Metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion/Caco-2 cell transport, and their prebiotic effects during colonic fermentation.

The health-promoting activities of polyphenols and their metabolites originating from germinated quinoa (GQ) are closely related to their digestive behavior, absorption, and colonic fermentation; however, limited knowledge regarding these properties hinder further development. The aim of this study was to provide metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion and Caco-2 cell transport, whilst also investigating the changes in the major polyphenol metabolites and the effects of prebiotics during colonic fermentation. It was found that germination treatment increased the polyphenol content of quinoa by 21.91%. Compared with RQ group, 23 phenolic differential metabolites were upregulated and 47 phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after simulated digestion, 7 kinds of phenolic differential metabolites were upregulated and 17 kinds of phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after cell transport, 7 kinds of phenolic differential metabolites were upregulated and 9 kinds of phenolic differential metabolites were downregulated in GQ group. In addition, GQ improved the bioaccessibilities and transport rates of various polyphenol metabolites. During colonic fermentation, GQ group can also increase the content of SCFAs, reduce pH value, and adjust gut microbial populations by increasing the abundance of Actinobacteria, Bacteroidetes, Verrucomicrobiota, and Spirochaeota at the phylum level, as well as Bifidobacterium, Megamonas, Bifidobacterium, Brevundimonas, and Bacteroides at the genus level. Furthermore, the GQ have significantly inhibited the activity of α-amylase and α-glucosidase. Based on these results, it was possible to elucidate the underlying mechanisms of polyphenol metabolism in GQ and highlight its beneficial effects on the gut microbiota.

A reliable fluorescence "turn-on" aptasensor based on dual-emitting europium metal-organic frameworks for ultrasensitive and selective detection of sulfamethazine.

A high-performance fluorescent "turn-on" aptasensor (Eu-MOFs@SMZ-Apt) for sulfamethazine (SMZ) determination was designed using dual-emitting europium metal-organic frameworks (Eu-MOFs) as a signal transducer and an amplifier. Eu-MOFs featuring dual emission peaks (430 nm and 620 nm) were first prepared via a facile self-assembly strategy employing Eu (III) ions and 2-aminoterephthalic acid as precursors. The high-affinity aptamer was bonded with Eu-MOFs to form Eu-MOFs@SMZ-Apt through the amidation reaction. Benefiting from the integration of inherent virtues from Eu-MOFs and aptamer, the Eu-MOFs@SMZ-Apt-based sensor allowed sensitive and selective determination of SMZ with good linear relationships in a range of 1.4-40 ng mL-1 and a low detection line (0.379 ng mL-1). This sensor was successfully applied to the determination of trace SMZ in real samples with satisfactory recoveries (86.47-113.52%) and a relative standard deviation (<6.51). Consequently, the Eu-MOFs@SMZ-Apt ratiometric fluorescence sensor furnishes new possibilities for the accurate detection of various pollutants in food.

Supercapacitor Performance of Sulfonyldibenzene Derivative-Functionalized Graphene Aerogel.

3D aerogels incorporating functionalized reduced graphene oxide (SUL/rGO) were prepared as a hydrothermal method utilizing graphene oxide (GO) and a sulfonyldibenzene derivative (SUL) as raw materials. The aromatic compound SUL, which contains hydroxyl and sulfonyl groups, was bonded to reduced graphene oxide (rGO) through π-π connections. The obtained composite material exhibited porosity within its structure with improved hydrophilicity, along with excellent electrochemical characteristics. This improvement was ascribed to the specific rGO structure, as well as the pseudocapacitance inherent in SUL, both of which synergistically contribute to improvement in the characteristics of the prepared electrode materials. Also, an analysis was performed employing density functional theory from which the density of states and adsorption energy of SUL on the surface of rGO were computed to further investigate the charge storage process within the prepared composite. The prepared SUL/rGO-2 electrode exhibited the highest specific capacitance value of 388 F/g at a current density equal to 1 A/g. The constructed symmetrical supercapacitor, SUL/rGO-2//SUL/rGO-2, attained an energy density value of 14.55 Wh/kg at a power density equal to 350 W/kg with an exceptional galvanostatic charge-discharge (GCD) cyclic stability equal to 91% following 10 000 cycles. Therefore, this review presents a novel functionalized graphene-based material incorporating hydroxyl and sulfonyl groups, which holds promise in future energy storage applications.

Duoculture diminishes social interaction costs and improves growth rates of two fish species at different temperatures.

Duoculture has been reported to increase growth rates of some fishes when reared in combination, due to "shading" effects between the species. Two experiments, one involving outdoor cage-rearing in a reservoir, and the other, indoor tank-rearing, were conducted within each of three temperatures ranges (means of ~18.0°C, ~22.0°C and ~26.5°C), to determine whether duoculture of bluegill (BG) Lepomis macrochirus and yellow perch (YP) Perca flavescens would lead to improved growth relative to when the two species were reared separately. Juvenile bluegill and yellow perch were reared in triplicated groups each involving monoculture sets of 100% BG and 100% YP, and a duoculture set of 50% BG + 50% YP. Experiments in cages (Exp. 1) ran for 150 days while those in tanks ran for 126 days (Exp. 2). In Experiment 1, bluegill exhibited significantly greater (P<0.05) mean weight (P<0.05) in duoculture than in monoculture, under the high summer-like range of temperature (~26.5°C) over most of the experiment, whereas yellow perch showed no significant difference in mean weight in duoculture versus monoculture. By the end of a 150-d experiment, bluegill in duoculture outweighed those in monoculture by 62.5%. In Experiment 2, yellow perch in duoculture grew significantly larger than in monoculture (P<0.05) under the warm thermal regime (mean of ~22°C), while no significant differences were detected in mean weight of bluegill in monoculture versus duoculture. Yellow perch in duoculture outweighed those in monoculture by 33.1% at the end of the experiment. Yellow perch performed better in duoculture than in monoculture under the low thermal regime (mean of ~18°C) in both experiments. A significantly greater reduction of CVwt was observed for both bluegill and yellow perch in duoculture than in monoculture in Experiment 1, while no differences in CVwt reduction were detected for bluegill in Experiment 2. Feed conversion ratios (FCR) of bluegill and yellow perch reared in duoculture were significantly lower than for both fishes reared in monoculture in Experiment 1, while there were no significant differences in FCR among the three groups throughout most of Experiment 2. Findings indicate that duoculture of yellow perch and bluegill holds good potential to improve growth and FCR, and to reduce size variation by diminishing social interaction costs.

Bioinformatics leading to conveniently accessible, helix enforcing, bicyclic ASX motif mimics (BAMMs).

Helix mimicry provides probes to perturb protein-protein interactions (PPIs). Helical conformations can be stabilized by joining side chains of non-terminal residues (stapling) or via capping fragments. Nature exclusively uses capping, but synthetic helical mimics are heavily biased towards stapling. This study comprises: (i) creation of a searchable database of unique helical N-caps (ASX motifs, a protein structural motif with two intramolecular hydrogen-bonds between aspartic acid/asparagine and following residues); (ii) testing trends observed in this database using linear peptides comprising only canonical L-amino acids; and, (iii) novel synthetic N-caps for helical interface mimicry. Here we show many natural ASX motifs comprise hydrophobic triangles, validate their effect in linear peptides, and further develop a biomimetic of them, Bicyclic ASX Motif Mimics (BAMMs). BAMMs are powerful helix inducing motifs. They are synthetically accessible, and potentially useful to a broad section of the community studying disruption of PPIs using secondary structure mimics.

Association of urinary bisphenol A levels with heart failure risk in U.S. adults from the NHANES (2003-2016).

Introduction: Although heart failure (HF) has been linked to bisphenol A (BPA), few studies have investigated the cut-off values for the effects of urinary BPA levels on heart failure risk. The association between urinary BPA levels and HF prognosis has not been investigated. Methods: This study included 11,849 adults over 20 years old using information from the National Health and Nutrition Examination Survey (NHANES), which was conducted from 2003 to 2016. The relationship between urinary BPA levels and the risk of HF was determined via a multivariable logistic regression model, and restricted cubic spline (RCS) methods were used to determine the cut-off for the effect of BPA levels on HF risk. Based on the available NT-proBNP concentration data from the NHANES (2003-2004), multivariable linear regression was applied to determine the linear association between the NT-proBNP concentration and urinary BPA concentration. Results: The results revealed a positive correlation between a urinary BPA concentration in the fourth quartile and the occurrence of heart failure [OR 1.49, 95% CI (1.09, 2.04), p = 0.012]. A one-unit increase (1 ng/mg creatinine) in the ln-transformed BPA concentration was linked to a 15% increase in the incidence of HF [OR 1.15, 95% CI (1.03, 1.29), p = 0.014]. The cut-off urinary BPA concentration for HF risk was 1.51 ng/mg creatinine. There was a positive correlation between urinary BPA and NT-proBNP concentrations [ß = 0.093, 95% CI (0.014, 0.171), p = 0.02] in males, but there was no linear association [ß = 0.040, 95% CI (-0.033, 0.113), p = 0.283] in females. Discussion: Increased urinary BPA levels are linked to an increased risk of heart failure and poor prognosis. There is a significant increase in the risk of heart failure if the urinary concentration of BPA exceeds 1.51 ng/mg creatinine.

Injectable isoniazid-loaded bone cement based on hydrazone bonds achieving long-term release and decent mechanical properties.

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.

Dual-Capped Helical Interface Mimics.

Disruption of protein-protein interactions is medicinally important. Interface helices may be mimicked in helical probes featuring enhanced rigidities, binding to protein targets, stabilities in serum, and cell uptake. This form of mimicry is dominated by stapling between side chains of helical residues: there has been less progress on helical N-caps, and there were no generalizable C-caps. Conversely, in natural proteins, helicities are stabilized and terminated by C- and N-caps but not staples. Bicyclic caps previously introduced by us enable interface helical mimicry featuring rigid synthetic caps at both termini in this work. An unambiguously helical dual-capped system proved to be conformationally stable, binding cyclins A and E, and showed impressive cellular uptake. In addition, the dual-capped mimic was completely resistant to proteolysis in serum over an extended period when compared with "gold standard" hydrocarbon-stapled controls. Dual-capped peptidomimetics are a new, generalizable paradigm for helical interface probe design.

Resveratrol Delays Diabetic Cardiomyopathy Fibrosis by Regulating Mitochondrial Autophagy.

Objective: To explore whether resveratrol can postpone the fibrosis associated with diabetic cardiomyopathy (DCM) by modulating the mitochondrial autophagy response through the AMPK/SIRT1-mediated IRE1α/PINK signaling pathway. Methods: A DCM mouse model was established using a high-sugar high-fat diet and streptozotocin. Resveratrol was administered to a subset of the DCM mouse models for comparison. Echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy were employed to evaluate the cardiac status, myocardial fibrosis, myocardial cell apoptosis, and morphological changes of myocardial cells and their internal mitochondria in each group of mice. Western blot staining was performed on myocardial tissues to assess the protein expression levels of p-AMPK, SIRT1, SIRT3, p22, GP91, p-IRE1α, XBP1s PINK, Parkin, LC3I, and Beclin. Mouse myocardial cells were cultured in vitro and intervened with a high-sugar high-fat diet, resveratrol, and GSK690693 (an AMPK inhibitor) to observe the protein expression levels of p-AMPK, p22, XBP1s, and PINK in mouse myocardial cells in each group. Results: Results from echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy showed that resveratrol administration alleviated cardiac damage, myocardial fibrosis, myocardial cell apoptosis, and mitochondrial autophagy in DCM mice. Resveratrol administration promoted the expression of phosphorylated AMP-activated protein kinase (p-AMPK), sirtuin 1 (SIRT1), and sirtuin 3 (SIRT3) in the myocardial tissue of mice, while lowering the elevated protein expression levels of p22 subunit (p22), guanine nucleotide-binding protein q polypeptide 1 (GP91), phosphorylated inositol-requiring enzyme 1 alpha (p-IRE1α), X-box binding protein 1 spliced form (XBP1s), PTEN-induced putative kinase 1 (PINK), Parkin, microtubule-associated proteins light chain 3 isoform I (LC3I), and Beclin (Bcl-2 interacting protein) caused by DCM. GSK690693 (an AMPK inhibitor) suppressed the expression of p-AMPK, SIRT1, and SIRT3 and enhanced the protein expression of p22, XBP1s, and PINK. Conclusion: Resveratrol postpones dilated cardiomyopathy fibrosis by regulating the mitochondrial autophagy response through the AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1)-mediated inositol-requiring enzyme 1 alpha (IRE1α)/PTEN-induced putative kinase 1 (PINK) signaling pathway.

The anti-cholestatic effects of Coptis chinensis Franch. alone and combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley: dual effects on fecal metabolism and microbial diversity.

Introduction: Drug dosages and combinations are the main factors that affect the efficacy of pleiotropic traditional Chinese medicine (TCM). Coptis chinensis Franch. (CF) is a representative TCM with multiple effects and is often combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley (TR) to treat cholestasis. The present study assessed the influence of CF dose and its combination with TR on the efficacy of CF in cholestasis treatment, including their effects on fecal metabolism and fecal microorganisms. Methods: Rats with α-naphthylisothiocyanate (ANIT, 50 mg/kg)-induced cholestasis were administered low (0.3 g/kg) and high (0.6 g/kg) doses of CF, as well as CF combined with TR at doses of 0.6 g/kg and 0.9 g/kg, respectively. The anti-cholestatic effects of these treatments were assessed by determining their anti-inflammatory, hypolipidemic, and anti-oxidative stress properties. Additionally, fecal metabolomics and fecal microorganisms were analyzed. Results: Low dose CF had a more potent hypolipidemic effect than high dose CF, whereas high dose CF had more potent anti-inflammatory and anti-oxidative stress effects. Combination with TR enhanced the hypolipidemic effect, but antagonized the anti-inflammatory effect, of CF. Analyses of fecal metabolomics and fecal microorganisms showed differences in the regulation of lipid- and amino acid metabolism-related pathways, including pathways of linoleic acid, tyrosine, and arachidonic acid metabolism, and amino acid biosynthesis between different doses of CF as well as between different doses of CF in combination with TR. These differences may contribute to differences in the anti-cholestatic effects of these preparations. Conclusion: CF dose influences its anti-cholestatic efficacy. The combination with TR had synergistic or antagonistic effects on the properties of CF, perhaps by altering fecal metabolism and fecal microbial homeostasis.

Effect of photodynamic therapy mediated by hematoporphyrin derivatives on small cell lung cancer H446 cells and bronchial epithelial BEAS-2B cells.

To investigate the effects of photodynamic therapy (PDT) mediated by hematoporphyrin derivatives (HPD) on the proliferation of small cell lung cancer H446 cells and bronchial epithelial BEAS-2B cells. H446 cells and BEAS-2B cells were cultured in vitro with different concentrations of HPD(0, 5, 10, 12, 15, 20 µg/mL) for 4 h, and then irradiated with 630 nm laser with different energy densities (0, 25, 50, 75, 100 mW/cm2). Cell viability of H446 cells and BEAS-2B cells were detected by CCK8 assay. The cell apoptosis was observed with Annexin V-FTTC/PI double staining and Hoechst 33258. The RT-PCR examination was applied to detect the transcriptional changes of the mRNA of Bax、Bcl-2, and Caspase-9. The results of CCK8 showed that when the HPD was 15 µg/mL and the laser power density reached 50 mW/cm2, the cell viability was significantly decreased compared with the black control group. Hoechst 33258 staining showed that with the increase of HPD concentration, the cell density was reduced, and apoptotic cells increased. Flow cytometry assay revealed that the apoptotic rates of the HPD-PDT group of H446 cells and BEAS-2B cells were significantly different from those of the blank control group. The RT-PCR examination showed that the expression levels of Bax and Caspase-9 mRNA in the HPD-PDT group were up-regulated, while the expression levels of Bcl-2 mRNA were down-regulated significantly. HPD-PDT can inhibit H446 cells and BEAS-2B cells growth. The mechanism may be related to up-regulating the expression levels of Bax and Caspase-9 mRNA and down-regulating the expression levels of Bcl-2 mRNA.

The association between polychlorinated dibenzo-p-dioxin exposure and cancer mortality in the general population: a cohort study.

Introduction: Earlier research has indicated that being exposed to polychlorinated dibenzo-p-dioxins (PCDDs) in the workplace can heighten the likelihood of cancer-related deaths. Nevertheless, there is limited information available regarding the connection between PCDD exposure and the risk of cancer mortality in the general population (i.e., individuals not exposed to these substances through their occupation). Methods: The National Health and Nutrition Examination Survey (NHANES) detected PCDDs in the general population, and the death data were recently updated as of December 31, 2019. We conducted Cox regression analysis and controlled for covariates including age, gender, ethnicity, educational attainment, physical activity, alcohol intake, NHANES survey period, BMI category, cotinine concentration, and household earnings. Results: After accounting for confounding factors, the findings indicated that for each incremental rise of 1 log unit in 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, there was a 76% rise in the likelihood of death from any cause, with a p value of 0.003. An increase of 1 log unit in the concentration of 1,2,3,4,6,7,8-heptachlorodibenzofuran could potentially lead to a 90% higher risk of cancer mortality, as indicated by a p value of 0.034 and a 95% confidence interval of 0.05-2.43. As the concentrations of 1,2,3,4,6,7,8-heptachlorodibenzofuran increased, the dose-response curve indicated a proportional rise in the risk of cancer mortality, accompanied by a linear p value of 0.044. The sensitivity analysis demonstrated that our findings were resilient. Discussion: In the general population, an elevated risk of cancer mortality was observed in PCDDs due to the presence of 1,2,3,4,6,7,8-heptachlorodibenzofuran. Mechanistic research is required to further confirm it.

Association of organophosphate flame retardants with all-cause and cause-specific mortality among adults aged 40 years and older.

The longitudinal associations of urinary concentrations of diphenyl phosphate (DPHP), bis(2-chloroethyl) phosphate (BCEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCPP) with all-cause, cardiovascular, and cancer mortality in a population of adults aged 40 years and older are still unclear. A total of 3238 participants were included in this cohort study. Urinary BCEP levels were positively associated with all-cause mortality and cardiovascular mortality. Specifically, a logarithmic increase in BCEP concentration was related to a 26 % higher risk of all-cause mortality and a 32 % higher risk of cardiovascular mortality. No significant associations were observed for DPHP and BDCPP in relation to mortality. Doseresponse analysis confirmed the linear associations of BCEP with all-cause and cardiovascular mortality and the nonlinear inverted U-shaped association between DPHP exposure and all-cause mortality. Notably, the economic burden associated with BCEP exposure was estimated, and it was shown that concentrations in the third tertile of BCEP exposure incurred approximately 507 billion dollars of financial burden for all-cause mortality and approximately 717 billion dollars for cardiovascular mortality. These results highlight the importance of addressing exposure to BCEP and its potential health impacts on the population. More research is warranted to explore the underlying mechanisms and develop strategies for reducing exposure to this harmful chemical.

Notable Performance Enhancement of CsPbI2Br Solar Cells by a Dual-Function Strategy with CsPbBr3 Nanocrystals.

Herein, a dual-function strategy, in which CsPbI2Br is treated by CsPbBr3 nanocrystals (NCs) via addition and surface modification to construct the "electron bridge" and gradient heterojunction, respectively, to notably improve the performance of the CsPbI2Br solar cells, is proposed. The "electron bridge" formed by the CsPbBr3 NCs provides an extra transport channel for the photogenerated electrons in the CsPbI2Br layer, thus facilitating electron transport. Meanwhile, surface modification of CsPbI2Br by the CsPbBr3 NCs forms a gradient heterojunction between the CsPbI2Br layer and the P3HT layer, enhancing hole extraction accordingly. In addition, the CsPbBr3 NC treatment passivates the defects at the bulk and surface of the CsPbI2Br layers, thus suppressing carrier recombination. Thanks to these positive effects of the CsPbBr3 NCs, the demonstration device with a simple configuration of ITO/SnO2/CsPbI2Br/P3HT/Ag achieves a notable power conversion efficiency of 17.03%, which is among the highest efficiencies reported for CsPbI2Br-based solar cells.

Effect of long-acting versus short-acting glucagon-like peptide-1 receptor agonists on improving body weight and related metabolic parameters in type 2 diabetes: A head-to-head meta-analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) showed great value in treating nonalcoholic fatty liver disease (NAFLD). We aimed to compare the effectiveness of long-acting and short-acting GLP-1RAs on improving body weight and related metabolic parameters in patients with type 2 diabetes (T2DM) as a reference for the treatment of NAFLD with T2DM. METHODS: We searched eligible randomized controlled trials (RCTs) in PubMed, Embase, Cochrane and web of science database until August 2023. The risk of bias of included RCTs were assessed by the Risk Assessment of Cochrane Review items. We mainly drew forest plots to compare the effects of long and short acting GLP-1 RAs using RevMan 5.4. RESULTS: Twelve RCTs involving 2751 patients were included in our meta-analysis. Compared with short-acting GLP-1 RAs, the long-acting group was better in body weight (P < .00001, MD = -0.65, 95% confidence interval [CI] [-0.90, -0.40], I2 = 20%), and the same results in glycosylated hemoglobin (HbA1c) (P < .00001, MD = -0.43, 95% CI [-0.54, -0.33], I2 = 55%) and fasting plasma glucose (FPG) (P < .00001, MD = -0.77, 95% CI [-1.01, -0.52], I2 =70%). For the lipid parameters, long-acting drugs lowered cholesterol (TC) (P = .02, SMD = -0.19, 95% CI [-0.35, -0.03], I2 =57%) and low-density lipoprotein (LDL) (P = .02, SMD = -0.17, 95% CI [-0.33, -0.02], I2 =51%) more significantly compared with short-acting drugs. But treatment differences were not significant in triglycerides (TG) (P = .40, SMD = -0.05, 95% CI [-0.15, -0.06], I2 = 0%), and high-density lipoprotein (HDL) (P = .85, SMD = -0.01, 95% CI [-0.11, -0.09], I2 = 0%). CONCLUSION: Long-acting GLP-1RAs may be more promise than short-acting GLP-1RAs in improving weight and related metabolic parameters.

Compressive sensing-based tomography for Absolute X-ray UltraViolet (AXUV) diagnostics.

Absolute x-ray ultraviolet diagnostics ensures 2D coverage of the radiation emission region that enables tomographic reconstruction. However, retrieving the local emissivity via tomography remains a challenge due to its ill-posed nature. Tikhonov regularization with smoothness operation generally performs well but tends to over-smooth regions with steep gradients and local structure in the radiation profile and may introduce artifacts. In this paper, a tomography method based on compressive sensing theory with Tikhonov regularization terms is developed. Experimental results on multiple phantom sets show that the proposed method improves the reconstruction accuracy and quality in regions with steep gradients compared with the Tikhonov regularization method and suppresses the unphysical negative emissivity. The analysis of reconstruction uncertainty shows that the dictionary learning process provides more accurate prior information about steep gradients to improve the quality of reconstructed images, and compressive sensing has the denoising capability to reduce the impact of noise. Finally, the method is validated by data from the Sino-UNIted Spherical Tokamak, showing fewer artifacts and more reliable reconstruction images than the earlier method.

Catalyzing Generation and Stabilization of Oxygen Vacancies on CeO2-x Nanorods by Pt Nanoclusters as Nanozymes for Catalytic Therapy.

Although CeO2 nanomaterials have been widely explored as nanozymes for catalytic therapy, they still suffer from relatively low activities. Herein, the catalyzing generation and stabilization of oxygen vacancies on CeO2 nanorods by Pt nanoclusters via H2 gas reduction under mild temperature (350 °C) to obtain Pt/CeO2- x , which can serve as a highly efficient nanozyme for catalytic cancer therapy, is reported. The deposited Pt on CeO2 by the atomic layer deposition technique not only can serve as the catalyst to generate oxygen vacancies under mild temperature reduction through the hydrogen spillover effect, but also can stabilize the generated oxygen vacancies. Meanwhile, the oxygen vacancies also provide anchoring sites for Pt forming strong metal-support interactions and thus preventing their agglomerations. Importantly, the Pt/CeO2- x reduced at 350 °C (Pt/CeO2- x -350R) exhibits excellent enzyme-mimicking catalytic activity for generation of reactive oxygen species (e.g., ·OH) as compared to other control samples, including CeO2 , Pt/CeO2 , and Pt/CeO2- x reduced at other temperatures, thus achieving excellent performance for tumor-specific catalytic therapy to efficiently eliminate cancer cells in vitro and ablate tumors in vivo. The excellent enzyme-mimicking catalytic activity of Pt/CeO2- x -350R originates from the good catalytic activities of oxygen vacancy-rich CeO2- x and Pt nanoclusters.

Mediation analysis of urinary metals and stroke risk by inflammatory markers.

BACKGROUND: The association between metals and stroke has been reported, but the mediating role of inflammation between metals and stroke remains unclear. METHODS: We included 9326 adults from the National Health and Nutrition Examination Survey in this study. Through least absolute selection and shrinkage operator (LASSO) regression, weighted quantile sum (WQS) regression, logistic regression, linear regression, restricted cubic spline analysis, and mediation analysis, we explored the association between metals and stroke, as well as the association between metals and inflammatory indicators, and further evaluated the mediating effect of inflammatory indicators on the association between selected metals and stroke risk. RESULTS: The results of the present study suggested positive associations between mixed metals, cadmium and uranium and stroke risk. There is a positive correlation and dose‒response relationship between cadmium and C-reactive protein (CRP). Moreover, CRP mediates 10.1% of the association between cadmium and stroke. CONCLUSIONS: At the epidemiological level, CRP mediates the association between cadmium and stroke risk, suggesting that inflammation may be a potential mechanism for metal-induced stroke.

Flexible nanofibrous membranes of dual metallic metal-organic framework with enhanced Lewis basic sites and high loading mass for efficient CO2 capture.

Excessive CO2 emissions and the resultant global warming present significant environmental challenges, posing threats to human health and public safety. Metal-organic frameworks (MOFs), known for their high specific area and large porosity, hold the promise for CO2 capture. However, a major obstacle is the low loading mass of MOFs and the limited interface affinity and compatibility between MOFs and substrates. In this study, we present an electrospinning-assisted in-situ synthesis dual metallic framework strategy for preparing flexible Zn/Co-ZIF nanofibrous membranes (NFMs). This method achieves the high loading mass of MOFs and introduces abundant Lewis basic sites, thereby enhancing the CO2 adsorption. The dual metallic Zn/Co-ZIF NFMs exhibit remarkable features, including high MOF loading mass (70.23 wt%), high specific surface area (379.63 m2g-1), large porosity (92.34 %), high CO2 adsorption capacity (4.43 mmol/g), high CO2/N2 adsorption selectivity (37), and high CO2/CH4 adsorption selectivity (31). Moreover, the dual metallic Zn/Co-ZIF NFMs demonstrate robust structural stability and durability attributed to the excellent interface affinity between MOFs and NFMs, retaining 96.56 % of their initial capacity after 10 adsorption-desorption cycles. This work presents a prospective direction for developing flexible dual metallic MOF NFMs for the efficient capture of CO2.

PROTAC-mediated CDK degradation differentially impacts cancer cell cycles due to heterogeneity in kinase dependencies.

BACKGROUND: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We investigate whether the differential requirements of CDKs in multiple cell lines function as determinant of response to pharmacological agents that target these kinases. METHODS: We utilized proteolysis-targeted chimeras (PROTACs) that are conjugated with palbociclib (Palbo-PROTAC) to degrade both CDK4 and CDK6. FN-POM was synthesized by chemically conjugating pomalidomide moiety with a multi-kinase inhibitor, FN-1501. Patient derived PDAC organoids and PDX model were utilized to investigate the effect of FN-POM in combination with palbociclib. RESULTS: Palbo-PROTAC mediates differential impact on cell cycle in different tumor models, indicating that the dependencies to CDK4 and 6 kinases are heterogenous. Cyclin E overexpression uncouples cell cycle from CDK4/6 and drives resistance to palbo-PROTAC. Elevated expression of P16INK4A antagonizes PROTAC-mediated degradation of CDK4 and 6. FN-POM degrades cyclin E and CDK2 and inhibits cell cycle progression in P16INK4A-high tumor models. Combination of palbociclib and FN-POM cooperatively inhibit tumor cell proliferation via RB activation. CONCLUSION: Resistance to CDK4/6 inhibition could be overcome by pharmacologically limiting Cyclin E/CDK2 complex and proves to be a potential therapeutic approach.