Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics.

New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, the sublineage-defining mutations vary between the VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for mutations at each spike position or the stochastic nature of their appearance. Here we show that SARS-CoV-2 lineages have distinct evolutionary spaces (a probabilistic definition of the sequence states that can be occupied by expanding virus subpopulations). This space can be accurately inferred from the patterns of amino acid variability at the whole-protein level. Robust networks of co-variable sites identify the highest-likelihood mutations in new VOC sublineages and predict remarkably well the emergence of subvariants with resistance mutations to COVID-19 therapeutics. Our studies reveal the contribution of low frequency variant patterns at heterologous sites across the protein to accurate prediction of the changes at each position of interest.

Immune Regulation Patterns in Response to Environmental Pollutant Chromate Exposure-Related Genetic Damage: A Cross-Sectional Study Applying Machine Learning Methods.

Exposure to hexavalent chromium damages genetic materials like DNA and chromosomes, further elevating cancer risk, yet research rarely focuses on related immunological mechanisms, which play an important role in the occurrence and development of cancer. We investigated the association between blood chromium (Cr) levels and genetic damage biomarkers as well as the immune regulatory mechanism involved, such as costimulatory molecules, in 120 workers exposed to chromates. Higher blood Cr levels were linearly correlated with higher genetic damage, reflected by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and blood micronucleus frequency (MNF). Exploratory factor analysis revealed that both positive and negative immune regulation patterns were positively associated with blood Cr. Specifically, higher levels of programmed cell death protein 1 (PD-1; mediated proportion: 4.12%), programmed cell death ligand 1 (PD-L1; 5.22%), lymphocyte activation gene 3 (LAG-3; 2.11%), and their constitutive positive immune regulation pattern (5.86%) indirectly positively influenced the relationship between blood Cr and urinary 8-OHdG. NOD-like receptor family pyrin domain containing 3 (NLRP3) positively affected the association between blood Cr levels and inflammatory immunity. This study, using machine learning, investigated immune regulation and its potential role in chromate-induced genetic damage, providing insights into complex relationships and emphasizing the need for further research.

Relationships between blood chromium exposure and liver injury: Exploring the mediating role of systemic inflammation in a chromate-exposed population.

Hexavalent chromium and its compounds are prevalent pollutants, especially in the work environment, pose a significant risk for multisystem toxicity and cancers. While it is known that chromium accumulation in the liver can cause damage, the dose-response relationship between blood chromium (Cr) and liver injury, as well as the possible potential toxic mechanisms involved, remains poorly understood. To address this, we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), and to evaluate the mediating effects of systemic inflammation. Platelet (PLT) and the platelet-to-lymphocyte ratio (PLR) were utilized as biomarkers of systemic inflammation. In the linear mixed-effects analyses, each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82% (0.11%, 1.53%) in TBIL, 1.67% (0.06%, 3.28%) in DBIL, 0.73% (0.04%, 1.43%) in ALT and 2.08% (0.29%, 3.87%) in AST, respectively. Furthermore, PLT mediated 10.04%, 11.35%, and 10.77% increases in TBIL, DBIL, and ALT levels induced by chromate, respectively. In addition, PLR mediated 8.26% and 15.58% of the association between blood Cr and TBIL or ALT. These findings shed light on the mechanisms underlying blood Cr-induced liver injury, which is partly due to worsening systemic inflammation.

Perspectives of Genetic Damage and Epigenetic Alterations by Hexavalent Chromium: Time Evolution Based on a Bibliometric Analysis.

Compounds containing hexavalent chromium [Cr(VI)] have been classified as Group I human carcinogens in 1990 by the International Agency for Research on Cancer, known to induce human lung cancers. To determine the nature of Cr(VI) carcinogenesis, much has been learned about genetic damage and epigenetic alterations. On the basis of bibliometric analysis of the available literature found between 1966 and 2020, the present study investigated the evolution of author keywords; provided a summary of relevant studies focused on populations, animals/plants, or cells; and depicted the co-operation among countries or institutions and research group development. Additionally, multiomics technology and bioinformatics analysis can be a valuable tool for figuring out new biomarkers from different molecular levels like gene, RNA, protein, and metabolite and ascertaining the mechanism pathways of Cr(VI) genotoxicity and carcinogenesis.

Different adiposity indices and their associations with hypertension among Chinese population from Jiangxi province.

BACKGROUND: To date, the best adiposity index that predicts or associates strongly with hypertension remains controversial. Therefore, we aimed to compare the performance of different adiposity indices [BMI (body mass index), WC (waist circumference), WHtR (waist-to-height ratio), ABSI (a body shape index), VAI (visceral adipose index), BFP (body fat percentage)] as associates and potential predictors of risk of hypertension among Chinese population. METHODS: A cross-sectional survey was conducted in Jiangxi province, China from 2013 to 2014. A total of 14,573 participants were included in the study. The physical measurements included body height, weight, WC, BFP and VAI. Multivariate logistic regression analysis was performed to assess the associations between different adiposity indices and the prevalence of hypertension. Receiver operating characteristic (ROC) analysis was also performed. RESULTS: All adiposity indices were independently and positively associated with the prevalence of hypertension in a dose response fashion. The area under the curves (AUCs) for WHtR, BFP and VAI were significantly larger than those for other adiposity indices in both males and females (all P < 0.01). For males, no statistically significant difference was found in AUCs among WHtR and BFP (0.653 vs. 0.647, P = 0.4774). The AUC of WHtR was significantly higher than VAI (0.653 vs. 0.636, P < 0.01). For females, the AUCs demonstrated that WHtR was significantly more powerful than BFP and VAI (both P < 0.05) for predicting hypertension [WHtR, 0.689 (0.677-0.702); BFP, 0.677 (0.664-0.690); VAI, 0.668 (0.655-0.680)]. Whereas no significant differences were found in AUCs for hypertension among BFP and VAI in both sexes (all P > 0.1). The AUCs for hypertension associated with each adiposity index declined with age in both males and females. For subjects aged < 65 years, WHtR still had the largest AUC. However, for participants aged ≥65 years, BMI had the largest AUC. CONCLUSION: The findings indicated that WHtR was the best for predicting hypertension, followed by BFP and VAI, especially in younger population.

Threshold Effects of Serum Uric Acid on Chronic Kidney Disease in US Women without Hypertension and Diabetes: A Cross-Sectional Study.

BACKGROUND: Serum uric acid (SUA) has been associated with increased risk of chronic kidney disease (CKD) in observational studies; however, data in women without hypertension and diabetes are sparse. PURPOSE: To examine the association between SUA and CKD among women without hypertension and diabetes. METHODS: In this cross-sectional study of 6,776 US women without hypertension and diabetes from the National Health and Nutrition Examination Survey (1999-2006), we investigated the relationship between SUA and CKD using multivariable logistic regression models. Moreover, a generalized additive model and smooth curve fitting (penalized spline method) and a 2 piecewise logistic regression models were conducted to address for nonlinearity. RESULTS: The prevalence of CKD was 8.3%. Multiple logistic analyses showed that per 1 mg/dL increase in SUA was associated with 39% increased prevalence of CKD. Analyses using restricted cubic spline confirmed that the association between SUA and CKD was nonlinear. Further, threshold and saturation effect analysis showed that the inflection point of SUA was 4.5 mg/dL. The ORs (95% CIs) were 0.84 (0.66-1.08) on the left side of inflection point and 1.87 (1.56-2.24) on the right side of inflection point, respectively. Subgroup analysis showed that the stronger association between SUA and CKD was observed in elder women with never/former smoking and higher fasting blood glucose levels (all p values for interaction <0.05). CONCLUSION: Our study suggested threshold effects of SUA on the prevalence of CKD among US women without hypertension and diabetes. SUA levels >4.5 mg/dL were positively and independently associated with CKD.

Association of low-level blood lead with serum uric acid in U.S. adolescents: a cross-sectional study.

BACKGROUND: Uncertainty remains regarding the association between blood lead levels (BLL) and serum uric acid (SUA) with relatively low BLL exposure because of limited data in the adolescent population. We examined the association between BLL and SUA in U.S. adolescents. METHODS: In this cross-sectional study, 8303 adolescents aged 12-19 years from NHANES 1999-2006 were analyzed. BLL was Ln-transformed for analysis for the skewed distribution. Elevated SUA was defined as ≥5.5 mg/dL. Multivariate linear and multiple logistic regression analyses were performed to evaluate the association of BLL with SUA and elevated SUA. Moreover, a generalized additive model (GAM) and a fitted smoothing curve (penalized spline method) were conducted. RESULTS: The overall mean BLL was 1.3 µg/dL. Multivariate linear regression analyses showed that LnBLL was independently and positively correlated with SUA level (ß = 0.13, 95%CI: 0.09-0.17). Multiple logistic analyses showed that LnBLL was associated with a 24% increased prevalence of elevated SUA (OR = 1.24; 95% CI, 1.11-1.38). Analyses using restricted cubic spline confirmed that the associations of LnBLL with SUA and elevated SUA were linear. Subgroup analyses showed that stronger associations between LnBLL and SUA were detected in adolescents with lower levels of education and estimated glomerular filtration rate (eGFR) (all P for interaction < 0.05). CONCLUSIONS: BLL was independently and positively correlated with SUA level and elevated SUA among U.S. adolescents, particularly with lower levels of education and eGFR. The data suggest that there is no "safe" threshold level of exposure to lead.

Combined effect of titanium dioxide nanoparticles and glucose on the cardiovascular system in young rats after oral administration.

Titanium dioxide nanoparticles (TiO2 NPs) have already been used as food additive in various products and are usually consumed with a considerable amount of sugar. Oral consumption of TiO2 NPs poses concerning health risks; however, research on the combined effect of ingested TiO2 NPs and glucose is limited. We examined young Sprague-Dawley rats administrated TiO2 NPs orally at doses of 0, 2, 10 and 50 mg/kg body weight per day with and without 1.8 g/kg body weight glucose for 30 and 90 days. Heart rate, systolic and diastolic blood pressure, blood biochemical parameters and histopathology of cardiac tissues was assessed to quantify cardiovascular damage. The results showed that oral exposure to TiO2 NPs and high doses of glucose both could induce cardiovascular injuries. The toxic effects were dose-, time- and gender-dependent. The interaction effects between oral-exposed TiO2 NPs and glucose existed and revealed to be antagonism in most of the biological parameters. However, toxic effects of the high-dose glucose seemed to be more severe than TiO2 NPs and the interaction of TiO2 NPs with glucose. These results suggest that it may be more important to control the sugar intake than TiO2 NPs for protecting the health of TiO2 NP consumers.

Engineering a Zirconium MOF through Tandem "Click" Reactions: A General Strategy for Quantitative Loading of Bifunctional Groups on the Pore Surface.

Metal-organic frameworks (MOFs) assembled from linkers of identical length but with different functional groups have gained increasing interests recently. However, it is very challenging for precise control of the ratios of different functionalities. Herein, we reported a stable azide- and alkyne-appended Zr-MOF that can undergo quantitative tandem click reactions on the different functional sites, thus providing a unique platform for quantitative loading of bifunctional moieties. As an added advantage, the same MOF product can be obtained via two independent routes. The method is versatile and can tolerate a wide variety of functional groups, and furthermore, a heterogeneous acid-base MOF organocatalyst was synthesized by tandemly introducing both acidic and basic groups onto the predesigned pore surface. The presented strategy provides a general way toward the construction of bifunctional MOFs with a precise control of ratio of different functionalities for desirable applications in future.

Ozonized carbon black induces mitochondrial dysfunction and DNA damage.

Black carbon and tropospheric ozone (O3 ), which are major air pollutants in China, are hazardous to humans following inhalation. Black carbon can be oxidized by O3 forming secondary particles of which the health effects are unknown. The present study utilized carbon black as a representative of black carbon to characterize the cytotoxicity induced by secondary particles in bronchial epithelial cells (16HBE) and C57BL/6J mice, and to investigate the implicated molecular pathways. Two types of carbon black including untreated carbon black (UCB) and ozonized carbon black (OCB) were presented. The effects of carbon black on cell viability, intracellular reactive oxygen species (ROS), oxidized/reduced glutathione ratio, mitochondrial membrane potential (MMP), intracellular ATP, and mitochondrial cytochrome c to cytoplasmic cytochrome c ratio were assessed in 16HBE. In addition, an alkaline comet assay and a cytokinesis-block micronucleus (CBMN) test with 16HBE cells in vitro and ELISA method for serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) and a bone marrow micronucleus (BMN) test with C57BL/6J mice in vivo were performed to detect the genotoxicity. When compared with UCB exposed cells, OCB exposed cells had decreased cell viability, increased cell death rate, increased comet length and decreased MMP at 24 h exposure. UCB induced higher level of intracellular ROS than OCB from 4 to 23 h. No changes were observed for both OCB and UCB in serum 8-OHdG, intracellular ATP and mitochondrial cytochrome c to cytoplasmic cytochrome c ratio. The results of CBMN and BMN tests are negative. Intracellular ROS induced by OCB was lower than that of UCB. In summary, ozonization enhances the mitochondrial toxicity and genotoxicity of carbon black. Oxidative stress may not dominate in toxic effects of OCB. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 944-955, 2017.

Postsynthetic Modification of an Alkyne-Tagged Zirconium Metal-Organic Framework via a "Click" Reaction.

Herein, we report the synthesis and postsynthetic modification of a novel alkyne-tagged zirconium metal-organic framework, UiO-68-alkyne. The alkynyl groups in the pore surface were subjected to a "click" reaction, achieving quantitative conversion and maintaining the crystallinity of the framework.

[Effect of 1,4-naphthoquinone aged black carbon on reactive oxygen species and DNA strand breaks in human bronchial epithelial cells].

OBJECTIVE: To study the effect of 1,4-naphthoquinone aged black carbon (BC/1,4-NQ) on reactive oxygen species and DNA strand breaks in human bronchial epithelial cells (16HBE). METHODS: In the study, 16HBE cells were exposed to BC/1,4-NQ, BC and 1,4-NQ at the concentrations of BC/1,4-NQ (10.0/0.2, 20.0/0.4, 40.0/0.8, 80.0/1.6, 160.0/3.2 mg/L), BC (10.0, 20.0, 40.0, 80.0, 160.0 mg/L), 1,4-NQ (0.2, 0.4, 0.8, 1.6, 3.2 mg/L) for 24, 48, and 72 h, respectively. Cytotoxicity was detected by cell count kit 8 (CCK-8) at the end point. Then the 16HBE cells were exposed to BC/1,4-NQ (20.0/0.4, 40.0/0.8, 80.0/1.6 mg/L), BC (20.0, 40.0, 80.0 mg/L), 1,4-NQ (0.4, 0.8, 1.6 mg/L) for 24 h. The reactive oxygen species (ROS) generation was determined via flow cytometry with DCFH-DA probe. Single cell gel electrophoresis (SCGE) assay was performed to evaluate genotoxicity by Olive tail moment (OTM) value. RESULTS: Except for the concentration of 10.0/0.2 mg/L within the exposure time 24 h, the cell viabilities of BC/1,4-NQ were significantly lower than the control (P<0.05) within the exposure time 24-72 h, showing a dose-dependent cytotoxicity. Especially, BC/1,4-NQ showed greater cytotoxicity than BC single exposure, lower than 1,4-NQ at the concentration of BC/1,4-NQ≥80.0/1.6 mg/L. BC/1,4-NQ also showed greater ROS generation and OTM value than the control within the exposure time 24 h at each concentration (P<0.05). Especially, the ROS generation and OTM value of BC/1,4-NQ were greater than BC single exposure, lower than 1,4-NQ at the concentration of 80.0/1.6 mg/L (P<0.05). CONCLUSION: BC/1,4-NQ can induce intracellular ROS generation, cytotoxicity and genotoxicity in 16HBE cells. And at high concentration, the intracellular ROS level, cytotoxicity and genotoxicity induced by BC/1,4-NQ were greater than those by BC single exposure, but lower than those by 1,4-NQ.

Interleukin 1ß and interleukin 1 receptor antagonist gene polymorphisms and cervical cancer: a meta-analysis.

OBJECTIVES: Previous studies investigating the association between interleukin 1ß (IL-1ß) and its receptor antagonist (IL-1RN) polymorphism and cervical cancer risk have reported controversial results. Thus, we examined these associations by performing meta-analyses. METHODS AND MATERIALS: Fourteen studies testing the association between IL-1ß and/or IL-1RN gene polymorphisms and cervical cancer were examined: 5 studies of IL-1ß-511C/T, 3 studies of IL-1ß-31T/C, and 6 studies of IL-1RN. Overall and ethnicity-specific summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for cervical cancer associated with these polymorphisms were estimated using fixed- and random-effects models. Heterogeneity and publication bias were evaluated. RESULTS: Meta-analysis of all 6 studies showed variant genotypes of IL-1RN to be associated with an elevated cervical cancer risk (RN2/RN2 vs RN1/RN1: OR, 2.64; 95% CI, 1.29-5.40; recessive: OR, 2.15; 95% CI, 1.06-4.38; dominant: OR, 1.60; 95% CI, 1.07-2.38). Combined analysis indicated that IL-1ß-511C/T polymorphism was also associated with increased risk of cervical cancer (TT vs CC: OR, 1.56; 95% CI, 1.22-1.99; CT vs CC: OR, 1.61; 95% CI, 1.31-1.99; dominant: OR, 1.60; 95% CI, 1.31-1.95). No significant association of IL-1ß-31T/C and cervical cancer risk was detected. There was no evidence of publication bias. CONCLUSIONS: This meta-analysis suggested that the IL-1RN and IL-1ß-511C/T polymorphisms may contribute to genetic susceptibility of cervical cancer. More studies are needed to further evaluate the role of the IL-1ß-31T/C polymorphism in the etiology of cancer.

Bacillus bingmayongensis sp. nov., isolated from the pit soil of Emperor Qin's Terra-cotta warriors in China.

A Bacillus-like isolate, strain FJAT-13831(T), isolated from the No. 1 pit soil of Emperor Qin's Terra-cotta Warriors in Xi'an City, China, was studied to determine its taxonomic status. Dominant fatty acids of this organism included iso-C15:0, iso-C17:0, C16:0, iso-C13:0, anteiso-C15:0, and iso-C17:1ω5c. Comparative 16S rRNA gene sequence analysis confirmed the affiliation of this isolate to the genus Bacillus and indicated that it was closely related to Bacillus pseudomycoides DSM 12442(T) (99.72 % similarity). A phylogenetic analysis of the gyrB gene sequence similarities exhibited independent clustering of the isolate FJAT-13831(T) and showed 93.8 % (<95 %) sequence similarity with its closest phylogenetic neighbour B. pseudomycoides DSM 12442(T). Separate standing of the strain FJAT-13831(T) was supported by a whole genome-based phylogenetic analysis with an average nucleotide identity value of 91.47 (<95 %) between isolate FJAT-13831(T) and B. pseudomycoides DSM 12442(T) and was consistent with the results of DNA-DNA hybridization (69.1 % relatedness). These findings support the conclusion that the isolate FJAT-13831(T) represents a novel species, for which the name Bacillus bingmayongensis sp. nov. is proposed. The type strain is FJAT-13831(T) (= CGMCC 1.12043(T) = DSM 25427(T)).

The application of nanomaterials in tumor therapy based on the regulation of mechanical properties.

Mechanical properties, as crucial physical properties, have a significant impact on the occurrence, development, and metastasis of tumors. Regulating the mechanical properties of tumors to enhance their sensitivity to radiotherapy and chemotherapy has become an important strategy in the field of cancer treatment. Over the past few decades, nanomaterials have made remarkable progress in cancer therapy, either based on their intrinsic properties or as drug delivery carriers. However, the investigation of nanomaterials of mechanical regulation in tumor therapy is currently in its initial stages. The mechanical properties of nanomaterials themselves, drug carrier targeting, and regulation of the mechanical environment of tumor tissue have far-reaching effects on the efficient uptake of drugs and clinical tumor treatment. Therefore, this review aims to comprehensively summarize the applications and research progress of nanomaterials in tumor therapy based on the regulation of mechanical properties, in order to provide strong support for further research and the development of treatment strategies in this field.

Potential mechanisms of lung injury and repair after hexavalent chromium [Cr(VI)] aerosol whole-body dynamic exposure.

Hexavalent chromium [Cr(VI)], known as "Top Hazardous Substances", poses a significant threat to the respiratory system. Nevertheless, the potential mechanisms of toxicity and the lung's repair ability after injury remain incompletely understood. In this study, Cr(VI) aerosol whole-body dynamic exposure system simulating real exposure scenarios of chromate workers was constructed to evaluate the lung injury and repair effects. Subsequently, miRNA sequencing, mRNA sequencing and metabolomics analyses on lung tissue were performed to explore the underlying mechanisms. Our results revealed that Cr(VI) exposure led to an increase in lactic dehydrogenase activity and a time-dependent decline in lung function. Notably, after 13 w of Cr(VI) exposure, alveolar hemorrhage, thickening of alveolar walls, emphysema-like changes, mitochondrial damage of alveolar epithelial cells and macrophage polarization changes were observed. Remarkably, a two-week repair intervention effectively ameliorated lung function decline and pulmonary injury. Furthermore, significant disruptions in the expressions of miRNAs and mRNAs involved in oxidative phosphorylation, glycerophospholipid metabolism and inflammatory signaling pathways were found. The two-week repair period resulted in the reversal of expression of oxidative phosphorylation related genes, and inhibited the inflammatory signaling pathways. This study concluded that the inhibition of the mitochondrial oxidative phosphorylation pathway and the subsequent enhancement of inflammatory response might be key mechanisms underlying Cr(VI) pulmonary toxicity, and timely cessation of exposure could effectively alleviate the pulmonary injury. These findings shed light on the potential mechanisms of Cr(VI) toxicity and provide crucial insights into the health protection for occupational populations exposed to Cr(VI).

Cellular senescence mediates hexavalent chromium-associated lung function decline: Insights from a structural equation Model.

There is sufficient evidence suggesting that exposure to hexavalent chromium [Cr(VI)] can cause a decline in lung function and the onset of lung diseases. However, no studies have yet explored the underlying mechanisms of these effects from various perspectives such as systemic inflammation, oxidative stress, and cellular senescence, simultaneously. This cross-sectional study was conducted among 304 workers engaged in chromate production and processing in China. Urine was used for detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α), while RNA and DNA extraction from peripheral blood cells was used for detection of mRNA, telomere length, and ribosomal DNA copy numbers (rDNA CNs). A 2.7-fold elevation in blood chromate (Cr) corresponded to a 7.86% (95% CI: 2.57%, 13.42%) rise in urinary 8-OHdG and a 4.14% (0.02%, 8.42%) increase in urinary 8-iso-PGF2α, indicating that exposure to chromates can cause oxidative stress. Furthermore, strong correlations emerged between blood Cr concentration and mRNA levels of P16, P21, TP53, and P15 in the cellular senescence pathway. Simultaneously, a 2.7-fold elevation in blood Cr associated with a -5.47% (-8.72%, -2.1%) change in telomere length, while rDNA CNs (5S, 5.8S, 18S, and 28S) changed by -3.91% (-7.99%, 0.34%), -9.4% (-15.73%, -2.6%), -8.06% (-14.01%, -1.69%), and -5.86% (-10.67%, -0.78%), respectively. Structural equation model highlighted that cellular senescence exerted significant indirect effects on Cr(VI)-associated lung function decline, with a mediation proportion of 23.3%. This study provided data supporting for 8-iso-PGF2α, telomere length, and rDNA CNs as novel biomarkers of chromate exposure, emphasizing the significant role of cellular senescence in the mechanism underlying chromate-induced lung function decline.

A machine learning approach for potential Super-Agers identification using neuronal functional connectivity networks.

INTRODUCTION: Aging is often associated with cognitive decline. Understanding neural factors that distinguish adults in midlife with superior cognitive abilities (Positive-Agers) may offer insight into how the aging brain achieves resilience. The goals of this study are to (1) introduce an optimal labeling mechanism to distinguish between Positive-Agers and Cognitive Decliners, and (2) identify Positive-Agers using neuronal functional connectivity networks data and demographics. METHODS: In this study, principal component analysis initially created latent cognitive trajectories groups. A hybrid algorithm of machine learning and optimization was then designed to predict latent groups using neuronal functional connectivity networks derived from resting state functional magnetic resonance imaging. Specifically, the Optimal Labeling with Bayesian Optimization (OLBO) algorithm used an unsupervised approach, iterating a logistic regression function with Bayesian posterior updating. This study encompassed 6369 adults from the UK Biobank cohort. RESULTS: OLBO outperformed baseline models, achieving an area under the curve of 88% when distinguishing between Positive-Agers and cognitive decliners. DISCUSSION: OLBO may be a novel algorithm that distinguishes cognitive trajectories with a high degree of accuracy in cognitively unimpaired adults. Highlights: Design an algorithm to distinguish between a Positive-Ager and a Cognitive-Decliner.Introduce a mathematical definition for cognitive classes based on cognitive tests.Accurate Positive-Ager identification using rsfMRI and demographic data (AUC = 0.88).Posterior default mode network has the highest impact on Positive-Aging odds ratio.

Exploration of Whole Blood Chromium as Biomarker of Hexavalent Chromium Exposure: Based on Literature Review and Monte Carlo Simulation.

Hexavalent chromium (Cr(VI)) is a sort of common industrial poison and environmental pollutant posing great health threat to the population. Appropriate biomarkers are indispensable indicative tools in the biological monitoring and health risk assessment of Cr(VI). In this study, we explored the rationality and feasibility of whole blood Cr serving as the biomarker of internal exposure with corroboration drawn from literature review and Monte Carlo simulation. It was indicated that the whole blood Cr had practical operability in the large-scale population researches and robust biological significance with broad association with various Cr(VI)-related effect indices. The simulated distribution of whole blood Cr concentration in exposed populations was about three times higher than that of the control (13.52 ± 24.99 vs. 4.25 ± 11.37 µg/L, P < 0.05; 6.73 ± 10.92 µg/L vs. 1.96 ± 2.05 µg/L in China, P < 0.05), which suggested a great discriminatory ability that might be supported as evidence for its reasonable application.