Occurrence and Prioritization of Human Androgen Receptor Disruptors in Sewage Sludges Across China.

The global practice of reusing sewage sludge in agriculture and its landfill disposal reintroduces environmental contaminants, posing risks to human and ecological health. This study screened sewage sludge from 30 Chinese cities for androgen receptor (AR) disruptors, utilizing a disruptor list from the Toxicology in the 21st Century program (Tox21), and identified 25 agonists and 33 antagonists across diverse use categories. Predominantly, natural products 5α-dihydrotestosterone and thymidine emerged as agonists, whereas the industrial intermediate caprolactam was the principal antagonist. In-house bioassays for identified disruptors displayed good alignment with Tox21 potency data, validating employing Tox21 toxicity data for theoretical toxicity estimations. Potency calculations revealed 5α-dihydrotestosterone and two pharmaceuticals (17ß-trenbolone and testosterone isocaproate) as the most potent AR agonists and three dyes (rhodamine 6G, Victoria blue BO, and gentian violet) as antagonists. Theoretical effect contribution evaluations prioritized 5α-dihydrotestosterone and testosterone isocaproate as high-risk AR agonists and caprolactam, rhodamine 6G, and 8-hydroxyquinoline (as a biocide and a preservative) as key antagonists. Notably, 16 agonists and 20 antagonists were newly reported in the sludge, many exhibiting significant detection frequencies, concentrations, and/or toxicities, demanding future scrutiny. Our study presents an efficient strategy for estimating environmental sample toxicity and identifying key toxicants, thereby supporting the development of appropriate sludge management strategies.

High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review.

Organic contaminants are ubiquitous in the environment, with mounting evidence unequivocally connecting them to aquatic toxicity, illness, and increased mortality, underscoring their substantial impacts on ecological security and environmental health. The intricate composition of sample mixtures and uncertain physicochemical features of potential toxic substances pose challenges to identify key toxicants in environmental samples. Effect-directed analysis (EDA), establishing a connection between key toxicants found in environmental samples and associated hazards, enables the identification of toxicants that can streamline research efforts and inform management action. Nevertheless, the advancement of EDA is constrained by the following factors: inadequate extraction and fractionation of environmental samples, limited bioassay endpoints and unknown linkage to higher order impacts, limited coverage of chemical analysis (i.e., high-resolution mass spectrometry, HRMS), and lacking effective linkage between bioassays and chemical analysis. This review proposes five key advancements to enhance the efficiency of EDA in addressing these challenges: (1) multiple adsorbents for comprehensive coverage of chemical extraction, (2) high-resolution microfractionation and multidimensional fractionation for refined fractionation, (3) robust in vivo/vitro bioassays and omics, (4) high-performance configurations for HRMS analysis, and (5) chemical-, data-, and knowledge-driven approaches for streamlined toxicant identification and validation. We envision that future EDA will integrate big data and artificial intelligence based on the development of quantitative omics, cutting-edge multidimensional microfractionation, and ultraperformance MS to identify environmental hazard factors, serving for broader environmental governance.

Inflammatory burden of adolescents with childhood maltreatment: results from baseline data of a school cohort.

Increasing studies have investigated inflammatory burden of adults with childhood adversity, but less is known about how childhood maltreatment affects the inflammation level of adolescents. Baseline data of a school cohort of physical and mental health status and life experience survey on primary and secondary school students in Anhui Province, China was used. Childhood maltreatment of children and adolescents was assessed by Chinese version of Childhood Trauma Questionnaire-Short Form (CTQ-SF). Urine samples were collected to assess levels of soluble urokinase Plasminogen Activator Receptor (suPAR), C-reactive protein (CRP) and cytokines interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA). Logistic regression was conducted to examine the association between childhood maltreatment exposure and risk of high inflammation burden. A total of 844 students were included with mean age 11.41 ± 1.57 years old. Adolescents with emotional abuse were significantly more likely to have high level of IL-6 (OR = 3.59, 95% CI 1.16-11.14). In addition, adolescents with emotional abuse were more likely to show high IL-6 and high suPAR combination (OR = 33.41, 95% CI 1.69-659.22), and high IL-6 and low CRP combination (OR = 4.34, 95% CI 1.29-14.55). Subgroup analyses showed that emotional abuse was associated with high IL-6 burden among boys or adolescents with depression. Childhood emotional abuse was positively associated with higher burden of IL-6. Early detection and prevention of emotional abuse for children and adolescents, especially for boys or adolescents with depression status, may be helpful for preventing elevated inflammatory burden and related health problems.

Association between adverse childhood experiences and sleep quality, emotional and behavioral problems and academic achievement of children and adolescents.

The impact of adverse childhood experiences (ACEs) on adult health has been extensively examined, but the association between ACEs and sleep, emotion, behavior and academic outcomes of children and adolescents is not well known. A total of 6363 primary and middle school students were included to examine the effect of ACEs on sleep quality, emotional and behavioral problems and academic achievement and further explore the mediation role of sleep quality and emotional and behavioral problems. Children and adolescents with ACE exposure had 1.37 times risk of poor sleep quality (adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI]: 1.21-1.55), 1.91 times risk of emotional and behavioral problems (adjusted OR = 1.91, 95%CI: 1.69-2.15) and 1.21 times risk of self-reported lower academic achievement (adjusted OR = 1.21, 95%CI: 1.08-1.36). Most types of ACEs were significantly associated with poor sleep quality, emotional and behavioral problems and lower academic achievement. There were dose-response relationships between cumulative ACE exposure and risk of poor sleep quality, emotional and behavioral problems, and lower academic achievement. Sleep quality and emotional and behavioral performance mediated 45.9% of the effect of ACEs exposure on math scores and 15.2% of the effect of ACEs exposure on English scores. Early detection and prevention of ACEs among children and adolescents are urgent and essential, and targeted interventions for sleep and emotional and behavioral performance as well as early educational interventions are recommended for children with ACEs exposure.

Longitudinal association of nighttime sleep duration with emotional and behavioral problems among rural preschool children.

This study aimed to examine the association between nighttime sleep duration and emotional and behavioral problems (EBPs) among rural preschool children. This longitudinal study including 1595 preschool children aged 3-6 years from 26 kindergartens in four counties was conducted in Anhui Province rural areas. Cross-lagged panel models and multivariable logistic regressions were performed to examine the bidirectional association between nighttime sleep duration and EBPs and further explore the predictive effect of nighttime sleep duration on EBPs. Compared to baseline, preschool children at follow-up had significantly more nighttime sleep duration (10.01 ± 0.68 vs. 10.15 ± 0.69) and lower EBPs (total difficulties: 15.8% vs. 11.2%; prosocial behavior problems: 12.4% vs. 7.0%). Results of cross-lagged panel models indicated that nighttime sleep duration was a predictor for EBPs, but not vice versa. Results of logistic regression analysis showed that each 1-h increase in nighttime sleep duration at T1 was associated with a 0.77-fold reduction in the risk of total difficulties at T2 (the most adjusted OR = 0.774, 95% CI 0.607-0.988, P = 0.040), but not with the prosocial behavior. Interestingly, the predictive effect of nighttime sleep duration at T1 on EBPs at T2 was only found in girls, children aged 3 years and children with lower maternal education. The decreased nighttime sleep duration may predict future EBPs, especially in girls, younger preschool children and children with lower maternal education. Extending sleep duration may improve EBPs in preschool children.

Renaissance of elemental phosphorus materials: properties, synthesis, and applications in sustainable energy and environment.

The polymorphism of phosphorus-based materials has garnered much research interest, and the variable chemical bonding structures give rise to a variety of micro and nanostructures. Among the different types of materials containing phosphorus, elemental phosphorus materials (EPMs) constitute the foundation for the synthesis of related compounds. EPMs are experiencing a renaissance in the post-graphene era, thanks to recent advancements in the scaling-down of black phosphorus, amorphous red phosphorus, violet phosphorus, and fibrous phosphorus and consequently, diverse classes of low-dimensional sheets, ribbons, and dots of EPMs with intriguing properties have been produced. The nanostructured EPMs featuring tunable bandgaps, moderate carrier mobility, and excellent optical absorption have shown great potential in energy conversion, energy storage, and environmental remediation. It is thus important to have a good understanding of the differences and interrelationships among diverse EPMs, their intrinsic physical and chemical properties, the synthesis of specific structures, and the selection of suitable nanostructures of EPMs for particular applications. In this comprehensive review, we aim to provide an in-depth analysis and discussion of the fundamental physicochemical properties, synthesis, and applications of EPMs in the areas of energy conversion, energy storage, and environmental remediation. Our evaluations are based on recent literature on well-established phosphorus allotropes and theoretical predictions of new EPMs. The objective of this review is to enhance our comprehension of the characteristics of EPMs, keep abreast of recent advances, and provide guidance for future research of EPMs in the fields of chemistry and materials science.

Associations of toxic metals and their mixture with hyperuricemia in Chinese rural older adults.

Previous studies have related single toxic metals (TMs) to hyperuricemia (HUA) among the general population, however, the association of the TM mixture with HUA, especially in older adults, remains poorly understood. We aimed to examine the relationships between individual TMs and their mixture and HUA in Chinese rural older adults. This study consisted of 2075 rural older adults aged 60 years or over. Blood concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), gallium (Ga), mercury (Hg), lead (Pb), thallium (Tl), and uranium (U) were detected using inductively coupled plasma mass spectrometry. The associations of single TMs with HUA were assessed using logistic regression and restricted cubic spline (RCS) models, and the association of TM mixture with HUA was explored using the elastic net with environmental risk score (ENET-ERS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted logistic regression model showed that Cs (OR = 1.65, 95% CI 1.37-1.99) and Pb (OR = 1.46, 95% CI 1.28-1.67) were positively related to HUA, and RCS model exhibited a positive linear association of Cs and Pb with HUA. ENET-ERS and QGC models quantified a positive correlation between the TM mixture and the odds of HUA, with estimated ORs of 1.15 (95% CI 1.11-1.19) and 1.84 (95% CI 1.37-2.47), respectively, and Cs and Pb had the most weight. BKMR model demonstrated a significant linear association between the TM mixture and increased odds of HUA, with the posterior inclusion probabilities (PIPs) of both Cs and Pb being 1.00. Moreover, we observed a positive interaction between Cs and Pb on HUA. The TM mixture is associated with increased odds of HUA in rural older adults, which may mainly be driven by Cs and Pb. Subsequent studies are warranted to confirm these findings and clarify the mechanisms linking multiple TMs with HUA.

Effect of physical activity on incidence and mortality in patients with gastric cancer: evidence from real-world studies.

PURPOSE: Physical activity (PA) has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between PA and the risk of developing gastric cancer (GC). The purpose of this study was to evaluate the impact of PA on the incidence and mortality risk of GC through a meta-analysis, as well as investigate potential dose-response relationships. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of PA on the risk of GC. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The results showed that PA correlated with lower incidence of GC (RR: 0.83, 95% CI: 0.77-0.90), decreased risk of GC mortality (RR: 0.76, 95% CI: 0.66-0.89). The results of the subgroup analysis showed that PA was associated with reduced incidence of GC across gender, different regions, study designs, different sites of GC and different types of PA. A linear relationship was found for frequency of PA. CONCLUSIONS: This meta-analysis found that PA was associated with a reduced risk of GC incidence and mortality. The correlation between PA and GC occurrence was in a dose-response relationship.

Is early time to positivity of blood culture associated with clinical prognosis in patients with Klebsiella pneumoniae bloodstream infection?

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 (<9.4 h) was a risk factor for in-hospital mortality by univariate analysis (OR = 2.5, 95% CI 1.2-5.0, 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.

Exogenous Chemicals Impact Virus Receptor Gene Transcription: Insights from Deep Learning.

Despite the fact that coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been disrupting human life and health worldwide since the outbreak in late 2019, the impact of exogenous substance exposure on the viral infection remains unclear. It is well-known that, during viral infection, organism receptors play a significant role in mediating the entry of viruses to enter host cells. A major receptor of SARS-CoV-2 is the angiotensin-converting enzyme 2 (ACE2). This study proposes a deep learning model based on the graph convolutional network (GCN) that enables, for the first time, the prediction of exogenous substances that affect the transcriptional expression of the ACE2 gene. It outperforms other machine learning models, achieving an area under receiver operating characteristic curve (AUROC) of 0.712 and 0.703 on the validation and internal test set, respectively. In addition, quantitative polymerase chain reaction (qPCR) experiments provided additional supporting evidence for indoor air pollutants identified by the GCN model. More broadly, the proposed methodology can be applied to predict the effect of environmental chemicals on the gene transcription of other virus receptors as well. In contrast to typical deep learning models that are of black box nature, we further highlight the interpretability of the proposed GCN model and how it facilitates deeper understanding of gene change at the structural level.

Application of Ion Mobility Spectrometry and the Derived Collision Cross Section in the Analysis of Environmental Organic Micropollutants.

Ion mobility spectrometry (IMS) is a rapid gas-phase separation technique, which can distinguish ions on the basis of their size, shape, and charge. The IMS-derived collision cross section (CCS) can serve as additional identification evidence for the screening of environmental organic micropollutants (OMPs). In this work, we summarize the published experimental CCS values of environmental OMPs, introduce the current CCS prediction tools, summarize the use of IMS and CCS in the analysis of environmental OMPs, and finally discussed the benefits of IMS and CCS in environmental analysis. An up-to-date CCS compendium for environmental contaminants was produced by combining CCS databases and data sets of particular types of environmental OMPs, including pesticides, drugs, mycotoxins, steroids, plastic additives, per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), as well as their well-known transformation products. A total of 9407 experimental CCS values from 4170 OMPs were retrieved from 23 publications, which contain both drift tube CCS in nitrogen (DTCCSN2) and traveling wave CCS in nitrogen (TWCCSN2). A selection of publicly accessible and in-house CCS prediction tools were also investigated; the chemical space covered by the training set and the quality of CCS measurements seem to be vital factors affecting the CCS prediction accuracy. Then, the applications of IMS and the derived CCS in the screening of various OMPs were summarized, and the benefits of IMS and CCS, including increased peak capacity, the elimination of interfering ions, the separation of isomers, and the reduction of false positives and false negatives, were discussed in detail. With the improvement of the resolving power of IMS and enhancements of experimental CCS databases, the practicability of IMS in the analysis of environmental OMPs will continue to improve.

PM2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice.

Although PM2.5 (fine particles with aerodynamic diameter <2.5 µm) exposure shows the potential to impact normal hematopoiesis, the detailed alterations in systemic hematopoiesis and the underlying mechanisms remain unclear. For hematopoiesis under steady-state or stress conditions, nuclear factor erythroid 2-related factor 2 (NRF2) is essential for regulating hematopoietic processes to maintain blood homeostasis. Herein, we characterized changes in the populations of hematopoietic stem progenitor cells and committed hematopoietic progenitors in the lungs and bone marrow (BM) of wild-type and Nrf2-/- C57BL/6J male mice. PM2.5-induced NRF2-dependent biased hematopoiesis toward myeloid lineage in the lungs and BM generates excessive numbers of various inflammatory immune cells, including neutrophils, monocytes, and platelets. The increased population of these immune cells in the lungs, BM, and peripheral blood has been associated with observed pulmonary fibrosis and high disease risks in an NRF2-dependent manner. Therefore, although NRF2 is a protective factor against stressors, upon PM2.5 exposure, NRF2 is involved in stress myelopoiesis and enhanced PM2.5 toxicity in pulmonary injury, even leading to systemic inflammation.

Disposable Polypropylene Face Masks: A Potential Source of Micro/Nanoparticles and Organic Contaminates in Humans.

We have been effectively protected by disposable propylene face masks during the COVID-19 pandemic; however, they may pose health risks due to the release of fine particles and chemicals. We measured micro/nanoparticles and organic chemicals in disposable medical masks, surgical masks, and (K)N95 respirators. In the breathing-simulation experiment, no notable differences were found in the total number of particles among mask types or between breathing intensities. However, when considering subranges, <2.5 µm particles accounted for ∼90% of the total number of micro/nanoparticles. GC-HRMS-based suspect screening tentatively revealed 79 (semi)volatile organic compounds in masks, with 18 being detected in ≥80% of samples and 44 in ≤20% of samples. Three synthetic phenolic antioxidants were quantified, and AO168 reached a median concentration of 2968 ng/g. By screening particles collected from bulk mask fabrics, we detected 18 chemicals, including four commonly detected in masks, suggesting chemical partition between the particles and the fabric fibers and chemical exposure via particle inhalation. These particles and chemicals are believed to originate from raw materials, intentionally and nonintentionally added substances in mask production, and their transformation products. This study highlights the need to study the long-term health risks associated with mask wearing and raises concerns over mask quality control.

Exogenous Metals Atlas in Spermatozoa at Single-Cell Resolution in Relation to Human Semen Quality.

While exogenous metal/metalloid (metal) exposure has been associated with reduced human semen quality, no study has assessed the associations of exogenous metals in human spermatozoa with semen quality. Here, we developed a strategy to explore the associations between exogenous metals in spermatozoa at single-cell resolution and human semen quality among 84 men screened as sperm donors, who provided 266 semen samples within 90 days. A cellular atlas of exogenous metals at the single-cell level was created with mass cytometry (CyTOF) technology, which concurrently displayed 18 metals in more than 50 000 single sperm. Exogenous metals in spermatozoa at single-cell resolution were extremely heterogeneous and diverse. Further analysis using multivariable linear regression and linear mixed-effects models revealed that the heterogeneity and prevalence of the exogenous metals at single-cell resolution were associated with semen quality. The heterogeneity of lead (Pb), tin (Sn), yttrium (Y), and zirconium (Zr) was negatively associated with sperm concentration and count, while their prevalence showed positive associations. These findings revealed that the heterogeneous properties of exogenous metals in spermatozoa were associated with human semen quality, highlighting the importance of assessing exogenous metals in spermatozoa at single-cell resolution to evaluate male reproductive health risk precisely.

Effect of aspirin on incidence, recurrence, and mortality in prostate cancer patients: integrating evidence from randomized controlled trials and real-world studies.

PURPOSE: Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of prostate cancer (PCa). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with PCa in a meta-analysis and to explore the possible dose-response relationship. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of PCa. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The across studies results show that aspirin use associated with lower incidence of PCa (RR: 0.96, 95% CI: 0.95-0.98), and reduced mortality (RR: 0.88, 95% CI: 0.82-0.95). The results of the subgroup analysis indicated that both cohort and population studies in the Americas showed a reduction in PCa incidence and mortality with aspirin use. A linear correlation was observed between dosage/duration of aspirin use and its protective effect. Additionally, post-diagnosis aspirin use was associated with decreased risk of PCa mortality. CONCLUSIONS: This meta-analysis revealed an independent correlation between the use of aspirin and reductions in both the incidence and mortality rates of PCa. However, randomized controlled trials did not find any association between aspirin use and PCa. Furthermore, the impact of aspirin on PCa occurrence was found to be dependent on both dosage and duration.

Does aspirin reduce the incidence, recurrence, and mortality of hepatocellular carcinoma? A GRADE-assessed systematic review and dose-response meta-analysis.

PURPOSE: Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of hepatocellular carcinoma (HCC). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with HCC in a meta-analysis and to explore the possible dose-response relationship. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined hazard ratios (HRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of HCC. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The results show that aspirin use correlated with lower incidence of HCC (HR: 0.75, 95% CI: 0.71-0.80), decreased risk of HCC recurrence (HR: 0.79, 95% CI: 0.65-0.96), and reduced mortality (HR: 0.72, 95% CI: 0.60-0.87). The results of the subgroup analysis showed that aspirin use was consistently associated with reduced incidence of HCC across different regions, study designs, and populations. A linear relationship was found for both dosage and duration of aspirin use. An increased of bleeding with aspirin use among patients was also observed (HR 1.10, 95% CI: 1.02-1.20). CONCLUSIONS: This meta-analysis found that aspirin use was independently associated with a reduced risk of HCC incidence, recurrence, and death. Furthermore, aspirin use influenced HCC occurrence in a dose-dependent and duration-dependent manner. However, an increased risk of bleeding with aspirin use was noted.

The association between family function and sleep disturbances of preschool children in rural areas of China: a cross-sectional study.

This study aimed to explore the association between family function and sleep disturbances in preschool children in rural areas of China. Caregivers of preschool children completed sociodemographic questionnaires, the Children's Sleep Habits Questionnaire (CSHQ), the Self-rating Anxiety Scale (SAS) and the Family APGAR scale. Using sleep disturbances in children as the dependent variable, family function and other related factors as independent variables, binary logistic regression analyses were performed to examine associations between family function and sleep disturbances in children. A total of 3,636 caregivers of preschool children were enrolled in our study, and the prevalence of sleep disturbances among their preschool children was 89.4%. In our study, lower family function was associated with higher risk of sleep disturbances among preschool children. After adjusting for age (years), education level of mother, discipline attitudes of father and mother, only child status and caregivers' anxiety, the associations were statistically significant both in families of which caregivers of children are their parents or other relatives. (AOR for parents = 1.487, 95% CI:1.152-1.919, P = 0.002; AOR for other relatives = 1.963, 95% CI:1.302-2.958, P = 0.001). Our study results indicated that family function was associated with sleep disturbances in preschool children, and future high-quality cohort studies are needed to explore this topic in more detail.

Matrix Thermal Shift Assay for Fast Construction of Multidimensional Ligand-Target Space.

Existing thermal shift-based mass spectrometry approaches are able to identify target proteins without chemical modification of the ligand, but they are suffering from complicated workflows with limited throughput. Herein, we present a new thermal shift-based method, termed matrix thermal shift assay (mTSA), for fast deconvolution of ligand-binding targets and binding affinities at the proteome level. In mTSA, a sample matrix, treated horizontally with five different compound concentrations and vertically with five technical replicates of each condition, was denatured at a single temperature to induce protein precipitation, and then, data-independent acquisition was employed for quick protein quantification. Compared with previous thermal shift assays, the analysis throughput of mTSA was significantly improved, but the costs as well as efforts were reduced. More importantly, the matrix experiment design allowed simultaneous computation of the statistical significance and fitting of the dose-response profiles, which can be combined to enable a more accurate identification of target proteins, as well as reporting binding affinities between the ligand and individual targets. Using a pan-specific kinase inhibitor, staurosporine, we demonstrated a 36% improvement in screening sensitivity over the traditional thermal proteome profiling (TPP) and a comparable sensitivity with a latest two-dimensional TPP. Finally, mTSA was successfully applied to delineate the target landscape of perfluorooctanesulfonic acid (PFOS), a persistent organic pollutant that is hard to perform modification on, and revealed several potential targets that might account for the toxicities of PFOS.

Property-Activity Relationship of Black Phosphorus at the Nano-Bio Interface: From Molecules to Organisms.

As a novel member of the two-dimensional nanomaterial family, mono- or few-layer black phosphorus (BP) with direct bandgap and high charge carrier mobility is promising in many applications such as microelectronic devices, photoelectronic devices, energy technologies, and catalysis agents. Due to its benign elemental composition (phosphorus), large surface area, electronic/photonic performances, and chemical/biological activities, BP has also demonstrated a great potential in biomedical applications including biosensing, photothermal/photodynamic therapies, controlled drug releases, and antibacterial uses. The nature of the BP-bio interface is comprised of dynamic contacts between nanomaterials (NMs) and biological systems, where BP and the biological system interact. The physicochemical interactions at the nano-bio interface play a critical role in the biological effects of NMs. In this review, we discuss the interface in the context of BP as a nanomaterial and its unique physicochemical properties that may affect its biological effects. Herein, we comprehensively reviewed the recent studies on the interactions between BP and biomolecules, cells, and animals and summarized various cellular responses, inflammatory/immunological effects, as well as other biological outcomes of BP depending on its own physical properties, exposure routes, and biodistribution. In addition, we also discussed the environmental behaviors and potential risks on environmental organisms of BP. Based on accumulating knowledge on the BP-bio interfaces, this review also summarizes various safer-by-design strategies to change the physicochemical properties including chemical stability and nano-bio interactions, which are critical in tuning the biological behaviors of BP. The better understanding of the biological activity of BP at BP-bio interfaces and corresponding methods to overcome the challenges would promote its future exploration in terms of bringing this new nanomaterial to practical applications.

Exogenous Chemical Exposure Increased Transcription Levels of the Host Virus Receptor Involving Coronavirus Infection.

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.