ABSTRACT: Acute liver injury (ALI) is an important medical problem that requires effective therapy. Astaxanthin (AST) is a carotenoid, and the beneficial effects of astaxanthin, including anti-oxidative, anti-inflammatory and anti-tumour activities, have been identified. The present study was designed to elucidate the protective effects of astaxanthin against ALI and their underlying mechanisms. RAW264.7 macrophages were treated with dimethyl sulfoxide combined with different doses of astaxanthin for 12 h. Mice were fed with or without astaxanthin for up to 7 days. LPS was administered to induce inflammation. We assessed histopathology, oxidative stress, inflammation and apoptosis .The results indicated that astaxanthin attenuated LPS-induced oxidative stress, inflammation and cell apoptosis both in vivo and in vitro. In vivo and in vitro experiments showed that astaxanthin down regulated the nuclear factor-kappa beta (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2) and NLR family pyrin domain containing 3 (NLRP3) signalling pathways, inhibiting the LPS-induced inflammatory response, oxidative stress and cell apoptosis, and alleviating LPS-induced ALI in mice.

RESUMO: A lesão hepática aguda (ALI) é um problema médico importante que requer terapia eficaz. A astaxantina (AST) é um carotenóide, e os efeitos benéficos da astaxantina, incluindo atividades antioxidantes, anti-inflamatórias e antitumorais, foram identificados. O presente estudo foi desenhado para elucidar os efeitos protetores da astaxantina contra ALI e seus mecanismos subjacentes. Macrófagos RAW264.7 foram tratados com dimetil sulfóxido combinado com diferentes doses de astaxantina por 12 h. Os camundongos foram alimentados com ou sem astaxantina por até sete dias. O LPS foi administrado para induzir a inflamação. Histopatologia, estresse oxidativo, inflamação e apoptose foram avaliados. Os resultados indicaram que a astaxantina atenuou o estresse oxidativo induzido por LPS, inflamação e apoptose celular in vivo e in vitro. Experimentos in vivo e in vitro mostraram que a astaxantina regulou negativamente as vias de sinalização do fator nuclear-kappa beta (NF-κB), fator nuclear 2 relacionado ao eritróide 2 (Nrf2) e domínio de pirina da família NLR contendo 3 (NLRP3), inibindo o LPS- resposta inflamatória induzida, estresse oxidativo e apoptose celular e alívio da ALI induzida por LPS em camundongos.

SUMMARY OBJECTIVE: Pelvic organ prolapse affects women’s quality of life through symptoms such as vaginal laxity, urinary incontinence, defecation and sexual dysfunction, and pelvic pain. Given the challenges in managing recurrent cases, understanding risk factors and the effect of surgical choices on recurrence is vital for guiding clinical decisions. This study explores how uterine preservation influences postoperative recurrence and develops predictive models to aid in assessing recurrence risk. METHODS: A total of 87 patients diagnosed with pelvic organ prolapse who underwent laparoscopic sacral fixation were included. Patients were classified into two groups based on the occurrence of pelvic organ prolapse recurrence within 3 years post-surgery (recurrence: n=22; no recurrence: n=65). Follow-up over 3 years was recorded. Factors including age, body mass index, birth order, occupation, and uterus preservation during surgery were evaluated. The relationship between pelvic floor muscle strength and pelvic organ prolapse recurrence was also examined. Logistic regression analysis assessed the correlation between pelvic organ prolapse recurrence and levels of serum elastase inhibitor and osteopontin. RESULTS: In a follow-up of 87 patients with pelvic organ prolapse, 22 experienced recurrences within 3 years, marking a 25.29% recurrence rate. Multivariate analysis identified older age, higher parity, and sustained contraction of type II muscle fibers as independent risk factors for recurrence (all p<0.05). Lower systolic blood pressure in type I and II muscle fibers was associated with decreased serum elastase inhibitor and osteopontin levels, increasing pelvic organ prolapse recurrence risk. Logistic regression identified age, multiple deliveries, and low systolic pressure in type II muscle fibers as independent recurrence factors. The constructed nomogram risk prediction model, incorporating these factors, showed good discrimination ability with an area under the receiver operating characteristic curve of 0.891 (95%CI 0.871, 0.921), indicating accurate predictions and high net benefit. CONCLUSION: Factors such as age, birth order, uterine preservation, and pelvic floor muscle strength impact postoperative pelvic organ prolapse recurrence. Older age, a higher number of deliveries, and reduced systolic pressure of class II muscle fibers are independent risk factors for pelvic organ prolapse recurrence after surgery. OBJECTIVE womens women s laxity incontinence dysfunction pain cases decisions METHODS 8 included postsurgery post (recurrence n=22 n22 n n=65. n65 n=65 . 65 n=65) Followup Follow up recorded age index order occupation evaluated examined RESULTS followup follow 2 2529 25 29 25.29 rate parity all p<0.05. p005 p p<0.05 0 05 p<0.05) deliveries model 0891 891 0.89 95%CI 95CI CI 95 0871 871 0.871 0.921, 0921 0.921 , 921 0.921) benefit CONCLUSION n=2 n2 n6 n=6 6 252 25.2 p00 p<0.0 089 89 0.8 9 087 0.87 092 0.92 92 n= 25. p0 p<0. 08 0. 09 0.9 p<0 p<

Abstract Objective: Aortic Dissection (AD) is one of the most fatal acute diseases in cardiovascular diseases, with rapid onset and progression and a high fatality rate. This study aims to investigate the clinical values of non-enhancement peripheral pulse-gating rapid magnetic resonance imaging in deterministic diagnosis of AD. Methods: Aorta magnetic resonance imaging was performed in 21 healthy volunteers at a 1.5t MR scanner sequences including cardiac-gated and peripheral pulse-gated True-FISP and HASTE were carried out separately. Acquisition Time (TA), Signal to Noise Ratio (SNR), Contrast Noise Ratio (CNR), and entirety of vessel wall blood flow artifacts were measured and compared. A total of 56 AD cases were displayed by non-enhancement peripheral pulse-gating fast MR imaging, and the results were compared with pathological findings or CTA of the aorta. The dissection rupture, tear film, true and false lumen, thrombosis, hydropericardium, and the main branches of AD were evaluated respectively. Results: There were no significant differences in SNR, CNR, entirety of the vessel wall, and blood flow artifact between cardiac-gated and peripheral pulse-gated fast MR imaging. Non-enhancement pulse-gated fast scanning takes less TA time. By the pulse-gated non-enhancement fast MR imaging, the dissection rupture, tear film, true and false cavity, thrombosis, hydropericardium, and the main branches of aortic dissection were shown clearly. Multi-planar and multi-angle scans helped to show the extent of entrapment rupture, whereas partial complex tears or bi-directional tears were slightly less well visualized. Conclusion: Non-enhancement peripheral pulse-gated rapid magnetic resonance imaging can be used for deterministic diagnosis of AD. Objective (AD rate nonenhancement non enhancement pulsegating pulse gating Methods 2 15t t 1 5t cardiacgated cardiac gated pulsegated TrueFISP True FISP separately TA, , (TA) SNR (SNR) CNR (CNR) 5 aorta rupture film lumen thrombosis hydropericardium respectively Results Nonenhancement Non time cavity clearly Multiplanar Multi planar multiangle multi angle bidirectional bi directional visualized Conclusion (TA (SNR (CNR

Resumo Fundamento A hipertrofia cardíaca patológica (HC) sustentada é um fator de risco independente para aumento da incidência e mortalidade de eventos cardiovasculares. Objetivos Esta pesquisa foi projetada para desvendar o papel do RNA não codificante longo (LncRNA) CCAT2 na progressão da HC. Métodos Procedimentos de constrição aórtica transversal (TAC) foram conduzidos para construir um modelo de HC in vivo induzido por sobrecarga de pressão. O tratamento com angiotensina II (Ang II) foi utilizado para induzir células hipertróficas de cardiomiócitos de rato H9c2. Resultados Os resultados in vivo mostraram que o silenciamento de CCAT2 reduziu a área de superfície dos cardiomiócitos, aliviou a fibrose cardíaca e diminuiu os níveis de β-MHC, ANP e BNP em modelos de camundongos HC. Os resultados in vitro revelaram que o knockdown de CCAT2 reduziu a área de superfície celular e atenuou os níveis de β-MHC, ANP e BNP em células hipertróficas H9c2. Além disso, o silenciamento de CCAT2 diminuiu os níveis de β-catenina ativa, GSK-3β fosforilada e genes alvo Wnt (c-Myc, ciclinaD1 e c-Jun) em camundongos HC e células H9c2 hipertróficas. É importante ressaltar que o tratamento com o ativador da via Wnt / β-catenina LiCl reverteu a supressão do knockdown de CCAT2 na área de superfície celular H9c2 e nos níveis de MHC, ANP e BNP. Conclusões Coletivamente, o silenciamento do CCAT2 desempenha um papel protetor contra a HC através da inativação da sinalização Wnt/β-catenina, o que sugere que o CCAT2 pode se tornar um alvo terapêutico promissor para o HC. (HC cardiovasculares LncRNA (LncRNA CCAT TAC (TAC pressão Ang Hc H c βMHC, βMHC β MHC β-MHC disso βcatenina catenina ativa GSK3β GSKβ GSK 3β cMyc, cMyc Myc, Myc (c-Myc ciclinaD cJun Jun c-Jun H9c Coletivamente Wnt/βcatenina, Wntβcatenina Wnt/β catenina, Wnt/β-catenina Wnt/βcatenina Wntβ

Abstract Background Sustained pathological cardiac hypertrophy (CH) is an independent risk factor for increased incidence and mortality of cardiovascular events. Objectives This research was designed to unravel the role of long non-coding RNA (LncRNA) CCAT2 in CH progression. Methods Transverse aortic constriction (TAC) procedures were conducted to construct a pressure overload-induced in vivo CH model. Angiotensin II (Ang II) treatment was utilized to induce hypertrophic rat cardiomyocyte H9c2 cells. Results In vivo results showed that silencing of CCAT2 reduced cardiomyocyte surface area, alleviated cardiac fibrosis, and decreased β-MHC, ANP, and BNP levels in CH mouse models. In vitro results revealed that CCAT2 knockdown reduced cell surface area and attenuated β-MHC, ANP, and BNP levels in hypertrophic H9c2 cells. Besides, CCAT2 silencing decreased the levels of active β-catenin, phosphorylated-GSK-3β, and Wnt target genes (c-Myc, cyclinD1, and c-Jun) in CH mice and hypertrophic H9c2 cells. Importantly, treatment with the Wnt/β-catenin pathway activator LiCl reversed the suppression of CCAT2 knockdown on H9c2 cell surface area and MHC, ANP, and BNP levels. Conclusions Collectively, CCAT2 silencing plays a protective role against CH through inactivating the Wnt/β-catenin signaling, which suggests that CCAT2 might become a promising therapeutic target for CH. (CH events noncoding non coding LncRNA (LncRNA CCAT progression TAC (TAC overloadinduced overload induced model Ang Hc H c H9c cells fibrosis βMHC, βMHC β MHC β-MHC ANP models Besides βcatenin, βcatenin catenin, catenin β-catenin phosphorylatedGSK3β, phosphorylatedGSK3β phosphorylatedGSKβ phosphorylated GSK 3β, 3β phosphorylated-GSK-3β cMyc, cMyc Myc, Myc (c-Myc cyclinD1 cyclinD cJun Jun c-Jun Importantly Wnt/βcatenin Wntβcatenin Wnt/β Collectively signaling phosphorylatedGSK Wntβ

Both embryonic stem cells (ESCs) and the successful reprogramming of induced pluripotent stem cells (iPSCs) offer an unprecedented therapeutic potential for Parkinson's disease (PD), allowing for the replacement of depleted neurons in PD-affected brain regions, thereby achieving therapeutic goals. This study explored the differences in cell types between iPSCs and ESCs in the PD brain to provide a feasible theoretical basis for the improved use of iPSCs as a replacement for ESCs in treating PD. Signal cell RNA sequencing data and microarray data of ESCs and iPSCs were collected from the GEO database. scRNA-seq data were subjected to quality control, clustering, and identification using the Seurat R package to determine cell types and proportions in ESCs and iPSCs. Differential expression analysis was performed to identify differentially expressed genes between ESCs and iPSCs, and PPI network analysis was conducted using String. Based on scRNA-seq data, we identified 13 cell clusters in ESCs and 13 cell clusters in iPSCs. iPSCs were predominantly composed of immune cells and lacked astrocytes, neurons, and dopamine neurons compared to ESCs. iPSCs also exhibited lower cell type diversity compared to ESCs. At the gene level, iPSCs lacked key genes, such as TH and GAP43 for nerve growth and development. At the metabolic level, the difference between ESCs and iPSC was mainly reflected in nerve cells and was closely related to the tumor-proliferation signature. iPSCs can be promoted to differentiate into cell types closer to or even replace ESCs, providing a better therapeutic option for PD treatment. (ESCs (iPSCs Parkinsons Parkinson s PD, , (PD) PDaffected affected regions goals database scRNAseq scRNA seq control clustering String 1 astrocytes level GAP GAP4 development tumorproliferation tumor proliferation signature treatment (PD

Emerging evidence demonstrates that curcumin has an inhibitory effect on non-small cell lung cancer (NSCLC), and its targets and mechanism of action need further exploration. The goal of this study was to explore the potential targets and mechanism of curcumin against NSCLC by network pharmacology, bioinformatics, and experimental validation, thereby providing more insight into combination treatment with curcumin for NSCLC in preclinical and clinical research. Curcumin targets against NSCLC were predicted based on HIT2.0, STD, CTD, and DisGeNET, and the core targets were analyzed via protein-protein interaction network construction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking. The gene expression levels of samples in A549 cells, NCI-H460, and curcumin treated groups were detected by real-time quantitative PCR. A total of 67 common targets between curcumin and NSCLC were collected by screening public databases. GO and KEGG analysis suggested that curcumin treatment of NSCLC mainly involves cancer-related pathways, such as PI3K-AKT signaling pathway, Foxo signaling pathway, microRNAs, MAPK signaling pathway, HIF-1 signaling pathway, etc. The targets with the highest degree were identified through the PPI network, namely CASP3, CTNNB1, JUN, IL6, MAPK3, HIF1A, STAT3, AKT1, TP53, CCND1, VEGFA, and EGFR. The results of the in vitro experiments showed that curcumin treatment of NSCLC down-regulated the gene expressions of CCND1, CASP3, HIF1A, IL-6, MAPK3, STAT3, AKT1, and TP53. Our findings revealed that curcumin functions as a potential therapeutic candidate for NSCLC by suppressing multiple signaling pathways and interacting with multiple gene targets. nonsmall non small NSCLC, , (NSCLC) exploration pharmacology bioinformatics validation research HIT20 HIT HIT2 0 HIT2.0 STD CTD DisGeNET proteinprotein protein PPI, (PPI) GO, (GO) KEGG, (KEGG) docking A54 cells NCIH460, NCIH460 NCIH NCI H460, H460 H NCI-H460 realtime real time PCR 6 databases cancerrelated related PI3KAKT PIKAKT PI3K AKT PI K pathway microRNAs HIF1 HIF 1 HIF- etc CASP3 CASP CTNNB1 CTNNB JUN IL6 IL MAPK3 HIF1A HIFA STAT3 STAT AKT1 TP53 TP CCND1 CCND VEGFA EGFR downregulated down regulated 6, IL-6 (NSCLC HIT2. (PPI (GO (KEGG A5 NCIH46 H46 NCI-H46 KAKT PIK TP5 IL- NCIH4 H4 NCI-H4 NCI-H

Jun N-terminal kinase pathway-associated phosphatase (JKAP) regulates CD4+ T-cell differentiation and immunity, which are linked to mental disorders. This study aimed to explore the relationships between JKAP and T helper 17 (Th17)/regulatory T (Treg) ratio, as well as their associations with anxiety and depression in postpartum women. Serum JKAP were measured by enzyme-linked immunosorbent assay and blood Th17 and Treg cells were measured by flow cytometry in 250 postpartum women. Anxiety and depression were evaluated by the 6-item State-Trait Anxiety Inventory (STAI6) and Edinburgh Postnatal Depression Scale (EPDS). Anxiety and depression rates were 22.0 and 28.4%, respectively, among postpartum women. Notably, JKAP was negatively associated with the STAI6 (P=0.002) and EPDS scores (P<0.001) in postpartum women and was lower in postpartum women with anxiety (P=0.023) or depression (P=0.002) than in those without. Moreover, JKAP was inversely related to Th17 cells and Th17/Treg ratio but positively correlated with Treg cells in postpartum women (all P<0.001). Interestingly, Th17 cells and Th17/Treg ratio were both positively associated with STAI6 and EPDS scores in postpartum women (all P<0.001). Furthermore, Th17 cells and Th17/Treg ratio were lower in postpartum women with anxiety or depression than in those without (all P<0.01). Nevertheless, Treg cells were not linked to anxiety or depression in postpartum women. JKAP was negatively associated with Th17 cells and Th17/Treg ratio; moreover, they all related to anxiety and depression in postpartum women, indicating that JKAP may be involved in postpartum anxiety and depression via interactions with Th17 cells. Nterminal N terminal pathwayassociated pathway (JKAP CD4 CD Tcell cell immunity disorders 1 Th17/regulatory Th17regulatory Thregulatory /regulatory regulatory Th (Treg enzymelinked enzyme Th1 25 6item item 6 StateTrait State Trait STAI (STAI6 EPDS. . (EPDS) 220 22 0 22. 284 28 4 28.4% respectively Notably P=0.002 P0002 P 002 (P=0.002 P<0.001 P0001 001 (P<0.001 P=0.023 P0023 023 (P=0.023 Moreover Th17Treg ThTreg P<0.001. P<0.001) Interestingly Furthermore P<0.01. P001 P<0.01 01 P<0.01) Nevertheless moreover 2 (STAI (EPDS 28.4 P=0.00 P000 00 (P=0.00 P<0.00 (P<0.00 P=0.02 P002 02 (P=0.02 P00 P<0.0 28. P=0.0 (P=0.0 (P<0.0 P0 P<0. P=0. (P=0. (P<0. P<0 P=0 (P=0 (P<0 P< P= (P= (P< (P

Abstract Background In contemporary society, with the accelerated pace of work and life, more and more people feel different degrees of stress. Long-term stress may not only lead to insomnia, but also to mental health problems (e.g., anxiety and depression), which has a significant impact on people's quality of life and mental health. Objective This study primarily investigates the mechanism through which stress affects sleep quality among college students. Methods We conducted research on 1653 Chinese college students using four scales with high reliability and validity: stress, the Pittsburgh Sleep Quality Index, social anxiety, and rumination. Results The study found: (1) Stress can significantly and positively predict sleep quality and rumination; (2) Rumination can positively predict social anxiety; (3) Social anxiety can positively predict sleep quality; (4) Stress can affect sleep quality through social anxiety and rumination separately, and stress can also affect sleep quality through the chained mediation of rumination and social anxiety. Conclusion This study reveals the relationship and mechanisms between stress and sleep quality. It not only deepens the research on the impact of stress on sleep quality but also provides theoretical support and new methods for mental health professionals to help clients improve their sleep quality. In practice, in addition to using some common psychological intervention methods to help individuals reduce stress, we should pay more attention to how to help clients reduce rumination and social anxiety, This is significant in improving the quality of an individual's sleep. society Longterm Long term insomnia e.g., eg e g (e.g. depression, depression , depression) peoples s 165 validity Index found 1 (1 2 (2 3 (3 4 (4 separately practice individual e.g. (e.g 16 ( e.g

Abstract Background Glomus Tumor (GT) are benign neoplasms that originate from mesenchymal cells. It presents as tenderness and cold allodynia in the digits, especially in the subungual region. There are a few studies that investigated the mechanism of pain. Objectives To analyze the clinical-pathologic characteristics of GT and to identify the expression of IL-1β, IL-6, and CGRP in it, further, to explore the possible mechanism of pain. Methods The clinical and pathological data of 60 GT patients were retrospectively analyzed. Tissue microarrays and immunohistochemistry were used to measure the expression of IL-1β, IL-6 and CGRP. Results GT is more common in females and the ratio of male to was near to 1:2, mostly in middle-aged people. It often occurs in fingertips, especially the thumbs. Patients often present with spontaneous pain, tenderness, and cold hypersensitivity. Both the two pain mediators IL-1β and IL-6 were highly expressed in GT cells of patients with and without cold hypersensitivity. While CGRP was not expressed in GT. Study limitations Low sample size and further research is needed to explore the specific mechanism. Conclusions IL-1β and IL-6 were highly expressed in GT cells, suggesting that IL-1β and IL-6 have certain nociceptive roles in GT. In the 4 patients with cold intolerance, the intensity of IL-1β and IL-6 staining was also strong, suggesting that they may not play a role in the cold hypersensitivity. However, since there are only 4 patients with cold intolerance, it’s necessary to conduct further in-depth research using a larger sample size. The specific role of CGRP in GT has not been found yet. (GT digits region clinicalpathologic pathologic IL1β, IL1β ILβ IL 1β, 1β β IL6, IL6 6, 6 it analyzed IL- 12, 12 1 2, 2 1:2 middleaged middle aged people fingertips thumbs hypersensitivity intolerance strong However its s indepth depth yet 1:

Resumo Fundamento: O antibiótico quimioterápico antraciclina doxorrubicina (DOX) pode induzir cardiotoxicidade cumulativa e levar à disfunção cardíaca. RNAs não codificantes longos (lncRNAs) podem funcionar como importantes reguladores na lesão miocárdica induzida por DOX. Objetivo: Este estudo tem como objetivo investigar o papel funcional e o mecanismo molecular do RNA antisense lncRNA OXCT1 1 (OXCT1-AS1) na lesão celular miocárdica induzida por DOX in vitro. Métodos: Cardiomiócitos humanos (AC16) foram estimulados com DOX para induzir um modelo de lesão celular miocárdica. A expressão de OXCT1-AS1, miR-874-3p e BDH1 em células AC16 foi determinada por RT-qPCR. A viabilidade das células AC16 foi medida pelo ensaio XTT. A citometria de fluxo foi empregada para avaliar a apoptose de células AC16. Western blotting foi utilizado para avaliar os níveis proteicos de marcadores relacionados à apoptose. O ensaio repórter de luciferase dupla foi conduzido para verificar a capacidade de ligação entre miR-874-3p e OXCT1-AS1 e entre miR-874-3p e BDH1. O valor de p<0,05 indicou significância estatística. Resultados: A expressão de OXCT1-AS1 foi diminuída em células AC16 tratadas com DOX. A superexpressão de OXCT1-AS1 reverteu a redução da viabilidade celular e a promoção da apoptose celular causada pela DOX. OXCT1-AS1 está ligado competitivamente ao miR-874-3p para regular positivamente o BDH1. A superexpressão de BDH1 restaurou a viabilidade das células AC16 e suprimiu a apoptose celular sob estimulação com DOX. A derrubada do BDH1 reverteu a atenuação da apoptose de células AC16 mediada por OXCT1-AS1 sob tratamento com DOX. Conclusão: LncRNA OXCT1-AS1 protege células miocárdicas humanas AC16 da apoptose induzida por DOX através do eixo miR-874-3p/BDH1. Fundamento (DOX cardíaca lncRNAs (lncRNAs Objetivo OXCT OXCT1AS1 OXCTAS AS1 AS (OXCT1-AS1 vitro Métodos AC (AC16 OXCT1AS1, AS1, miR8743p miRp miR 874 3p p BDH AC1 RTqPCR. RTqPCR RT qPCR. qPCR RT-qPCR XTT OXCT1-AS p005 0 05 p<0,0 estatística Resultados Conclusão miR8743p/BDH1. miR8743pBDH1 miRpBDH 3p/BDH1. miR-874-3p/BDH1 OXCT1AS (OXCT1-AS (AC1 87 p00 p<0, miR8743p/BDH1 pBDH miR8743pBDH 3pBDH1 3p/BDH1 miR-874-3p/BDH (AC 8 p0 p<0 miR8743p/BDH 3pBDH 3p/BDH p<

Abstract Background: The anthracycline chemotherapeutic antibiotic doxorubicin (DOX) can induce cumulative cardiotoxicity and lead to cardiac dysfunction. Long non-coding RNAs (lncRNAs) can function as important regulators in DOX-induced myocardial injury. Objective: This study aims to investigate the functional role and molecular mechanism of lncRNA OXCT1 antisense RNA 1 (OXCT1-AS1) in DOX-induced myocardial cell injury in vitro. Methods: Human cardiomyocytes (AC16) were stimulated with DOX to induce a myocardial cell injury model. OXCT1-AS1, miR-874-3p, and BDH1 expression in AC16 cells were determined by RT-qPCR. AC16 cell viability was measured by XTT assay. Flow cytometry was employed to assess the apoptosis of AC16 cells. Western blotting was used to evaluate protein levels of apoptosis-related markers. Dual-luciferase reporter assay was conducted to verify the binding ability between miR-874-3p and OXCT1-AS1 and between miR-874-3p and BDH1. The value of p<0.05 indicated statistical significance. Results: OXCT1-AS1 expression was decreased in DOX-treated AC16 cells. Overexpression of OXCT1-AS1 reversed the reduction of cell viability and promotion of cell apoptosis caused by DOX. OXCT1-AS1 is competitively bound to miR-874-3p to upregulate BDH1. BDH1 overexpression restored AC16 cell viability and suppressed cell apoptosis under DOX stimulation. Knocking down BDH1 reversed OXCT1-AS1-mediated attenuation of AC16 cell apoptosis under DOX treatment. Conclusion: LncRNA OXCT1-AS1 protects human myocardial cells AC16 from DOX-induced apoptosis via the miR-874-3p/BDH1 axis. Background (DOX dysfunction noncoding non coding lncRNAs (lncRNAs DOXinduced induced Objective OXCT OXCT1AS1 OXCTAS AS1 AS (OXCT1-AS1 vitro Methods AC (AC16 model OXCT1AS1, AS1, miR8743p, miR8743p miRp miR 874 3p, 3p p BDH AC1 RTqPCR. RTqPCR RT qPCR. qPCR RT-qPCR apoptosisrelated related markers Dualluciferase Dual luciferase OXCT1-AS p005 0 05 p<0.0 significance Results DOXtreated treated stimulation OXCT1AS1mediated OXCTASmediated mediated treatment Conclusion miR8743p/BDH1 miR8743pBDH1 miRpBDH 3p/BDH1 miR-874-3p/BDH axis OXCT1AS (OXCT1-AS (AC1 87 p00 p<0. miR8743p/BDH pBDH miR8743pBDH 3pBDH1 3p/BDH (AC 8 p0 p<0 3pBDH p<

Abstract Fast calculations are widely required in the traditional applications and the emerging digital twin fields. For those considerations, a novel physics-based fast algorithm, namely generalized rotation-superposition method, is proposed for fast calculating linear elastic responses of generalized rotationally axisymmetric structures under arbitrary mechanical loads. This improved method breaks through the limitations of the previous basic rotation-superposition method in rotational similarity of load and structural axisymmetry, and greatly expands its application scope. In this paper, firstly, the basic theory of the rotation-superposition algorithm is introduced; secondly, the theoretical model of the generalized rotation-superposition method is established; thirdly, the effectiveness and accuracy are verified by using finite element simulations; finally, through a complex case study, the applicability of the generalized rotation-superposition method for complex engineering problems and its advantages in efficiently obtaining massive amounts of data are further illustrated. fields considerations physicsbased physics based rotationsuperposition rotation superposition loads axisymmetry scope paper firstly introduced secondly established thirdly simulations finally study illustrated

The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that counteract ABCB1-mediated multidrug resistance. FRAX486 is a p21-activated kinase (PAK) inhibitor. The objective of this study was to investigate whether FRAX486 can reverse ABCB1-mediated multidrug resistance, while also exploring its mechanism of action. The CCK8 assay demonstrated that FRAX486 significantly reversed ABCB1-mediated multidrug resistance. Furthermore, western blotting and immunofluorescence experiments revealed that FRAX486 had no impact on expression level and intracellular localization of ABCB1. Notably, FRAX486 was found to enhance intracellular drug accumulation and reduce efflux, resulting in the reversal of multidrug resistance. Docking analysis also indicated a strong affinity between FRAX486 and ABCB1. This study highlights the ability of FRAX486 to reverse ABCB1-mediated multidrug resistance and provides valuable insights for its clinical application. Pglycoprotein P glycoprotein Pgp/ABCB1 PgpABCB1 PgpABCB gp/ABCB1 gp ABCB1 ABCB (P-gp/ABCB1 MDR. MDR . (MDR) Hence ABCB1mediated ABCBmediated mediated FRAX FRAX48 p21activated pactivated p21 activated p PAK (PAK inhibitor action CCK Furthermore Notably efflux application Pgp Pgp/ABCB gpABCB1 gpABCB gp/ABCB (P-gp/ABCB (MDR FRAX4 p2

In this study, Al-Si-Cu-Mg composites reinforced with Silicon carbide (SiC) particles and/or Carbon nanotubes (CNTs) were fabricated using semi-solid stirring casting technology (SSC). The aim of the study was to investigate the influence of SiC and/or CNTs on the mechanical properties, microstructural evolution, and deformation mechanisms of the Al-Si-Cu-Mg alloy. The findings indicated that the presence of SiC/CNTs in the composite had a significant effect on refining the α-Al phase and altering its grain orientation. Additionally, the results obtained from EBSD and TEM revealed that the microstructure of the Al-Si-Cu-Mg-SiC/CNTs hybrid composite (HAMC) underwent dynamic recrystallization (DRX) and static recrystallization (SRX), resulting in a fine equiaxed recrystallized structure. This process also led to the formation of high-angle grain boundaries (HAGBs) through dislocation rearrangement. The SiC particles were evenly distributed within the matrix, ensuring good interface bonding between SiC and α-Al phases. Moreover, the CNTs reacted with the matrix, resulting in the in-situ formation of the Al4C3 phase at the interface. The addition of SiC/CNTs significantly increased the tensile strength of HAMC at 25°C and 250°C, from 319MPa and 178MPa to 438MPa and 331MPa. Examination of the fracture surface of the hybrid composite unveiled that void formation occurred primarily at the regions surrounding the matrix-particle interface. AlSiCuMg Al Si Cu Mg (SiC andor or (CNTs semisolid semi solid SSC. SSC . (SSC) properties evolution alloy SiCCNTs αAl α orientation Additionally AlSiCuMgSiC/CNTs AlSiCuMgSiCCNTs (HAMC DRX (DRX SRX, SRX , (SRX) structure highangle high angle HAGBs (HAGBs rearrangement matrix phases Moreover insitu situ AlC C Al4C 25C 25 250C 250 250°C MPa 331MPa matrixparticle particle (SSC AlSiCuMgSiC (SRX 2

ABSTRACT Through a long-term micro-area positioning experiment (2006-2017), the precise fertilization locations of spring maize (Zea mays L.) in Jilin, China, were investigated using an embedded cement bucket pot. The effects of different fertilization placements and additional application of organic manure on maize yield, biomass, grain nutrient uptake, and soil fertility were examined. Six treatments were designed: base fertilizer + topdressing shallow application (BF1TD1); base fertilizer deep + topdressing shallow application (BF2TD1); base fertilizer + topdressing deep application (BF1TD2); base fertilizer deep + topdressing deep application (BF2TD2); base fertilizer + topdressing + organic manure shallow application (BF1TD1 + OS); and base fertilizer + topdressing shallow application + organic manure deep application (BF1TD1 + OD). After 12 years of continuous experimentation, the findings revealed that BF2TD2, BF1TD1 + OS, and BF1TD1 + OD exhibited 10.59 %, 25.17 %, and 29.34 % higher average yields than BF1TD1, respectively. Deep topdressing was more beneficial in increasing maize yield and nutrient accumulation, and additionally, increasing the use of organic fertilizer enhanced plant biomass and nutrient uptake. Over the 12 years considered, the soil organic matter in the 0-20 cm and 20-40 cm layers increased by 45.96 % and 80.61 %, respectively, and the soil pH increased from 0.38 to 0.48. In general, the deep application of organic manure was more beneficial for soil retention as it can increase soil fertility in the 0-40 cm layer. Considering the high yield and nutrient absorption and utilization of maize, technical advancement for soil fertilizer in whole-field tillage layers was crucial. longterm long term microarea micro area 20062017, 20062017 2006 2017 , (2006-2017) Zea L. L Jilin China pot uptake examined designed BFTD BF TD (BF1TD1) BF2TD1 (BF2TD1) BF1TD2 (BF1TD2) BF2TD2 (BF2TD2) (BF1TD OS OS) OD. . OD) 1 experimentation BF1TD 1059 10 59 10.5 2517 25 17 25.1 2934 29 34 29.3 respectively accumulation additionally considered 020 0 20 0-2 2040 40 20-4 4596 45 96 45.9 8061 80 61 80.6 038 38 0.3 048 48 0.48 general 040 0-4 layer wholefield whole field crucial 2006201 200 201 (2006-2017 BF2TD (BF2TD1 (BF1TD2 (BF2TD2 105 5 10. 251 2 25. 293 3 29. 02 0- 204 4 20- 459 9 45. 806 8 6 80. 03 0. 04 0.4 200620 (2006-201 (BF2TD 20062 (2006-20 (2006-2 (2006- (2006 (200 (20 (2 (

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5’end or 3’end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5’ end or 3’ end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.