method. The results show that the Environmental Protection Index (EPI) of Shanghai Stock Exchange (SSE) and China Securities Index (CSI) have no significant volatility spillover from Shanghai Stock index, S &P index, gold price, oil future prices of USA and China. During COVID-19 pandemic, we find Green stock index is a suitable safe-haven with low volatility spillover. Green stock indexes has a strongly one-way spillover to the crude oil future price. Environmentally friendly investor can use diversity green assets to provide a low risk investment portfolio in EPI stock market. The DCGCt-MSV model using machine learning of MCMC method is accurate and outperform others in Bayes parameter estimation.

Risk factors and mortality of pulmonary embolism in COVID-19 patients: Evidence based on fifty observational studies.

BACKGROUND: At present, many studies have described acute pulmonary embolism (PE) as a frequent and prognostically relevant complication of coronavirus disease 2019 (COVID-19) infection. Thus we performed the present analysis of 50 studies to evaluate the risk factors and mortality of PE in COVID-19 patients. METHOD: Databases including PubMed, Embase, Cochrane Library and Web of Science were searched to October, 2021. Odds ratio (OR), mean difference (MD) or standard MD was used to evaluate the outcomes. The primary outcomes were the difference of mortality between PE and non-PE COVID-19 patients as well as relevant risk factors of PE in COVID-19 patients. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. RESULT: A total of 50 studies including 10053 patients were included in this meta-analysis. Our results indicated that COVID-19 patients with PE experienced significantly higher mortality than non-PE patients (21.9% vs. 10.7%), with a pooled OR of 2.21 (95% CI 1.30 - 3.76; P = .003). In addition, COVID-19 patients with PE also experienced more mechanical ventilation (MV) (OR 2.21; 95% CI 1.30 - 3.75; P = .003) and invasive mechanical ventilation (IMV) (OR 3.58; 95% CI 2.47 - 5.20; P < .0001) respectively. Univariate analysis (UVA) results indicated the Sequential Organ Failure Assessment (SOFA) score, time to deep venous thrombosis (DVT), nonintensive care unit (non-ICU) patients and no anticoagulation as risk factors of PE for COVID-19 patients. In addition, multivariate analysis also found that SOFA score, D-dimer, BMI > 30 kg/m2 and history of PE were risk factors of PE for COVID-19 patients. CONCLUSION: The present analysis indicated that PE increased the mortality of COVID-19 patients. Mechanical ventilation, especially invasive mechanical ventilation, is correlated with an increased incidence of PE in patients with COVID-19. The incidence of PE for COVID-19 patients may be multifactorial and further researches focused on risk factors were needed in the future.

Dynamic Analysis of a VSEIR Model with Vaccination Efficacy and Immune Decline

Vaccination is an effective way to prevent the spread of infectious diseases. In this study, we formulate a VSEIR mathematical model to explore the effects of vaccination rate, vaccine efficacy, and immune decline on the COVID-19 transmission. The existence and stability criteria of equilibrium states were determined by analyzing the model. Model analysis was performed. One of the interesting phenomena involved in this issue is that diseases may or may not die out when the basic reproduction number falls below unity (i.e., a backward bifurcation may exist and cause multistability). The disease eventually becomes endemic in the population when the basic reproduction number exceeds one. By comparing different vaccination rates, vaccine efficacy, and infection rate factors, the diseases can be eliminated, not only by vaccines but also by strict protective measures. In addition, we used the COVID-19 number of reported cases in Xiamen in September 2021 to fit the model, and the model and the reported data were well matched.

A CRISPR-based ultrasensitive assay detects attomolar concentrations of SARS-CoV-2 antibodies in clinical samples.

CRISPR diagnostics are powerful tools for detecting nucleic acids but are generally not deployable for the detection of clinically important proteins. Here, we report an ultrasensitive CRISPR-based antibody detection (UCAD) assay that translates the detection of anti-SARS-CoV-2 antibodies into CRISPR-based nucleic acid detection in a homogeneous solution and is 10,000 times more sensitive than the classic immunoassays. Clinical validation using serum samples collected from the general population (n = 197), demonstrates that UCAD has 100% sensitivity and 98.5% specificity. With ultrahigh sensitivity, UCAD enables the quantitative analysis of serum anti-SARS-CoV-2 levels in vaccinated kidney transplant recipients who are shown to produce "undetectable" anti-SARS-CoV-2 using standard immunoassay. Because of the high sensitivity and simplicity, we anticipate that, upon further clinical validation against large cohorts of clinical samples, UCAD will find wide applications for clinical uses in both centralized laboratories and point-of-care settings.

To Create a Safe and Healthy Place for Children: The Associations of Green Open Space Characteristics With Children's Use.

Green open space (GOS) is an important outdoor resource for the well-being of children by providing places for physical activity (PA), especially in the highly urbanized environment. The COVID-19 lockdowns have made children have more sedentary time than before due to less access to public places. This article aims to examine the associations of GOS characteristics (environmental and surrounding) and children's use (visitation and PA pattern) to provide evidence for promoting their PA during the pandemic. This study employed the method of GPS positioner, accelerometer, and survey to measure the children's actual use in GOS. A total of 179 children participated in the study and 10 GOSs were selected. The children were provided with the accelerometers and GPS positioners to track their walking steps, duration, and locations. The environmental characteristics and 1 km buffer of the selected GOSs were explored as extended study area. Results showed that 49.16% of children reported more visitations than before the pandemic, and 48.60% of them preferred to go on weekdays during the pandemic. Both environmental and surrounding characteristics could affect the visitation pattern. The size (p < 0.000), residential ratio (p < 0.000), and intersection density (p < 0.000) were found as the factors significantly associated with visitation pattern. The children's PA pattern was mainly associated with the environmental characteristics of size (p < 0.000), sports, and playground proportion (p < 0.000). The locations of children's PA were mainly around square, playground, sheltered place, and waterside areas. COVID-19 has transformed the children's use of GOS, as well as their relationship with GOS. The large GOS was more likely to promote PA and its use by the children. The environmental and surrounding characteristics of GOS could affect their use pattern, whereas their PA pattern was mainly associated with the environmental characteristics. The findings suggest that GOS characteristics could be an effective solution to respond the challenge from the pandemic, and promote their visitation and PA.

The Environmental Factors Associated With Fatigue of Frontline Nurses in the Infection Disease Nursing Unit.

The workload in the Infection Disease Nursing Unit (IDNU) is increasing dramatically due to COVID-19, and leads to the prevalence of fatigue among the frontline nurses, threatening their health, and safety. The built environment and design could fundamentally affect the fatigue of nurses for a long-term perspective. This article aims to extract the environmental factors of IDNU and explore nurses' perceptions of these factors on the work-related fatigue. It would produce evidences for mitigating the fatigue by environmental interferons. A cross-sectional design was employed by combination of focus group interview and written survey. Environmental factors of IDNU were collected from healthcare design experts (n = 8). Nurses (n = 64) with frontline COVID-19 experiences in IDNU were recruited to assess these factors individually. Four environmental factors were identified as: Nursing Distance (ND), Spatial Crowdness (SC), Natural Ventilation, and Light (NVL), and Spatial Privacy (SP). Among them, ND was considered as the most influential factor on the physical fatigue, while SP was on the psychological fatigue. Generally, these environmental factors were found to be more influential on the physical fatigue than the psychological fatigue. Technical titles were found to be associated with the nurses' perceptions of fatigue by these environmental factors. Nurse assistant and practical nurse were more likely to suffer from the physical fatigue by these factors than senior nurse. The result indicated that environmental factors of IDNU were associated with the nurses' fatigue, particularly on the physical aspect. Environmental interventions of design could be adopted to alleviate the fatigue by these factors such as reducing the ND and improving the spatial privacy. The accurate interventional measures should be applied to fit nurses' conditions due to their technical titles. More attention should be given to the low-ranking nurses, who account for the majority and are much vulnerable to the physical fatigue by environmental factors.

Functional Settings of Hospital Outdoor Spaces and the Perceptions from Public and Hospital Occupant during COVID-19.

Hospital outdoor spaces play an important role for the safety and well-being of users (patients, visitors, and staff), particularly during a pandemic. However, the actual needs of these spaces are often overlooked due to the design and management process. This study investigates the perceptions of the public and occupants on the functional settings of outdoor spaces, and provides evidence for building a safe and resilient hospital during (and after) COVID-19. A multi-method approach of web content analysis (WCA) and a web-based survey was employed. Reports were collected from three mainstream websites; keywords were extracted and then categorized, pertaining to the functional settings of outdoor spaces. Three groups of occupants from Southwest Hospital (staff n = 47, patients n = 64, visitors n = 73) participated in the survey to identify their perceptions of these functional settings. Based on the 657 reports and 33 keywords selected, 7 functional settings were identified: health check (HC), quarantine and observation (QO), food and delivery (FD), healing and restoration (HR), waiting and rest (WR), transportation and parking (TP), load and unload (LU). From all users, HC (4.13) was thought to be the most expected function setting while FD (2.61) was the least. Regarding the satisfaction level, most users were satisfied with HC (3.22) while WR (2.16) was the least satisfying. The users also showed significant differences regarding expectation and satisfaction pertaining to their groups. The results indicate that the current outdoor space could not fully meet the needs of users, regarding the emerging functional setting, due to the pandemic. Users showed significant different perceptions on the functional setting due to their roles. The mismatch between the outdoor space and the users' needs on emerging functional settings resulted in low satisfaction and high expectation in the survey. Environmental interventions with adaptive and flexible strategies should be adapted for these functional settings. The differences of users should be fully recognized by administrators, decision-makers, and designers.

COVID-ONE-hi: The One-stop Database for COVID-19-specific Humoral Immunity and Clinical Parameters.

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (named COVID-ONE-hi). COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients. In addition, 96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database. Furthermore, COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the "START" button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-hi is freely available at www.COVID-ONE.cn.

Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease.

BACKGROUND: Mutations in PKD1 and PKD2, which encode the transmembrane proteins polycystin-1 and polycystin-2, respectively, cause autosomal dominant polycystic kidney disease (ADPKD). Polycystins are expressed in the primary cilium, and disrupting cilia structure significantly slows ADPKD progression following inactivation of polycystins. The cellular mechanisms of polycystin- and cilia-dependent cyst progression in ADPKD remain incompletely understood. METHODS: Unbiased transcriptional profiling in an adult-onset Pkd2 mouse model before cysts formed revealed significant differentially expressed genes (DEGs) in Pkd2 single-knockout kidneys, which were used to identify candidate pathways dysregulated in kidneys destined to form cysts. In vivo studies validated the role of the candidate pathway in the progression of ADPKD. Wild-type and Pkd2/Ift88 double-knockout mice that are protected from cyst growth served as controls. RESULTS: The RNASeq data identified cell proliferation as the most dysregulated pathway, with 15 of 241 DEGs related to cell cycle functions. Cdk1 appeared as a central component in this analysis. Cdk1 expression was similarly dysregulated in Pkd1 models of ADPKD, and conditional inactivation of Cdk1 with Pkd1 markedly improved the cystic phenotype and kidney function compared with inactivation of Pkd1 alone. The Pkd1/Cdk1 double knockout blocked cyst cell proliferation that otherwise accompanied Pkd1 inactivation alone. CONCLUSIONS: Dysregulation of Cdk1 is an early driver of cyst cell proliferation in ADPKD due to Pkd1 inactivation. Selective targeting of cyst cell proliferation is an effective means of slowing ADPKD progression caused by inactivation of Pkd1.

Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease.

BACKGROUND: Mutations in PKD1 and PKD2, which encode the transmembrane proteins polycystin-1 and polycystin-2, respectively, cause autosomal dominant polycystic kidney disease (ADPKD). Polycystins are expressed in the primary cilium, and disrupting cilia structure significantly slows ADPKD progression following inactivation of polycystins. The cellular mechanisms of polycystin- and cilia-dependent cyst progression in ADPKD remain incompletely understood. METHODS: Unbiased transcriptional profiling in an adult-onset Pkd2 mouse model before cysts formed revealed significant differentially expressed genes (DEGs) in Pkd2 single-knockout kidneys, which were used to identify candidate pathways dysregulated in kidneys destined to form cysts. In vivo studies validated the role of the candidate pathway in the progression of ADPKD. Wild-type and Pkd2/Ift88 double-knockout mice that are protected from cyst growth served as controls. RESULTS: The RNASeq data identified cell proliferation as the most dysregulated pathway, with 15 of 241 DEGs related to cell cycle functions. Cdk1 appeared as a central component in this analysis. Cdk1 expression was similarly dysregulated in Pkd1 models of ADPKD, and conditional inactivation of Cdk1 with Pkd1 markedly improved the cystic phenotype and kidney function compared with inactivation of Pkd1 alone. The Pkd1/Cdk1 double knockout blocked cyst cell proliferation that otherwise accompanied Pkd1 inactivation alone. CONCLUSIONS: Dysregulation of Cdk1 is an early driver of cyst cell proliferation in ADPKD due to Pkd1 inactivation. Selective targeting of cyst cell proliferation is an effective means of slowing ADPKD progression caused by inactivation of Pkd1.

Tri-primer-enhanced strand exchange amplification combined with rapid lateral flow fluorescence immunoassay to detect SARS-CoV-2.

The novel coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been surging rapidly around the world, which has exposed humanity to unprecedented economic, social and health impacts. To achieve efficient and accurate detection of SARS-CoV-2 on site, we developed and verified a rapid and sensitive fluorescence lateral flow immunoassay based on the innovative enhanced strand exchange amplification (ESEA-LFIA) in this study. With good amplification efficiency for short-sequence targets, ESEA is an ideal choice for the point-of-care testing of SARS-CoV-2 with a high mutation rate. ESEA reaction can be completed in one step and verified by restriction enzyme digestion. The design consisting of three working primers greatly improved the amplification efficiency. Amplification of the target sequences of the RdRP and N genes can be accomplished under the same reaction conditions, and does not require expensive instruments. The sensitivity of the ESEA-LFIA assay targeting the RdRP and N genes was 90 copies per µL and 70 copies per µL, respectively. Specificity tests showed that the novel assay can specifically detect SARS-CoV-2, and had no cross-reactivity with 9 closely-related human pathogenic coronaviruses and other common respiratory pathogens with similar clinical manifestations. The cutoff values of the RdRP and N gene assays are 11 and 12, respectively, and the assays can be completed within 1 h. The novel strategy proposed in this study is a sensitive and specific method for the rapid detection of SARS-CoV-2, and is suitable as an effective potential bioanalytical tool to respond to future regional or global outbreaks of emerging infectious pathogens with high mutation rates.

Systematic profiling of SARS-CoV-2-specific IgG responses elicited by an inactivated virus vaccine identifies peptides and proteins for predicting vaccination efficacy.

One of the best ways to control COVID-19 is vaccination. Among the various SARS-CoV-2 vaccines, inactivated virus vaccines have been widely applied in China and many other countries. To understand the underlying protective mechanism of these vaccines, it is necessary to systematically analyze the humoral responses that are triggered. By utilizing a SARS-CoV-2 microarray with 21 proteins and 197 peptides that fully cover the spike protein, antibody response profiles of 59 serum samples collected from 32 volunteers immunized with the inactivated virus vaccine BBIBP-CorV were generated. For this set of samples, the microarray results correlated with the neutralization titers of the authentic virus, and two peptides (S1-5 and S2-22) were identified as potential biomarkers for assessing the effectiveness of vaccination. Moreover, by comparing immunized volunteers to convalescent and hospitalized COVID-19 patients, the N protein, NSP7, and S2-78 were identified as potential biomarkers for differentiating COVID-19 patients from individuals vaccinated with the inactivated SARS-CoV-2 vaccine. The comprehensive profile of humoral responses against the inactivated SARS-CoV-2 vaccine will facilitate a deeper understanding of the vaccine and provide potential biomarkers for inactivated virus vaccine-related applications.

Rapid in-situ analysis of phthalates in face masks by desorption corona beam ionization tandem mass spectrometry.

Phthalates (PAEs) are known as endocrine disruptors that can have adverse effects on human hormonal balance and development. Due to PAEs being semi-volatile chemical compounds, they can sustainably emit from the surfaces of objects containing PAEs. Face masks are commonly used to safeguard human health especially during periods of high prevalence of infectious diseases. As masks come into direct contact with the human respiratory system, PAEs from masks will enter the human body directly from the respiratory system thus potentially threatening human health. In this study, the desorption corona beam ionization (DCBI)-MS/MS method for the rapid in-situ detection of PAEs in face masks was established, which could perform ultra-fast, high-throughput identification and quantitative analysis on 13 kinds of PAEs, and the limits of detection (LODs) were 0.7 µg m-2 for DAP, BBP, DBP, DPP, DHXP, DEHP, DINP and DDP, 1.4 µg m-2 for DMEP, DEP, DPhP, DBEP and DNOP. Compared with the traditional liquid chromatography tandem mass spectrometry, this study shows that the DCBI-MS/MS method has the following advantages: 1) short analysis time, less than 1 min; 2) small solvent consumption, less than 10 µL; 3) the PAEs in face masks can be quickly in-situ screened.