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.

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.

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.

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.

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.

The safety and feasibility Assessment of Overlap Esophagojejunostomy with Self-pulling and Latter Transection Technique in Totally Laparoscopic Total Gastrectomy.

BACKGROUND: This study presents an innovative technique in totally laparoscopic total gastrectomy (TLTG) for Overlap esophagojejunostomy, termed self-pulling and latter transection (Overlap SPLT). It evaluates the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end esophagojejunostomy incorporating self-pulling and latter transection (FETE SPLT). METHODS: From September 2018 to September 2023, this study enrolled 68 gastric cancer patients who underwent totally laparoscopic total gastrectomy (TLTG) with Overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathological characteristics, 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 ± 7.4minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0minutes, P = 0.031). Perioperatively, one anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = 0.682). No statistically significant differences were found between the two 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 = 0.676). 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 one additional stapler cartridge and required a longer duration.

Ultrathin, Mechanically Durable, and Scalable Polymer-in-Salt Solid Electrolyte for High-Rate Lithium Metal Batteries.

Polymer-in-salt solid-state electrolytes (PIS SSEs) are emerging for high room-temperature ionic conductivity and facile handling, but suffer from poor mechanical durability and large thickness. Here, Al2O3-coated PE (PE/AO) separators are proposed as robust and large-scale substrates to trim the thickness of PIS SSEs without compromising mechanical durability. Various characterizations unravel that introducing Al2O3 coating on PE separators efficiently improves the wettability, thermal stability, and Li-dendrite resistance of PIS SSEs. The resulting PE/AO@PIS demonstrates ultra-small thickness (25 µm), exceptional mechanical durability (55.1 MPa), high decomposition temperature (330 °C), and favorable ionic conductivity (0.12 mS cm-1 at 25 °C). Consequently, the symmetrical Li cells remain stable at 0.1 mA cm-2 for 3000 h, without Li dendrite formation. Besides, the LiFePO4|Li full cells showcase excellent rate capability (131.0 mAh g-1 at 10C) and cyclability (93.6% capacity retention at 2C after 400 cycles), and high-mass-loading performance (7.5 mg cm-2). Moreover, the PE/AO@PIS can also pair with nickel-rich layered oxides (NCM811 and NCM9055), showing a remarkable specific capacity of 165.3 and 175.4 mAh g-1 at 0.2C after 100 cycles, respectively. This work presents an effective large-scale preparation approach for mechanically durable and ultrathin PIS SSEs, driving their practical applications for next-generation solid-state Li-metal batteries.

Synthesis of Indolyl Phenyl Diketones through Visible-Light-Promoted Ni-Catalyzed Intramolecular Cyclization/Oxidation Sequence of Ynones.

The combination of visible light catalysis and Ni catalysis has enabled the synthesis of indolyl phenyl diketones through the cyclization/oxidation process of ynones. This reaction proceeded under mild and base-free conditions and showed a broad scope and feasibility for gram-scale synthesis. Several natural products and biologically interesting molecules could be readily postfunctionalized by this method.

Technical guideline for intra-prepontine cisternal drug delivery via spinal puncture through subarachnoid catheterization. / ç»è„ŠæŸ±æ¤Žé—´éš™ç©¿åˆºè››ç½‘è†œä¸‹è ”è„‘æ¡¥å‰æ± ç½®ç®¡è¯ç‰©è¾“æ³¨æŠ€æœ¯åº”ç”¨æŒ‡å—.

OBJECTIVES: The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain, such as trigemina neuralgia. This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. METHODS: A modified Delphi approach was used to work for this guideline. On the issues related to the intra-prepontine cisternal targeted drug delivery technique, the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. RESULTS: For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique, a consensus was formed on 7 topics (with an agreement rate of more than 80%), including the principles of the technique, indications and contraindications, patient preparation, surgical specifications for intra-prepontine cisternal catheter placement, analgesic dosage coordination, analgesic management, and prevention and treatment of complications. CONCLUSIONS: Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive, secure, and effective treatment. This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments, justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

Genome-Wide Analysis Elucidates the Roles of GhTIR1/AFB Genes Reveals the Function of Gh_D08G0763 (GhTIR1) in Cold Stress in G. hirsutum.

This study identified 13 GhTIR1/AFB members in G. hirsutum through bioinformatics methods and divided them into three subgroups by phylogenetic tree analysis. Motif and gene structure analysis showed that the genes in this family were highly conserved. Promoter cis-acting element analysis found that the promoters of GhTIR1/AFBs contained a large number of cis-acting elements in response to growth and development and abiotic stress. Further RT-qPCR results showed that GhTIR1/AFB genes responded to various abiotic stresses such as IAA, ABA, cold, and heat, and the expression levels of each gene changed obviously, especially Gh_D08G0763 (GhTIR1), which responded significantly to cold injury. Using VIGS (virus-induced gene silencing) technology to silence Gh_D08G0763 in the cold-tolerant cotton variety ZM36, it was found that the resistance of ZM36 to cold damage was significantly reduced. The physiological response mechanism of the Gh_D08G0763 in resisting cold damage was further analyzed through trypan blue staining of leaves and determination of enzyme activity levels. This study provided effective genetic resources for cotton cold-tolerance breeding.

Engineering Nanomedicine for Non-Viral RNA-Based Gene Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of malignant tumor of the central nervous system, characterized by aggressiveness, genetic instability, heterogenesis, and unpredictable clinical behavior. Disappointing results from the current clinical therapeutic methods have fueled a search for new therapeutic targets and treatment modalities. GBM is characterized by various genetic alterations, and RNA-based gene therapy has raised particular attention in GBM therapy. Here, we review the recent advances in engineered non-viral nanocarriers for RNA drug delivery to treat GBM. Therapeutic strategies concerning the brain-targeted delivery of various RNA drugs involving siRNA, microRNA, mRNA, ASO, and short-length RNA and the therapeutical mechanisms of these drugs to tackle the challenges of chemo-/radiotherapy resistance, recurrence, and incurable stem cell-like tumor cells of GBM are herein outlined. We also highlight the progress, prospects, and remaining challenges of non-viral nanocarriers-mediated RNA-based gene therapy.

Lineage Replacement and Genetic Changes of Four HR-HPV Types during the Period of Vaccine Coverage: A Six-Year Retrospective Study in Eastern China.

OBJECTIVE: This study aimed to provide clinical evidence for lineage replacement and genetic changes of High-Risk Human Papillomavirus (HR-HPV) during the period of vaccine coverage and characterize those changes in eastern China. METHODS: This study consisted of two stages. A total of 90,583 patients visiting the Obstetrics and Gynecology Hospital of Fudan University from March 2018 to March 2022 were included in the HPV typing analysis. Another 1076 patients who tested positive for HPV31, 33, 52, or 58 from November 2020 to August 2023 were further included for HPV sequencing. Vaccination records, especially vaccine types and the third dose administration time, medical history, and cervical cytology samples were collected. Viral DNA sequencing was then conducted, followed by phylogenetic analysis and sequence alignment. RESULTS: The overall proportion of HPV31 and 58 infections increased by 1.23% and 0.51%, respectively, while infection by HPV33 and 52 decreased by 0.42% and 1.43%, respectively, within the four-year vaccination coverage period. The proportion of HPV31 C lineage infections showed a 22.17% increase in the vaccinated group, while that of the HPV58 A2 sublineage showed a 12.96% increase. T267A and T274N in the F-G loop of HPV31 L1 protein, L150F in the D-E loop, and T375N in the H-I loop of HPV58 L1 protein were identified as high-frequency escape-related mutations. CONCLUSIONS: Differences in epidemic lineage changes and dominant mutation accumulation may result in a proportional difference in trends of HPV infection. New epidemic lineages and high-frequency escape-related mutations should be noted during the vaccine coverage period, and regional epidemic variants should be considered during the development of next-generation vaccines.

Cell communication pathway prognostic model identified detrimental neurodevelopmental pathways in neuroblastoma.

Neurodevelopmental cell communication plays a crucial role in neuroblastoma prognosis. However, determining the impact of these communication pathways on prognosis is challenging due to limited sample sizes and patchy clinical survival information of single cell RNA-seq data. To address this, we have developed the cell communication pathway prognostic model (CCPPM) in this study. CCPPM involves the identification of communication pathways through single-cell RNA-seq data, screening of prognosis-significant pathways using bulk RNA-seq data, conducting functional and attribute analysis of these pathways, and analyzing the post-effects of communication within these pathways. By employing the CCPPM, we have identified ten communication pathways significantly influencing neuroblastoma, all related to axongenesis and neural projection development, especially the BMP7-(BMPR1B-ACVR2B) communication pathway was found to promote tumor cell migration by activating the transcription factor SMAD1 and regulating UNK and MYCBP2. Notably, BMP7 expression was higher in neuroblastoma samples with distant metastases. In summary, CCPPM offers a novel approach to studying the influence of cell communication pathways on disease prognosis and identified detrimental communication pathways related to neurodevelopment.

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.

Atractylodin ameliorates lipopolysaccharide-induced depressive-like behaviors in mice through reducing neuroinflammation and neuronal damage.

Depression is a psychiatric disorder associated with multiple factors including microglia-mediated neuroinflammation. Although atractylodin exerted a variety of biological activities, however the effect of atractylodin on neuroinflammation-related depression was still unclear. In this study, the lipopolysaccharide (LPS)-induced mouse model was used to explore the antidepressant effects and molecular mechanisms of atractylodin. The results showed that atractylodin increased sugar preference, also reduced immobility time in FST and TST. Further study showed atractylodin reduced the oxidative stress and the activation of microglia in mouse hippocampus, also inhibited the level of cytokine release, especially IL-1ß. The results of western blotting showed that atractylodin significantly inhibited the expression of NLRP3 and pro-IL1ß via inhibition of NF-κB pathway. Our studies showed that atractylodin upregulated BDNF/Akt pathway in mouse hippocampus. Therefore, this study firstly indicated that atractylodin can ameliorate lipopolysaccharide-induced depressive-like behaviors in mice through reducing neuroinflammation and neuronal damage, and its molecular mechanism may be associated with the decrease of the expression of NLRP3 inflammasome and upregulation of BDNF/Akt pathway.

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.

FishSNP: a high quality cross-species SNP database of fishes.

The progress of aquaculture heavily depends on the efficient utilization of diverse genetic resources to enhance production efficiency and maximize profitability. Single nucleotide polymorphisms (SNPs) have been widely used in the study of aquaculture genomics, genetics, and breeding research since they are the most prevalent molecular markers on the genome. Currently, a large number of SNP markers from cultured fish species are scattered in individual studies, making querying complicated and data reuse problematic. We compiled relevant SNP data from literature and public databases to create a fish SNP database, FishSNP ( http://bioinfo.ihb.ac.cn/fishsnp ), and also used a unified analysis pipeline to process raw data that the author of the literature did not perform SNP calling on to obtain SNPs with high reliability. This database presently contains 45,690,243 (45 million) nonredundant SNP data for 13 fish species, with 30,288,958 (30 million) of those being high-quality SNPs. The main function of FishSNP is to search, browse, annotate and download SNPs, which provide researchers various and comprehensive associated information.