High Uric Acid Orchestrates Ferroptosis to Promote Cardiomyopathy Via ROS-GPX4 Signaling.

Aims: High uric acid (HUA), as a pro-oxidant, plays a significant role in the pathophysiology of cardiovascular disease. Studies have indicated that elevated uric acid levels can adversely affect cardiovascular health. Nevertheless, the impact of hyperuricemia on cardiomyopathy remains uncertain. Further research is needed to elucidate the relationship between HUA and cardiomyopathy, shedding light on its potential implications for heart health. Results: We demonstrated that uricase knockout (Uox-KO) mice accelerated the development of cardiomyopathy, causing significantly impaired cardiac function and myocardial fibrosis. Meanwhile, the mitochondrial morphology was destroyed, the lipid peroxidation products increased in number and the antioxidant function was weakened. In addition, we evaluated the effects of ferrostatin-1 (Fer-1), the ferroptosis inhibitor. Myocardial damage can be reversed by the Fer-1 treatment caused by HUA combined with doxorubicin (DOX) treatment. Benzbromarone, a uric acid-lowering drug, decreases myocardial fibrosis, and ferroptosis by alleviating hyperuricemia in Uox-KO mice by DOX administration. In vitro, we observed that the activity of cardiomyocytes treated with HUA combined with DOX decreased significantly, and lipid reactive oxygen species (ROS) increased significantly. Afterward, we demonstrated that HUA can promote oxidative stress in DOX, characterized by increased mitochondrial ROS, and downregulate protein levels of glutathione peroxidase 4 (GPX4). N-acetyl-l-cysteine, an antioxidant, inhibits the process by which HUA promotes DOX-induced ferroptosis by increasing the GPX4 expression. Innovation: We verified that HUA can exacerbate myocardial damage. This has clinical implications for the treatment of cardiac damage in patients with hyperuricemia. Conclusions: Our data suggested that HUA promotes the cardiomyopathy. HUA promotes DOX-induced ferroptosis by increasing oxidative stress and downregulating GPX4. Antioxid. Redox Signal. 00, 00-00.

Production of Four-Gene (GTKO/hCD55/hTBM/hCD39)-Edited Donor Pigs and Kidney Xenotransplantation.

BACKGROUND: The number of multigene-modified donor pigs for xenotransplantation is increasing with the advent of gene-editing technologies. However, it remains unclear which gene combination is suitable for specific organ transplantation. METHODS: In this study, we utilized CRISPR/Cas9 gene editing technology, piggyBac transposon system, and somatic cell cloning to construct GTKO/hCD55/hTBM/hCD39 four-gene-edited cloned (GEC) pigs and performed kidney transplantation from pig to rhesus monkey to evaluate the effectiveness of these GEC pigs. RESULTS: First, 107 cell colonies were obtained through drug selection, of which seven were 4-GE colonies. Two colonies were selected for somatic cell nuclear transfer (SCNT), resulting in seven fetuses, of which four were GGTA1 biallelic knockout. Out of these four, two fetuses had higher expression of hCD55, hTBM, and hCD39. Therefore, these two fetuses were selected for two consecutive rounds of cloning, resulting in 97 live piglets. After phenotype identification, the GGTA1 gene of these pigs was inactivated, and hCD55, hTBM, and hCD39 were expressed in cells and multiple tissues. Furthermore, the numbers of monkey IgM and IgG binding to the peripheral blood mononuclear cells (PBMCs) of the 4-GEC pigs were markedly reduced. Moreover, 4-GEC porcine PBMCs had greater survival rates than those from wild-type pigs through complement-mediated cytolysis assays. In pig-to-monkey kidney xenotransplantation, the kidney xenograft successfully survived for 11 days. All physiological and biochemical indicators were normal, and no hyperacute rejection or coagulation abnormalities were found after transplantation. CONCLUSION: These results indicate that the GTKO/hCD55/hTBM/hCD39 four-gene modification effectively alleviates immune rejection, and the pig kidney can functionally support the recipient monkey's life.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

Preparation of Ir/TiO2 Composite Oxygen Evolution Catalyst and Load Analysis as Anode Catalyst Layer of Proton Exchange Membrane Water Electrolyzer.

Electrochemical water splitting is regarded as an emerging green and sustainable hydrogen production technology because of its zero-carbon process. However, the overall cost of anode materials in a proton exchange membrane water electrolyzer (PEMWE) is high due to the use of noble metal Ir. It has been proved that introducing carrier materials to reduce the content of Ir element is a feasible cost-reduction program. Here, the Ir/TiO2 composite material was prepared by the polyol method and used to catalyze the oxygen evolution reaction, which could effectively reduce the load amount of Ir in the membrane electrode assembly (MEA). In addition, the theoretical load of Ir was obtained by model calculation and the polarization curve test and electrochemical impedance spectroscopy (EIS) were used to discuss the relationship between Ir load in MEA and voltage loss and conductivity. The results show that MEA has lower voltage loss and better conductivity as the Ir load is in the range of 0.204-0.304 mgIr/cm2. Altogether, an effective method to reduce the Ir load of PEMWE anode was proposed under the premise comprehensive consideration of both catalyst design and MEA preparation in this work.

Efgartigimod as a fast-acting add-on therapy in manifest and impending myasthenic crisis: A single-center case series.

Efgartigimod was the first-in-class neonatal Fc receptor antagonist approved for the treatment of acetylcholine receptor antibody positive (AChR+), Myasthenia Gravis Foundation of America (MGFA) Class II-IV generalized myasthenia gravis (gMG) patients. As a novel therapy, the clinical experiences are still lacking, especially for the use of efgartigimod in manifest and impending myasthenic crisis (IMC). We reported three AChR+, gMG patients, two with myasthenic crisis (MC) and one with IMC, treated with efgartigimod. MGFA class, MG-Activity of Daily Living score (MG-ADL), Quantitative MG score (QMG), and Muscle Research Council sum score (MRC), concentration of anti-AChR antibody, IgG, globulin, and albumin, subsets of T and B lymphocyte were evaluated or measured before, during and after efgartigimod treatment. All patients showed fast and robust response to efgartigimod with marked improvement in MGFA, MG-ADL, QMG, and MRC scores. Patient 1 did not respond effectively to IVIg but was successfully rescued by add-on efgartigimod. She extubated at 7 days after the first infusion and got rid of NIV after 14-days treatment. Patient 2 and patient 3 directly used efgartigimod when symptoms were not ameliorated by adjusting of oral drugs. Patient 2 wean from BiPAP at seven days after the first infusion. Patient 3 in IMC status, overcame the severe dysphagia at three days after the first infusion. Clinical symptoms continued to improve 1-2 weeks after discharge. Concentration of anti-AChR antibody, IgG and globulin were remarkably reduced by efgartigimod treatment. Our study supported that efgartigimod could act as a fast-acting rescue therapy for patients with MC or IMC. Larger studies from multicenter are required to provide further evidence.

Variation characteristics and clinical significance of TP53 in patients with myeloid neoplasms.

Objectives: MDS and AML characterized by TP53 variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different TP53 variants and VAFs.Methods: Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable TP53 variations were screened. Demographic data and clinical data were collected, and the relationship between TP53 alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of TP53 variations and prognoses was analyzed using data from the present study.Results: Sixty-two variants of TP53 were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of TP53. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency TP53 mutations, and DNMT3A and TET2 were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new TP53 variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered TP53 had a shorter OS than patients in the unaltered group (P<0.01), low TP53 mRNA levels were associated with shorter OS in patients with AML (P<0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (P<0.01).Conclusion: TP53 mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of TP53 mutations associated with a shorter OS in patients with MDS.

Lateral pelvic lymph nodes dissection of rectal neuroendocrine neoplasms: A prospective case-series and literature review.

BACKGROUND: Rectal neuroendocrine neoplasms are relatively rare. Patients with rectal neuroendocrine neoplasms undergoing radical surgery have a higher rate of lymph node metastases. Robust evidence on the status of lateral pelvic lymph node metastases and the role of lateral pelvic lymph node dissection in those patients is lacking. This case-series study aimed to explore and address these issues. METHODS: This single-center, prospective case series consecutively enrolled patients with biopsy-proven rectal neuroendocrine neoplasms in a tertiary referral hospital between June 2022 and January 2024. All eligible patients underwent laparoscopic total mesorectal excision surgery and bilateral lateral pelvic lymph node dissection under general anesthesia. The clinicopathologic features, surgical outcomes, and postoperative complications were presented. The last follow-up was conducted in March 2024. RESULTS: A total of 11 patients with rectal neuroendocrine neoplasms-3 female and 8 male-were enrolled. The average age was 60.0 years (range, 53.5-65.5 years), and the median tumor size was 2.0 cm (range, 1.6-2.5 cm). Tumors invaded the muscularis propria in 7 patients. There were 3 cases of neuroendocrine tumor G1, 6 cases of neuroendocrine tumor G2, and 2 cases of neuroendocrine carcinoma. Among these patients, 11 (100.0%) had lymph node metastases, and 6 (54.5%) had lateral pelvic lymph node metastases. In addition, in 2 patients, only lateral pelvic lymph node metastases were observed, without involvement of the mesenteric lymph nodes. Five patients had tumors located on the left wall of the rectum, and only left-sided lateral pelvic lymph node metastases were observed. The other patient had both sides of lateral pelvic lymph node metastases due to circumferential growth of the tumor around the rectum. Anal preservation was achieved in all patients. The median operating time was 235.0 minutes (range, 210.5-335.5 minutes), and the median estimated blood loss was 50.0 mL (range, 45.0-75.0 mL). Two patients experienced postoperative dysuria and recovered spontaneously within 2-4 months after surgery. CONCLUSION: On the basis of a prospective case series, we demonstrate, for the first time, the lateral pelvic lymph node metastasis status in patients with rectal neuroendocrine neoplasms requiring radical total mesorectal excision surgery. Simultaneous bilateral lateral pelvic lymph node dissection may be a feasible and beneficial procedure for preventing local recurrence in these patients due to the lack of definitive neoadjuvant or adjuvant therapy options.

Profiles and interactions of gut microbiome and intestinal microRNAs in pediatric Crohn's disease.

Gut dysbiosis is closely related to dysregulated microRNAs (miRNAs) in the intestinal epithelial cells, which plays an important role in the pathogenesis of Crohn's disease (CD). We investigated the relationship between fecal gut microbiome (GM) and intestinal tissue miRNAs in different stages of pediatric CD. Metagenomic analysis and miRNA sequencing were conducted to examine the GM and intestinal miRNA profiles of CD patients before and after clinical induction therapy and the controls. Twenty-seven newly diagnosed, therapy-naïve pediatric patients with active CD and 11 non-inflammatory bowel disease (IBD) controls were recruited in this study. Among CD patients, 11 patients completed induction treatment and reached clinical remission. Both GM and miRNA profiles were significantly changed between CD patients and controls. Seven key bacteria were identified at species level including Defluviitalea raffinosedens, Thermotalea metallivorans, Roseburia intestinalis, Dorea sp. AGR2135, Escherichia coli, Shigella sonnei, and Salmonella enterica, the exact proportions of which were further validated by real-time quantitative PCR analysis. Eight key miRNAs were also identified including hsa-miR-215-5p, hsa-miR-194-5p, hsa-miR-12135, hsa-miR-509-3-5p, hsa-miR-212-5p, hsa-miR-4448, hsa-miR-501-3p, and hsa-miR-503-5p. The functional enrichment analysis of differential miRNAs indicated the significantly altered cyclin protein, cyclin-dependent protein, and cell cycle pathway. The close interactions between seven key bacteria and eight key miRNAs were further investigated by miRNA target prediction. The association between specific miRNA expressions and key gut bacteria at different stages of CD supported their important roles as potential molecular biomarkers. Understanding the relationship between them will help us to explore the molecular mechanisms of CD. IMPORTANCE: Since previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn's disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn's Disease Activity Index (PCDAI). Crohn's Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction.

Artificial Intelligence Measurement of Preoperative Radiographs in Adolescent Idiopathic Scoliosis Based on Multiple-View Semantic Segmentation.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Imaging classification of adolescent idiopathic scoliosis (AIS) is directly related to the surgical strategy, but the artificial classification is complex and depends on doctors' experience. This study investigated deep learning-based automated classification methods (DL group) for AIS and validated the consistency of machine classification and manual classification (M group). METHODS: A total of 506 cases (81 males and 425 females) and 1812 AIS full spine images in the anteroposterior (AP), lateral (LAT), left bending (LB) and right bending (RB) positions were retrospectively used for training. The mean age was 13.6 ± 1.8. The mean maximum Cobb angle was 46.8 ± 12.0. U-Net semantic segmentation neural network technology and deep learning methods were used to automatically segment and establish the alignment relationship between multiple views of the spine, and to extract spinal features such as the Cobb angle. The type of each test case was automatically calculated according to Lenke's rule. An additional 107 cases of adolescent idiopathic scoliosis imaging were prospectively used for testing. The consistency of the DL group and M group was compared. RESULTS: Automatic vertebral body segmentation and recognition, multi-view alignment of the spine and automatic Cobb angle measurement were implemented. Compare to the M group, the consistency of the DL group was significantly higher in 3 aspects: type of lateral convexity (0.989 vs 0.566), lumbar curvature modifier (0.932 vs 0.738), and sagittal plane modifier (0.987 vs 0.522). CONCLUSIONS: Deep learning enables automated Cobb angle measurement and automated Lenke classification of idiopathic scoliosis whole spine radiographs with higher consistency than manual measurement classification.

Effects of personalized music listening on post-stroke cognitive impairment: A randomized controlled trial.

BACKGROUND AND PURPOSE: Previous studies have suggested that music listening has the potential to positively affect cognitive functions and mood in individuals with post-stroke cognitive impairment (PSCI), with a preference for self-selected music likely to yield better outcomes. However, there is insufficient clinical evidence to suggest the use of music listening in routine rehabilitation care to treat PSCI. This randomized control trial (RCT) aims to investigate the effects of personalized music listening on mood improvement, activities of daily living (ADLs), and cognitive functions in individuals with PSCI. MATERIALS AND METHODS: A total of 34 patients with PSCI were randomly assigned to either the music group or the control group. Patients in the music group underwent a three-month personalized music-listening intervention. The intervention involved listening to a personalized playlist tailored to each individual's cultural, ethnic, and social background, life experiences, and personal music preferences. In contrast, the control group patients listened to white noise as a placebo. Cognitive function, neurological function, mood, and ADLs were assessed. RESULTS: After three months of treatment, the music group showed significantly higher Montreal Cognitive Assessment (MoCA) scores compared to the control group (p=0.027), particularly in the domains of delayed recall (p=0.019) and orientation (p=0.023). Moreover, the music group demonstrated significantly better scores in National Institutes of Health Stroke Scale (NIHSS) (p=0.008), Barthel Index (BI) (p=0.019), and Zarit Caregiver Burden Interview (ZBI) (p=0.008) compared to the control group. No effects were found on mood as measured by the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD). CONCLUSION: Personalized music listening promotes the recovery of cognitive and neurological functions, improves ADLs, and reduces caregiver burden in patients with PSCI.

Rapid photothermal assay for ultrasensitive point-of-care detection of tumor markers based on a filter membrane.

An ultrasensitive photothermal assay was designed for point-of-care testing (POCT) of tumor markers based on a filter membrane. Firstly, Cu2-xSe was successfully encapsulated in liposome spheres with biotin on the surface and connected to carcinoembryonic antigen (CEA) aptamer with 3'end modified biotin by streptavidin. Secondly, the CEA antibody was successfully modified on the surface of the nitrocellulose membrane through simple incubation. Finally, the assay process was completed using a disposable syringe, and the temperature was recorded using a handheld infrared temperature detector. In the range 0-50 ng mL-1, the temperature change of the nitrocellulose membrane has a strong linear relationship with CEA concentration, and the detection limit is 0.097 ng mL-1. It is worth noting that the entire testing process can be easily performed in 10 min, much shorter than traditional clinical methods. In addition, this method was successfully applied to the quantitative determination of CEA levels in human serum samples with a recovery of 96.2-103.3%. This rapid assay can be performed by "one suction and one push" through a disposable syringe, which is simple to operate, and the excellent sensitivity reveals the great potential of the proposed strategy in the POCT of tumor biomarkers.

Improved YOLOv8 Algorithm for Water Surface Object Detection.

To address the issues of decreased detection accuracy, false detections, and missed detections caused by scale differences between near and distant targets and environmental factors (such as lighting and water waves) in surface target detection tasks for uncrewed vessels, the YOLOv8-MSS algorithm is proposed to be used to optimize the detection of water surface targets. By adding a small target detection head, the model becomes more sensitive and accurate in recognizing small targets. To reduce noise interference caused by complex water surface environments during the downsampling process in the backbone network, C2f_MLCA is used to enhance the robustness and stability of the model. The lightweight model SENetV2 is employed in the neck component to improve the model's performance in detecting small targets and its anti-interference capability. The SIoU loss function enhances detection accuracy and bounding box regression precision through shape awareness and geometric information integration. Experiments on the publicly available dataset FloW-Img show that the improved algorithm achieves an mAP@0.5 of 87.9% and an mAP@0.5:0.95 of 47.6%, which are improvements of 5% and 2.6%, respectively, compared to the original model.

Adjuvant camrelizumab plus apatinib in resected hepatocellular carcinoma with microvascular invasion: a multi-center real world study.

Background: Hepatocellular carcinoma (HCC) treatment currently lacks adjuvant therapy with a high level of supporting evidence to reduce recurrence after hepatectomy. This study aimed to assess the safety and efficacy of camrelizumab plus apatinib in the adjuvant therapy of patients with HCC with microvascular invasion (MVI). Methods: Data were retrospectively collected on consecutive patients with HCC who underwent radical resection and were diagnosed with MVI-positive tumors between October 2019 and June 2022 at four centers. The association between adjuvant therapy and prognosis [recurrence-free survival (RFS), overall survival (OS)] was evaluated by propensity score matching (PSM), the log-rank test, Cox regression analysis, and subgroup analysis. Furthermore, grade 3 or 4 treatment-related adverse events (TRAEs) of adjuvant therapy were reported. Results: Among the 111 patients in the adjuvant therapy group and 276 patients in the observation group at enrolment, there were 99 and 172 in the adjuvant therapy and observation groups after PSM, respectively. RFS was better in the adjuvant therapy group [hazard ratio (HR) 0.52; 95% confidence interval (CI): 0.39 to 0.69; P<0.001], whereas OS was not (HR 0.62; 95% CI: 0.39 to 0.99; P=0.079). These results were confirmed after PSM. Subgroup analyses were generally consistent in favour of adjuvant camrelizumab plus apatinib with better RFS. Grade 3 or 4 TRAEs accounted for 20.7% during adjuvant therapy; the most common TRAEs included hypertension and proteinuria. Conclusions: Postoperative adjuvant camrelizumab plus apatinib significantly improved the RFS benefits with acceptable toxicities in patients with HCC with MVI.

Vinpocetine alleviates the abdominal aortic aneurysm progression via VSMCs SIRT1-p21 signaling pathway.

Abdominal aortic aneurysm (AAA) is a degenerative disease that caused mortality in people aged >65. Senescence plays a critical role in AAA pathogenesis. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. Our Previous study found cyclic nucleotide phosphodiesterase 1C (PDE1C) exacerbate AAA through aggravate vascular smooth muscle cells (VSMCs) senescence by downregulating Sirtuin1 (SIRT1) expression and activity. Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation, it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA. This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice. In addition, the elastin degradation, MMP (matrix metalloproteinase) activity, macrophage infiltration, ROS production, collagen fibers remodeling, and VSMCs senescence were decreased in AAA treated with vinpocetine. While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice. Accordingly, we revealed that vinpocetine suppressed migration, proliferation, and senescence in VSMCs. Moreover, vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy. In conclusion, this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.

Epimedin A inhibits the PI3K/AKT/NF-κB signalling axis and osteoclast differentiation by negatively regulating TRAF6 expression.

BACKGROUND: Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. METHODS: Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. RESULTS: After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. CONCLUSIONS: The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.

Solution-plasma interaction for synthesizing highly active Pt-Ni alloy oxygen reduction nanocatalysts for PEMFCs.

A highly active PtNi-alloy catalyst (p-PtNi/KB) is synthesized using solution-plasma interaction. The plasma effect results in a substantial increase of active sites on the support surface. This facilitates the alloying and functionalization of supports, enabling achievement of enhanced catalytic activity and effective resolution of cost-related challenges in fuel cells.

A novel system with robust compatibility and stability for detecting Sugarcane yellow leaf virus based on CRISPR-Cas12a.

Sugarcane yellow leaf virus (SCYLV) can reduce sugarcane productivity. A novel detection system based on reverse transcription-multienzyme isothermal rapid amplification (RT-MIRA) combined with CRISPR-Cas12a, named RT-MIRA-CRISPR-Cas12a, was developed. This innovative approach employs crude leaf extract directly as the reaction template, streamlining the extraction process for simplicity and speed. Combining RT-MIRA and CRISPR-Cas12a in one reaction tube increases the ease of operation while reducing the risk of aerosol contamination. In addition, it exhibits sensitivity equivalent to qPCR, boasting a lower detection limit of 25 copies. Remarkably, the entire process, from sample extraction to reaction completion, requires only 52-57 minutes, just a thermostat water bath. The result can be observed and judged by the naked eye.IMPORTANCESugarcane yellow leaf disease (SCYLD) is an important viral disease that affects sugarcane yield. There is an urgent need for rapid, sensitive, and stable detection methods. The reverse transcription-multienzyme isothermal rapid amplification combined with CRISPR-Cas12a (RT-MIRA-CRISPR-Cas12a) method established in this study has good specificity and high sensitivity. In addition, the system showed good compatibility and stability with the crude leaf extract, as shown by the fact that the crude extract of the positive sample could still be stably detected after 1 week when placed at 4°C. RT-MIRA-CRISPR-Cas12a, reverse transcription polymerase chain reaction (RT-PCR), and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect SCYLV on 33 sugarcane leaf samples collected from the field, and it was found that the three methods reached consistent conclusions. This Cas12a-based detection method proves highly suitable for the rapid on-site detection of the SCYLV.

[Correlation Analysis between Serum Fibronectin 3 Levels and Early Severe Bleeding in Patients with Newly Diagnosed Acute Promyelocytic Leukemia].

OBJECTIVE: To analyze the correlation between serum fibronectin 3 (Ficolin-3) levels and early severe bleeding in newly diagnosed acute promyelocytic leukemia (APL) patients. METHODS: A total of 125 patients with newly diagnosed APL admitted to Shanxi Bethune Hospital from January 2020 to August 2023 were selected. All patients were given all-trans retinoic acid+arsenic for induction therapy. The severe bleeding events within 30 days of induction therapy (assessed by WHO bleeding score, grade 0, grade 1 and grade 2 were no bleeding or mild bleeding, grade 3 and grade 4 were severe or fatal bleeding) were used as observation endpoints. The serum Ficolin-3 levels was dected by ELISA method, baseline data and other laboratory indicators were counted, and the correlation between serum Ficolin-3 levels and early severe bleeding in newly diagnosed APL patients was analyzed. RESULTS: 23 out of 125 APL patients experienced early severe bleeding during induction therapy, including 13 cases of grade 3 bleeding and 10 cases of grade 4 bleeding. There were 102 cases of non-serious bleeding, including 30 cases of grade 0, 24 cases of grade 1 bleeding, and 48 cases of grade 2 bleeding. The proportion of serum promyelocytes, white blood cell count, and D-D level in the severe bleeding group were significantly higher than those in the non severe bleeding group (P < 0.05), while the levels of PLT and FIB were significantly lower than those in the non-serious bleeding group (P < 0.05). The serum Ficolin-3 levels in the severe bleeding group were significantly lower than those in the non severe bleeding group before treatment, days of treatment, 14 days of treatment, and 30 days of treatment (P < 0.05). Confirmed by point two column correlation, serum Ficolin-3 levels were negatively correlated with early severe bleeding in newly diagnosed APL patients before treatment, 7 days, 14 days, and 30 days after treatment (r values were -0.485, -0.397, -0.304, and -0.183, respectively). The receiver operating characteristic curve (ROC) graph of the subjects was drawn, and the results showed that the area under the curve (AUC) of serum Ficolin-3 levels before treatment and at 7 and 14 days after treatment for predicting early severe bleeding in newly diagnosed APL patients was greater than 0.7, all of which had certain predictive efficacy, and the serum Ficolin-3 level before treatment had the best predictive efficacy. CONCLUSION: The serum Ficolin-3 levels in newly diagnosed APL patients are associated with early severe bleeding, and the serum Ficolin-3 levels before treatment have a significant advantage in predicting early severe bleeding in newly diagnosed APL patients.

[Genetic Variation of SH2B3 in Patients with Myeloid Neoplasms].

OBJECTIVE: To observe the genetic variation of SH2B3 in patients with myeloid neoplasms. METHODS: The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology, Xuanwu Hospital, Capital Medical University from November 2017 to November 2022 were retrospectively analyzed, and the patients with SH2B3 gene mutations were identified. The demographic and clinical data of these patients were collected, and characteristics of SH2B3 gene mutation, co-mutated genes and their correlations with diseases were analyzed. RESULTS: The sequencing results were obtained from 1 005 patients, in which 19 patients were detected with SH2B3 gene mutation, including 18 missense mutations (94.74%), 1 nonsense mutation (5.26%), and 10 patients with co-mutated genes (52.63%). Variant allele frequency (VAF) ranged from 0.03 to 0.66. The highest frequency mutation was p.Ile568Thr (5/19, 26.32%), with an average VAF of 0.49, involving 1 case of MDS/MPN-RS (with SF3B1 mutation), 1 case of MDS-U (with SF3B1 mutation), 1 case of aplastic anemia with PNH clone (with PIGA and KMT2A mutations), 2 cases of MDS-MLD (1 case with SETBP1 mutation). The other mutations included p.Ala567Thr in 2 cases (10.53%), p.Arg566Trp, p.Glu533Lys, p.Met437Arg, p.Arg425Cys, p.Glu314Lys, p.Arg308*, p.Gln294Glu, p.Arg282Gln, p.Arg175Gln, p.Gly86Cys, p.His55Asn and p.Gln54Pro in 1 case each. CONCLUSION: A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms, among of them, p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.