Low Rh doping accelerated HER/OER bifunctional catalytic activities of nanoflower-like Ni-Co sulfide for greatly boosting overall water splitting.

Facile synthesis of high-efficiency and stable bifunctional electrocatalyst is essential for producing clean hydrogen in energy storage systems. Herein, low Rh-doped flower-like Ni3S2/Co3S4 heterostructures were facilely prepared on porous nickel foam (labeled Rh-Ni3S2/Co3S4/NF) by a hydrothermal method. The correlation of the precursors types with the morphological structures and catalytic properties were rigorously investigated for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in the control groups. The low Rh doping within the catalyst played important role in boosting the catalytic characteristics. The resulting catalyst showed the smaller overpotentials of 197 and 78 mV to drive a current density of 10 mA cm-2 for the OER and HER in alkaline electrolyte, respectively. And the potential only required 1.71 V to drive a current density of 100 mA cm-2 in a water splitting device. It reflects excellent overall water splitting of the home-made Rh-Ni3S2/Co3S4/NF. This strategy shed some constructive light for preparing transition metal sulfide-based electrocatalysts in water splitting devices.

Atomically dispersed ternary FeCoNb active sites anchored on N-doped honeycomb-like mesoporous carbon for highly catalytic degradation of 4-nitrophenol.

In the last decades, 4-nitrophenol is regarded as one of highly toxic organic pollutants in industrial wastewater, which attracts great concern to earth sustainability. Herein, atomically dispersed ternary FeCoNb active sites were incorporated into nitrogen-doped honeycomb-like mesoporous carbon (termed FeCoNb/NHC) by a two-step pyrolysis strategy, whose morphology, structure and size were characterized by a set of techniques. Further, the catalytic activity and reusability of the as-prepared FeCoNb/NHC were rigorously examined by using 4-NP catalytic hydrogenation as a proof-of-concept model. The influence of the secondary pyrolysis temperature on the catalytic performance was investigated, combined by illuminating the catalytic mechanism. The resultant catalyst exhibited significantly enhanced catalytic features with a normalized rate constant (kapp) of 1.2 × 104 min-1g-1 and superior stability, surpassing the home-made catalysts in the control groups and earlier research. This study provides some constructive insights for preparation of high-efficiency and cost-effectiveness single-atom nanocatalysts in organic pollutants environmental remediation.

Comparative analysis of the effects of cyclophosphamide and dexamethasone on intestinal immunity and microbiota in delayed hypersensitivity mice.

BACKGROUND: The T cell-mediated delayed-type hypersensitivity (DTH) response is critical for elucidating cellular immune mechanisms, especially the role of memory T cells upon antigen re-exposure. This study aimed to investigate the specific effects of the immunosuppressive drugs Cyclophosphamide (CY) and Dexamethasone (DEX) on intestinal immunity and microbiota in a DTH mouse model, contributing to a more nuanced understanding of their immunomodulatory mechanisms. METHODS: Female BALB/c mice were sensitized to 2,4-dinitrofluorobenzene (DNFB) and randomly allocated into control, CY, and DEX groups. The impact of CY and DEX on immune function was assessed through measurement of thymus and spleen indices, lymphocyte proliferation in mesenteric lymph nodes (MLNs) using MTT assay, and flow cytometric analysis of T cell subsets and TCR expression. Intestinal secretory IgA (sIgA) was quantified by ELISA, and gut microbiota diversity was evaluated using 16S rRNA gene sequencing. RESULTS: CY and DEX significantly reduced the immune function in DNFB-induced sensitized mice, as indicated by decreased thymus and spleen indices, MLN enlargement, intestinal sIgA content, and ear swelling degree. Flow cytometry revealed that CY increased the proportion of total CD3+ T cells but reduced CD3+CD69+ activated T cells and CD3+TCRγ/δ+ T cells, while DEX increased CD3+CD4+ helper T cells. Both drugs induced distinct changes in gut microbiota diversity and structure, with CY enhancing α diversity and DEX reducing it. CONCLUSIONS: The study demonstrates that CY and DEX have distinct regulatory effects on the immune organ index, distribution of T cell subsets, and diversity and structure of gut microbiota on DTH-induced immune responses mice, suggesting their differential influence on intestinal mucosal immunity. These findings have implications for the development of targeted immunotherapies and understanding the interplay between immunosuppressive drugs and gut microbiota.

Comparative analysis of amide proton transfer and diffusion-weighted imaging for assessing Ki-67, p53 and PD-L1 expression in bladder cancer.

RATIONALE AND OBJECTIVES: To evaluate amide proton transfer (APT) imaging for assessing Ki-67, p53 and PD-L1 status in bladder cancer (BC) and compare its diagnostic efficacy with that of diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Consecutive patients suspected of BC were recruited for preoperative multiparametric MRI. APT signal was quantified by asymmetric magnetization transfer ratio (MTRasym). MTRasym and apparent diffusion coefficient (ADC) were measured by two radiologists, with interobserver agreement assessed. Spearman's correlation analyzed MTRasym values and molecular markers. The Whitney U test evaluated MTRasym and ADC variation based on molecular marker status. Optimal cutoff points were determined using area under the curve (AUC) analysis. RESULTS: 88 patients (72 ± 10 years; 77 men) with BC were studied. MTRasym values were significantly correlated with Ki-67, p53 and PD-L1 levels (P < 0.05). Higher MTRasym values were found in high Ki-67 expression BCs (1.89% [0.73%] vs. 1.23% ± 0.26%; P < 0.001), high p53 expression BCs (1.63% [0.56%] vs. 1.24% [0.56%]; P < 0.001) and positive PD-L1 expression BCs (2.02% [0.81%] vs. 1.48% [0.38%]; P < 0.001). Lower ADCs were found in high Ki-67 expression BCs (1.06 ×10-3 mm2/s [0.32 ×10-3 mm2/s] vs. 1.38 ×10-3 mm2/s [0.39 ×10-3 mm2/s]; P < 0.001). For p53 status, an MTRasym threshold of 1.27% had 95% sensitivity, 60% specificity, and AUC of 0.781. For PD-L1 status, a 1.90% threshold had 88% sensitivity, 92% specificity, and AUC of 0.859. CONCLUSION: APT may significantly enhance the preoperative assessment of BC aggressiveness and inform targeted immunotherapy decisions, with performance superior to DWI.

DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway.

Cullin-RING ubiquitin ligase 4 (CRL4) is closely correlated with the incidence and progression of ovarian cancer. DDB1- and CUL4-associated factor 13 (DCAF13), a substrate-recognition protein in the CRL4 E3 ubiquitin ligase complex, is involved in the occurrence and development of ovarian cancer. However, its precise function and the underlying molecular mechanism in this disease remain unclear. In this study, we confirmed that DCAF13 is highly expressed in human ovarian cancer and its expression is negatively correlated with the overall survival rate of patients with ovarian cancer. We then used CRISPR/Cas9 to knockout DCAF13 and found that its deletion significantly inhibited the proliferation, colony formation, and migration of human ovarian cancer cells. In addition, DCAF13 deficiency inhibited tumor proliferation in nude mice. Mechanistically, CRL4-DCAF13 targeted Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation. FRAS1 influenced the proliferation and migration of ovarian cancer cell through induction of the focal adhesion kinase (FAK) signaling pathway. These findings collectively show that DCAF13 is an important oncogene that promotes tumorigenesis in ovarian cancer cells by mediating FRAS1/FAK signaling. Our findings provide a foundation for the development of targeted therapeutics for ovarian cancer.

Synchronous and efficient removal of carbon, nitrogen, and phosphorus from actual rural sewage by composite wetlands enhanced with functional fillers.

A composite wetland (CECW) was constructed by introducing P-adsorption filler (EPAF) and activated sludge into traditional wetlands for treating actual sewage. The results showed that EPAF improved P removal through physico-chemical adsorption, and it could be stably regenerated after adsorption saturation without potential risks. Meanwhile, zeolite promoted NH4+-N reduction in sewage by cation exchange. In addition, simultaneous biological removal of carbon, nitrogen, and phosphorus was achieved through nitrification, denitrification, anammox, and aerobic P-accumulation processes induced by Nitrobacter, Proteus Hauser, Candidatus Paracaedibacter, and Brevundimonas. Under the coupling of filler interception/adsorption, microbial assimilation/transformation, flocculation, and plant uptake, CECW obtained the removal rates of 93.22 %, 85.75 %, 91.80 %, 95.38 %, 97.07 %, and 78.05 % for turbidity, TN, NH4+-N, TP, PO43--P, and TCOD, which met the Class 1A standard (GB18918-2002). Therefore, the experiment systematically investigated the effects and mechanism of CECW in treating actual sewage, which could provide reference for rural sewage treatment and sludge utilization.

Integrated induction of silver resistance determinants and production of extracellular polymeric substances in Cupriavidus metallidurans BS1 in response to silver ions and silver nanoparticles.

Although the antimicrobial mechanisms of nanomaterials have been extensively investigated, bacterial defense mechanisms associated with AgNPs have not been fully elucidated. We here report that dissolved Ag+ (>0.05 µg mL-1) displayed higher toxicity on cell growth of strain Cupriavidus metallidurans BS1 (GCA_003260185.2) in comparison to 2 and 20 nm AgNPs. The genes necessary for synthesis of distinct abundance and composition of extracellular polymeric substances (EPS) were induced in strain BS1 exposed to Ag stress. This resulted in 20.1% (Ag(I)-EPS) and 24.2% (2 nm AgNPs-EPS) of the CO band integrated intensities being converted into C-OH/C-O-C group vibrations and the Ag-O bond was formed between EPS and 20 nm AgNPs. Meanwhile, the expression of primary resistance genes of the cus, sil and cup operon encoding HME-RND-driven efflux systems as well as a PIB1-type ATPase (CupA) were significantly induced after exposure to Ag(I), 2 and 20 nm AgNPs, respectively. Furthermore, distinct genes involved in biosynthesis pathways responsible for production of EPS were induced to relieve the toxicity of Ag(I), 2 nm and 20 nm AgNPs. This combined action is one potential reason why strain BS1 displayed distinct resistances in response to Ag(I) compared to 2 and 20 nm AgNPs. This work will help in understanding processes important in bacterial defensive mechanisms to AgNPs.

Direct determination of silicon overestimates the accumulation and translocation of SiO2 nanoparticles in rice seedlings.

Silica nanoparticles (SiO2 NPs) have numerous applications in agriculture, but may also pose significant risks to plants. Nevertheless, their bioaccumulation, an important determinant of their risks, was often not accurately measured due to the lack of reliable methods. In this study, the accumulation in rice seedlings of SiO2 NPs of different sizes without and with a gold nanoparticle core (Au@SiO2 NPs) was examined. Potential interference from SiO2 NP dissolution was minimized by lowering the pH of the uptake medium, which did not result in any observable adverse bioeffects. Under this condition, the direct determination of Si showed the significant accumulation of SiO2 NPs in roots and shoots and a decrease in the accumulation of SiO2 NPs in shoots with increasing particle size. However, when accumulation was monitored using Au@SiO2 NPs, SiO2 NP accumulation was significantly higher when measured by direct Si determination than by Au determination, indicating that the former overestimates the accumulation of SiO2 NPs. Consequently, unlike direct Si determination, tracking the gold nanoparticle core revealed an increase in SiO2 NP accumulation in shoots with increasing particle size. Overall, accurate determination of SiO2 NP bioaccumulation is imperative for appropriate bioapplications and reliable biosafety assessments of these particles.

Quantification of silica nanoparticle uptake at environmentally relevant concentrations by gold-core embedding.

The increasing use of silica nanoparticles (SiO2 NPs) has raised concerns about potential human exposure. Assessing the health risks associated with SiO2 NPs necessitates understanding their cellular uptake, yet measuring this uptake at low, environmentally relevant concentrations presents a significant challenge. In this study, we synthesized core-shell structured Au@SiO2 NPs with diameters ranging from 50 to 200 nm and quantified their cellular uptake by analyzing the concentrations of Si and Au in A549 human lung carcinoma cells. No significant differences in cytotoxicity or cellular uptake were observed between Au@SiO2 NPs and their core-less counterparts. Additionally, the comparable cellular uptake of Au@SiO2 NPs, as evidenced by both Si and Au content, supports the use of the Au core as a tracer for SiO2 NP uptake. The inclusion of the Au core facilitated the examination of SiO2 NP uptake at concentrations an order of magnitude lower than previously possible, aligning more closely with environmental exposure levels. This is important because uptake at low concentrations cannot be accurately predicted from high-concentration data due to concentration-dependent changes in particle aggregation. Overall, Au@SiO2 NPs provide a precise method for evaluating SiO2 NP uptake at low concentrations, offering a more realistic assessment of their potential health risks compared to studies conducted at higher concentrations.

Organic matter excreted by the protozoan Tetrahymena thermophila and its effects on the bioaccumulation of nanoparticles.

Although organic matter (exudate) excreted by aquatic organisms is an important component of dissolved organic matter (DOM) in the natural environment, its potential effects on the bioaccumulation of nanoparticles (NPs) remain unclear. In the present study, we examined the effects of the exudates from the protozoan Tetrahymena thermophila on the bioaccumulation (including uptake and cell surface adsorption) of iron oxide (Fe2O3, polyacrylate coated) and silica (SiO2) NPs in T. thermophila. The exudates were mostly (93.6 %, in carbon) composed of < 1-kDa molecules (e.g., lipids). When the exudates were mixed with the NPs, significant adsorption occurred on SiO2 NPs but not on Fe2O3 NPs. Independent of their adsorption by the NPs, the exudates significantly inhibited the bioaccumulation of both SiO2 NPs and Fe2O3 NPs by T. thermophila. This inhibitory effect was shown to be mainly due to their inhibition of NP adsorption on the cell surface. By contrast, the exudates had negligible effects on the uptake of either NP type, most likely due to their low molecular weight. Since DOM in the aquatic environment is dominated by molecules < 1 kDa, the potential effects of low-molecular-weight DOM, such as exudates from aquatic organisms, on the bioaccumulation of NPs merits greater attention. ENVIRONMENTAL IMPLICATION: Nanoparticles (NPs) are hazardous materials widespread in the natural environment. Previous studies showed that dissolved organic matter (DOM) in aquatic environments determine the environmental behavior and ecological effects of NPs. Although organic matter (exudate) excreted by aquatic organisms is an important component of DOM, its potential effects on the bioaccumulation of NPs remain unclear. In the present study, we found that the exudates inhibited the cell-surface adsorption of NPs but had no effects on NP uptake, as different from the well-known effects of DOM on NP bioaccumulation. This finding merits attention during evaluations of the environmental risks of NPs.

Automated ECL Aptasensing Platform from an Intrarticular Radical Annihilation Route for Distinguishing Glioma Stages.

Nowadays, continuous efforts have been devoted to designing stable and high-efficiency electrochemiluminescence (ECL) emitters as alternatives for tris(2,2'-bipyridine)-ruthenium(II) (Ru(bpy)32+) in medical research. Herein, a novel ECL emitter was obtained by coordinating crystalline covalent triazinyl frameworks (cCTFs) with Ru2+ (termed Ru-cCTFs), which exhibited strong ECL emission by the ligand to metal charge transfer (LMCT) route. After its integration with 4-mercaptopyridine (SH-Py), the resultant SH-Py-Ru-cCTFs achieved 2.3-fold enhancement in the ECL efficiency by employing Ru(bpy)32+ as a standard, which involved a dynamic "intrarticular radical annihilation" ECL pathway. On such foundation, an automated ECL (A-ECL) aptasensor was constructed with an "on-off-on" model and magnetic separation upon linkage of the SH-Py-Ru-cCTFs with streptavidin (SA) magnetic beads (MBs). This automatic assay of miRNA-182 showed a wider linear range from 1.0 to 100.0 fM with a correlation coefficient (R2) of 0.994, a lower limit of detection (LOD) down to 0.28 fM, and faster operation within 41 min. Impressively, this bioassay facilely distinguished the stages of glioma disease from clinical blood samples with high accuracy. Hence, this research sheds light on how to develop advanced ECL luminophores and an automatic method, showing substantial insights into pathogenesis research of gliomas.

A novel quantitative real-time PCR with the GAPDH reference gene for peste des petits ruminants.

Peste des petits ruminants (PPR) is a serious acute, highly contagious disease caused by the peste des petits ruminants virus (PPRV). This study aims to establish a qRT-PCR assay with an internal amplification control for the rapid and accurate detection of PPRV. The primers and probes for PPRV N were based on the national standard of the diagnostic techniques for PPR of China, and a pair of primers and TaqMan probes for the internal reference gene of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was designed. Optimisation of the reaction conditions, specificity, sensitivity and reproducibility tests, and clinical sample detection were conducted. The results showed that the optimal primers and probe concentrations of PPRV were 0.4 µmol/l and 0.4 µmol/l, respectively, and were 0.4 µmol/l and 0.2 µmol/l for the reference gene GAPDH, respectively. The established method has no cross-reaction with other viruses. The minimum detection limit was 6.8 copies/µl for PPRV and 190 copies/µl for GAPDH. The coefficients of variation (CV%) of PPRV and GAPDH were both lower than 2%. The results suggest that the PPRV qRT-PCR method containing internal reference genes has strong specificity, high sensitivity, and good reproducibility. The addition of internal reference genes for the sample quality control improves the accuracy of the detection.

Diastereoselective and Enantioselective Hydrophosphinylations of Conjugated Enynes, Allenes and Dienes via Synergistic Pd/Co Catalysis.

Different from the reported work focusing on the construction of single P- or C-stereocenter via hydrophosphinylation of unsaturated carbon bonds, the highly diastereo- and enantioselective hydrophosphinylation reaction of allenes, conjugated enynes and 1,3-dienes is achieved via a designed Pd/Co dual catalysis and newly modified masked phosphinylating reagent. A series of allyl motifs bearing both a tertiary C- and P-stereocenter are prepared in generally good yields, >20:1 dr, >20:1 rr and 99% ee. The unprecedented diastereo- and enantioselective hydrophosphinylation of 1,3-enynes is established to generate skeletons containing both a P-stereocenter and a nonadjacent chiral axis. The first stereodivergent hydrophosphinylation reaction is also developed to achieve all four P-containing stereoisomers. The present protocol features the use of only 3-minutes reaction time and 0.1% catalyst, and with the observation of up to 730 TON. A set of mechanistic studies reveal the necessity and roles of two metal catalysts and corroborate the designed synergistic process.

Activation of ß3-AR by mirabegron prevents aortic dissection/aneurysm by promoting lymphangiogenesis in perivascular adipose tissue.

AIMS: ß3-AR (ß3-adrenergic receptor) is essential for cardiovascular homeostasis through regulating adipose tissue function. Perivascular adipose tissue (PVAT) has been implicated in the pathogenesis of aortic dissection and aneurysm (AD/AA). Here, we aim to investigate ß3-AR activation-mediated PVAT function in AD/AA. METHODS AND RESULTS: Aortas from patients with thoracic aortic dissection (TAD) were collected to detect ß3-AR expression in PVAT. ApoE-/- and ß-aminopropionitrile monofumarate (BAPN)-treated C57BL/6 mice were induced with Angiotensin II (AngII) to simulate AD/AA, and subsequently received either placebo or mirabegron, a ß3-AR agonist. The results demonstrated an up-regulation of ß3-AR in PVAT of TAD patients and AD/AA mice. Moreover, activation of ß3-AR by mirabegron significantly prevented AngII-induced AD/AA formation in mice. RNA-sequencing analysis of adipocytes from PVAT revealed a notable increase of the lymphangiogenic factor VEGF-C in mirabegron-treated mice. Consistently, enhanced lymphangiogenesis was found in PVAT with mirabegron treatment. Mechanistically, the number of CD4+/CD8+ T cells and CD11c+ cells was reduced in PVAT but increased in adjacent draining lymph nodes (LNs) of mirabegron-treated mice, indicating the improved draining and clearance of inflammatory cells in PVAT by lymphangiogenesis. Importantly, adipocyte-specific VEGF-C knockdown by the adeno-associated virus system restrained lymphangiogenesis and exacerbated inflammatory cell infiltration in PVAT, which ultimately abolished the protection of mirabegron on AD/AA. In addition, the conditional medium derived from mirabegron-treated adipocytes activated the proliferation and tube formation of lymphatic endothelial cells (LECs), which was abrogated by the silencing of VEGF-C in adipocytes. CONCLUSIONS: Our findings illustrated the therapeutic potential of ß3-AR activation by mirabegron on AD/AA, which promoted lymphangiogenesis by increasing adipocyte-derived VEGF-C and, therefore, ameliorated PVAT inflammation.

Apelin-13-Loaded Macrophage Membrane-Encapsulated Nanoparticles for Targeted Ischemic Stroke Therapy via Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis.

Purpose: Ischemic stroke is a refractory disease wherein the reperfusion injury caused by sudden restoration of blood supply is the main cause of increased mortality and disability. However, current therapeutic strategies for the inflammatory response induced by cerebral ischemia-reperfusion (I/R) injury are unsatisfactory. This study aimed to develop a functional nanoparticle (MM/ANPs) comprising apelin-13 (APNs) encapsulated in macrophage membranes (MM) modified with distearoyl phosphatidylethanolamine-polyethylene glycol-RVG29 (DSPE-PEG-RVG29) to achieve targeted therapy against ischemic stroke. Methods: MM were extracted from RAW264.7. PLGA was dissolved in dichloromethane, while Apelin-13 was dissolved in water, and CY5.5 was dissolved in dichloromethane. The precipitate was washed twice with ultrapure water and then resuspended in 10 mL to obtain an aqueous solution of PLGA nanoparticles. Subsequently, the cell membrane was evenly dispersed homogeneously and mixed with PLGA-COOH at a mass ratio of 1:1 for the hybrid ultrasound. DSPE-PEG-RVG29 was added and incubated for 1 h to obtain MM/ANPs. Results: In this study, we developed a functional nanoparticle delivery system (MM/ANPs) that utilizes macrophage membranes coated with DSPE-PEG-RVG29 peptide to efficiently deliver Apelin-13 to inflammatory areas using ischemic stroke therapy. MM/ANPs effectively cross the blood-brain barrier and selectively accumulate in ischemic and inflamed areas. In a mouse I/R injury model, these nanoparticles significantly improved neurological scores and reduced infarct volume. Apelin-13 is gradually released from the MM/ANPs, inhibiting NLRP3 inflammasome assembly by enhancing sirtuin 3 (SIRT3) activity, which suppresses the inflammatory response and pyroptosis. The positive regulation of SIRT3 further inhibits the NLRP3-mediated inflammation, showing the clinical potential of these nanoparticles for ischemic stroke treatment. The biocompatibility and safety of MM/ANPs were confirmed through in vitro cytotoxicity tests, blood-brain barrier permeability tests, biosafety evaluations, and blood compatibility studies. Conclusion: MM/ANPs offer a highly promising approach to achieve ischemic stroke-targeted therapy inhibiting NLRP3 inflammasome-mediated pyroptosis.

Melatonin derivative 6a protects Caenorhabditis elegans from formaldehyde neurotoxicity via ADH5.

Formaldehyde (FA) is a carcinogen that is not only widespread in the environment, but is also produced endogenously by metabolic processes. In organisms, FA is converted to formic acid in a glutathione (GSH)-dependent manner by alcohol dehydrogenase 5 (ADH5). The abnormal accumulation of FA in the body can cause a variety of diseases, especially cognitive impairment leading to Alzheimer's disease (AD). In this study, melatonin derivative 6a (MD6a) markedly improved the survival and chemotactic performance of wild-type Caenorhabditis elegans exposed to high concentrations of FA. MD6a lowered FA levels in the nematodes by enhancing the release of covalently-bound GSH from S-hydroxymethyl-GSH in an adh-5-dependent manner. In addition, MD6a protected against mitochondrial dysfunction and cognitive impairment in beta-amyloid protein (Aß) transgenic nematodes by lowering endogenous FA levels and reducing Aß aggregation in an adh-5-dependent manner. Our findings suggest that MD6a detoxifies FA via ADH5 and protects against Aß toxicity by reducing endogenous FA levels in the C. elegans AD models. Thus, ADH5 might be a potential therapeutic target for FA toxicity and AD.

An Empirical Study on the Effect of Training Data Perturbations on Neural Network Robustness.

The vulnerability of modern neural networks to random noise and deliberate attacks has raised concerns about their robustness, particularly as they are increasingly utilized in safety- and security-critical applications. Although recent research efforts were made to enhance robustness through retraining with adversarial examples or employing data augmentation techniques, a comprehensive investigation into the effects of training data perturbations on model robustness remains lacking. This paper presents the first extensive empirical study investigating the influence of data perturbations during model retraining. The experimental analysis focuses on both random and adversarial robustness, following established practices in the field of robustness analysis. Various types of perturbations in different aspects of the dataset are explored, including input, label, and sampling distribution. Single-factor and multi-factor experiments are conducted to assess individual perturbations and their combinations. The findings provide insights into constructing high-quality training datasets for optimizing robustness and recommend the appropriate degree of training set perturbations that balance robustness and correctness, and contribute to understanding model robustness in deep learning and offer practical guidance for enhancing model performance through perturbed retraining, promoting the development of more reliable and trustworthy deep learning systems for safety-critical applications.

Effectiveness of chest pain center accreditation on the hospital outcome of acute aortic dissection: a nationwide study in China.

BACKGROUND: The National Chest Pain Center Program (NCPCP) is a nationwide, quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China. The benefits of chest pain center (CPC) accreditation on acute coronary syndrome have been demonstrated. However, there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection (AAD). METHODS: We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China, using data from the NCPCP spanning the period from January 1, 2016 to December 31, 2022. The patients were divided into 2 groups: pre-accreditation and post-accreditation admissions. The outcomes examined included in-hospital mortality, misdiagnosis, and Stanford type A AAD surgery. Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes. Furthermore, we stratified the hospitals based on their geographical location (Eastern/Central/Western regions) or administrative status (provincial/non-provincial capital areas) to assess the impact of CPC accreditation on AAD patients across various regions. RESULTS: The analysis encompassed a total of 40,848 patients diagnosed with AAD. The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis (12.1% vs. 16.3%, P < 0.001 and 2.9% vs. 5.4%, P < 0.001, respectively) as well as a notably higher rate of Stanford type A AAD surgery (61.1% vs. 42.1%, P < 0.001) compared with the pre-accreditation group. After adjusting for potential covariates, CPC accreditation was associated with substantially reduced risks of in-hospital mortality (adjusted OR 0.644, 95% CI 0.599-0.693) and misdiagnosis (adjusted OR 0.554, 95% CI 0.493-0.624), along with an increase in the proportion of patients undergoing Stanford type A AAD surgery (adjusted OR 1.973, 95% CI 1.797-2.165). Following CPC accreditation, there were significant reductions in in-hospital mortality across various regions, particularly in Western regions (from 21.5 to 14.1%). Moreover, CPC accreditation demonstrated a more pronounced impact on in-hospital mortality in non-provincial cities compared to provincial cities (adjusted OR 0.607 vs. 0.713). CONCLUSION: CPC accreditation is correlated with improved management and in-hospital outcomes for patients with AAD.

Cyclo(L-Pro-L-Trp) from Chilobrachys jingzhao alleviates formalin-induced inflammatory pain by suppressing the inflammatory response and inhibiting TRAF6-mediated MAPK and NF-κB signaling pathways.

Chronic pain has emerged as a significant public health issue, seriously affecting patients' quality of life and psychological well-being, with a lack of effective pharmacological treatments. Numerous studies have indicated that macrophages play a crucial role in inflammatory pain, and targeting neuro-immune interactions for drug development may represent a promising direction for pain management. Chilobrachys jingzhao (C. jingzhao) is used as a folk medicine of the Li nationality with the efficacy of eliminating swelling, detoxicating, and relieving pain, and the related products are widely used in the market. However, the chemical constituents of C. jingzhao have not been reported, and the pharmacodynamic substance and the precise functional mechanism are unrevealed. Here we isolated a cyclic dipeptide, cyclo(L-Pro-L-Trp) (CPT) from C. jingzhao for the first time. CPT remarkably alleviated formalin-induced inflammatory pain and significantly inhibited inflammatory responses. In vivo, CPT attenuated neutrophil infiltration and plantar tissue edema and suppressed the mRNA expression of pro-inflammatory molecules. In vitro, CPT suppressed inflammation triggered by lipopolysaccharide (LPS) in both RAW 264.7 and iBMDM cells, reducing expressions of inducible nitric oxide synthase (iNOS), superoxide, and pro-inflammatory molecules. A mechanistic study revealed that CPT exerted an anti-inflammatory activity by blocking the mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, as well as alleviating the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). Our results elucidated the pharmacodynamic material basis of C. jingzhao, and CPT can be a promising lead for alleviating inflammation and inflammatory pain.