A Monte Carlo simulation-based health risk assessment of heavy metals in soils of the tropical region in southern China.

The disturbance of ecological stability may take place in tropical regions due to the elevated biomass density resulting from heavy metal and other contaminant pollution. In this study, 62 valid soil samples were collected from Sanya. Source analysis of heavy metals in the area was carried out using absolute principal component-multiple linear regression receptor modelling (APCS-MLR); the comprehensive ecological risk of the study area was assessed based on pollution sources; the Monte-Carlo model was used to accurately predict the health risk of pollution sources in the study area. The results showed that: The average contents of soil heavy metals Cu, Ni and Cd in Sanya were 5.53, 6.56 and 11.66 times higher than the background values of heavy metals. The results of soil geo-accumulation index (Igeo) showed that Cr, Mo, Mn and Zn were unpolluted to moderately polluted, Cu and Ni were moderately polluted, and Cd was moderately polluted to strongly polluted. The main sources of heavy metal pollution were natural sources (57.99%), agricultural sources (38.44%) and traffic sources (3.57%). Natural and agricultural sources were jointly identified as priority control pollution sources and Cd was the priority control pollution element for soil ecological risk. Heavy metal content in Sanya did not pose a non-carcinogenic risk to the population, but there was a carcinogenic risk to children. The element Zn had a high carcinogenic risk to children, and was a priority controlling pollutant element for the risk of human health, with agricultural sources as the priority controlling pollutant source.

Enhancing Performance and Stability of Perovskite Solar Cells with a Novel Formamidine Group Additive.

Perovskite materials, particularly FAPbI3, have emerged as promising candidates for solar energy conversion applications. However, these materials are plagued by well-known defects and suboptimal film quality. Enhancing crystallinity and minimizing defect density are therefore essential steps in the development of high-performance perovskite solar cells. In this study, 1H-Pyrazole-1-carboximidamide hydrochloride (PCH) is introduced into FAPbI3 perovskite films. The molecular structure of PCH features a pyrazole ring bonded to formamidine (FA). The FA moiety of PCH facilitated the incorporation of this additive into the film lattice, while the negatively charged pyrazole ring effectively passivated positively charged iodine vacancies. The presence of PCH led to the fabrication of an FAPbI3 device with improved crystallinity, a smoother surface, and reduced defect density, resulting in enhanced Voc and fill factor. A record power conversion efficiency of 24.62% is achieved, along with exceptional stability under prolonged air exposure and thermal stress. The findings highlight the efficacy of PCH as a novel additive for the development of high-performance perovskite solar cells.

Reactivity-Tunable Fluorescent Platform for Selective and Biocompatible Modification of Cysteine or Lysine.

Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine-selective warheads face challenges due to cross-reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro- or phenoxy-substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy-NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH-overexpressed cancer cells. Conversely, alkoxy-NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti-interfering ability against thiols. Leveraging a proximity-driven approach, alkoxy-NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins.

Kidney Bean Protein Prevents High-Fat and High-Fructose Diet-Induced Obesity, Cognitive Impairment, and Disruption of Gut Microbiota Composition.

A long-term intake of a high-fat and high-fructose diet (HFFD), even a high-fat, high-fructose but low-protein diet (HFFD + LP), could cause obesity associated with cognitive impairments. In the present study, rats were subjected to a normal diet (ND), an HFFD diet, an HFFD + LP diet, and an HFFD with kidney bean protein (KP) diet for 8 weeks to evaluate the effect of KP on HFFD- or HFFD + LP-induced obesity and cognitive impairment. The results demonstrated that compared with the HFFD diet, KP administration significantly decreased the body weight by 7.7% and the serum Angiotensin-Converting Enzyme 2 (ACE-2) and Insulin-like Growth Factor 1 (IGF-1) levels by 14.4% and 46.8%, respectively (p < 0.05). In addition, KP suppressed HFFD-induced cognitive impairment, which was evidenced by 8.7% less time required to pass the water maze test. The 16s RNA analysis of the colonic contents showed that the relative abundance of Bifidobacterium, Butyricimonas, and Alloprevotella was increased by KP by 5.9, 44.2, and 79.2 times. Additionally, KP supplementation primarily affected the choline metabolic pathway in the liver, and the synthesis and functional pathway of neurotransmitters in the brain, thereby improving obesity and cognitive function in rats.

Resveratrol alleviates endoplasmic reticulum stress-induced cell death and improves functional prognosis after traumatic brain injury in mice.

Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice associated with endoplasmic reticulum stress (ERS). After establishing three experimental groups (sham, TBI, and TBI+RSV), we explored the results of RSV after TBI on ERS and caspase-12 apoptotic pathways. The expression levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were assessed by western blotting. The qPCR analysis was also performed on mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in cortical brain tissue. In addition, the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1; Iba-1) and neurons (neuronal nuclei; NeuN) was identified by immunofluorescence staining. The neurological function of mice was assessed by modified neurological severity scores (mNSS). After drug treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed that TNF-α and IL-1ß were down-regulated. Immunofluorescence staining showed down-regulation of Iba-1+/GRP78+ and NeuN+/GRP78+ cells after RSV treatment. The mNSS analysis confirmed improvement after RSV treatment. RSV improved apoptosis by downregulating the ERS signaling pathway and improved neurological prognosis in mice with TBI.

Recent advances on anti-HIV chimeric antigen receptor-T-cell treatment to provide sustained HIV remission.

PURPOSE OF REVIEW: Successful sustained remission of HIV infection has been achieved after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation for treatment of leukemia in a small cohort of people living with HIV (PLWH). This breakthrough demonstrated that the goal of curing HIV was achievable. However, the high morbidity and mortality associated with bone marrow transplantation limits the routine application of this approach and provides a strong rationale for pursuing alternative strategies for sustained long-term antiretroviral therapy (ART)-free HIV remission. Notably, long-term immune-mediated control of HIV replication observed in elite controllers and posttreatment controllers suggests that potent HIV-specific immune responses could provide sustained ART-free remission in PLWH. The capacity of chimeric antigen receptor (CAR)-T cells engineered to target malignant cells to induce remission and cure in cancer patients made this an attractive approach to provide PLWH with a potent HIV-specific immune response. Here, we review the recent advances in the design and application of anti-HIV CAR-T-cell therapy to provide a functional HIV cure. RECENT FINDINGS: HIV reservoirs are established days after infection and persist through clonal expansion of infected cells. The continuous interaction between latently infected cells and the immune system shapes the landscape of HIV latency and likely contributes to ART-free viral control in elite controllers. CAR-T cells can exhibit superior antiviral activity as compared with native HIV-specific T cells, particularly because they can be engineered to have multiple HIV specificities, resistance to HIV infection, dual costimulatory signaling, immune checkpoint inhibitors, stem cell derivation, CMV TCR coexpression, and tissue homing ligands. These modifications can significantly improve the capacities of anti-HIV CAR-T cells to prevent viral escape, resist HIV infection, and enhance cytotoxicity, persistence, and tissue penetration. Collectively, these novel modifications of anti-HIV CAR-T cell design have increased their capacity to control HIV infection. SUMMARY: Anti-HIV CAR-T cells can be engineered to provide potent and sustained in-vitro and in-vivo antiviral function. The combination of anti-HIV CAR-T cells with other immunotherapeutics may contribute to long-term HIV remission in PLWH.

A novel mechanism of major ginsenosides from Panax ginseng against multiple organ aging in middle-aged mice: Phosphatidylcholine-myo-inositol metabolism based on metabolomic analysis.

Aging is a complex, degenerative process associated with various metabolic abnormalities. Ginsenosides (GS) is the main active components of Panax ginseng, which has anti-aging effects and improves metabolism. However, the anti-aging effect and the mechanism of GS in middle-aged mice has not been elucidated. In this study, GS after 3-month treatment significantly improved the grip strength, fatigue resistance, cognitive indices, and cardiac function of 15-month-old mice. Meanwhile, GS treatment reduced the fat content and obviously inhibited histone H2AX phosphorylation at Ser 139 (γ-H2AX), a marker of DNA damage in major organs, especially in the heart and liver. Further, the correlation analysis of serum metabolomics combined with aging phenotype suggested that myo-inositol (MI) upregulated by GS was positively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), the main indicators of cardiac function. More importantly, liver tissue metabolomic analysis showed that GS increased MI content by promoting the synthesis pathway from phosphatidylcholine (PC) to MI for the inhibition of liver aging. Finally, we proved that MI reduced the percentage of senescence-associated ß-galactosidase staining, γ-H2AX immunofluorescence staining, p21 expression, and the production of reactive oxygen species in H2O2-induced cardiomyocytes. These results suggest that GS can enhance multiple organ functions, especially cardiac function for promoting the healthspan of aging mice, which is mediated by the conversion of PC to MI in the liver and the increase of MI level in the serum. Our study might provide new insights into the potential mechanisms of ginsenosides for prolonging the healthspan of natural aging mice.

Glued-bamboo composite based on a highly cross-linked cellulose-based adhesive and an epoxy functionalized bamboo surface.

Bamboo, as a renewable bioresource, exhibits advantages of fast growth cycle and high strength. Bamboo-based composite materials are a promising alternative to load-bearing structural materials. It is urgent to develop high-performance glued-bamboo composite materials. This study focused on the chemical bonding interface to achieve high bonding strength and water resistance between bamboo and dialdehyde cellulose-polyamine (DAC-PA4N) adhesive by activating the bamboo surface. The bamboo surface was initially modified in a directional manner to create an epoxy-bamboo interface using GPTES. The epoxy groups on the interface were then chemically crosslinked with the amino groups of the DAC-PA4N adhesive, forming covalent bonds within the adhesive layer. The results demonstrated that the hot water strength of the modified bamboo was improved by 75.8 % (from 5.17 to 9.09 MPa), and the boiling water strength was enhanced by 232 % (from 2.10 to 6.99 MPa). The bonding and flexural properties of this work are comparable to those of commercial phenolic resin. The activation modification of the bamboo surface offers a novel approach to the development of low-carbon, environmentally friendly, and sustainable bamboo engineering composites.

Toxicokinetics Explain Differential Freshwater Ecotoxicity of Nanoencapsulated Imidacloprid Compared to Its Conventional Active Ingredient.

Agricultural applications of nanotechnologies necessitate addressing safety concerns associated with nanopesticides, yet research has not adequately elucidated potential environmental risks between nanopesticides and their conventional counterparts. To address this gap, we investigated the risk of nanopesticides by comparing the ecotoxicity of nanoencapsulated imidacloprid (nano-IMI) with its active ingredient to nontarget freshwater organisms (embryonic Danio rerio, Daphnia magna, and Chironomus kiinensis). Nano-IMI elicited approximately 5 times higher toxicity than IMI to zebrafish embryos with and without chorion, while no significant difference was observed between the two invertebrates. Toxicokinetics further explained the differential toxicity patterns of the two IMI analogues. One-compartmental two-phase toxicokinetic modeling showed that nano-IMI exhibited significantly slower elimination and subsequently higher bioaccumulation potential than IMI in zebrafish embryos (dechorinated), while no disparity in toxicokinetics was observed between nano-IMI and IMI in D. magna and C. kiinensis. A two-compartmental toxicokinetic model successfully simulated the slow elimination of IMI from C. kiinensis and confirmed that both analogues of IMI reached toxicologically relevant targets at similar levels. Although nanopesticides exhibit comparable or elevated toxicity, future work is of utmost importance to properly understand the life cycle risks from production to end-of-life exposures, which helps establish optimal management measures before their widespread applications.

Exploring the Potential of Biochar Derived from Chinese Herbal Medicine Residue for Efficient Removal of Norfloxacin.

One-step carbonization was explored to prepare biochar using the residue of a traditional Chinese herbal medicine, Atropa belladonna L. (ABL), as the raw material. The resulting biochar, known as ABLB4, was evaluated for its potential as a sustainable material for norfloxacin (NOR) adsorption in water. Subsequently, a comprehensive analysis of adsorption isotherms, kinetics, and thermodynamics was conducted through batch adsorption experiments. The maximum calculated NOR adsorption capacity was 252.0 mg/g at 298 K, and the spontaneous and exothermic adsorption of NOR on ABLB4 could be better suited to a pseudo-first-order kinetic model and Langmuir model. The adsorption process observed is influenced by pore diffusion, π-π interaction, electrostatic interaction, and hydrogen bonding between ABLB4 and NOR molecules. Moreover, the utilization of response surface modeling (RSM) facilitated the optimization of the removal efficiency of NOR, yielding a maximum removal rate of 97.4% at a temperature of 304.8 K, an initial concentration of 67.1 mg/L, and a pH of 7.4. Furthermore, the biochar demonstrated favorable economic advantages, with a payback of 852.5 USD/t. More importantly, even after undergoing five cycles, ABLB4 exhibited a consistently high NOR removal rate, indicating its significant potential for application in NOR adsorption.

Generation of Anti-HIV CAR-T Cells for Preclinical Research.

The inability of people living with HIV (PLWH) to eradicate human immunodeficiency virus (HIV) infection is due in part to the inadequate HIV-specific cellular immune response. The antiviral function of cytotoxic CD8+ T cells, which are crucial for HIV control, is impaired during chronic viral infection because of viral escape mutations, immune exhaustion, HIV antigen downregulation, inflammation, and apoptosis. In addition, some HIV-infected cells either localize to tissue sanctuaries inaccessible to CD8+ T cells or are intrinsically resistant to CD8+ T cell killing. The novel design of synthetic chimeric antigen receptors (CARs) that enable T cells to target specific antigens has led to the development of potent and effective CAR-T cell therapies. While initial clinical trials using anti-HIV CAR-T cells performed over 20 years ago showed limited anti-HIV effects, the improved CAR-T cell design, which enabled its success in treating cancer, has reinstated CAR-T cell therapy as a strategy for HIV cure with notable progress being made in the recent decade.Effective CAR-T cell therapy against HIV infection requires the generation of anti-HIV CAR-T cells with potent in vivo activity against HIV-infected cells. Preclinical evaluation of anti-HIV efficacy of CAR-T cells and their safety is fundamental for supporting the initiation of subsequent clinical trials in PLWH. For these preclinical studies, we developed a novel humanized mouse model supporting in vivo HIV infection, the development of viremia, and the evaluation of novel HIV therapeutics. Preclinical assessment of anti-HIV CAR-T cells using this mouse model involves a multistep process including peripheral blood mononuclear cells (PBMCs) harvested from human donors, T cell purification, ex vivo T cell activation, transduction with lentiviral vectors encoding an anti-HIV CAR, CAR-T cell expansion and infusion in mice intrasplenically injected with autologous PBMCs followed by the determination of CAR-T cell capacity for HIV suppression. Each of the steps described in the following protocol were optimized in the lab to maximize the quantity and quality of the final anti-HIV CAR-T cell products.

A dual-responsive RhB-doped MOF probe for simultaneous recognition of Cu2+ and Fe3.

Based on the dual response of RhB@UiO-67 (1:6) to Cu2+ and Fe3+, a proportional fluorescent probe with (I392/I581) as the output signal was developed to recognize Cu2+ and Fe3+. Developing highly sensitive and selective trace metal ions probes is crucial to human health and ecological sustainability. In this work, a series of ratio fluorescent probes (RhB@UiO-67) were successfully synthesized using a one-pot method to enable fluorescence sensing of Cu2+ and Fe3+ at low concentrations. The proportional fluorescent probe RhB@UiO-67 (1:6) exhibited simultaneous quenching of Cu2+ and Fe3+, which was found to be of interest. Furthermore, the limits of detection (LODs) for Cu2+ and Fe3+ were determined to be 2.76 µM and 0.76 µM, respectively, for RhB@UiO-67 (1:6). These values were significantly superior to those reported for previous sensors, indicating the probe's effectiveness in detecting Cu2+ and Fe3+ in an ethanol medium. Additionally, RhB@UiO-67 (1:6) demonstrated exceptional immunity and reproducibility towards Cu2+ and Fe3+. The observed fluorescence quenching of Cu2+ and Fe3+ was primarily attributed to the mechanisms of fluorescence resonance energy transfer (FRET), photoinduced electron transfer (PET), and competitive absorption (CA). This work establishes a valuable foundation for the future study and utilization of Cu2+ and Fe3+ sensing technologies.

Prediction of martensite start temperature of steel combined with expert experience and machine learning.

The martensite start temperature (MS) plays a pivotal role in formulating heat treatment regimes for steel. This paper, through the compilation of experimental data from literature and the incorporation of expert knowledge to construct features, employs machine learning algorithms to predict the MS of steel. The study highlights that the ETR algorithm attains optimal prediction accuracy, and the inclusion of atomic features enhances the model's performance. Feature selection is accomplished by evaluating linear and nonlinear relationships between data using the Pearson correlation coefficient (PCC), variance inflation factor (VIF), and maximum information coefficient (MIC). Subsequently, the performance of machine learning models on unknown data is compared to validate the model's generalization ability. The introduction of SHAP values for model interpretability analysis unveils the influencing mechanisms between features and the target variable. Finally, utilizing a specific steel type as an illustration, the paper underscores the practical value of the model.

This study innovatively integrates experimental data, expert knowledge, and ETR algorithm for accurate MS prediction in steel, enhancing model performance with systematic feature selection and interpretability analysis, demonstrating practical utility.

Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma: A case report and review of literature.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is very rare, and the treatment and prognosis are unclear. Herein, we report the case of a middle-aged female with primary large cell NEC (LCNEC) of the common hepatic duct combined with distal cholangiocarcinoma (dCCA). Additionally, after a review of the relevant literature, we summarize and compare mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease. CASE SUMMARY: A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months. Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign. Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels. Imaging examination revealed a 1-cm tumour in the middle and lower segments of the common bile duct. Pancreaticoduodenectomy + lymph node dissection was performed, and hepatic duct tumours were unexpectedly found during surgery. Pathology suggested poorly differentiated LCNEC (approximately 0.5 cm × 0.5 cm × 0.4 cm), Ki-67 (50%), synaptophysin+, and chromogranin A+. dCCA pathology suggested moderately differentiated adenocarcinoma. The patient eventually developed lymph node metastasis in the liver, bone, peritoneum, and abdominal cavity and died 24 months after surgery. Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours. CONCLUSION: The prognosis of MiNEN and pure NEC alone is different, and the selection of treatment options needs to be differentiated.

Reducing Soil-Emitted Nitrous Acid as a Feasible Strategy for Tackling Ozone Pollution.

Severe ozone (O3) pollution has been a major air quality issue and affects environmental sustainability in China. Conventional mitigation strategies focusing on reducing volatile organic compounds and nitrogen oxides (NOx) remain complex and challenging. Here, through field flux measurements and laboratory simulations, we observe substantial nitrous acid (HONO) emissions (FHONO) enhanced by nitrogen fertilizer application at an agricultural site. The observed FHONO significantly improves model performance in predicting atmospheric HONO and leads to regional O3 increases by 37%. We also demonstrate the significant potential of nitrification inhibitors in reducing emissions of reactive nitrogen, including HONO and NOx, by as much as 90%, as well as greenhouse gases like nitrous oxide by up to 60%. Our findings introduce a feasible concept for mitigating O3 pollution: reducing soil HONO emissions. Hence, this study has important implications for policy decisions related to the control of O3 pollution and climate change.

The Long Hazy Tail: Analysis of the Impacts and Trends of Severe Outdoor and Indoor Air Pollution in North China.

China, especially the densely populated North China region, experienced severe haze events in the past decade that concerned the public. Although the most extreme cases have been largely eliminated through recent mitigation measures, severe outdoor air pollution persists and its environmental impact needs to be understood. Severe indoor pollution draws less public attention due to the short visible distance indoors, but its public health impacts cannot be ignored. Herein, we assess the trends and impacts of severe outdoor and indoor air pollution in North China from 2014 to 2021. Our results demonstrate the uneven contribution of severe hazy days to ambient and exposure concentrations of particulate matter with an aerodynamic diameter <2.5 (PM2.5). Although severe indoor pollution contributes to indoor PM2.5 concentrations (23%) to a similar extent as severe haze contributes to ambient PM2.5 concentrations (21%), the former's contribution to premature deaths was significantly higher. Furthermore, residential emissions contributed more in the higher PM2.5 concentration range both indoors and outdoors. Notably, severe haze had greater health impacts on urban residents, while severe indoor pollution was more impactful in rural areas. Our findings suggest that, besides reducing severe haze, mitigating severe indoor pollution is an important aspect of combating air pollution, especially toward improving public health.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Urolithin A's Role in Alleviating Severe Acute Pancreatitis via Endoplasmic Reticulum-Mitochondrial Calcium Channel Modulation.

Severe acute pancreatitis (SAP), characterized by pancreatic acinar cell death, currently lacks effective targeted therapies. Ellagic acid (EA), rich in pomegranate, shows promising anti-inflammatory and antioxidant effects in SAP treatment. However, the roles of other forms of EA, such as plant extracellular vesicles (EVs) extracted from pomegranate, and Urolithin A (UA), converted from EA through gut microbiota metabolism in vivo, have not been definitively elucidated. Our research aimed to compare the effects of pomegranate-derived EVs (P-EVs) and UA in the treatment of SAP to screen an effective formulation and to explore its mechanisms in protecting acinar cells in SAP. By comparing the protective effects of P-EVs and UA on injured acinar cells, UA showed superior therapeutic effects than P-EVs. Subsequently, we further discussed the mechanism of UA in alleviating SAP inflammation. In vivo animal experiments found that UA could not only improve the inflammatory environment of pancreatic tissue and peripheral blood circulation in SAP mice but also revealed that the mechanism of UA in improving SAP might be related to mitochondria and endoplasmic reticulum (ER) through the results including pancreatic tissue transcriptomics and transmission electron microscopy. Further research found that UA could regulate ER-mitochondrial calcium channels and reduce pancreatic tissue necroptosis. In vitro experiments of mouse pancreatic organoids and acinar cells also confirmed that UA could improve pancreatic inflammation by regulating the ER-mitochondrial calcium channel and necroptosis pathway proteins. This study not only explored the therapeutic effect of plant EVs on SAP but also revealed that UA could alleviate SAP by regulating ER-mitochondrial calcium channel and reducing acinar cell necroptosis, providing insights into the pathogenesis and potential treatment of SAP.

Primary catastrophic antiphospholipid syndrome in children with midbrain infarction: a case report.

Background: Catastrophic antiphospholipid syndrome (CAPS) is a multi-system autoimmune disease characterized by extensive thrombosis. Pediatric CAPS is extremely rare and associated with a high mortality rate, especially when midbrain infarction is involved. Hence, early diagnosis and prompt initiation of appropriate treatment for CAPS complicated by midbrain infarction are of utmost importance in achieving favorable outcomes. Case presentation: In this report, we present the case of a 14-year-old girl who presented with neurological symptoms and digestive system infection and was initially diagnosed with an "intracranial infection". After a series of rigorous diagnostic procedures, the patient was ultimately diagnosed with primary CAPS and was immediately transferred to the intensive care unit where she was treated with anticoagulation, glucocorticoids, intravenous immunoglobulin (IVIG) therapy, and multiple plasma infusions. Twenty-seven days after admission, the patient's condition improved with standardized treatment, and she was discharged and followed up regularly. Conclusion: This case report provides a description of the clinical features observed in a pediatric patient with CAPS and concurrent midbrain infarction, highlighting the crucial role of early diagnosis and timely treatment in influencing patient prognosis.