ITPRIPL1 binds CD3ε to impede T cell activation and enable tumor immune evasion.

Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation. Treatment with a neutralizing antibody against ITPRIPL1 restrained tumor growth and promoted T cell infiltration in mouse models across various solid tumor types. The antibody targeting canine ITPRIPL1 exhibited notable therapeutic efficacy against naturally occurring tumors in pet clinics. These findings highlight the role of ITPRIPL1 (or CD3L1, CD3ε ligand 1) in impeding T cell activation during the critical "signal one" phase. This discovery positions ITPRIPL1 as a promising therapeutic target against multiple tumor types.

Proteogenomic Analysis of Human Colon Cancer Reveals New Therapeutic Opportunities.

We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development.

On-chip multi-degree-of-freedom control of two-dimensional materials.

Two-dimensional materials (2DM) and their heterostructures offer tunable electrical and optical properties, primarily modifiable through electrostatic gating and twisting. Although electrostatic gating is a well-established method for manipulating 2DM, achieving real-time control over interfacial properties remains challenging in exploring 2DM physics and advanced quantum device technology1-6. Current methods, often reliant on scanning microscopes, are limited in their scope of application, lacking the accessibility and scalability of electrostatic gating at the device level. Here we introduce an on-chip platform for 2DM with in situ adjustable interfacial properties, using a microelectromechanical system (MEMS). This platform comprises compact and cost-effective devices with the ability of precise voltage-controlled manipulation of 2DM, including approaching, twisting and pressurizing actions. We demonstrate this technology by creating synthetic topological singularities, such as merons, in the nonlinear optical susceptibility of twisted hexagonal boron nitride (h-BN)7-10. A key application of this technology is the development of integrated light sources with real-time and wide-range tunable polarization. Furthermore, we predict a quantum analogue that can generate entangled photon pairs with adjustable entanglement properties. Our work extends the abilities of existing technologies in manipulating low-dimensional quantum materials and paves the way for new hybrid two- and three-dimensional devices, with promising implications in condensed-matter physics, quantum optics and related fields.

Transcriptome Landscape of Human Folliculogenesis Reveals Oocyte and Granulosa Cell Interactions.

The dynamic transcriptional regulation and interactions of human germlines and surrounding somatic cells during folliculogenesis remain unknown. Using RNA sequencing (RNA-seq) analysis of human oocytes and corresponding granulosa cells (GCs) spanning five follicular stages, we revealed unique features in transcriptional machinery, transcription factor networks, and reciprocal interactions in human oocytes and GCs that displayed developmental-stage-specific expression patterns. Notably, we identified specific gene signatures of two cell types in particular developmental stage that may reflect developmental competency and ovarian reserve. Additionally, we uncovered key pathways that may concert germline-somatic interactions and drive the transition of primordial-to-primary follicle, which represents follicle activation. Thus, our work provides key insights into the crucial features of the transcriptional regulation in the stepwise folliculogenesis and offers important clues for improving follicle recruitment in vivo and restoring fully competent oocytes in vitro.

The gender gap in the ownership of promising land.

Using millions of observations compiled from the public administrative data of Taiwan, we find a surprising gender inequity in terms of real estate: Men own more land than women, and the annual rate of return (ROR) of men's land outperform women's by almost 1% per year. The latter finding of gender-based ROR difference is in sharp contrast to prior evidence that women outperform men in security investment, and also suggests a quantity-and-quality double jeopardy in female land ownership which, given the heavy weight of real estate in individual wealth, has important implications for wealth inequality among men and women. Our statistical analyses suggest that such a gender-based difference in land ROR cannot be attributed to individual-level factors such as liquidity preferences, risk attitudes, investment experience, and behavioral biases, as described in the literature. Rather, we hypothesize parental gender bias-a phenomenon that is still prevalent today-to be the key macrolevel factor. To test our hypothesis, we partition our observations into two groups: an experimental group in which parents can exercise gender discretion, and a control group in which parents cannot exercise such discretion. Our empirical evidence shows that the gender difference with respect to land ROR only exists in the experimental group. For many societies with long-lasting patriarchal traditions, our analysis provides a perspective to help explain gender differences in wealth distribution and social mobility.

Bayesian mixed model inference for genetic association under related samples with brain network phenotype.

Genetic association studies for brain connectivity phenotypes have gained prominence due to advances in noninvasive imaging techniques and quantitative genetics. Brain connectivity traits, characterized by network configurations and unique biological structures, present distinct challenges compared to other quantitative phenotypes. Furthermore, the presence of sample relatedness in the most imaging genetics studies limits the feasibility of adopting existing network-response modeling. In this article, we fill this gap by proposing a Bayesian network-response mixed-effect model that considers a network-variate phenotype and incorporates population structures including pedigrees and unknown sample relatedness. To accommodate the inherent topological architecture associated with the genetic contributions to the phenotype, we model the effect components via a set of effect network configurations and impose an inter-network sparsity and intra-network shrinkage to dissect the phenotypic network configurations affected by the risk genetic variant. A Markov chain Monte Carlo (MCMC) algorithm is further developed to facilitate uncertainty quantification. We evaluate the performance of our model through extensive simulations. By further applying the method to study, the genetic bases for brain structural connectivity using data from the Human Connectome Project with excessive family structures, we obtain plausible and interpretable results. Beyond brain connectivity genetic studies, our proposed model also provides a general linear mixed-effect regression framework for network-variate outcomes.

DNA hypomethylation of Syk induces oxidative stress and apoptosis via the PKCß/P66shc signaling pathway in diabetic kidney disease.

Epigenetic alterations, especially DNA methylation, have been shown to play a role in the pathogenesis of diabetes mellitus (DM) and its complications, including diabetic kidney disease (DKD). Spleen tyrosine kinase (Syk) is known to be involved in immune and inflammatory disorders. We, therefore, investigated the possible involvement of Syk promoter methylation in DKD, and the mechanisms underlying this process. Kidney tissues were obtained from renal biopsies of patients with early and advanced DKD. A diabetic mouse model (ApoE-/- DM) was generated from ApoE knockout (ApoE-/-) mice using a high-fat and high-glucose diet combined with low-dose streptozocin intraperitoneal injection. We also established an in vitro model using HK2 cells. A marked elevation in the expression levels of Syk, PKCß, and P66shc in renal tubules was observed in patients with DKD. In ApoE-/- DM mice, Syk expression and the binding of Sp1 to the Syk gene promoter were both increased in the kidney. In addition, the promoter region of the Syk gene exhibited hypomethylation. Syk inhibitor (R788) intervention improved renal function and alleviated pathologic changes in ApoE-/- DM mice. Moreover, R788 intervention alleviated oxidative stress and apoptosis and downregulated the expression of PKCß/P66shc signaling pathway proteins. In HK2 cells, oxLDL combined with high-glucose stimulation upregulated Sp1 expression in the nucleus (compared with control and oxLDL groups), and this was accompanied by an increase in the binding of Sp1 to the Syk gene promoter. SP1 silencing downregulated the expression of Syk and inhibited the production of reactive oxygen species and cell apoptosis. Finally, PKC agonist intervention reversed the oxidative stress and apoptosis induced by Syk inhibitor (R406). In DKD, hypomethylation at the Syk gene promoter was accompanied by an increase in Sp1 binding at the promoter. As a consequence of this enhanced Sp1 binding, Syk gene expression was upregulated. Syk inhibitors could attenuate DKD-associated oxidative stress and apoptosis via downregulation of PKCß/P66shc signaling pathway proteins. Together, our results identify Syk as a promising target for intervention in DKD.

LncRNA-Snhg3 regulates mouse hepatic glycogenesis under normal chow diet.

Long noncoding RNAs (lncRNAs) are strongly associated with glucose homeostasis, but their roles remain largely unknown. In this study, the potential role of lncRNA-Snhg3 in glucose metabolism was evaluated both in vitro and in vivo. Here, we found a positive relationship between Snhg3 and hepatic glycogenesis. Glucose tolerance improved in hepatocyte-specific Snhg3 knock-in (Snhg3-HKI) mice, while it worsened in hepatocyte-specific Snhg3 knockout (Snhg3-HKO) mice. Furthermore, hepatic glycogenesis had shown remarkable increase in Snhg3-HKI mice and reduction in Snhg3-HKO mice, respectively. Mechanistically, Snhg3 increased mRNA and protein expression levels of PPP1R3B through inducing chromatin remodeling and promoting the phosphorylation of protein kinase B. Collectively, these results suggested that lncRNA-Snhg3 plays a critical role in hepatic glycogenesis.

Sex-specific modulation of amyloid-ß on tau phosphorylation underlies faster tangle accumulation in females.

Females are disproportionately affected by dementia due to Alzheimer's disease. Despite a similar amyloid-ß (Aß) load, a higher load of neurofibrillary tangles (NFTs) is seen in females than males. Previous literature has proposed that Aß and phosphorylated-tau (p-tau) synergism accelerates tau tangle formation, yet the effect of biological sex in this process has been overlooked. In this observational study, we examined longitudinal neuroimaging data from the TRIAD and ADNI cohorts from Canada and USA, respectively. We assessed 457 participants across the clinical spectrum of Alzheimer's disease. All participants underwent baseline multimodal imaging assessment, including MRI and PET, with radioligands targeting Aß plaques and tau tangles, respectively. CSF data were also collected. Follow-up imaging assessments were conducted at 1- and 2-year intervals for the TRIAD cohort and 1-, 2- and 4-year intervals for the ADNI cohort. The upstream pathological events contributing to faster tau progression in females were investigated-specifically, whether the contribution of Aß and p-tau synergism to accelerated tau tangle formation is modulated by biological sex. We hypothesized that cortical Aß predisposes tau phosphorylation and tangle accumulation in a sex-specific manner. Findings revealed that Aß-positive females presented higher CSF p-tau181 concentrations compared with Aß-positive males in both the TRIAD (P = 0.04, Cohen's d = 0.51) and ADNI (P = 0.027, Cohen's d = 0.41) cohorts. In addition, Aß-positive females presented faster NFT accumulation compared with their male counterparts (TRIAD: P = 0.026, Cohen's d = 0.52; ADNI: P = 0.049, Cohen's d = 1.14). Finally, the triple interaction between female sex, Aß and CSF p-tau181 was revealed as a significant predictor of accelerated tau accumulation at the 2-year follow-up visit (Braak I: P = 0.0067, t = 2.81; Braak III: P = 0.017, t = 2.45; Braak IV: P = 0.002, t = 3.17; Braak V: P = 0.006, t = 2.88; Braak VI: P = 0.0049, t = 2.93). Overall, we report sex-specific modulation of cortical Aß in tau phosphorylation, consequently facilitating faster NFT progression in female individuals over time. This presents important clinical implications and suggests that early intervention that targets Aß plaques and tau phosphorylation may be a promising therapeutic strategy in females to prevent the further accumulation and spread of tau aggregates.

Thickness- and Field-Dependent Magnetic Domain Evolution in van der Waals Fe3GaTe2.

The discovery of room-temperature ferromagnetism in van der Waals (vdW) materials opens new avenues for exploring low-dimensional magnetism and its applications in spintronics. Recently, the observation of the room-temperature topological Hall effect in the vdW ferromagnet Fe3GaTe2 suggests the possible existence of room-temperature skyrmions, yet skyrmions have not been directly observed. In this study, real-space imaging was employed to investigate the domain evolution of the labyrinth and skyrmion structure. First, Néel-type skyrmions can be created at room temperature. In addition, the influence of flake thickness and external magnetic field (during field cooling) on both labyrinth domains and the skyrmion lattice is unveiled. Due to the competition between magnetic anisotropy and dipole interactions, the specimen thickness significantly influences the density of skyrmions. These findings demonstrate that Fe3GaTe2 can host room-temperature skyrmions of various sizes, opening up avenues for further study of magnetic topological textures at room temperature.

In-Depth Proteome Profiling of Small Extracellular Vesicles Isolated from Cancer Cell Lines and Patient Serum.

Extracellular vesicle (EV) secretion has been observed in many types of both normal and tumor cells. EVs contain a variety of distinctive cargoes, allowing tumor-derived serum proteins in EVs to act as a minimally invasive method for clinical monitoring. We have undertaken a comprehensive study of the protein content of the EVs from several cancer cell lines using direct data-independent analysis. Several thousand proteins were detected, including many classic EV markers such as CD9, CD81, CD63, TSG101, and Syndecan-1, among others. We detected many distinctive cancer-specific proteins, including several known markers used in cancer detection and monitoring. We further studied the protein content of EVs from patient serum for both normal controls and pancreatic cancer and hepatocellular carcinoma. The EVs for these studies have been isolated by various methods for comparison, including ultracentrifugation and CD9 immunoaffinity column. Typically, 500-1000 proteins were identified, where most of them overlapped with the EV proteins identified from the cell lines studied. We were able to identify many of the cell-line EV protein markers in the serum EVs, in addition to the large numbers of proteins specific to pancreatic and HCC cancers.

Metal Phosphide Anodes in Sodium-Ion Batteries: Latest Applications and Progress.

Sodium-ion batteries (SIBs), as the next-generation high-performance electrochemical energy storage devices, have attracted widespread attention due to their cost-effectiveness and wide geographical distribution of sodium. As a crucial component of the structure of SIBs, the anode material plays a crucial role in determining its electrochemical performance. Significantly, metal phosphide exhibits remarkable application prospects as an anode material for SIBs because of its low redox potential and high theoretical capacity. However, due to volume expansion limitations and other factors, the rate and cycling performance of metal phosphides have gradually declined. To address these challenges, various viable solutions have been explored. In this paper, the recent research progress of metal phosphide materials for SIBs is systematically reviewed, including the synthesis strategy of metal phosphide, the storage mechanism of sodium ions, and the application of metal phosphide in electrochemical aspects. In addition, future challenges and opportunities based on current developments are presented.

Identification of novel protein biomarkers from the blood and urine for the early diagnosis of bladder cancer via proximity extension analysis.

BACKGROUND: Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. METHODS: Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p < 0.05). The expression of the selected potential marker was further verified in BC and adjacent tissues by immunohistochemistry (IHC) and single-cell sequencing. A model was constructed to differentiate BC from HC by LASSO regression and compared to the detection capability of FISH. RESULTS: The univariate analysis revealed significant differences in the expression levels of 40 proteins in the serum (p < 0.05) and 17 proteins in the urine (p < 0.05) between BC patients and HC. Six proteins (AREG, RET, WFDC2, FGFBP1, ESM-1, and PVRL4) were selected as potential BC biomarkers, and their expression was evaluated at the protein and transcriptome levels by IHC and single-cell sequencing, respectively. A diagnostic model (a signature) consisting of 14 protein markers (11 in serum and three in urine) was also established using LASSO regression to distinguish between BC patients and HC (area under the curve = 0.91, PPV = 0.91, sensitivity = 0.87, and specificity = 0.82). Our model showed better diagnostic efficacy than FISH, especially for early-stage, small, and low-grade BC. CONCLUSION: Using the PEA method, we identified a panel of potential protein markers in the serum and urine of BC patients. These proteins are associated with the development of BC. A total of 14 of these proteins can be used to detect early-stage, small, low-grade BC. Thus, these markers are promising for clinical translation to improve the prognosis of BC patients.

METTL3-mediated lncRNA HNF1A-AS1/HNF4A-AS1 m6A modification regulates CYP expression.

Interindividual variations in the expression and activity of cytochrome P450 enzymes (CYPs) led to lower therapeutic efficacy or adverse drug events. We previously demonstrated that CYPs are regulated by the long non-coding RNAs (lncRNAs) HNF1A-AS1 and HNF4A-AS1 via transcription factors (TFs) including hepatocyte nuclear factor 1a (HNF1A), hepatocyte nuclear factor 4a (HNF4A), and pregnane X receptor (PXR). However, the upstream mechanisms regulating HNF1A-AS1 and HNF4A-AS1 are poorly understood. N6-methyladenosine (m6A) is a prevalent epi transcriptomic modification in mammalian RNA. Therefore, the aim of this study was to investigate whether m6A modification regulates the expression of HNF1A-AS1 and HNF4A-AS1 and affects CYP expression in HepG2 and Huh7 cells. The methyltransferase-like 3 (METTL3) inhibitor, STM2457, significantly suppressed the expression of HNF1A-AS1 and induced HNF4A-AS1 expression. Consistent with this, a loss-of-function assay of METTL3 in the cell lines resulted in the down-regulation of HNF1A-AS1 and its downstream HNF1A, PXR, and CYPs at the RNA level, as well as the down-regulation of some CYPs proteins, and up-regulation of HNF4A-AS1. The results of gain-of-function experiments showed the opposite trend. Mechanistically, subsequent RNA stability experiments confirmed that METTL3 affected the stability of both lncRNAs, but in opposite ways; that is, METTL3 reduced HNF1A-AS1 stability and increased HNF4A-AS1 stability. Rescue experiments confirmed that the regulation of METTL3 on TFs and CYPs may require the involvement of these two lncRNAs. Altogether, our study demonstrates that METTL3 is involved in TFs-mediated CYP expression by affecting HNF1A-AS1/HNF4A-AS1 stability. Significance Statement While the impact of lncRNAs (HNF1A-AS1 and HNF4A-AS1) on the downstream TF and CYP expression is well studied, the upstream regulation of these two lncRNAs by METTL3 remains unexplored. This study systematically investigated the regulation by METTL3 on the expression of lncRNAs (HNF1A-AS1 and HNF4A-AS1) and their downstream TFs (HNF1A, HNF4A, and PXR) and CYPs in HepG2 and Huh7 cells, revealing that METTL3 is involved in the regulation of lncRNA-TF-CYP expression by affecting the stability of HNF1A-AS1 and HNF4A-AS1.

Diagnostic efficacy of an optimized nucleotide MALDI-TOF-MS assay for anti-tuberculosis drug resistance detection.

PURPOSE: We aimed at evaluating the diagnostic efficacy of a nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) assay to detect drug resistance of Mycobacterium tuberculosis. METHODS: Overall, 263 M. tuberculosis clinical isolates were selected to evaluate the performance of nucleic MALDI-TOF-MS for rifampin (RIF), isoniazid (INH), ethambutol (EMB), moxifloxacin (MXF), streptomycin (SM), and pyrazinamide (PZA) resistance detection. The results for RIF, INH, EMB, and MXF were compared with phenotypic microbroth dilution drug susceptibility testing (DST) and whole-genome sequencing (WGS), and the results for SM and PZA were compared with those obtained by WGS. RESULTS: Using DST as the gold standard, the sensitivity, specificity, and kappa values of the MALDI-TOF-MS assay for the detection of resistance were 98.2%, 98.7%, and 0.97 for RIF; 92.8%, 99%, and 0.90 for INH; 82.4%, 98.0%, and 0.82 for EMB; and 92.6%, 99.5%, and 0.94 for MXF, respectively. Compared with WGS as the reference standard, the sensitivity, specificity, and kappa values of the MALDI-TOF-MS assay for the detection of resistance were 97.4%, 100.0%, and 0.98 for RIF; 98.7%, 92.9%, and 0.92 for INH; 96.3%, 100.0%, and 0.98 for EMB; 98.1%, 100.0%, and 0.99 for MXF; 98.0%, 100.0%, and 0.98 for SM; and 50.0%, 100.0%, and 0.65 for PZA. CONCLUSION: The nucleotide MALDI-TOF-MS assay yielded highly consistent results compared to DST and WGS, suggesting that it is a promising tool for the rapid detection of sensitivity to RIF, INH, EMB, and MXF.

Characteristics of T-Cell Receptor Repertoire for Differential Response to Methotrexate Treatment for Rheumatoid Arthritis.

BACKGROUND: Methotrexate (MTX) serves as the initial treatment for rheumatoid arthritis (RA). However, a substantial proportion of RA patients, estimated between 30% and 50%, do not respond positively to MTX. While the T-cell receptor (TCR) is crucial for the immune response during RA, its role in differentiating MTX responsiveness has not been thoroughly investigated. METHODS: This study used next-generation sequencing to analyze the TCR ß-chain complementary determining region sequences in peripheral blood mononuclear cells obtained from RA patients before MTX treatment. This study aimed to compare the characteristics of the TCR repertoire between the MTX responder and non-responder groups. RESULTS: The study identified a significant difference in the TRBV6-6 gene (p = .003) concerning MTX treatment response. Additionally, a significant difference was found in the number of "3" nucleotide deletions at the 5'Jdels site (p = .023) in the VDJ rearrangement. CONCLUSION: These findings suggest distinct TCR repertoire characteristics between MTX responder and non-responder groups among RA patients. This discovery offers new insights into understanding the variable responses of RA patients to MTX therapy.

Co-metabolic degradation and metabolite detection of hexabromocyclododecane by Shewanella oneidensis MR-1.

Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant; however, it is a persistent organic pollutant as well as affects the human thyroid hormones and causes cancer. However, the degradation of HBCD has received little attention from researchers. Due to its bioaccumulative and hazardous properties, an appropriate strategy for its remediation is required. In this study, we investigated the biodegradation of HBCD using Shewanella oneidensis MR-1 under optimized conditions. The Box-Behnken design (BBD) was implemented for the optimization of the physical degradation parameters of HBCD. S. oneidensis MR-1 showed the best degradation performance at a temperature of 30 °C, pH 7, and agitation speed of 115 rpm, with an HBCD concentration of 1125 µg/L in mineral salt medium (MSM). The strain tolerated up to 2000 µg/L HBCD. Gas chromatography-mass spectrometry analysis identified three intermediates, including 2-bromo dodecane, 2,7,10-trimethyldodecane, and 4-methyl-1-decene. The results provide an insightful understanding of the biodegradation of HBCD by S. oneidensis MR-1 under optimized conditions and could pave the way for further eco-friendly applications. KEY POINTS: • HBCD biodegradation by Shewanella oneidensis • Optimization of HBCD biodegradation by the Box-Behnken analysis • Identification of useful metabolites from HBCD degradation.

Different effects of vitamin supplementation on arsenic bioaccessibility in contaminated soils using multiple in vitro methods and their relevant mechanisms.

Exposure to arsenic (As) induces adverse effects on human health. Vitamins B1, B6, and C, as indispensable micronutrients for humans, have been proven to influence the metabolism and toxicity of ingested As. To determine the effect of vitamins on health risks associated with soil exposure, As bioaccessibility in 14 soil samples using four in vitro methods of IVG, PBET, SBRC, and UBM was measured with the addition of vitamins B1, B6, and C. With vitamins B1 and B6 addition, the gastric As bioaccessibility in 14 soil samples was reduced by 1.14-3.52 and 1.14-5.02 fold, respectively, and instead an increase in the intestinal bioaccessibility was presented in some cases. Vitamin C supplementation yielded higher As bioaccessibility in the gastric (1.13-13.02 fold) and small intestinal (1.21-33.35 fold) phases, respectively. As evidenced by the X-ray absorption near-edge spectroscopy (XANES) and Fourier transform infrared spectroscopy (FTIR) analysis, arsenic dissolution was promoted by Fe-As and hindered by the formation of Al-As fractions. Soil As dissolution in the simulated gastrointestinal tract was strongly influenced by soil minerals and ingested vitamins, due to the chelation of arsenic with vitamins and soil minerals such as Fe (hydr)oxides, and Fe(III) reductive dissolution to enhance As release by vitamin C as an iron reducer. These findings will expand the knowledge of health risks of exposure to As-contaminated soils and nutritional interventions aiming at the mitigation of As toxicity.

Evolutionary game analysis for multi-level collaborative governance under public crisis in China: From a value perception perspective.

In a risk society, the survival and development of humans are facing threats of complex and severe public crisis events. Public participation in collaborative governance (CG) of public crisis events is increasingly recognized as an important direction for the reform of the current and future emergency management system. Previous studies of CG have mainly focused on the macro level and ignored to address micro-level discussions of the behavioral strategy evolution of stakeholders. From a fresh value perception perspective, this study constructs an evolutionary game model to clarify the evolution mechanism of multi-level emergency CG. First, the value perception model is built based on Prospect Theory and Mental Accounting to optimize the traditional game matrix. Second, the evolutionary stability is analyzed to solve the system evolution law. Finally, numerical simulation is conducted in the case of Heilongjiang province, a main region of food and energy supply in China. Results showed that (1) the CG game system has a complex evolutionary path; (2) the behavior of game players is affected by perceived incomes and perceived costs; (3) compared with the reference value and the risk aversion coefficient of income accounts, game players are more sensitive to that of cost accounts; (4) enhancing the perceived value of public psychological satisfaction and government reputation is helpful for the long-term construction of CG. Overall, this study aims to highlight the potential utility of value perception in promoting effective implementations of CG and to provide new insights for the development of CG in China and other countries.

Plasma pTau-217 and N-terminal tau (NTA) enhance sensitivity to identify tau PET positivity in amyloid-ß positive individuals.

INTRODUCTION: We set out to identify tau PET-positive (A+T+) individuals among amyloid-beta (Aß) positive participants using plasma biomarkers. METHODS: In this cross-sectional study we assessed 234 participants across the AD continuum who were evaluated by amyloid PET with [18 F]AZD4694 and tau-PET with [18 F]MK6240 and measured plasma levels of total tau, pTau-181, pTau-217, pTau-231, and N-terminal tau (NTA-tau). We evaluated the performances of plasma biomarkers to predict tau positivity in Aß+ individuals. RESULTS: Highest associations with tau positivity in Aß+ individuals were found for plasma pTau-217 (AUC [CI95% ] = 0.89 [0.82, 0.96]) and NTA-tau (AUC [CI95% ] = 0.88 [0.91, 0.95]). Combining pTau-217 and NTA-tau resulted in the strongest agreement (Cohen's Kappa = 0.74, CI95%  = 0.57/0.90, sensitivity = 92%, specificity = 81%) with PET for classifying tau positivity. DISCUSSION: The potential for identifying tau accumulation in later Braak stages will be useful for patient stratification and prognostication in treatment trials and in clinical practice. HIGHLIGHTS: We found that in a cohort without pre-selection pTau-181, pTau-217, and NTA-tau showed the highest association with tau PET positivity. We found that in Aß+ individuals pTau-217 and NTA-tau showed the highest association with tau PET positivity. Combining pTau-217 and NTA-tau resulted in the strongest agreement with the tau PET-based classification.