Synthesis and Antifungal Activity of Norbornene Carboxamide/sulfonamide Derivatives as Potential Fungicides Targeting Laccase.

To explore more potential fungicides with new scaffolds, thirty-seven norbornene carboxamide/sulfonamide derivatives were designed, synthesized, and assayed for inhibitory activity against six plant pathogenic fungi and oomycetes. The preliminary antifungal assay suggested that the title derivatives showed moderate to good antifungal activity against six plant pathogens. Especially, compound 6 e presented excellent in vitro antifungal activity against Sclerotinia sclerotiorum (EC50=0.71 mg/L), which was substantially stronger than pydiflumetofen. In vivo antifungal assay indicated 6 e displayed prominent protective and curative effects on rape leaves infected by S. sclerotiorum. The preliminary mechanism research displayed that 6 e could damage the surface morphology and inhibit the sclerotia formation of S. sclerotiorum. In addition, the in vitro enzyme inhibition bioassay indicated that 6 e displayed pronounced laccase inhibition activity (IC50=0.63 µM), much stronger than positive control cysteine. Molecular docking elucidated the binding modes between 6 e and laccase. The bioassay results and mechanism investigation demonstrated that this class of norbornene carboxamide/sulfonamide derivatives could be promising laccase inhibitors for novel fungicide development.

Design, synthesis, antifungal evaluation and mechanism study of novel norbornene derivatives as potential laccase inhibitors.

BACKGROUND: To discover novel fungicide candidates, five series of novel norbornene hydrazide, bishydrazide, oxadiazole, carboxamide and acylthiourea derivatives (2a-2t, 3a-3f, 4a-4f, 5a-5f and 7a-7f) were designed, synthesized and assayed for their antifungal activity toward seven representative plant fungal pathogens. RESULTS: In the in vitro antifungal assay, some title norbornene derivatives presented good antifungal activity against Botryosphaeria dothidea, Sclerotinia sclerotiorum and Fusarium graminearum. Especially, compound 2b exhibited the best inhibitory activity toward B. dothidea with the median effective concentration (EC50) of 0.17 mg L-1, substantially stronger than those of the reference fungicides boscalid and carbendazim. The in vivo antifungal assay on apples revealed that 2b had significant curative and protective effects, both of which were superior to boscalid. In the preliminary antifungal mechanism study, 2b was able to injure the surface morphology of hyphae, destroy the cell membrane integrity and increase the intracellular reactive oxygen species (ROS) level of B. dothidea. In addition, 2b could considerably inhibit the laccase activity with the median inhibitory concentration (IC50) of 1.02 µM, much stronger than that of positive control cysteine (IC50 = 35.50 µM). The binding affinity and interaction mode of 2b with laccase were also confirmed by molecular docking. CONCLUSION: This study presented a promising lead compound for the study of novel laccase inhibitors as fungicidal agrochemicals, which demonstrate significant anti-B. dothidea activity and laccase inhibitory activity. © 2024 Society of Chemical Industry.

Increased glycemic variability results in abnormal differentiation of T cell subpopulation in type 2 diabetes patients.

AIMS: We aimed to investigate the association between glycemic variability (GV) and the abnormal differentiation of T-cell subpopulations in patients with type 2 diabetes mellitus (T2DM). METHODS: In total, 108 hospitalized patients with T2DM were enrolled and divided into two subgroups (normal glycemic excursion (NGE) and high glycemic excursion (HGE)) according to their mean amplitude of glycemic excursion (MAGE) level. The MAGE was evaluated via continuous glucose monitoring for 72 h consecutively. Flow cytometry was used to determine the proportions of T cell subpopulations. RESULTS: The T helper (Th) 1 cell/Th2 cell ratio was significantly higher, and the proportion of regulatory T cells (Tregs) was significantly lower in the NGE group than in the HGE group (all P < 0.05). After fully adjusting for confounders, the MAGE was positively associated with the Th1 cell/Th2 cell ratio (ß = 0.370; P = 0.009) and negatively associated with the proportion of Tregs (ß = -0.554; P = 0.001). CONCLUSION: The MAGE was an independent risk factor for abnormally high Th1 cell/Th2 cell ratio and proportion of Tregs. Abnormal differentiation of T cell subpopulations induced by GV may impair ß-cell function, aggravate insulin resistance, and contribute to the development of diabetic complications.

Increased miR-3074-5p expression promotes M1 polarization and pyroptosis of macrophages via ERα/NLRP3 pathway and induces adverse pregnancy outcomes in mice.

Decidual macrophages (dMϕs) play critical roles in regulation of immune-microhomeostasis at maternal-fetal interface during pregnancy, but the underlying molecular mechanisms are still unclear. In this study, it was found that litter size and fetal weight were significantly reduced, whereas the rate of embryo resorption was increased in miR-3074-5p knock-in (3074-KI) pregnant mice, compared to that of wild-type (WT) pregnant mice. Plasma levels of pro-inflammatory cytokines in 3074-KI pregnant mice were also significantly elevated compared to WT pregnant mice at GD7.5. The quantity of M1-Mϕs in uterine tissues of 3074-KI pregnant mice was significantly increased compared to WT pregnant mice at GD13.5. Estrogen receptor-α (ERα) was validated to be a target of miR-3074-5p. Either miR-3074-5p overexpression or ERα knockdown promoted transcriptional activity of NF-κB/p65, induced M1-polarization and pyroptosis of THP1-derived Mϕs, accompanied with increased intracellular levels of cleaved Caspase-1, cleaved IL-1ß, NLRP3, cleaved GSDMD and ASC aggregation. Furthermore, ERα could not only bind to NLRP3 or ASC directly, but also inhibit the interaction between NLRP3 and ASC. The endometrial miR-3074-5p expression level at the middle secretory stage of repeated implantation failure (RIF) patients was significantly decreased compared to that of control fertile women. These data indicated that miR-3074-5p could promote M1 polarization and pyroptosis of Mϕs via activation of NLRP3 inflammasome by targeting ERα, and the dysregulation of miR-3074-5p expression in dMϕs might damage the embryo implantation and placentation by interfering with inflammatory microenvironment at the maternal-fetal interface during early pregnancy.

Particulate polycyclic aromatic hydrocarbons and metals, DNA methylation and DNA methyltransferase among middle-school students in China.

The main components of particulate matter (PM) had been reported to change DNA methylation levels. However, the mixed effect of PM and its constituents on DNA methylation and the underlying mechanism in children has not been well characterized. To investigate the association between single or mixture exposures and global DNA methylation or DNA methyltransferases (DNMTs), 273 children were recruited (110 in low-exposed area and 163 in high-exposed area) in China. Serum benzo[a]pyridin-7,8-dihydroglycol-9, 10-epoxide (BPDE)-albumin adduct and urinary metals were determined as exposure markers. The global DNA methylation (% 5mC) and the mRNA expression of DNMT1, and DNMT3A were measured. The linear regression, quantile-based g-computation (QGC), and mediation analyses were performed to investigate the effects of individual and mixture exposure. We found that significantly lower levels of % 5mC (P < 0.001) and the mRNA expression of DNMT3A in high-PM exposed group (P = 0.031). After adjustment for age, gender, BMI z-score, detecting status of urinary cotinine, serum folate, and white blood cells, urinary arsenic (As) was negatively correlated with the % 5mC. One IQR increase in urinary As (19.97 µmol/mol creatinine) was associated with a 11.06 % decrease in % 5mC (P = 0.026). Serum BPDE-albumin adduct and urinary cadmium (Cd) were negatively correlated with the levels of DNMT1 and DNMT3A (P < 0.05). Mixture exposure was negatively associated with expression of DNMT3A in QGC analysis (ß: -0.19, P < 0.001). Mixture exposure was significantly associated with decreased % 5mC in the children with non-detected cotinine or normal serum folate (P < 0.05), which the most contributors were PAHs and As. The mediated effect of hypomethylation through DNMT1 or DNMT3A pathway was not observed. Our findings indicated that individual and mixture exposure PAHs and metal components had negative associations with global DNA methylation and decreased DNMT3A expression significantly in school-age individuals.

B-Myb deficiency boosts bortezomib-induced immunogenic cell death in colorectal cancer.

B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb-defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb-defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb-defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage-associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb-defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.

Economic Evaluation of COVID-19 Immunization Strategies: A Systematic Review and Narrative Synthesis.

OBJECTIVES: This study aimed to systematically assess global economic evaluation studies on COVID-19 vaccination, offer valuable insights for future economic evaluations, and assist policymakers in making evidence-based decisions regarding the implementation of COVID-19 vaccination. METHODS: Searches were performed from January 2020 to September 2023 across seven English databases (PubMed, Web of Science, MEDLINE, EBSCO, KCL-Korean Journal Dataset, SciELO Citation Index, and Derwent Innovations Index) and three Chinese databases (Wanfang Data, China Science and Technology Journal, and CNKI). Rigorous inclusion and exclusion criteria were applied. Data were extracted from eligible studies using a standardized data collection form, with the reporting quality of these studies assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). RESULTS: Of the 40 studies included in the final review, the overall reporting quality was good, evidenced by a mean score of 22.6 (ranging from 10.5 to 28). Given the significant heterogeneity in fundamental aspects among the studies reviewed, a narrative synthesis was conducted. Most of these studies adopted a health system or societal perspective. They predominantly utilized a composite model, merging dynamic and static methods, within short to medium-term time horizons to simulate various vaccination strategies. The research strategies varied among studies, investigating different doses, dosages, brands, mechanisms, efficacies, vaccination coverage rates, deployment speeds, and priority target groups. Three pivotal parameters notably influenced the evaluation results: the vaccine's effectiveness, its cost, and the basic reproductive number (R0). Despite variations in model structures, baseline parameters, and assumptions utilized, all studies identified a general trend that COVID-19 vaccination is cost-effective compared to no vaccination or intervention. CONCLUSIONS: The current review confirmed that COVID-19 vaccination is a cost-effective alternative in preventing and controlling COVID-19. In addition, it highlights the profound impact of variables such as dose size, target population, vaccine efficacy, speed of vaccination, and diversity of vaccine brands and mechanisms on cost effectiveness, and also proposes practical and effective strategies for improving COVID-19 vaccination campaigns from the perspective of economic evaluation.

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis.

Objective: To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis (EPTB). Methods: This study was conducted at the Shanghai Public Health Clinical Center. A total of 115 patients underwent ultrasound-guided puncture biopsy, followed by MGIT 960 culture (culture), smear, GeneXpert MTB/RIF (Xpert), and histopathological examination. These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria: liquid culture and composite reference standard (CRS). Results: When CRS was used as the reference standard, the sensitivity and specificity of culture, smear, Xpert, and histopathological examination were (44.83%, 89.29%), (51.72%, 89.29%), (70.11%, 96.43%), and (85.06%, 82.14%), respectively. Based on liquid culture tests, the sensitivity and specificity of smear, Xpert, and pathological examination were (66.67%, 72.60%), (83.33%, 63.01%), and (92.86%, 45.21%), respectively. Histopathological examination showed the highest sensitivity but lowest specificity. Further, we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80% and a specificity of 89.29%. Conclusion: Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB. Compared with culture, smear, and Xpert, histopathological examination showed higher sensitivity but lower specificity. The combination of histopathology with Xpert showed the best performance characteristics.

Phthalate metabolites and sex steroid hormones in relation to obesity in US adults: NHANES 2013-2016.

Background: Obesity and metabolic syndrome pose significant health challenges in the United States (US), with connections to disruptions in sex hormone regulation. The increasing prevalence of obesity and metabolic syndrome might be associated with exposure to phthalates (PAEs). Further exploration of the impact of PAEs on obesity is crucial, particularly from a sex hormone perspective. Methods: A total of 7780 adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 were included in the study. Principal component analysis (PCA) coupled with multinomial logistic regression was employed to elucidate the association between urinary PAEs metabolite concentrations and the likelihood of obesity. Weighted quartiles sum (WQS) regression was utilized to consolidate the impact of mixed PAEs exposure on sex hormone levels (total testosterone (TT), estradiol and sex hormone-binding globulin (SHBG)). We also delved into machine learning models to accurately discern obesity status and identify the key variables contributing most to these models. Results: Principal Component 1 (PC1), characterized by mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) as major contributors, exhibited a negative association with obesity. Conversely, PC2, with monocarboxyononyl phthalate (MCNP), monocarboxyoctyl phthalate (MCOP), and mono(3-carboxypropyl) phthalate (MCPP) as major contributors, showed a positive association with obesity. Mixed exposure to PAEs was associated with decreased TT levels and increased estradiol and SHBG. During the exploration of the interrelations among obesity, sex hormones, and PAEs, models based on Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) algorithms demonstrated the best classification efficacy. In both models, sex hormones exhibited the highest variable importance, and certain phthalate metabolites made significant contributions to the model's performance. Conclusions: Individuals with obesity exhibit lower levels of TT and SHBG, accompanied by elevated estradiol levels. Exposure to PAEs disrupts sex hormone levels, contributing to an increased risk of obesity in US adults. In the exploration of the interrelationships among these three factors, the RF and XGBoost algorithm models demonstrated superior performance, with sex hormones displaying higher variable importance.

Red ginseng ameliorates lipotoxicity-induced renal fibrosis in hyperuricemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic kidney disease can be caused by numerous diseases including obesity and hyperuricemia (HUA). Obesity may exacerbate the renal injury caused by HUA. Red ginseng, a steamed products of Panax ginseng Meyer root, is known for its remarkable efficacy in improving metabolic syndrome, such as maintaining lipid metabolic balance. However, the role of red ginseng on hyperuricemia-induced renal injury in obese cases remains unclear. AIM OF THE STUDY: This study aimed to investigate the action of red ginseng extract (RGE) on lipotoxicity-induced renal injury in HUA mice. MATERIALS AND METHODS: A high-fat diet (HFD)-induced obesity model was employed to initially investigate the effects of RGE on body weight, TC, OGTT, renal lipid droplets, and renal function indices such as uric acid, creatinine, and urea nitrogen. Renal structural improvement was demonstrated by H&E staining. Subsequently, an animal model combining obesity and HUA was established to further study the impact of RGE on OAT1 and ACC1 expression levels. The mechanisms underlying renal injury regulation by RGE were postulated on the basis of RNA sequencing, which was verified by immunohistochemical (including F4/80, Ki67, TGF-ß1, α-SMA, and E-cadherin), Masson, and Sirius red staining. RESULTS: RGE modulated HFD-induced weight gain, glucose metabolism, and abnormalities of uric acid, urea nitrogen, and creatinine. RGE alleviated the more severe renal histopathological changes induced by obesity combined with HUA, with down-regulated the protein levels of ACC1, F4/80, Ki67, TGF-ß1, and α-SMA, and up-regulated OAT1 and E-cadherin. CONCLUSIONS: RGE has ameliorative effects on chronic kidney disease caused by obesity combined with HUA by maintaining lipid balance and reducing renal inflammation and fibrosis.

Assessment of sedation by automated pupillometry in critically ill patients: a prospective observational study.

BACKGROUND: Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. METHODS: In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from -5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥-2), moderate (RASS =-3), and deep sedation (RASS ≤-4) was assessed by areas under receiver operating characteristic (ROC) curves. RESULTS: A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17-25%) to 36% (interquartile range 33-40%) (P<0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients.

A novel dual-responsive colorimetric/fluorescent probe for the detection of N2H4 and ClO- and its application in environmental analysis and bioimaging.

Hydrazine (N2H4) and hypochlorite (ClO-) are both reactive chemical substances extensively utilized across various industrial domains. Excessive hydrazine (N2H4) and hypochlorite (ClO-) can pose significant risks to the environment, ecosystems, and human health. In order to assess and control the environmental hazard caused by N2H4 and ClO-, there is an imperative need for efficient methods capable of rapid and precise detection of these contaminants. This paper introduces a novel dual-responsive colorimetric/fluorescent probe (MDT) for the detection of N2H4 and ClO- in environmental and biological samples. The probe exhibits turn-on fluorescent responses to N2H4 or ClO- with low detection limits (N2H4: 8 nM; ClO-: 15 nM), large Stokes shifts (N2H4: 175 nm; ClO-: 203 nm), short response time (N2H4: 4 min; ClO-: 5 s) and broad pH range (5-10). In practical applications, MDT has been successfully employed in detecting N2H4 and ClO- in water and soil samples from diverse locations. Test strips loaded with MDT offer a visual and convenient means to track N2H4 vapor and quantify N2H4 and ClO- concentrations in solutions. Finally, MDT has been utilized for sensing N2H4 and ClO- in Arabidopsis thaliana roots and living zebrafish. This study presents a promising tool for monitoring N2H4 and ClO- in the environment and living organisms.

The association between per-/polyfluoroalkyl substances in serum and thyroid function parameters: A cross-sectional study on teenagers living near a Chinese fluorochemical industrial plant.

Thyroid hormones (THs) play an important role in a wide range of crucial biological functions related to growth and development, and thyroid antibodies (TAs) can influence the biosynthesis of THs. Epidemiological studies have indicated that per- and polyfluoroalkyl substances (PFAS) could induce thyroid disruption, but studies on teenagers living in areas with high PFAS exposure are limited. This cross-sectional study focused on 836 teenagers (11- 15 years) living near a Chinese fluorochemical industrial plant. Decreased levels of free thyroxine (FT4, ﹤9.6 pmol/L, abnormal rate = 19.0 %) and elevated levels of free triiodothyronine (FT3, ï¹¥6.15 pmol/L, abnormal rate = 29.8 %) were observed. Correlations of serum PFAS concentrations and TAs/THs were analyzed. Increased PFOA was identified as a risk factor of decreased FT4 by using unadjusted (OR: 11.346; 95 % CI: 6.029, 21.352, p < 0.001) and adjusted (OR: 12.566; 95 % CI: 6.549, 24.115, p < 0.001) logistic regression models. In addition, significantly negative correlations were found between log10 transformed PFOA and FT4 levels using linear (unadjusted: ß = -1.543, 95 % CI: -1.937, -1.148, p < 0.001; adjusted: ß = -1.534, 95 % CI: -1.930, -1.137, p < 0.001) and BKMR models. For abnormal FT3, a significantly positive association between PFHxS and FT3 levels was observed in a regression model (unadjusted: ß = -0.903, 95 % CI: -1.212, -0.595, p < 0.001; adjusted: ß = -0.894, 95 % CI: -1.204, -0.583, p < 0.001), and PFHxS was identified as a risk factor (unadjusted: OR: 4.387; 95 % CI: 2.619, 7.346, p < 0.001; adjusted: OR: 4.527; 95 % CI: 2.665, 7.688, p < 0.001). Sensitivity analyses confirmed the robustness of the above results. This study reported the elevated PFAS exposure and thyroid function of teenagers living near a fluorochemical industrial plant from China.

Mesenchymal Stromal Cell Therapy Alleviates Ovalbumin-Induced Chronic Airway Remodeling by Suppressing M2 Macrophage Polarization.

Chronic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Previous studies have shown that mesenchymal stromal/stem cells (MSCs) exert anti-inflammatory effects on asthma via regulation of the immune cells. However, the therapeutic mechanism of MSCs, especially the mechanism of airway remodeling in chronic asthma, remains to be elucidated. Here, we aimed to investigate the therapeutic effect of MSCs on airway remodeling in chronic asthma and explored the mechanisms by analyzing the polarization phenotype of macrophages in the lungs. We established a mouse model of chronic asthma induced by ovalbumin (OVA) and evaluated the effect of MSCs on airway remodeling. The data showed that MSCs treatment before the challenge exerted protective effects on OVA-induced chronic asthma, i.e., decreased the inflammatory cell infiltration, Th2 cytokine levels, subepithelial extracellular matrix deposition, and transforming growth factor ß (TGF-ß)/Smad signaling. Additionally, we found that MSCs treatment markedly suppressed macrophage M2 polarization in lung tissue. At the same time, MSCs treatment inhibited NF-κB p65 nuclear translocation, ER stress, and oxidative stress in the OVA-induced chronic allergic airway remodeling mice model. In conclusion, these results demonstrated that MSCs treatment prevents OVA-induced chronic airway remodeling by suppressing macrophage M2 polarization, which may be associated with the dual inhibition of ER stress and oxidative stress. This discovery may provide a new theoretical basis for the future clinical application of MSCs.

Doping Ru on FeNi LDH/FeII/III-MOF heterogeneous core-shell structure for efficient oxygen evolution.

Noble metal-based catalysts such as RuO2 and IrO2 are widely used in the catalysis of the OER. However, because of their high price and poor stability, it is urgent to develop transition metal-based electrocatalysts with low precious metal doping as an alternative. Layered double hydroxides (LDHs) grown on 3D metal-organic frameworks (MOFs) are ideal for doping precious metals owing to abundant defects at the heterointerface, large surface area, and intrinsic oxygen evolution activity. In this study, a novel FeNi LDH/MOF heterostructure was prepared via a two-step solvothermal method using Fe-soc-MOFs as the substrate. Subsequently, Ru was introduced through a hydrothermal process. The as-synthesized Ru@FeNi LDH/MOF has an overpotential of only 242 mV at a current density of 10 mA cm-2 and can be used in continuous electrolysis for 48 h. Its unique nanocubic core-shell structure and flower-like LDHs on its surface provide a large number of active sites, which become the key to ensuring high activity and stability. With the doping of Ru, the electronic structure was adjusted and electron transfer was accelerated, further improving electrochemical activity. This study provides a new idea for developing transition metal-based catalysts with low noble metal loading.

Fe-Based Metal Organic Framework-Derived FeNiP/N-Doped Carbon Heterogeneous Core-Shell Structures for Oxygen Evolution.

It is of great significance to explore high activity, low overpotential, and outstanding durability electrocatalysts without precious metals for oxygen evolution reaction to reduce the energy consumption in the electrolysis of water to product hydrogen. Metal organic frameworks (MOFs) with periodic structure and uniform pore distribution have been widely used as precursors for the synthesis of transition metal electrocatalysts. Herein, we first synthesized nanoscale Fe-soc-MOFs with relatively high specific surface area and in situ converted it into nickel-iron double layer hydroxide/MOF (FeNi LDH/MOF) by Ni2+ etching. Finally, a nickel-iron phosphide/nitrogen-doped carbon cubic nanocage (FeNiP/NC) was obtained by calcination and phosphating. FeNiP/NC with its unique core-shell structure has an overpotential of only 240 mV at a current density of 10 mA/cm2 and can be continuously electrolyzed for 45 h. High catalytic activity of FeNiP/NC is mainly attributed to the action of Fe and Ni bimetals and the synergistic effect between FeNiP and N-doped porous carbon, which was confirmed by the calculation of density functional theory (i.e., Gibbs free energy). After a long period of electrolysis, FeNiP was converted to MOOH (M = Fe and Ni) and became the new active site. This study provides a feasible optimization strategy for the development of high-efficiency three-dimensional electrode materials without precious metals.

An interactive web application to identify early Parkinsonian non-tremor-dominant subtypes.

BACKGROUND: Parkinson's disease (PD) patients with tremor-dominant (TD) and non-tremor-dominant (NTD) subtypes exhibit heterogeneity. Rapid identification of different motor subtypes may help to develop personalized treatment plans. METHODS: The data were acquired from the Parkinson's Disease Progression Marker Initiative (PPMI). Following the identification of predictors utilizing recursive feature elimination (RFE), seven classical machine learning (ML) models, including logistic regression, support vector machine, decision tree, random forest, extreme gradient boosting, etc., were trained to predict patients' motor subtypes, evaluating the performance of models through the area under the receiver operating characteristic curve (AUC) and validating by the follow-up data. RESULTS: The feature subset engendered by RFE encompassed 20 features, comprising some clinical assessments and cerebrospinal fluid α-synuclein (CSF α-syn). ML models fitted in the RFE subset performed better in the test and validation sets. The best performing model was support vector machines with the polynomial kernel (P-SVM), achieving an AUC of 0.898. Five-fold repeated cross-validation showed the P-SVM model with CSF α-syn performed better than the model without CSF α-syn (P = 0.034). The Shapley additive explanation plot (SHAP) illustrated that how the levels of each feature affect the predicted probability as NTD subtypes. CONCLUSION: An interactive web application was developed based on the P-SVM model constructed from feature subset by RFE. It can identify the current motor subtypes of PD patients, making it easier to understand the status of patients and develop personalized treatment plans.

Dietary Inflammatory Index and diabetic retinopathy risk in US adults: findings from NHANES (2005-2008).

BACKGROUND: Inflammation is associated with the pathophysiology of diabetic retinopathy (DR). Within the framework of complete dietary patterns, the Dietary Inflammatory Index (DII) was formulated to evaluate the inflammatory properties inherent in a diet. The main purpose of the current study was to assess the relationship between DII and DR using National Health and Nutrition Examination Survey (NHANES). METHODS: The original sample size included 1,148 diabetes patients out of 2005-2008 NHANES surveys. Twenty-four-hour dietary consumptions were used to calculate the DII scores. Demographic characteristics and retina examinations were collected for the comparison between DR and non-DR groups in diabetes patients. The relationship between DII and DR was analyzed by a logistic regression model. RESULTS: 227 subjects (110 non-DR and 117 DR) were selected in the analyses by using undersampling method to balance the sample size. Compared with non-DR group, DR group had higher DII values (1.14 ± 0.29 vs. 1.49 ± 0.21, p = 0.32), higher levels of HbA1c (6.8 ± 1.1% vs. 7.7 ± 2.6%, p < 0.001), longer duration of diabetes (6.52 ± 12 years vs. 14 ± 11 years, p < 0.001). The odds rate (OR) of DII for DR from the logistic regression was 1.38 (95%CI 1.06-1.81, p < 0.001). HbA1c, diabetes duration and obesity were important influencing factors, and their ORs were 1.81 (95% CI:1.31-2.50), 1.12 (95%CI:1.04-1.20), 4.01 (95%CI:1.12-14.32), respectively. In addition, the most important dietary indices for DR were different across males and females. CONCLUSIONS: The current study demonstrates that a higher DII is associated with an increased risk of DR in US adults. Considering diet as a modifiable factor, limiting pro-inflammatory diets or encouraging an anti-inflammatory diet may be a promising and cost-effective method in the management of DR.

Exposure to Perfluoroalkyl Substances and Hyperlipidemia Among Adults: Data From NHANES 2017-2018.

BACKGROUND: The present study aims to explore the relationship between perfluoroalkyl substances (PFAS) exposure and hyperlipidemia using data from the National Health and Nutrition Examination Survey. METHODS: A total of 1600 subjects were included in the analysis, and nine kinds of PFAS were measured. Multivariate logistic regression analysis was performed to explore the association between serum PFAS and hyperlipidemia. RESULTS: Compared with the lowest quartile of perfluoromethylheptane sulfonic acid isomers (Sm-PFOS), the percentage change for hyperlipidemia was 57% and 41% in the third and highest quartile of PFOS. The positive association between Sm-PFOS and hyperlipidemia remained significant in population younger than 60 years, and the odds ratio for hyperlipidemia in fourth quartile of Sm-PFOS was 1.81. CONCLUSIONS: These findings indicated that serum Sm-PFOS was independently associated with a higher risk for hyperlipidemia. The epidemiological study warrants further study to elucidate the causal relationship between them.