Dual-level strategy for quantitative kinetics for the reaction between ethylene and hydroxyl radical.

The atmospheric reactions are mainly initiated by hydroxyl radical (OH). Here, we choose the C2H4 + OH reaction as a model reaction for other reactions of OH with alkenes. We use the GMM(P).L//CCSD(T)-F12a/cc-pVTZ-F12 theoretical method as the benchmark results close to the approximation of CCSDTQ(P)/CBS accuracy to investigate the C2H4 + OH reaction. The rate constants for the C2H4 + OH reaction at high-pressure limit were calculated by using the dual-level strategy. It integrates the transition state theory rate constant calculated by GMM(P).L//CCSD(T)-F12a/cc-pVTZ-F12 with the canonical variational transition state theory containing small-curvature tunneling (CVT/SCT) calculated by using the M11-L functional method with the MG3S basis set. The rate constants of C2H4 + OH at different pressures were obtained by using both the system-specific quantum Rice-Ramsperger-Kassel (SS-QRRK) theory and master equation method. The calculated results uncover that both the calculated rate constants at different pressures and temperatures are quantitatively consistent with the values obtained by the experimental measurements in the C2H4 + OH reaction. We find that the post-CCSD(T) contributions to the barrier height for the C2H4 + OH reaction are significant with the calculated value of -0.38 kcal/mol. We also find that the rate determining step is only dominated by the tight transition state under atmospheric conditions, whereas previous investigations indicated that the rate constants were controlled by both the loose and tight transition states in the C2H4 + OH reaction. The present findings unravel that it is an important factor for the effect of torsional anharmonicity on quantitative kinetics.

Quantification of peptide components in cinobufacini injection and toad skin by ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry.

Cinobufacini injection is commonly used in the clinical treatment of tumors and hepatitis B, but the quality is uneven. Currently, the main focus of its quality assessment is on steroids and alkaloids. Based on a previous study, we screened four peptides with high reproducibility, responsiveness, and specificity. This research was the first to develop an ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry approach for evaluating the quality of cinobufacini preparations from the peptide perspective. In this study, we have identified 230 peptides in cinobufacini injection by Q-Exactive mass spectrometry, which contains species-specific peptides. Then, we used ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry to establish a quantitative method for species-specific peptides and carried out method validation. The result revealed that four peptides were linear in a specific range, and had great reproducibility, accuracy, and stability. Eventually, we evaluated the quality of eight batches of cinobufacini injections and 26 batches of toad skins using the total content of target peptides as the criterion. The outcomes demonstrated that the quality of cinobufacini injection is generally stable and the toad skin from Shandong is of the best quality. In conclusion, the quantitative approach that focuses on peptides will offer innovative perspectives on assessing the quality of cinobufacini preparations.

Effect of estradiol as a continuous variable on breast cancer survival by menopausal status: a cohort study in China.

High levels of circulating estradiol (E2) are associated with increased risk of breast cancer, whereas its relationship with breast cancer prognosis is still unclear. We evaluated the effect of E2 concentration on survival endpoints among 8766 breast cancer cases diagnosed between 2005 and 2017 from the Tianjin Breast Cancer Cases Cohort. Levels of serum E2 were measured in pre-menopausal and post-menopausal women. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between quartile of E2 levels and overall survival (OS) and progression-free survival (PFS) of breast cancer. The penalized spline was then used to test for non-linear relationships between E2 (continuous variable) and survival endpoints. 612 deaths and 982 progressions occurred over follow-up through 2017. Compared to women in the quartile 3, the highest quartile of E2 was associated with reduced risk of both PFS in pre-menopausal women (HR 1.79, 95% CI 1.17-2.75, P = 0.008) and OS in post-menopausal women (HR 1.35, 95% CI 1.04-1.74, P = 0.023). OS and PFS in pre-menopausal women exhibited a nonlinear relation ("L-shaped" and "U-shaped", respectively) with E2 levels. However, there was a linear relationship in post-menopausal women. Moreover, patients with estrogen receptor-negative (ER-negative) breast cancer showed a "U-shaped" relationship with OS and PFS in pre-menopausal women. Pre-menopausal breast cancer patients have a plateau stage of prognosis at the intermediate concentrations of E2, whereas post-menopausal patients have no apparent threshold, and ER status may have an impact on this relationship.

Serum IL-17A concentration and a IL17RA single nucleotide polymorphism contribute to the risk of autoimmune type 1 diabetes.

AIMS: Interleukin (IL)-17 is associated with autoimmunity. This study aimed to affirm the role of IL-17A, IL-17F and single nucleotide polymorphisms (SNPs) in genes related to them and their receptors in autoimmune type 1 diabetes (T1D) for Chinese population. METHODS: In this study, 130 patients with autoimmune T1D and 140 non-T1D controls were included for analysis. Clinical and biochemical data were collected, and serum levels of IL-17A, IL-17F, IL-6, and high-sensitivity C reactive protein were measured using ELISA. The SNPs rs2275913, rs8193036, rs3819025, rs763780, rs879577, rs4819554, and rs708567 were genotyped using the SNaPshot assay. RESULTS: IL-17A levels were higher in patients with autoimmune T1D than in controls (median [IQR] 28.83[37.38] vs. 16.68[8.10], p < 0.001) and high IL-17A was a risk factor for autoimmune T1D (odds ratio (OR), 1.013; 95% CI, 1.003-1.023; p = 0.013) after adjusting for confounding factors. Linear regression analysis revealed that log10 IL-17A levels were independently associated with fasting C-peptide, IL-6, body mass index, and IL-17F. However, no independent association was found between IL-17F and autoimmune T1D. The GG genotype of SNP rs4819554 in the interleukin 17 receptor A (IL17RA) gene was associated with a decreased risk of autoimmune T1D (OR, 0.458; 95% CI, 0.246-0.852; p = 0.014) after adjusting for other confounders. The IL17RA rs4819554 GG genotype was negatively correlated with serum glutamic acid decarboxylase antibody appearance (p < 0.05). CONCLUSIONS: Increased serum IL-17A, but not IL-17F, is a risk factor for autoimmune T1D. The GG genotype of IL17RA rs4819554 might decrease the risk for autoimmune T1D.

Identification of peptides of cinobufacini by gel filter chromatography and peptidomics.

Aqueous extract of toad skin (named as Cinobufacini or Huachansu) provides plentiful sources of bioactive peptides that remain undetected and unidentified. High-resolution mass spectrometry-based peptidomics platforms have developed into a major approach to the discovery of natural peptides, with data-dependent acquisition modes providing a wealth of peptide profiling information. In this study, we used a gel- and HLB (a solid phase extraction cartridge)-based two-dimensional separation and purification system and nano-liquid chromatography-tandem mass spectrometry-based peptidomic studies with homology matching for the identification of peptides from Cinobufacini. We evaluated 232 multi-charged peptides and found several specific peptides, some of which were validated by target parallel reaction monitoring mode. These peptides are the first to be identified in Cinobufacini and are completely different from ones identified in toad venom. So, this mapping provides key peptide information for the quality control of Bufo bufo gargarizans skin and its preparation.

High level of complement factor Ba within first prenatal test of gestation increases the risk of subsequent gestational diabetes: a propensity score-matched study.

OBJECTIVE: This study was to assess the alteration of circulating complement factor Ba (CFBa) within 11 to 17 weeks of gestation and its association with subsequent gestational diabetes mellitus (GDM) and its delivery outcome. METHODS: Biochemical parameters and blood samples were collected from 399 pregnant women within 11 to 17 weeks of gestation. At 24 to 28 weeks of gestation, all participants underwent 75-g oral glucose tolerance test and were assigned to GDM group (n = 80) and normal control group (n = 319). Perinatal data were collected after delivery. A propensity score-matched (PSM) analysis was performed to reduce the impact of confounding factors on glucose metabolism during pregnancy between the two groups. RESULTS: Two groups of 74 well-matched patients who maintained balance in terms of baseline characteristics. The levels of CFBa in pregnant women who later developed GDM were significantly higher than those in healthy pregnant women [0.4(0.1-0.8) vs. 0.2(0.2-0.3), p = 0.024]. Logistic regression analysis results confirmed that the level of CFBa was an independent impact factor for the occurrence of GDM (OR = 1.57, 95% CI: 1.118-2.210, p = 0.009). Further grouping according to the median level of CFBa, it was found that the incidence of GDM in category two (>0.23 ng/ml, n = 74) was markedly higher than that in the first category (≤0.23 ng/ml, n = 74) (p = 0.021). CONCLUSIONS: High level of the CFBa within 11 to 17 weeks of gestation increases the risk of subsequent GDM, and maybe a biomarker for predicting GDM.

A Novel and Fast Encryption System Based on Improved Josephus Scrambling and Chaotic Mapping.

To address the shortcomings of weak confusion and high time complexity of the existing permutation algorithms, including the traditional Josephus ring permutation (TJRP), an improved Josephus ring-based permutation (IJRBP) algorithm is developed. The proposed IJRBP replaces the remove operation used in TJRP with the position exchange operation and employs random permutation steps instead of fixed steps, which can offer a better scrambling effect and a higher permutation efficiency, compared with various scrambling methods. Then, a new encryption algorithm based on the IJRBP and chaotic system is developed. In our scheme, the plaintext feature parameter, which is related to the plaintext and a random sequence generated by a chaotic system, is used as the shift step of the circular shift operation to generate the diffusion matrix, which means that a minor change in the source image will generate a totally different encrypted image. Such a strategy strikes a balance between plaintext sensitivity and ciphertext sensitivity to obtain the ability to resist chosen-plaintext attacks (CPAs) and the high robustness of resisting noise attacks and data loss. Simulation results demonstrate that the proposed image cryptosystem has the advantages of great encryption efficiency and the ability to resist various common attacks.

The role of complement factor H in gestational diabetes mellitus and pregnancy.

BACKGROUND: Complement factor H (CFH) has been found to be associated with insulin resistance. This study assessed the correlation between CFH and other clinical parameters, and determined whether CFH played a role in gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. METHODS: A total of 397 pregnant women were included for analysis in this nested case-control study. Clinical parameters and serum were collected within the 11-17th gestational age at the first prenatal visit. At 24-28 weeks of gestation, a 75 g oral glucose tolerance test was performed and subjects were divided into a GDM (n = 80) and a non-GDM control group (n = 317). The delivery data were also followed. The serum CFH level was assayed by ELISA. RESULTS: CFH was higher in GDM than in non-GDM controls (280.02 [58.60] vs. 264.20 [68.77]; P = 0.014). CFH level was moderately associated with pre-pregnancy body mass index (BMI), BMI and total triglycerides (TG), and slightly associated with gestational age, low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) in GDM and non-GDM (all P <  0.05). Moreover, CFH level was moderately correlated with alkaline phosphatase (ALP) and slightly correlated with age, uric acid (UA) and total bilirubin (TB) in non-GDM (all P <  0.05). After adjustment for clinical confounding factors, BMI, TG, gestational age, ALP, TB, age and UA were independent risk factors for log10 CFH levels (all P <  0.05) in all subjects. In addition, overweight or obese pregnant women, women with hypertriglyceridemia and women in the second trimester had significantly higher CFH levels than normal weight and underweight group (P <  0.001), the non-hypertriglyceridemia group (P <  0.001) and women in the first trimester group (P < 0.05) in all pregnant women respectively. Following binary logistic regression, CFH was not independently associated with GDM and related pregnant outcomes. CONCLUSIONS: The CFH in 11-17th weeks of gestation might be affected by many factors, including BMI, TG, gestational age, ALP, TB, age and UA. CFH was not an independent risk factor for GDM and avderse pregnancy outcomes.

Route to Substituted Furan-2(5H)-ones from cyclo-Alkenecarboxylic Acids and Acrylates via C-H Activation.

Under rhodium(III) catalysis, four kinds of cycloalkenecarboxylic acids successfully reacted with acrylates via direct activation of the ß-alkenyl C-H bond. The present protocol provides the facile and highly efficient synthesis of substituted furan-2(5H)-ones from readily available starting materials with moderate to good yields. In addition, their possible reaction mechanisms were also discussed.

Progress on Transition Metal Ions Dissolution Suppression Strategies in Prussian Blue Analogs for Aqueous Sodium-/Potassium-Ion Batteries.

Aqueous sodium-ion batteries (ASIBs) and aqueous potassium-ion batteries (APIBs) present significant potential for large-scale energy storage due to their cost-effectiveness, safety, and environmental compatibility. Nonetheless, the intricate energy storage mechanisms in aqueous electrolytes place stringent requirements on the host materials. Prussian blue analogs (PBAs), with their open three-dimensional framework and facile synthesis, stand out as leading candidates for aqueous energy storage. However, PBAs possess a swift capacity fade and limited cycle longevity, for their structural integrity is compromised by the pronounced dissolution of transition metal (TM) ions in the aqueous milieu. This manuscript provides an exhaustive review of the recent advancements concerning PBAs in ASIBs and APIBs. The dissolution mechanisms of TM ions in PBAs, informed by their structural attributes and redox processes, are thoroughly examined. Moreover, this study delves into innovative design tactics to alleviate the dissolution issue of TM ions. In conclusion, the paper consolidates various strategies for suppressing the dissolution of TM ions in PBAs and posits avenues for prospective exploration of high-safety aqueous sodium-/potassium-ion batteries.

Sparse Wasserstein stationary subspace analysis for fault detection and diagnosis of nonstationary industrial processes.

Fault detection and diagnosis of nonstationary processes are crucial for ensuring the safety of industrial production systems. However, the nonstationarity of process data poses multifaceted challenges to them. First, conventional stationary fault detection methods encounter difficulties in discerning evolving trends within nonstationary data. Secondly, the majority of current nonstationary fault detection methods directly extract features from all variables, rendering them susceptible to redundant interference. Moreover, nonstationary trends possess the capacity to conceal and modify the correlations among variables. Coupled with the smearing effect of faults, it is challenging to achieve accurate fault diagnosis. To address these challenges, this paper proposes sparse Wasserstein stationary subspace analysis (SWSSA). Specifically, a ℓ2,p-norm constraint is introduced to endow the stationary subspace model with excellent sparse representation capability. Furthermore, recognizing that fault variables within the sparse stationary subspace influence only a limited subset of stationary sources, this paper proposes a novel contribution analysis method based on local dynamic preserving projection (LDPP), termed LDPPBC, which can effectively mitigate the smearing effect on nonstationary fault diagnosis. LDPPBC establishes a LDPP matrix by extracting the latent positional information of fault variables within the stationary subspace. This allows LDPPBC to selectively analyze the contributions of variables within the latent fault subspace to achieve precise fault diagnosis while avoiding the interference of variable contributions from the fault-free subspace. Finally, the superiority of the proposed method is thoroughly validated through a numerical simulation, a continuous stirred tank reactor, and a real industrial roaster.

Computational Analysis of B-Cell Receptor (BCR) Immune Repertoires with Abalign.

The widespread application of high-throughput sequencing technology has generated massive sequences of B-cell receptor (BCR) immune repertoires. Computational analysis of these data has gained significant attention due to the increasing importance of immunotherapy and precision medicine. It not only reveals the diversity and dynamic changes in immune responses, contributing to the study of associated diseases, but also provides valuable information for immunodiagnostics and drug development. Recently, we introduced a BCR-specific multiple sequence alignment (MSA) method along with a comprehensive platform software called Abalign, which stands out as an excellent choice for analyzing BCR immune repertoires due to its unique high-throughput processing capability. It offers ultra-fast MSA functionality and a wide range of analytical features, including BCR/antibody extraction, clonal grouping, lineage tree construction, mutation profiling, diversity statistics, VJ gene assignment, antibody humanization, and more. Importantly, users can perform these analyses using the graphical user interface without any programming skills or scripts. In this article, we present a series of protocols that integrate Abalign's analysis modules into a cohesive workflow. This step-by-step workflow provides detailed instructions for software installation, data preparation, and comprehensive analysis of BCR immune repertoires. This workflow facilitates the efficient acquisition of comprehensive results in profiling BCR immune repertoires, offering insights into the impacts of infectious diseases, allergies, autoimmune disorders, tumor immunology, and antibody drugs. Abalign is freely available at http://cao.labshare.cn/abalign/. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Resource preparation Basic Protocol 2: Analyzing BCR immune repertoires Support Protocol 1: Aiding antibody humanization Support Protocol 2: Constructing B-cell lineage trees Alternate Protocol: Running with Linux command line Basic Protocol 3: Comparing BCR immune repertoires.

Enhanced sensitivity and linear-response in iontronic pressure sensors for non-contact, high-frequency vibration recognition.

Monitoring non-contact high-frequency vibrations requires improving the sensitivity and linear response of iontronic pressure sensors (IPSs). In this study, we incorporate composite electrodes comprising silver nanowires (Ag NWs) and MXene into IPSs to enhance electronic conduction and pseudocapacitance. Moreover, we utilize a novel surface-pillar microstructure, along with an internally randomized multi-bubble structure within the dielectric layer, to significantly expand the linear response range of the sensor. The resulting IPS device demonstrates exceptional linear sensitivity, measuring approximately 153.83 kPa-1, across a broad pressure range of up to 260 kPa. Additionally, it exhibits long-term stability, rapid response and recovery characteristics, and remains functional underwater. Notably, these devices exhibit remarkable capabilities in monitoring ultrasonic vibrations and accurately identifying sound wave vibrations. The integration of composite electrodes, microstructure designs, and their compatibility with underwater applications positions these IPSs as highly promising tools for precise measurements and advancements in flexible electronics technology.

Co/Al Co-Substituted Layered Manganese-Based Oxide Cathode for Stable and High-Rate Potassium-Ion Batteries.

Manganese-based layered oxides are promising cathode materials for potassium-ion batteries (PIBs) due to their low cost and high theoretical energy density. However, the Jahn-Teller effect of Mn3+ and sluggish diffusion kinetics lead to rapid electrode deterioration and a poor rate performance, greatly limiting their practical application. Here, we report a Co/Al co-substitution strategy to construct a P3-type K0.45Mn0.7Co0.2Al0.1O2 cathode material, where Co3+ and Al3+ ions occupy Mn3+ sites. This effectively suppresses the Jahn-Teller distortion and alleviates the severe phase transition during K+ intercalation/de-intercalation processes. In addition, the Co element contributes to K+ diffusion, while Al stabilizes the layer structure through strong Al-O bonds. As a result, the K0.45Mn0.7Co0.2Al0.1O2 cathode exhibits high capacities of 111 mAh g-1 and 81 mAh g-1 at 0.05 A g-1 and 1 A g-1, respectively. It also demonstrates a capacity retention of 71.6% after 500 cycles at 1 A g-1. Compared to the pristine K0.45MnO2, the K0.45Mn0.7Co0.2Al0.1O2 significantly alleviates severe phase transition, providing a more stable and effective pathway for K+ transport, as investigated by in situ X-ray diffraction. The synergistic effect of Co/Al co-substitution significantly enhances the structural stability and electrochemical performance, contributing to the development of new Mn-based cathode materials for PIBs.

In situ formation of solidified supramolecular solvent based dispersive liquid-liquid microextraction for the enrichment of phenylurea herbicides in water, fruit juice, and milk.

A convenient, efficient, and green dispersive liquid-liquid microextraction based on the in situ formation of solidified supramolecular solvents combined with high performance liquid chromatography was developed for the determination of four phenylurea herbicides in liquid samples, including monuron, monolinuron, isoproturon, and chlortoluron. Herein, a novel supramolecular solvent was prepared by the in situ reaction of [P4448]Br and NH4PF6, which had the advantages of low melting point, high density, and good dispersibility. In addition, the microscopic morphology and physical properties of supramolecular solvent were characterized, and the extraction conditions were optimized. The results showed that the analytes had good linearity (R2 > 0.9998) within the linear range. The limits of detection and quantification for the four phenylurea herbicides were in the range of 0.13-0.19 µg L-1 and 0.45-0.65 µg L-1, respectively. The prepared supramolecular solvent is suitable for the efficient extraction of phenylurea herbicides in water, fruit juice, and milk.

Lightweight Dual-Functional Segregated Nanocomposite Foams for Integrated Infrared Stealth and Absorption-Dominant Electromagnetic Interference Shielding.

Lightweight infrared stealth and absorption-dominant electromagnetic interference (EMI) shielding materials are highly desirable in areas of aerospace, weapons, military and wearable electronics. Herein, lightweight and high-efficiency dual-functional segregated nanocomposite foams with microcellular structures are developed for integrated infrared stealth and absorption-dominant EMI shielding via the efficient and scalable supercritical CO2 (SC-CO2) foaming combined with hydrogen bonding assembly and compression molding strategy. The obtained lightweight segregated nanocomposite foams exhibit superior infrared stealth performances benefitting from the synergistic effect of highly effective thermal insulation and low infrared emissivity, and outstanding absorption-dominant EMI shielding performances attributed to the synchronous construction of microcellular structures and segregated structures. Particularly, the segregated nanocomposite foams present a large radiation temperature reduction of 70.2 °C at the object temperature of 100 °C, and a significantly improved EM wave absorptivity/reflectivity (A/R) ratio of 2.15 at an ultralow Ti3C2Tx content of 1.7 vol%. Moreover, the segregated nanocomposite foams exhibit outstanding working reliability and stability upon dynamic compression cycles. The results demonstrate that the lightweight and high-efficiency dual-functional segregated nanocomposite foams have excellent potentials for infrared stealth and absorption-dominant EMI shielding applications in aerospace, weapons, military and wearable electronics.

Linker substitution influences succinimide ring hydrolysis equilibrium impacting the stability of attachment to antibody-drug conjugates.

Maleimide chemistry is widely used in antibody-drug conjugate (ADC) generation to connect drugs to antibodies through a succinimide linker. The resulting ADC is prone to payload loss via a reverse Michael reaction, leading to premature drug release in vivo. Complete succinimide hydrolysis is an effective strategy to overcome the instability of ADC. However, we discovered through previous work that hydrolysed succinimide rings can close again in a liquid formulation during storage and under thermal stress conditions. In this work, a set of maleimide linkers with hydrolysis-prone groups were designed. The corresponding ADCs were prepared and subjected to thermal stress conditions. The extent of succinimide hydrolysis and drug release was measured, and ADC properties such as SEC, DAR, pI and clog P of linkers were calculated. Our results demonstrated that even though all these groups increased the hydrolysis rate, they have different impacts on maintaining the hydrolysed succinimide ring in an open conformation and ADC stability in a liquid formulation.

[Microcalorimetric investigation on the interaction of six alkaloids from rhizoma coptidis].

How to identify active constituents of traditional Chinese medicines (TCMs) and study their interactions are key problems in the development of TCMs. The inhibitory effect of six alkaloids from Rhizoma Coptidis (RC) on Shigella dysenteriae (S. dysenteria) growth had been investigated by microcalorimetry in this study. Main active constituents of RC were confirmed by comparing their contributions to the bacteriostatic effect, and the interactions among active constituents were further researched. According to the result, in 0.8 mg-mL-1 extract of RC, the contributions of six active alkaloids including berberine, coptisine, epiberberine, palmatine and the combination of jatrorrhizine and columbamine were 52.83%, 36.31%, 2.49%, 4.27% and 3.21%, respectively. Therefore, berberine and coptisine were the main active constituents of RC that inhibited the growth of S. dysenteria. The study of interactions among the six alkaloids indicated that, 1 there were some contstituents antagonizing the inhibitory effect of RC, 2 there was a synergy effect between berberine and coptisine, 3 there were additive effects between other four alkaloids and the main active constituents. These results may provide some useful references for the establishment of the quality standard for RC and the development of multi-component TCMs.

A causal relationship between antioxidants, minerals and vitamins and metabolic syndrome traits: a Mendelian randomization study.

BACKGROUND: The available evidence regarding the association of antioxidants, minerals, and vitamins with the risk of metabolic syndrome (MetS) traits is currently limited and inconsistent. Therefore, the purpose of this Mendelian randomization (MR) study was to investigate the potential causal relationship between genetically predicted antioxidants, minerals, and vitamins, and MetS. METHODS: In this study, we utilized genetic variation as instrumental variable (IV) to capture exposure data related to commonly consumed dietary nutrients, including antioxidants (ß-carotene, lycopene, and uric acid), minerals (copper, calcium, iron, magnesium, phosphorus, zinc, and selenium), and vitamins (folate, vitamin A, B6, B12, C, D, E, and K1). The outcomes of interest, namely MetS (n = 291,107), waist circumference (n = 462,166), hypertension (n = 463,010), fasting blood glucose (FBG) (n = 281,416), triglycerides (n = 441,016), and high-density lipoprotein cholesterol (HDL-C) (n = 403,943), were assessed using pooled data obtained from the most comprehensive genome-wide association study (GWAS) available. Finally, we applied the inverse variance weighting method as the result and conducted a sensitivity analysis for further validation. RESULTS: Genetically predicted higher iron (OR = 1.070, 95% CI 1.037-1.105, P = 2.91E-05) and magnesium levels (OR = 1.130, 95% CI 1.058-1.208, P = 2.80E-04) were positively associated with increased risk of MetS. For each component of MetS, higher level of genetically predicted selenium (OR = 0.971, 95% CI 0.957-0.986, P = 1.09E-04) was negatively correlated with HDL-C levels, while vitamin K1 (OR = 1.023, 95% CI 1.012-1.033, P = 2.90E-05) was positively correlated with HDL-C levels. Moreover, genetically predicted vitamin D (OR = 0.985, 95% CI 0.978-0.992, P = 5.51E-5) had a protective effect on FBG levels. Genetically predicted iron level (OR = 1.043, 95% CI 1.022-1.064, P = 4.33E-05) had a risk effect on TG level. CONCLUSIONS: Our study provides evidence that genetically predicted some specific, but not all, antioxidants, minerals, and vitamins may be causally related to the development of MetS traits.

Correlation between cellular uptake and cytotoxicity of polystyrene micro/nanoplastics in HeLa cells: A size-dependent matter.

The cytotoxicity of micro/nanoplastics (MNPs) is known to be strongly influenced by particle size, but the mechanism is not clear so far. We reported the ability of polystyrene MNPs to be internalized by HeLa cells could be a reason for the size dependent cytotoxicity of MNPs. We found that small MNPs (10 nm and 15 nm in radius) could be efficiently internalized by HeLa cells, MNPs of 25 nm in radius could be slightly internalized by the cells, and larger MNPs could not enter the cells at all. We showed that only MNPs, which could be internalized by cells, had a toxic effect on cell activity in a dose-dependent manner. In contrast, MNPs, which could not be internalized by cells, showed no cytotoxicity even if at extremely high concentrations. We attributed the correlation between the size-dependent uptake of MNPs and the size-dependent cytotoxicity of MNPs to the enhanced reactive oxygen species (ROS) level and abnormal gene expression. Our study pointed out that cellular uptake is one of the most fundamental mechanisms for the cytotoxicity of MNPs.