Epileptic seizures as an initial symptom for Sturge­Weber syndrome type III: A report of two cases.

Sturge-Weber syndrome (SWS) type III, a rare neurocutaneous disorder, presents diagnostic challenges due to its variable clinical manifestations. The present study focuses on enhancing the understanding of this syndrome by conducting a detailed analysis of two pediatric cases and providing a comprehensive review of the existing literature. The cases, managed at the Children's Hospital Affiliated to Shandong University (Jinan, China), highlight the diverse clinical presentations and successful management strategies for SWS type III. In the first case, a 4-year-old male patient exhibited paroxysmal hemiplegia, epileptic seizures and cerebral angiographic findings indicative of left pia mater and venous malformation. The second case involved a 2.5-year-old male patient presenting with recurrent seizures and angiographic findings on the right side. Both cases underscore the importance of considering epileptic seizures, acquired and transient hemiplegia and cognitive impairments in the diagnosis of SWS type III. The present study provides insights into the effective use of both pharmacological and surgical interventions, drawing from the positive outcomes observed in these cases. The findings emphasize the need for heightened awareness and a meticulous approach in diagnosing and treating SWS type III, contributing to the better management and prognosis of this condition.

Integrated Single-Cell RNA-seq and ATAC-seq Reveals Heterogeneous Differentiation of CD4+ Naive T Cell Subsets is Associated with Response to Antidepressant Treatment in Major Depressive Disorder.

The mechanism involved in major depressive disorder (MDD) is well-studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single-cell RNA-sequencing (scRNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA-seq analysis reveals a lower proportion of naive T cells, particularly CD4+ naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4+ naive T population in responders characterized by enhanced mitogen-activated protein kinases (MAPK) pathway is identified. E-twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4+ naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4+ naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.

Health-related quality of life in children with childhood acute myeloid leukemia in China: A five-year prospective study.

Purpose: This study aims to identify the key factors influencing health-related quality of life (HRQoL) of pediatric acute myeloid leukemia (AML) patients following their initial diagnosis and examine their impact on the five-year survival prognosis. Methods: A chart review and follow-up were conducted for children with AML who participated in a prospective cohort study between 2017 and 2020. We identified factors influencing HRQoL through Pediatric Quality of Life Inventory™ (PedsQL™ 4.0), PedsQL™ Cancer Module 3.0 (CM 3.0) and PedsQL™ Family Impact Module 2.0 (FIM 2.0), as well as assessed the impact of impaired HRQoL on the overall outcomes of patients. Results: Sixty-four subjects enrolled in the study had complete HRQoL outcome data, and 61 of them completed the 5-year follow-up. In CM 3.0, age was positively associated with parental proxy reports (p = 0.040), whereas divorced families were negatively associated with child self-reports (p = 0.045). A positive medical history correlates with FIM 2.0 (p = 0.025). Residence (p = 0.046), the occupation of caregivers (p = 0.014), disease severity (p = 0.024), and the only child (p = 0.029) exhibited statistically significant associations with the impairment of HRQoL. Impaired HRQoL scores shown by the PedsQL™4.0 parent proxy report (p = 0.013) and FIM 2.0 (p = 0.011) were associated with a reduced 5-year survival rate. Conclusions: This study demonstrated that early impairment of HRQoL in pediatric acute myeloid leukemia patients has predictive value for long-term prognosis. Once validated, these findings may provide some guidance to clinicians treating children with AML.

Comparative Analysis of Human-Chimpanzee Divergence in Brain Connectivity and its Genetic Correlates.

Chimpanzees (Pan troglodytes) are humans' closest living relatives, making them the most directly relevant comparison point for understanding human brain evolution. Zeroing in on the differences in brain connectivity between humans and chimpanzees can provide key insights into the specific evolutionary changes that might have occured along the human lineage. However, conducting comparisons of brain connectivity between humans and chimpanzees remains challenging, as cross-species brain atlases established within the same framework are currently lacking. Without the availability of cross-species brain atlases, the region-wise connectivity patterns between humans and chimpanzees cannot be directly compared. To address this gap, we built the first Chimpanzee Brainnetome Atlas (ChimpBNA) by following a well-established connectivity-based parcellation framework. Leveraging this new resource, we found substantial divergence in connectivity patterns across most association cortices, notably in the lateral temporal and dorsolateral prefrontal cortex between the two species. Intriguingly, these patterns significantly deviate from the patterns of cortical expansion observed in humans compared to chimpanzees. Additionally, we identified regions displaying connectional asymmetries that differed between species, likely resulting from evolutionary divergence. Genes associated with these divergent connectivities were found to be enriched in cell types crucial for cortical projection circuits and synapse formation. These genes exhibited more pronounced differences in expression patterns in regions with higher connectivity divergence, suggesting a potential foundation for brain connectivity evolution. Therefore, our study not only provides a fine-scale brain atlas of chimpanzees but also highlights the connectivity divergence between humans and chimpanzees in a more rigorous and comparative manner and suggests potential genetic correlates for the observed divergence in brain connectivity patterns between the two species. This can help us better understand the origins and development of uniquely human cognitive capabilities.

Hyaluronic-Acid-Nanomedicine Hydrogel for Enhanced Treatment of Rheumatoid Arthritis by Mediating Macrophage-Synovial Fibroblast Cross-Talk.

The occurrence of rheumatoid arthritis (RA) is highly correlated with progressive and irreversible damage of articular cartilage and continuous inflammatory response. Here, inspired by the unique structure of synovial lipid-hyaluronic acid (HA) complex, we developed supramolecular HA-nanomedicine hydrogels for RA treatment by mediating macrophage-synovial fibroblast cross-talk through locally sustained release of celastrol (CEL). Molecular dynamics simulation confirmed that HA conjugated with hydrophobic segments could interspersed into the CEL-loaded [poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolaone-co-1,4,8-trioxa[4.6]spiro-9-undecanone] (PECT) nanoparticles to form the supramolecular nanomedicine hydrogel HA-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-un-decanone)/PECT@CEL (HP@CEL), enabling fast hydrogel formation after injection and providing a 3-dimensional environment similar with synovial region. More importantly, the controlled release of CEL from HP@CEL inhibited the macrophage polarization toward the proinflammatory M1 phenotype and further suppressed the proliferation of synovial fibroblasts by regulating the Toll-like receptor pathway. In collagen-induced arthritis model in mice, HP@CEL hydrogel treatment substantial attenuated clinical symptoms and bone erosion and improved the extracellular matrix deposition and bone regeneration in ankle joint. Altogether, such a bioinspired injectable polymer-nanomedicine hydrogel represents an effective and promising strategy for suppressing RA progression through augmenting the cross-talk of macrophages and synovial fibroblast for regulation of chronic inflammation.

Translation and psychometric evaluation of the Chinese version of the Nursing Time Management Scale.

Background: Reasonable and effective time allocation can promote the improvement of medical care service quality. This study aimed to translate, cross-culturally adapt and validate the Chinese Nursing Time Management Scale (NTMS). Methods: Using a cross-sectional survey, 345 clinical nurses were selected from June to September 2023 for a general information questionnaire and Nursing Time Management Scale (NTMS) study. Item analysis, exploratory factor analysis and validation factor analysis were used to verify the reliability and validity of the Chinese version of Nursing Time Management Scale. Results: The Chinese version of the Nurses' Time Management Competency Scale includes 17 entries in 3 dimensions: planning activities and setting goals, coordinating activities and procedures, and organizing nursing activities. The Cronbach's alpha coefficient for the total scale was 0.966. Exploratory factor analysis showed that the cumulative variance contribution of the three male factors was 97.44%. Conclusion: The NTMS has acceptable validity and reliability and can be used to evaluate the nursing time management skills of Chinese clinical nurses.

In situ autophagy regulation in synergy with phototherapy for breast cancer treatment.

Autophagy is an important factor in reducing the efficacy of tumor phototherapy (including PTT and PDT). Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT. This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy. To achieve this goal, we first synthesized TRANSFERRIN (Tf) biomimetic mineralized nano-tellurium (Tf-Te) as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly. The autophagy inhibitor hydroxychloroquine (HCQ) and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ. After entering breast cancer cells through the "self-guidance system", Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation, to efficiently induce PTT/PDT effect. Meanwhile, the disulfide bond broke down in response to GSH, and the nanoparticles disintegrated to release Fe2+ and HCQ at fixed points. They simultaneously induce lysosomal alkalinization and increased osmotic pressure, effectively inhibit autophagy, and synergistically enhance the therapeutic effect of phototherapy. In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6% on 4T1 tumor-bearing mice. This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

Global, regional and national trends and impacts of natural floods, 1990-2022.

Objective: To assess global, regional and national trends in the impact of floods from 1990 to 2022 and determine factors influencing flood-related deaths. Methods: We used data on flood disasters from the International Disaster Database for 1990-2022 from 168 countries. We calculated the annual percentage change to estimate trends in the rates of people affected and killed by floods by study period, World Health Organization (WHO) region, country income level and flood type. We used multivariable logistic regression analysis to assess the factors associated with death from floods. Findings: From 1990 to 2022, 4713 floods were recorded in 168 countries, which affected > 3.2 billion people, caused 218 353 deaths and were responsible for more than 1.3 trillion United States dollars of economic losses. The WHO Western Pacific Region had the most people affected by floods (> 2.0 billion), accounting for 63.19% (2 024 599 380/3 203 944 965) of all affected populations. The South-East Asia Region had the most deaths (71 713, 32.84%). The African and Eastern Mediterranean Regions had the highest number of people affected and killed by floods per 100 000 population in 2022. The odds of floods causing more than 50 deaths were significantly higher in low-income countries (adjusted odds ratio: 14.34; 95% confidence interval: 7.46 to 30.04) compared with high-income countries. Numbers of people affected and mortality due to floods declined over time. Conclusion: Despite the decreases in populations affected and deaths, floods still have a serious impact on people and economies globally, particularly in lower-income countries. Action is needed to improve disaster risk management and flood mitigation.

Content of medicine prescription and clinical practice training for haematology advanced practice nurses in China: A modified Delphi study.

AIM: To explore the scope and form of prescriptions for blood and hematopoietic drugs that future advanced practice nurses (APNs) in the Department of Haematology and to establish a medicine prescription training content in China. BACKGROUND: Because the increasing number of doctors cannot meet the increasing demand for medical care with the population growth, many countries have begun to explore the medical team structure and practice areas, among which nurse prescribing rights have been the most effective. However, China's higher nursing education system still lacks education and training on nurse prescription. DESIGN: On the basis of literature research and semi-structured interviews, a set of nursing prescription content, education, training and practice system suitable for Chinese nurses was jointly created. METHODS: Two rounds of expert consultation between 23 haematology nursing experts and clinical experts determined the training content of blood system drugs and medicine prescriptions. Additionally, on the basis of the 23 experts，13 experts engaged in clinical and education, teaching and training experts were involved. Two rounds of expert consultation with 36 experts identified a general clinical practice training program for advanced practice nurses in China. RESULTS: Regarding contents and forms of hematopoietic drugs, the study concluded that advanced practice nurses in haematology department can prescribe anti-anemia drugs, anti-coagulant drugs and anti-thrombotic drugs in 2 categories and 16 drugs. Of these, four kinds of drugs should be prescribed in the form of protocol prescription. One kind of drug should be prescribed in the form of extended prescription and 11 drugs should be prescribed in the form of independent/extended or agreed/extended prescription. Regarding training content, the study obtained the training content of nurses' medicine prescriptions in eight clinical circumstances and the medicine prescription training content for common diseases of the blood system. The required specifications and the medicine prescription decision skills of nurses were sorted out according to different prescription types. CONCLUSIONS: The degrees of expert authority were both higher in consultations. Moreover, the results after consultation were reliable. It was recommended that haematology APNs could prescribe anti-anaemic drugs and anti-coagulation and anti-thrombotic drugs. Furthermore, most drugs should be prescribed in the form of independent/extended or agreed/extended prescriptions. The establishment of a medicine prescription training content for haematology APNs is expected to provide a reference for clinical practice education and training for drug prescriptive authority applicants for blood and hematopoietic system nurses in China.

Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application.

Pancreatic cancer is a highly aggressive malignant tumor, that is becoming increasingly common in recent years. Despite advances in intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted therapy, the overall survival rate has not significantly improved in patients with pancreatic cancer. This may be attributed to the insidious onset, unknown pathophysiology, and poor prognosis of the disease. It is therefore essential to identify and develop more effective and safer treatments for pancreatic cancer. Tumor immunotherapy is the new and fourth pillar of anti-tumor therapy after surgery, radiotherapy, and chemotherapy. Significant progress has made in the use of immunotherapy for a wide variety of malignant tumors in recent years; a breakthrough has also been made in the treatment of pancreatic cancer. This review describes the advances in immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, oncolytic virus, and matrix-depletion therapies for the treatment of pancreatic cancer. At the same time, some new potential biomarkers and potential immunotherapy combinations for pancreatic cancer are discussed. The molecular mechanisms of various immunotherapies have also been elucidated, and their clinical applications have been highlighted. The current challenges associated with immunotherapy and proposed strategies that hold promise in overcoming these limitations have also been discussed, with the aim of offering new insights into immunotherapy for pancreatic cancer.

The safety and feasibility assessment of overlap esophagojejunostomy with self-pulling and latter transection technique in totally laparoscopic total gastrectomy.

BACKGROUND: This study presented an innovative technique in totally laparoscopic total gastrectomy (TLTG) for overlap esophagojejunostomy (E-J), termed self-pulling and latter transection (SPLT) (overlap SPLT). It evaluated the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end (FETE) E-J incorporating SPLT. METHODS: From September 2018 to September 2023, this study enrolled 68 patients with gastric cancer who underwent TLTG with overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathologic characteristics and surgical and postoperative outcomes data for overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for overlap SPLT was 25.3 ± 7.4 minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0 minutes, P = .031). Perioperatively, 1 anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = .682). No statistically significant differences were found between the 2 groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs 5.8%, P = .676). CONCLUSION: The overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between overlap SPLT and FETE SPLT, but overlap SPLT costed 1 additional stapler cartridge and required a longer duration.

Risk assessment model based on nucleotide metabolism-related genes highlights SLC27A2 as a potential therapeutic target in breast cancer.

PURPOSE: Breast cancer (BC) is the most prevalent malignant tumor worldwide among women, with the highest incidence rate. The mechanisms underlying nucleotide metabolism on biological functions in BC remain incompletely elucidated. MATERIALS AND METHODS: We harnessed differentially expressed nucleotide metabolism-related genes from The Cancer Genome Atlas-BRCA, constructing a prognostic risk model through univariate Cox regression and LASSO regression analyses. A validation set and the GSE7390 dataset were used to validate the risk model. Clinical relevance, survival and prognosis, immune infiltration, functional enrichment, and drug sensitivity analyses were conducted. RESULTS: Our findings identified four signature genes (DCTPP1, IFNG, SLC27A2, and MYH3) as nucleotide metabolism-related prognostic genes. Subsequently, patients were stratified into high- and low-risk groups, revealing the risk model's independence as a prognostic factor. Nomogram calibration underscored superior prediction accuracy. Gene Set Variation Analysis (GSVA) uncovered activated pathways in low-risk cohorts and mobilized pathways in high-risk cohorts. Distinctions in immune cells were noted between risk cohorts. Subsequent experiments validated that reducing SLC27A2 expression in BC cell lines or using the SLC27A2 inhibitor, Lipofermata, effectively inhibited tumor growth. CONCLUSIONS: We pinpointed four nucleotide metabolism-related prognostic genes, demonstrating promising accuracy as a risk prediction tool for patients with BC. SLC27A2 appears to be a potential therapeutic target for BC among these genes.

Bone morphogenetic protein 4 derived from the cerebrospinal fluid in patients with postherpetic neuralgia induces allodynia via the crosstalk between microglia and astrocyte.

INTRODUCTION: During postherpetic neuralgia (PHN), the cerebral spinal fluid (CSF) possesses the capability to trigger glial activation and inflammation, yet the specific changes in its composition remain unclear. Recent findings from our research indicate elevations of central bone morphogenetic protein 4 (BMP4) during neuropathic pain (NP), serving as an independent modulator of glial cells. Herein, the aim of the present study is to test the CSF-BMP4 expressions and its role in the glial modulation in the process of PHN. METHODS: CSF samples were collected from both PHN patients and non-painful individuals (Control) to assess BMP4 and its antagonist Noggin levels. Besides, intrathecal administration of both CSF types was conducted in normal rats to evaluate the impact on pain behavior, glial activity, and inflammation.; Additionally, both Noggin and STAT3 antagonist-Stattic were employed to treat the PHN-CSF or exogenous BMP4 challenged cultured astrocytes to explore downstream signals. Finally, microglial depletion was performed prior to the PHN-CSF intervention so as to elucidate the microglia-astrocyte crosstalk. RESULTS: BMP4 levels were significantly higher in PHN-CSF compared to Control-CSF (P < 0.001), with a positive correlation with pain duration (P < 0.05, r = 0.502). Comparing with the Control-CSF producing moderate paw withdrawal threshold (PWT) decline and microglial activation, PHN-CSF further exacerbated allodynia and triggered both microglial and astrocytic activation (P < 0.05). Moreover, PHN-CSF rather than Control-CSF evoked microglial proliferation and pro-inflammatory transformation, reinforced iron storage, and activated astrocytes possibly through both SMAD159 and STAT3 signaling, which were all mitigated by the Noggin application (P < 0.05). Next, both Noggin and Stattic effectively attenuated BMP4-induced GFAP and IL-6 upregulation, as well as SMAD159 and STAT3 phosphorylation in the cultured astrocytes (P < 0.05). Finally, microglial depletion diminished PHN-CSF induced astrogliosis, inflammation and endogenous BMP4 expression (P < 0.05). CONCLUSION: Our study highlights the role of CSF-BMP4 elevation in glial activation and allodynia during PHN, suggesting a potential therapeutic avenue for future exploration.

Acoustofluidic manipulation for submicron to nanoparticles.

Particles, ranging from submicron to nanometer scale, can be broadly categorized into biological and non-biological types. Submicron-to-nanoscale bioparticles include various bacteria, viruses, liposomes, and exosomes. Non-biological particles cover various inorganic, metallic, and carbon-based particles. The effective manipulation of these submicron to nanoparticles, including their separation, sorting, enrichment, assembly, trapping, and transport, is a fundamental requirement for different applications. Acoustofluidics, owing to their distinct advantages, have emerged as a potent tool for nanoparticle manipulation over the past decade. Although recent literature reviews have encapsulated the evolution of acoustofluidic technology, there is a paucity of reports specifically addressing the acoustical manipulation of submicron to nanoparticles. This article endeavors to provide a comprehensive study of this topic, delving into the principles, apparatus, and merits of acoustofluidic manipulation of submicron to nanoparticles, and discussing the state-of-the-art developments in this technology. The discourse commences with an introduction to the fundamental theory of acoustofluidic control and the forces involved in nanoparticle manipulation. Subsequently, the working mechanism of acoustofluidic manipulation of submicron to nanoparticles is dissected into two parts, dominated by the acoustic wave field and the acoustic streaming field. A critical analysis of the advantages and limitations of different acoustofluidic platforms in nanoparticles control is presented. The article concludes with a summary of the challenges acoustofluidics face in the realm of nanoparticle manipulation and analysis, and a forecast of future development prospects.

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction.

BACKGROUND: Leukemia stem cells (LSCs) are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia (AML), as they are protected by the bone marrow microenvironment (BMM) against conventional therapies. Gossypol acetic acid (GAA), which is extracted from the seeds of cotton plants, exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2. AIM: To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism. METHODS: In this study, LSCs were magnetically sorted from AML cell lines and the CD34+CD38- population was obtained. The expression of leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) and forkhead box M1 (FOXM1) was evaluated in LSCs, and the effects of GAA on malignancies and mitochondrial function were measured. RESULTS: LRPPRC was found to be upregulated, and GAA inhibited cell proliferation by degrading LRPPRC. GAA induced LRPPRC degradation and inhibited the activation of interleukin 6 (IL-6)/janus kinase (JAK) 1/signal transducer and activator of transcription (STAT) 3 signaling, enhancing chemosensitivity in LSCs against conventional chemotherapies, including L-Asparaginase, Dexamethasone, and cytarabine. GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC. Furthermore, GAA induced reactive oxygen species accumulation, disturbed mitochondrial homeostasis, and caused mitochondrial dysfunction. By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC, GAA resulted in the elimination of LSCs. Meanwhile, GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage. CONCLUSION: Taken together, the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

A Study on the Efficient Preparation of α-Ketoglutarate with L-Glutamate Oxidase.

Alpha-ketoglutaric acid (α-KG), as an intermediate product of the tricarboxylic acid cycle, plays a crucial role in peptide and amino acid synthesis. In order to reduce costs and improve efficiency in the oxidative production of α-ketoglutaric acid, this study successfully synthesized and expressed L-glutamate oxidase (LGOXStr) from Streptomyces viridosporus R111 and catalase (KatGEsc) from Escherichia coli H736. Two immobilization methods and the conditions for one-step whole-cell catalysis of α-ketoglutaric acid were investigated. α-Ketoglutaric acid has broad applications in the pharmaceutical, food, and chemical industries. The specific research results are as follows: (1) By fusing the sfGFP tag, L-glutamate oxidase (LGOXStr r) and catalase (KatGEsc) were successfully anchored to the outer membrane of Escherichia coli cells, achieving one-step whole-cell catalysis of α-ketoglutaric acid with a conversion efficiency of up to 75%. (2) Through the co-immobilization of LGOXStr and KatGEsc, optimization of the preparation parameters of immobilized cells, and exploration of the immobilization method using E.coli@ZIF-8, immobilized cells with conversion rates of over 60% were obtained even after 10 cycles of reuse. Under the optimal conditions, the production rate of α-ketoglutaric acid reached 96.7% in a 12 h reaction, which is 1.1 times that of E. coli@SA and 1.29 times that of free cells.

Rhizoma Alismatis Decoction improved mitochondrial dysfunction to alleviate SASP by enhancing autophagy flux and apoptosis in hyperlipidemia acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, especially hyperlipidemia acute pancreatitis (HLAP) is the third leading cause of acute pancreatitis which is more severe with a greater incidence of persistent multiorgan failure. HLAP inflicts injury upon the organelles within the acinar cell, particularly mitochondria, the endolysosomal-autophagy system, and is accompanied by senescence-associated secretory phenotype (SASP). RAD, only two consists of Rhizoma Alismatis and Atractylodes macrocephala Rhizoma, which is best known for its ability to anti-inflammatory and lipid-lowering. Nevertheless, the mechanism by which RAD alleviates HLAP remains obscure, necessitating further investigation. PURPOSE: The study aimed to assess the effects of the RAD on HLAP and to elucidate the underlying mechanism in vivo and in vitro, offering a potential medicine for clinical treatment for HLAP. STUDY DESIGN AND METHODS: C57BL/6 mice with hyperlipidemia acute pancreatitis were induced by HFD and CER, then administrated with RAD. AR42J were stimulated by cerulein or conditioned medium and then cultured with RAD. Serums were analyzed to evaluate potential pancreas and liver damage. Furthermore, tissue samples were obtained for histological, and protein investigations by H&E, Oil red staining, and Western blot. In addition, western blot and immunofluorescent staining were utilized to estimate the effect of RAD on mitochondrial function, autophagy flux, and SASP. RESULTS: In vivo, RAD considerably alleviated systemic inflammation while attenuating TC, TG, AMY, LPS, inflammatory cytokines, histopathology changes, oxidative damage, mitochondrial fission, and autophagy markers in HLAP mice. Impaired autophagy flux and mitochondrial dysfunction resulted in a significant enhancement of NLRP3 and IL-1ß in the pancreas. RAD could reverse these changes. In vitro, RAD significantly restored mitochondrial membrane potential and oxidative phosphorylation levels. RAD decreased Beclin-1 and LC3-II expression and increased LAMP-1 and Parkin-Pink expression, which showed that RAD significantly ameliorated HLAP-induced damage to the mitochondria function by suppressing mitochondrial oxidative damage and enhancing autophagy flux and mitophagy to remove the damaged mitochondria. In addition, we found that RAD could up-regulate the expression of BAX, and Bad and down-regulate the expression of p16, and p21, indicating that RAD could promote damaged cell apoptosis and alleviate SASP. CONCLUSIONS: This study revealed that RAD ameliorates mitochondrial function to alleviate SASP through enhancing autophagy flux, mitophagy, and apoptosis which provided a molecular basis for the advancement and development of protection strategies against HLAP.

Microglial exosomes in paraquat-induced Parkinson's disease: Neuroprotection and biomarker clues.

The exact mechanisms underlying the initiation and exacerbation of Parkinson's disease (PD) by paraquat remain unclear. We have revealed that exosomes mediate neurotoxicity induced by low dose paraquat exposure by transmitting intercellular signaling. Exposure to 40 µM paraquat promoted exosome release from mouse microglia cells (BV2) in vitro. Paraquat exposure at 100 µM caused degeneration of mouse dopaminergic MN9D cells and inhibited microglia exosome uptake by fluorescently labeling exosomes. We established an incubation model for exosomes and dopaminergic neuron cells under PQ treatment. The results indicated that microglial exosomes alleviated degeneration, increasing proliferation and PD-related protein expression of dopaminergic neurons; however, paraquat reversed this effect. Then, through exosome high-throughput sequencing and qRT-PCR experiments, miR-92a-3p and miR-24-3p were observed to transfer from exosomes to dopaminergic neurons, inhibited by paraquat. The specificity of miR-92a-3p and miR-24-3p was verified in PD patients exosomes, indicating the potential diagnostic value of the exosomal miRNAs in paraquat-induced PD. These results suggest glia-neuron communication in paraquat-induced neurodegeneration and may identify stable paraquat-mediated PD biomarkers, offering clues for early recognition and prevention of pesticide-induced degenerative diseases.