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As an emerging two-dimensional nanomaterial with promising prospects, mono- or few-layer black phosphorus (BP) is potentially toxic to humans. We investigated the effects of two types of BPs on adult male mice through intratracheal instillation. Using the flow cytometry method, the generation, migration, and recruitment of immune cells in different organs have been characterized on days 1, 7, 14, and 21 post-exposure. Compared with small BP (S-BP, lateral size at ∼188 nm), large BP (L-BP, lateral size at ∼326 nm) induced a stronger stress lymphopoiesis and B cell infiltration into the alveolar sac. More importantly, L-BP dramatically increased peripheral neutrophil (NE) counts up to 1.9-fold on day 21 post-exposure. Decreased expression of the CXCR4 on NEs, an important regulator of NE retention in the bone marrow, explained the increased NE release into the circulation induced by L-BP. Therefore, BP triggers systemic inflammation via the disruption of both the generation and migration of inflammatory immune cells.

Virus receptors are highly involved in mediating the entrance of infectious viruses into host cells. Here, we found that typical chemical exposure caused the upregulation of virus receptor mRNA levels. Chemicals with the same structural characteristics can affect the transcription of angiotensin-converting enzyme 2 (ACE2), a dominant receptor of SARS-CoV-2. Some chemicals can also regulate the transcription of ACE2 by similar regulatory mechanisms, such as multilayer biological responses and the crucial role of TATA-box binding protein associated factor 6. The abovementioned finding suggested that chemical mixtures may have a joint effect on the ACE2 mRNA level in the real scenario, where humans are exposed to numerous chemicals simultaneously in daily life. Chemically regulated virus receptor transcription was in a tissue-dependent manner, with the highest sensitivity in pulmonary epithelial cells. Therefore, in addition to genetic factors, exogenous chemical exposure can be an emerging nongenetic factor that stimulates the transcription of virus receptor abundance and may elevate the protein expression. These alterations could ultimately give rise to the susceptibility to virus infection and disease severity. This finding highlights new requirements for sufficient epidemiological data about exposomes on pathogen receptors in the host., Pollutant exposure shows the upregulation of virus receptor mRNA levels, which could ultimately affect host susceptibility to virus infection and disease severity.

The association between time to positivity (TTP) of blood culture and the clinical prognosis of patients with Klebsiella pneumoniae bloodstream infection (BSI) remains unclear. A retrospective study of 148 inpatients with BSI caused by K. pneumoniae was performed at Shanghai Tongji Hospital, China, from October 2016–2020. The total in-hospital fatality rate was 32%. The median TTP was 11.0 (7.7–16.1) h and the optimal cutoff for prediction of in-hospital mortality was 9.4 h according to the ROC curve. Early TTP (P = 0.01), but not by multivariate analysis (OR = 2.7, 95% CI 1.0–7.4, P = 0.06). Old age, serum creatinine, white blood cells, and C-reactive protein values were risk factors for in-hospital mortality by multivariate analysis. Early TTP was not a risk factor for septic shock (OR = 1.8, 95% CI 0.6–5.1, P = 0.27) or ICU admission (OR = 1.0, 95% CI 1.0–1.0, P = 0.32). In conclusion, the in-hospital fatality rate of patients with K. pneumoniae BSI was relatively high and associated with an early TTP of blood cultures. However, no increased risk of mortality, septic shock or ICU admission was evident in early TTP patients.

Understanding the molecular mechanism of material transformation raises a great challenge for material characterization techniques. As a promising 2D material, the application potential of black phosphorus (BP) is seriously compromised...

The novel human infectious coronaviruses (CoVs) responsible for severe respiratory syndromes have raised concerns owing to the global public health emergencies they have caused repeatedly over the past two decades. However, the ongoing coronavirus disease 2019 (COVID-19) pandemic induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has received unprecedented attention internationally. Monitoring pathogenic CoVs in environmental compartments has been proposed as a promising strategy in preventing the environmental spread and tracing of infectious diseases, but a lack of reliable and efficient detection techniques is still a significant challenge. Moreover, the lack of information regarding the monitoring methodology may pose a barrier to primary researchers. Here, we provide a systematic introduction focused on the detection of CoVs in various environmental matrices, comprehensively involving methods and techniques of sampling, pretreatment, and analysis. Furthermore, the review addresses the challenges and potential improvements in virus detection techniques for environmental surveillance.

Exposure to electronic and electrical waste (e-waste) has been related to a few adverse health effects. In this study, sediment samples from an e-waste recycling town in China were collected, and aryl hydrocarbon receptor (AhR) agonists in the samples were identified using an effect-directed analysis (EDA) strategy. The CBG2.8D cell line reporter gene bioassay was used as a toxicity test, while suspect screening against chemical databases was performed for potential AhR agonist identification where both gas chromatography- and liquid chromatography-high resolution mass spectrometry analyses were run. When the original sample extract showed high AhR-mediated activity, sample fractionation was performed, and fractions exhibiting high bioactivity were chemically analyzed again to reveal the corresponding AhR agonists. In total, 23 AhR agonists were identified, including 14 commonly known ones and 9 new ones. Benzo [k]fluoranthene and 6-nitrochrysene were the dominant AhR agonists, covering 16-71% and 2.7-12%, respectively, of the AhR activation effects measured in the parent extracts. The newly identified AhR-active chemicals combined explained 0.13-0.20% of the parent extracts' effects, with 7,12-dimethylbenz [a]anthracene and 8,9,11-trimethylbenz [a]anthracene being the major contributors. A diagnostic isomer ratio analysis of polycyclic aromatic hydrocarbons suggested that the major source of AhR agonists identified in these e-waste related sediment samples were probably petroleum product combustion and biomass combustion. In the future, for a more comprehensive AhR agonist investigation, in-house chemical synthesis and purification, and, when necessary, a secondary sample fractionation, would be beneficial.

The pandemic of the Coronavirus Disease 2019 (COVID-19) has spread around the world. COVID-19 is one of the most serious infectious disease threats in the past 100 years. Epidemiological and clinical studies have shown that early diagnosis of infectious COVID-19 cases is of great help to slow down the spread of disease and reduce mortality. Therefore, the diagnosis of SARS-CoV-2 infection is of great significance in the control of the pandemic. However, because patients with COVID-19 show partially similar symptoms to diseases such as influenza-like illness, it is impossible to diagnose SARS-CoV-2 infection by relying solely on the patient’s clinical features. Meanwhile, there are a number of asymptomatic patients, who are capable of spreading the infection while passing general surveillance. The early diagnosis of such cases is also critical for the prevention of the outbreak and control of the pandemic. Given there is no effective SARS-CoV-2-specific anti-viral agents, chemists are engaging in the development of analytical strategies for the SARS-CoV-2 detection and antiviral drug to combat the spread of the COVID-19. In order to support the innovation in the ongoing research on fighting COVID-19 pandemic, we summarized part of the achievements in SARS-CoV-2 detection and drug development engaged by chemists in China. By summarizing the available products and patents with practical potentials in fast analysis, we discussed the recent advances in the techniques for SARS-CoV-2 detection and their application potentials in diagnosis of COVID-19. For the diagnosis of COVID-19, the most specific analysis method is polymerase chain reaction (PCR) based nucleic acid assay. At the end of March, National Medical Products Administration has approved more than 20 products aiming at SARS-CoV-2 test, most of which are kits based on the principle of real-time quantitative reverse transcription PCR (RT-qPCR). Because PCR-based method needs complex manual operation steps, the technique is limited due to the time-consuming reaction steps. Later on, techniques with multiple procedures including nucleic acid extraction, amplification, and virus detection have been integrated for rapid detection. In order to solve the problems caused by disadvantages of complex thermal cycling process in PCR, isothermal amplification has been applied for nucleic acid detection. Combined with isothermal amplification, rapid point-of-care test is applicable for the detection of collected SARS-CoV-2 viral RNA. Although viral RNA assay is the most specific method for diagnosis of COVID-19, it cannot be used to determine the post-infection or monitor the immunity of general populations. The immunological assays could be applied for the detection of antibodies themselves several days after the infection by SARS-CoV-2. Therefore, lateral flow assay, microfluidics, and other technologies have successfully applied for the immune assay. Some reagents, detection kits, and devices have been certificated and marketed internationally. Specific anti-SARS-CoV-2 agents have been designed and tested. Moreover, several small-molecule drug candidates with high efficacy and low toxicity showed great potential in clinical application. Facing the outbreak of epidemic of COVID-19, Department of Chemical Sciences, Department of Mathematical and Physical Sciences of National Natural Science Foundation of China have jointly funded three innovative projects to support the research on the effective and expedite control of the epidemic. These projects include “Research on rapid detection of new coronavirus in aerosol on site”, “A pre-clinical study of using small molecules to treat SARS-CoV-2-induced excessive inflammation and injury”, and “Polymer micro-/nano-fibrous non-woven fabrics prepared via flash-pressure- released technology and reusable high-quality medical protective suits produced with these fabrics”. The pandemic of COVID-19 is a major public health emergency, which poses a major challenge to health system worldwide and also has a major impact on economy and society. In response to sudden large-scale outbreaks, rapid, accurate and high-throughput detection technology is undoubtedly the priority of “anti-epidemic”. Focusing on the present and serving the long-term requirement, we still need to innovatively propose new ideas to meet the major needs in the diagnosis and treatment of major diseases based on a global perspective.

Electronic waste (e-waste) pollution is of great concern due to the release of hazardous chemicals during the improper e-waste disposal. Many chemicals leached from e-waste were reported to pose estrogenic effects. To date, little is known regarding the occurrence and biological effects of estrogenic chemicals in sediments near an e-waste area. In this study, an effect-directed analysis (EDA) is applied to determine the estrogenic chemicals in sediments of four sites collected from a typical e-waste recycling city in China. Following screening with the ER-CALUX assay, the extract of sample with the most potent effect was subjected in fractionation using reverse phase liquid chromatography. Based on a target analysis for the active fractions, four compounds, including estrone, 17β-estradiol, 17α-ethinylestradiol and bisphenol A, were identified, and these contributed to 17% of the total toxic effects in the sample. A further nontarget analysis screened four candidates, namely diethylstilbestrol (DES), hexestrol (HES), nandrolone and durabolin, and the total contribution was found to be 48% from the active sample. Specifically, DES and HES were only detected in the active sample and were found to be the primary drivers of estrogenic effects. An examination of the identified chemicals in the four sites indicated that these estrogenic chemicals may originate from e-waste recycling, livestock excretion and domestic waste. These findings uncovered the estrogenic pollutants in sediments from an e-waste area. Considering single endpoint in biological assay is not abundant to screen chemicals with different toxic effects, further EDA studies with multiple endpoints are required to better understand the occurrence of representative or unknown chemicals in e-waste-polluted areas.

SUMMARY OBJECTIVE Lung cancer is the leading cause of cancer-related death. To reduce lung cancer mortality and detect lung cancer in early stages, low dose CT screening is required. A meta-analysis was conducted to verify whether screening could reduce lung cancer mortality and to determine the optimal screening program. METHODS We searched PubMed, Web of Science, Cochrane library, ScienceDirect, and relevant Chinese databases. Randomized controlled trial studies with participants that were smokers older than 49 years (smoking >15 years or quit smoking 10 or 15 years ago) were included. RESULTS Nine RCT studies met the criteria. LDCT screening could find more lung cancer cases (RR=1.58, 95%CI=1.25-1.99, P15 anos ou parar de fumar 10 ou 15 anos atrás) foram incluídos. RESULTADOS Nove estudos RCT preencheram os critérios. O rastreamento de LDCT pôde encontrar mais cânceres de pulmão (RR=1,58, IC 95%=1,25-1,99, P

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers worldwide. Therefore, the potentially deleterious effect of OPE on human beings deserves extensive attention. The primary objective of this present study was to untangle the relationship between OPE exposure and cardiovascular disease (CVD) among general population. Detailed information about participants' baseline characteristics, involving socioeconomic data, demographic data and key covariates was obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2018. Multivariate logistic regression models with adjustment for prior-determined covariates were utilized to examine the relationship between various OPEs and CVD among US adults and calculate odd ratios (ORs) and corresponding confidence intervals (CIs). Two multi-pollutant statistical strategies (weighted quantile sum regression and Bayesian kernel machine regression) were employed to investigate the joint effect of OPE mixture on CVD. A total of 5067 participants were included in this study. In completely-adjusted logistic model, the highest tertiles of OPE metabolites were positively associated with CVD risk, while the relationships did not reach statistical significance. The weighted quantile sum (WQS) index was significantly correlated with increased prevalence of CVD (adjusted OR: 1.25; CI: 1.02, 1.53, p value = 0.032) and Diphenyl phosphate (DPHP) was the greatest contributor (31.38%). The BKMR also indicated that mixed OPE exposure associated with an increased risk of CVD. Taken together, the present study demonstrated that there were possible links between OPE exposures and increased risk of CVD, while the relationships did not reach statistical significance. Our study provided the suggestive evidence that cumulative effect of OPE mixtures on CVD. DPHP may be a major driver of this positive association. Given the limitation of cross-sectional design and relatively limited kinds of OPE metabolites, further studies are warranted to longitudinally evaluate the potential effect of a wider range of OPEs on CVD or cardiac metabolism.

Coronavirus disease (COVID-19) patients with cardiovascular and metabolic disorders have been found to have a high risk of developing severe conditions with high mortality, further affecting the prognosis of COVID-19. However, the effect of hypertension and angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB) agents on the clinical characteristics and inflammatory immune responses in COVID-19 patients is still undefined. In this study, 90 COVID-19 patients were divided into hypertension and nonhypertension groups. The hypertension group was divided into well-controlled and poorly controlled subgroups based on blood pressure levels; moreover, hypertensive patients were also divided into ACEI/ARB and non-ACEI/ARB subgroups according to the administration of ACEI/ARB antihypertensive agents. The clinical characteristics of and inflammatory immune biomarker levels in the different groups of COVID-19 patients were compared, and the association between the combined effect of hypertension with ACEI/ARB antihypertensive agents and the severity of COVID-19 was examined. The results showed that the levels of aminotransferase (AST) and hs-cTnI were higher in the hypertension group compared with the nonhypertension group. The long-term use of ACEI/ARB agents in patients had statistically significantly lower AST, low-density lipoprotein cholesterol (LDL-C), and oxygen uptake and lower white cell count, neutrophil count, and levels of CD4, CD8, CRP, and PCT but without statistical significance. In addition, compared with COVID-19 patients without hypertension, hypertensive patients without the use of ACEI/ARB had a higher risk of developing severity of COVID-19 (for poorly controlled patients: OR = 3.97, 95% CI = 1.03–15.30; for well-controlled patients: OR = 6.48, 95% CI = 1.77–23.81). Hypertension could cause organ damage in COVID-19 patients, but the long-term use of ACEI/ARB agents may be beneficial to alleviate this injury.

The widespread application of silver (Ag) nanomaterials raises health concerns due to the adverse effects that can be associated with silver nanoparticles (AgNPs) exposure. AgNPs can be introduced into human bodies via inhalation, either intentionally (intranasal administration of AgNPs) or unintentionally (environmental pollution, accidental release, or occupational exposure). Recent studies have shown that intranasal exposure of experimental animals to AgNPs can lead to the accumulation of Ag in brain tissues. However, there is little information available concerning what forms of Ag (particulate and ionic) exist in brain tissues. This study aimed to investigate whether particulate Ag exists in rat brains following intranasal exposure of AgNPs at 1 mg/kg/day using multiple analytical techniques. The results demonstrated that Ag-containing particles were presented in AgNPs-exposed rat brains, accounting for 20.2–68.1% of the total Ag. The mass concentrations of Ag-containing particles in brain tissues increased with exposure time but only decreased by 37.5% after elimination for 4 weeks upon exposure cessation. The size of Ag-containing particles identified in rat brains was larger than the original AgNPs. The Ag-containing particles identified in the rat brain were composed of multiple elements, including Ag, sulfur, and selenium with atomic percentages of 45.8%, 37.5%, and 16.7%, respectively. The finding highlighted the occurrence and accumulation of transformed AgNPs containing S and Se in rat brains after intranasal exposure to AgNPs, implying potential risks for brain health.

This study aimed to examine associations of the impact of COVID-19 pandemic on family life with emotional and behavioral health among preschool children.A longitudinal study including 1595 preschool children aged 3-6 years and their families was conducted in Anhui Province. The linear regression was applied to examine associations between the impact of COVID-19 pandemic on family life and emotional and behavioral health.Results of the multivariable linear regression indicated that the severe impact of COVID-19 pandemic on family life was significantly associated with more sleep problems, poor dietary behavior habits, more anxiety symptoms, and more problematic behaviors; and these effects exhibited gender and age differences.The severe impact of COVID-19 pandemic on family life significantly increased the risk for exacerbated emotional and behavioral health among preschool children. It is considered vital to identify risk factors for vulnerable families and then to implement precise interventions when necessary for emotional and behavioral health of children in these families.

Objective To investigate the effect of influenza vaccination on prevention of acute attack in elderly patients with chronic airway disease, and to provide evidence for the prevention and control strategy of chronic airway disease in elderly population. Methods Elderly patients in Linquan County of Anhui Province of China who under stationary phase of chronic airway disease were selected and randomly vaccinated with tetravalent or trivalent influenza vaccine. The number of patients with acute attack, the number of outpatients with acute attack, the number of outpatients, the number of inpatients, the number of inpatients, the total cost of patients, the cost of outpatients, the cost of hospitalization and the length of hospitalization were collected before vaccination and after one year follow up. Results A total of 348 subjects were included in this study, 248 were vaccinated with trivalent vaccination and 100 were vaccinated with tetravalent vaccination. There was no significant difference in age and sex ratio among two vaccination groups. The ratios of acute attack, outpatient visits and hospitalization, and number of outpatient visits, number of hospitalizations, total medical expenses, outpatient expenses and hospitalization expenses were significantly higher before vaccination than those after vaccination in both trivalent vaccination group and tetravalent vaccination group. While, there was no significant difference in the length of stay between before and after vaccination in neither trivalent vaccination group nor tetravalent vaccination group. The protection effect between trivalent vaccination group and tetravalent vaccination group was not significant. Conclusion Influenza vaccination can effectively prevent the acute attack of chronic airway disease and delay the progress of the chronic airway disease.

In this study, we comprehensively explored graphene oxide (GO)-induced systemic immune responses and interference with hematopoiesis in mice upon GO intravenous injection. In the liver and spleen, GO led to alterations in immune components at different time points. GO exposure showed an effect on the populations of different types of hepatic macrophages. In the liver, the populations of macrophages mainly affected by GO including Kupffer cells and monocyte-derived macrophages. Stimulated hepatic inflammation led to the infiltration of platelets from the circulation into the liver and decreased peripheral platelets population at day 1. Interestingly, a decreased platelet population was observed on day 7 in the spleen. GO also led to accelerated hematopoiesis in the spleen. Therefore, the possible forced generation of more platelets and the release of mature platelets from the spleen contributed to the increased circulating platelet count on day 7. Therefore, although GO showed a low potential to induce severe inflammation in the liver and spleen, it disrupted hematopoiesis in the spleen, which contributed to fluctuations in circulating platelet counts. The interaction of GO with the immune system warrants comprehensive study for gaining better understanding.

The present meta-analysis was performed to evaluate the efficacy of radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) patients. A systematic literature search was conducted of online databases prior to February 21, 2021. Eleven articles involving 8429 patients were included. The pooled hazard ratio for overall survival (OS) of RFA versus SBRT was 0.79 (p 0.001). Statistically significant differences were found in the 1-, 2-, 3-, 4- and 5-year pooled OS and freedom from local progression (FFLP) rates between the two groups, favoring the RFA arms. However, the pooled local control (LC) rates were higher in the SBRT arm. RFA provided better OS and FFLP for treating HCC, while SBRT achieved superior LC.Lay abstract Radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) are two common nonsurgical methods for the treatment of hepatocellular carcinoma patients. The purpose of this meta-analysis was to compare the efficacy of the two methods. The analysis included 11 original studies after online databases search prior to 21 February 2021. The results showed that RFA provided better survival benefits and less local disease progression for the treatment of HCC patients, while SBRT obtained superior local control of tumor tissues.

Background and Aims During the current Coronavirus Disease 2019 (COVID-19) pandemic, patients with diabetes face disproportionately more. This study was performed to clarify anti-inflammatory effects of anti-diabetic agents on COVID-19 in patients with diabetes. Methods and Results Relevant literature was searched on 15 databases up to November 14, 2020 and was updated on April 13, 2021. The pooled ORs along with 95% CIs were calculated to evaluate combined effects. 31 studies with 66,914 patients were included in qualitative and quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality (pooled OR = 0.62, 95% CI, 0.50–0.76, p = 0.000) and poor composite outcomes (pooled OR = 0.83, 95% CI, 0.71–0.97, p = 0.022) in diabetic patients with COVID-19. Significance of slight lower mortality remained in sulfonylurea/glinides (pooled OR = 0.93, 95% CI, 0.89–0.98, p = 0.004), but of poor composite outcomes was not (pooled OR = 1.48, 95% CI, 0.61–3.60, p = 0.384). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR = 0.95, 95% CI, 0.72–1.26, p = 0.739) or poor composite outcomes (pooled OR = 1.27, 95% CI, 0.91–1.77, p = 0.162) of COVID-19 in diabetic patients. Conclusion Metformin might be beneficial in decreasing mortality and poor composite outcomes in diabetic patients infected with SARS-CoV-2. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and GLP-1RA would not seem to be adverse. There was insufficient evidence to conclude effects of other anti-diabetic agents. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed. Registration number: PROSPERO-CRD42020221951.

As typical brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) and its derivative TBBPA-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) are ubiquitous in various environmental compartments. However, the potential health risk posed by these compounds, especially at environmentally relevant levels, remains unclear. In this study, using adult male mice, we investigated the toxicity of orally administered TBBPA and TBBPA-BDBPE at an environmentally relevant dose (57 nmol/kg body weight). After a single exposure and daily exposure, we assessed lipid metabolism homeostasis, the transcriptome, and immune cell components in the liver. We found that the single exposure to TBBPA or TBBPA-BDBPE alone increased the number of hepatic macrophages, induced alterations in the levels of lipids, including triacylglycerol and free fatty acids, and caused transcriptome perturbation. The results from the daily administration groups showed that TBBPA and TBBPA-BDBPE both significantly increased the triacylglycerol content; however, the elevation of hepatic macrophages was observed only in the TBBPA-BDBPE treatment group. This study confirmed that environmentally relevant levels of TBBPA and TBBPA-BDBPE are toxic to the liver. Our findings revealed that dysfunction of the liver is a health concern, following exposure to BFRs, even at very low concentrations. The chronic effects induced by TBBPA and its derivatives should be further investigated.

Background Very few studies have focused on the relationship between ambient apparent temperature (AT) and admission of mental and behaviour disorders (MDs). Therefore, a time-series study was conducted in Yancheng, China, to explore the effects of AT on the daily emergency admissions of patients with MDs over the period of 2014–17. Methods A quasi-Poisson generalized linear model (GLM) combined with a distributed lag non-linear model (DLNM) was adopted to explore the associations after adjusting for time trend, day of the week, humidity, sunshine duration, rainfall, holidays and air pollutants. In the subgroup analysis, the modification effects of age and sex were also examined. Results Overall, 8438 cases of MDs emergency admissions were identified. With the apparent temperature with the minimum number of admissions (− 3.4 °C) serving as a reference, a positive correlation emerged between high AT and daily emergency admissions of patients with MDs in Yancheng, China, with the lagged effect of 1 to 5 days. The subgroup analysis demonstrated a positive relationship between AT and MDs emergency admissions among males and individuals younger than 45 years old, with no lagged effect. Conclusions The results will provide important scientific evidence for mental health policy-makers and practitioners for possible intervention, especially among the vulnerable populations.

Although the abiotic and biotic transformation/degradation (T/D) processes of tetrabromobisphenol A (TBBPA) have been widely investigated in model experiments, few reviews have focused on these processes along with their metabolites or degradation products. In this paper, we summarize the current knowledge on the T/D of TBBPA and its derivatives, including abiotic and biotic T/D strategies/conditions, mechanisms, metabolites and environmental occurrences. Various treatments, such as pyrolysis, photolysis, chemical reactions and biotransformation, have been employed to study the metabolic mechanism of TBBPA and its derivatives and to remediate associated contaminated environments. To date, more than 100 degradation products and metabolites have been identified, dominated by less brominated compounds such as bisphenol A, 2,6-dibromo-4-isopropylphenol, 2,6-dibromo-4-hydroxyl-phenol, 2,6-dibromophenol, isopropylene-2,6-dibromophenol, 4-(2-hydroxyisopropyl)-2,6-dibromophenol, etc. It can be concluded that the T/D of TBBPA mainly takes place through debromination and β-scission. In some environmental media and human and animal tissues, brominated metabolites, glucoside and sulfate derivatives are also important T/D products. Here, the T/D products of TBBPA and its derivatives have been most comprehensively presented from the literature in recent 20 years. This review will enhance the understanding of the environmental behaviors of TBBPA-associated brominated flame retardants along with their ecological and health risks.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is spreading globally and has caused many deaths. This study investigated, for the first time, COVID-19 patients' nutrition status and its effects on their inflammatory and immune responses. METHODS: Forty-seven COVID-19 patients were recruited for this prospective study. According to the subjective global assessment at admission, patients were divided into the normal nutrition (NN), risk of malnutrition (RMN), or MN group. Serum cytokines and whole blood T-cell subpopulations were measured to assess the inflammatory and immune responses in COVID-19 patients. Analysis of covariance and χ2 tests were used. RESULTS: On admission, the incidences of MN and the RMN in COVID-19 patients were 17.0% and 38.3%, respectively. The MN group had a higher proportion with severe/critical COVID-19 and a longer hospitalization duration than the NN group. Serum interleukin (IL) 6 concentrations were elevated in 97.9% of the patients and were the highest in malnourished patients. The IL-4 and IL-10 levels were elevated in 46.8% and 48.9% of the patients, respectively. The proportion of CD8+ T cells was significantly lower in the MN group than in the NN group. CONCLUSION: A high proportion of COVID-19 patients are malnourished or at risk of malnuourishment, especially those with severe disease. MN is associated with hyperinflammation and immunosuppression in COVID-19 patients, and it may contribute to disease progression.

Introduction: The highly infectious coronavirus disease 2019 (COVID-19) has now rapidly spread around the world. This meta-analysis was strictly focused on the influence of smoking history on the severe and critical outcomes on people with COVID-19 pneumonia. Methods: A systematic literature search was conducted in eight online databases before 1 February 2021. All studies meeting our selection criteria were included and evaluated. Stata 14.0 software was used to analyze the data. Results: A total of 109 articles involving 517,020 patients were included in this meta-analysis. A statistically significant association was discovered between smoking history and COVID-19 severity, the pooled OR was 1.55 (95%CI: 1.41-1.71). Smoking was significantly associated with the risk of admission to intensive care unit (ICU) (OR=1.73, 95%CI: 1.36-2.19), increased mortality (OR=1.58, 95%CI: 1.38-1.81), and critical diseases composite endpoints (OR=1.61, 95%CI: 1.35-1.93), whereas there was no relationship with mechanical ventilation. The pooled prevalence of smoking using the random effects model (REM) was 15% (95%CI: 14%-16%). Meta-regression analysis showed that age (P=0.004), hypertension (P=0.007), diabetes (P=0.029), chronic obstructive pulmonary disease (COPD) (P=0.001) were covariates that affect the association. Conclusions: Smoking was associated with severe or critical outcomes and increased the risk of admission to ICU and mortality in COVID-19 patients, but not associated with mechanical ventilation. This association was more significant for former smokers than in current smokers. Current smokers also had a higher risk of developing severe COVID-19 compared with non-smokers. More detailed data, which are representative for more counties, are needed to confirm these preliminary findings.

Coronavirus is named for its crown shape. Encoded by the genetic material inherited from the coronavirus itself, this intrinsic well-known “viral corona” can be considered the “inherited corona”. After contact with mucosa or the entrance into the host, bare coronaviruses could become covered by a group of dissolved biomolecules to form one or multiple layers of biomolecules. Different from this inherited corona, the layers acquired from the surrounding environment could be named as “acquired corona”. We highlight here the possible role of the acquired corona absorbing onto the surface of coronaviruses, which will generate fresh insight into the nature of various coronavirus-host interactions., Graphical abstract

Background: During the current Coronavirus Disease 2019 (COVID-19) pandemic, diabetic patients face disproportionately more. Anti-inflammatory effects of hypoglycemic agents have been reported, and their effects in patients with diabetes and COVID-19 remain controversial. This study was performed to clarify this association. Methods: Relevant literature was searched on China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, Chinese periodical service platform VIP Database, Sinomed (China Biology Medicine, CBM), MedRxiv, PubMed, ScienceDirect, Web of Science, Ovid Databases (LWW), Springer Link, Wiley Online Library, Oxford Academic, Nature Press Group, Cochrane Library, and BMJ Evidence-Based Medicine up to November 14, 2020. Only observational studies of hypoglycemic agents vs. other drugs or therapy in adult diabetic patients with COVID-19 were included. Data of death and poor composite outcomes were extracted. The pooled effects of hypoglycemic agents on mortality and poor composite outcomes of COVID-19 in diabetic patients, pooled ORs along with 95% CIs, were calculated using the fixed-effects or random-effects models based on heterogeneity assessment. Registration number of PROSPERO is CRD42020221951. Findings: 16 studies were included in the qualitative analysis and 14 studies with 13,371 patients were included in quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality in diabetic patients with COVID-19 (pooled OR=0·56, 95% CI, 0·39-0·81, p=0·002), especially home use of metformin (pooled OR=0·60, 95%CI, 0·40-0·88, p=0·01). but in-hospital use of metformin was associated with statistically non-significant lower mortality (pooled OR=0·44, 95%CI, 0·15-1·33, p=0·14) or poor composite outcomes (pooled OR=0·93, 95% CI, 0·79-1·11, p=0·44). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR=0·63, 95% CI, 0·26-1·56, p=0·32) or poor composite outcomes of COVID-19 in diabetic patients (pooled OR=0·96, 95% CI, 0·74-1·26, p=0·78). Interpretation: Home use of metformin might be beneficial in decreasing mortality in diabetic patients infected with SARS-CoV-2. There is insufficient evidence to conclude that metformin and other hypoglycemic agents are associated with poor composite outcomes. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed. Funding Statement: This study is financially supported by Hunan Provincial Key Laboratory of Clinical Epidemiology (grant number: 2020ZNDXLCL002). Declaration of Interests: We declare no competing interests.

Aims and Objectives To determine the health‐related quality of life (HRQoL) of COVID‐19 patients after discharge and its predicting factors. Background COVID‐19 has caused a worldwide pandemic and led a huge impact on the health of human and daily life. It has been demonstrated that physical and psychological conditions of hospitalised COVID‐19 patients are impaired, but the studies focus on physical and psychological conditions of COVID‐19 patients after discharge from hospital are rare. Design A multicentre follow‐up study. Methods This was a multicentre follow‐up study of COVID‐19 patients who had discharged from six designated hospitals. Physical symptoms and HRQoL were surveyed at first follow‐up (the third month after discharge). The latest multiple laboratory findings were collected through medical examination records. This study was performed and reported in accordance with STROBE checklist. Results Three hundred eleven patients (57.6%) were reported with one or more physical symptoms. The scores of HRQoL of COVID‐19 patients at third month after discharge, except for the dimension of general health, were significantly lower than Chinese population norm (p

ObjectiveSleep disturbances have been serious since they are believed to be associated with various health problems in preschool children. In this study, we aimed to explore the prevalence of sleep disturbances amongst preschool children in rural areas of China and examine the underlying associated factors.MethodsA cross-sectional study was conducted in rural areas of Anhui province, China from September 2019 to January 2020. To explore the potential associated factors comprehensively, caregivers of children completed a structured questionnaire, the Children’s Sleep Habits Questionnaire (CSHQ), the Strengths and Difficulties Questionnaire (SDQ), Self-rating Anxiety Scale (SAS) and the Chinese version of the adapted Identification and Management of Feeding Difficulties (IMFeD). One-way ANOVA and hierarchical multiple regression are conducted to explore the potential influencing factors of sleep disturbances in preschool children.ResultsAbout 89.3% of the preschool children aged from 3 to 6 years had potential sleep disturbances (scored above the cutoff value). Besides, ages of children, discipline attitudes of father and mother, main educational methods, caregivers of children, caregiver anxiety and hyperactivity/inattention, prosocial behavior, conduct problems, emotional symptoms, peer problems, food preference, fear of feeding, parental misperception and organic disease all contributed significantly to CSHQ total score by accounting for approximately 27.4% (R2=0.274) of the variation.ConclusionsOur study indicated that the prevalence of sleep disturbances among preschool children in rural area of China is quite high. Furthermore, the potential risk factors are complicated which include factors related to both children and caregivers especially their parents.

Background: Tetrabromobisphenol A (TBBPA) mono-ether structural analogs, identified as the by-products or transformation products of commercial TBBPA bis-ether derivatives, have been identified as emerging widespread pollutants. However, there is very little information regarding their toxicological effects. Objective: We aimed to explore the potential thyroid hormone (TH) system–disrupting effect of TBBPA mono-ether structural analogs. Methods: The binding potencies of chemicals toward human TH transport proteins [transthyretin (TTR) and thyroxine-binding globulin (TBG)] and receptors [TRα ligand-binding domain (LBD) and TRβ-LBD] were determined by fluorescence competitive binding assays. Molecular docking was used to simulate the binding modes of the chemicals with the proteins. The cellular TR-disrupting potencies of chemicals were assessed by a GH3 cell proliferation assay. The intracellular concentrations of the chemicals were measured by high-performance liquid chromatography and mass spectrometry. Results: TBBPA mono-ether structural analogs bound to TTR with half maximal inhibitory concentrations ranging from 0.1μM to 1.0μM but did not bind to TBG. They also bound to both subtypes of TR-LBDs with 20% maximal inhibitory concentrations ranging from 4.0μM to 50.0μM. The docking results showed that the analogs fit into the ligand-binding pockets of TTR and TR-LBDs with binding modes similar to that of TBBPA. These compounds likely induced GH3 cell proliferation via TR [with the lowest effective concentrations (LOECs) ranging from 0.3μM to 2.5μM] and further enhanced TH-induced GH3 cell proliferation (with LOECs ranging from 0.3μM to 1.2μM). Compared with TBBPA, TBBPA-mono(2,3-dibromopropyl ether) showed a 4.18-fold higher GH3 cell proliferation effect and 105-fold higher cell membrane transportation ability. Conclusion: This study provided a possible mechanism underlying the difference in TTR or TR binding by novel TBBPA structural analogs. These compounds might exert TH system–disrupting effects by disrupting TH transport in circulation and TR activity in TH-responsive cells. https://doi.org/10.1289/EHP6498

The application and consumption of nanoparticles (NPs) inevitably result in the contamination of environmental water. The internalized NPs in unicellular organisms could travel to human bodies along food chains and raise health concerns. Current research failed to determine the characteristics of cellular uptake of NPs by unicellular organisms at extremely low concentration in the real environment. We here developed a label-free high-throughput mass cytometry method to investigate gold NP (AuNP) uptake in a unicellular organism (Tetrahymena thermophila) at the single-cell level. The limit of detection for Au is as low as to 6.67 × 10-18 g/cell, which equals ∼5.3 5 nm AuNPs. We demonstrated that active engulfment pathways were responsible for the cellular accumulation of AuNPs and T. thermophila could also eliminate the cellular AuNPs rapidly. The interaction between AuNPs and T. thermophila is highly dependent on the sizes of nanoparticles; i.e., the population of T. thermophila containing AuNPs decreased with the increment of the diameters of AuNPs when exposed to the same mass concentration. For each type of AuNP, distinct heterogeneous cellular uptake of AuNPs by T. thermophila was observed. Intriguingly, for 5 nm AuNP, even at 0.001 ng/mL, some T. thermophila cells could concentrate AuNPs, indicating a real environmental concern even when water was contaminated by only trace level of NPs. This method represents a promising tool for simultaneous determination of physiological status of cells together with the intracellular level of heavy metal or metallic NPs in study of biological effects.

BackgroundThe effect of using Angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin-receptor blockers (ARBs) on the risk of coronavirus disease 2019 (COVID-19) is a topic of recent debate. Although studies have examined the potential association between them, the results remain controversial. This study aims to determine the true effect of ACEI/ARBs use on the risk of infection and clinical outcome of COVID-19.MethodsFive electronic databases (PubMed, Web of science, Cochrane library, China National Knowledge Infrastructure database, medRxiv preprint server) were retrieved to find eligible studies. Meta-analysis was performed to examine the association between ACEI/ARBs use and the risk of infection and clinical outcome of COVID-19.Results22 articles containing 157,328 patients were included. Use of ACEI/ARBs was not associated with increased risk of infection (Adjusted OR: 0.96, 95% CI: 0.91-1.01, I2=5.8%) or increased severity (Adjusted OR: 0.90, 95% CI: 0.77-1.05, I2=27.6%) of COVID-19. The use of ACEI/ARBs was associated with lower risk of death from COVID-19 (Adjusted OR: 0.66, 95% CI: 0.44-0.99, I2=57.9%). Similar results of reduced risk of death were also found for ACEI/ARB use in COVID-19 patients with hypertension (Adjusted OR: 0.36, 95% CI: 0.17-0.77, I2=0).ConclusionThis study provides evidence that ACEI/ARBs use for COVID-19 patients does not lead to harmful outcomes and may even provide a beneficial role and decrease mortality from COVID-19. Clinicians should not discontinue ACEI/ARBs for patients diagnosed with COVID-19 if they are already on these agents.

BACKGROUND: To investigate the effect of cardiovascular disease (CVD) on the global pandemic, coronavirus disease 2019 (COVID-19), we analyzed the cases of laboratory-confirmed COVID-19 patients in Wuhan.Methods and Results:Data were extracted from the medical records. SARS-CoV-2 RNA was confirmed by RT-PCR. A total of 33 (53.2%) of 62 cases with CVD, who had higher prevalence of severe COVID-19 compared with non-CVD patients (P=0.027). The median age of all patients was 66.0 (53.3, 73.0) years old. Coronary artery disease (11.3%) and hypertension (38.7%) were the common coexisting CVDs in COVID-19 patients. High-sensitivity cardiac troponin I (hs-cTnI), creatinine, high-density lipoprotein-cholesterol, interleukin-6, C-reactive protein, prothrombin time, and D-dimer levels in the severe COVID-19 with CVD group were higher than in the non-severe COVID-19 with CVD group (P

Highlights • The COVID-19 patients had negative SARS-COV-2 RNA in EPS. • Serum SARS-CoV-2 IgM was positive in patients with positive pharyngeal RNA. • The inflammatory indictors were all elevated in COVID-19 patients., Due to the cellular entry of the novel coronavirus (SARS-CoV-2) modulated by angiotensin converting enzyme 2 (ACE2), the ACE2 bearing prostate is therefore hypothesized as a susceptible organ to COVID-19. To delineate whether the pathogenic SARS-CoV-2 of the coronavirus disease (COVID-19) could be detected in the expressed prostatic secretion (EPS), a total of ten male patients with confirmed COVID-19 were recruited. All patients were stratified into two groups: one group with positive nasopharyngeal swabbing SARS-CoV-2 within 3 days of the EPS taken day (PNS group, n = 3) and the other group with previously positive nasopharyngeal swabbing SARS-CoV-2 but turned negative before the taken day (PNNS group, n = 7). The COVID-19 patients showed elevated inflammatory indictors, i.e. C-reaction protein (3.28 (1.14, 33.33) mg/L), erythrocyte sedimentation rate (22.50 (8.00, 78.50) mm/h), and interleukin-6 (6.49 (4.96, 21.09) pg/ml). Serum IgM against SARS-CoV-2 was only positive in the PNS group, whereas serum IgG was positive for all patients. Furthermore, our data showed for the first time that none of the COVID-19 patients had positive SARS-CoV-2 RNA in EPS. To this end, this study found the negativity of SARS-CoV-2 in EPS and possibly exclude the sexual transmission of COVID-19.