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Phosphorylation of histone H3 at threonine 11 (H3T11ph) affects transcription and chromosome stability. However, the enzymes responsible for depositing H3T11ph and the functions of H3T11ph in plants remain unknown. Here we report that in Arabidopsis thaliana, PYRUVATE KINASE 6 (PK6), PK7 and PK8 enter the nucleus under conditions of sufficient glucose and light exposure, where they interact with SWI2/SNF2-RELATED 1 COMPLEX 4 (SWC4) and phosphorylate H3 at threonine 11. Mutations in these kinases or knockdown of SWC4 resulted in FLC-dependent early flowering, short hypocotyls and short pedicels. Genome-wide, H3T11ph is highly enriched at transcription start sites and transcription termination sites, and positively correlated with gene transcript levels. PK6 and SWC4 targeted FLC, MYB73, PRE1, TCP4 and TCP10, depositing H3T11ph at these loci and promoting their transcription, and PK6 occupancy at these loci requires SWC4. Together, our results reveal that nuclear-localized PK6, PK7 and PK8 modulate H3T11ph and plant growth.
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This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.
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Nomogramas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Adulto , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/virología , Virus de la Hepatitis B , Hepatitis B/mortalidad , Hepatitis B/complicaciones , Estudios Prospectivos , AncianoRESUMEN
Coronary artery disease (CAD), a critical condition resulting from systemic inflammation, metabolic dysfunction, and gut microbiota dysbiosis, poses a global public health challenge. ALW-II-41-27, a specific inhibitor of the EphA2 receptor, has shown anti-inflammatory prosperities. However, the impact of ALW-II-41-27 on atherosclerosis has not been elucidated. This study aimed to examine the roles of pharmacologically inhibiting EphA2 and the underlying mechanism in ameliorating atherosclerosis. ALW-II-41-27 was administered to apoE-/- mice fed a high-fat diet via intraperitoneal injection. We first discovered that ALW-II-41-27 led to a significant reduction in atherosclerotic plaques, evidenced by reduced lipid and macrophage accumulation, alongside an increase in collagen and smooth muscle cell content. ALW-II-41-27 also significantly lowered plasma and hepatic cholesterol levels, as well as the colonic inflammation. Furthermore, gut microbiota was analyzed by metagenomics and plasma metabolites by untargeted metabolomics. ALW-II-41-27-treated mice enriched Enterococcus, Akkermansia, Eggerthella and Lactobaccilus, accompanied by enhanced secondary bile acids production. To explore the causal link between ALW-II-41-27-associated gut microbiota and atherosclerosis, fecal microbiota transplantation was employed. Mice that received ALW-II-41-27-treated mouse feces exhibited the attenuated atherosclerotic plaque. In clinical, lower plasma DCA and HDCA levels were determined in CAD patients using quantitative metabolomics and exhibited a negative correlation with higher monocytes EphA2 expression. Our findings underscore the potential of ALW-II-41-27 as a novel therapeutic agent for atherosclerosis, highlighting its capacity to modulate gut microbiota composition and bile acid metabolism, thereby offering a promising avenue for CAD.
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Aterosclerosis , Ácidos y Sales Biliares , Dieta Alta en Grasa , Microbioma Gastrointestinal , Receptor EphA2 , Animales , Aterosclerosis/metabolismo , Aterosclerosis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Ácidos y Sales Biliares/metabolismo , Ratones , Receptor EphA2/metabolismo , Dieta Alta en Grasa/efectos adversos , Masculino , Humanos , Modelos Animales de Enfermedad , Placa Aterosclerótica/etiología , Ratones Endogámicos C57BL , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Bacterias/metabolismo , DisbiosisRESUMEN
The emergence of multidrug-resistant bacterial have caused severe burden for public health. Particularly, Staphylococcus aureus as one of ESKAPE pathogens have induced various infectious diseases and resulted in increasing deaths. Developing new antibacterial agents is still urgent and challenging. Fortunately, in this study, based on aggregation-induced emission (AIE) ruthenium complexes were designed and synthesized, which realized the high efficiency of reactive oxygen species generation and remarkably killed S. aureus unlike conventional antibiotics action. Significantly, owing to good singlet oxygen production ability, Ru1 at only 4 µg/mL of concentration displayed good antibacterial photodynamic therapy effect upon white light irradiation and could deplete essential coenzyme NADH to disrupt intracellular redox balance. Also, the electrostatic interaction between Ru1 and bacteria enhanced the possibility of antibacterial. Under light irradiation, Ru1 could efficiently inhibit the biofilm growth and avoid the development of drug-resistant. Furthermore, Ru1 possessed excellent biocompatibility and displayed remarkable therapy effect in treating mice-wound infections in vivo. These findings indicated that AIE-based ruthenium complexes as new antibacterial agent had great potential in photodynamic therapy of bacteria and addressing the drug-resistance crisis.
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Modulating the electronic structure is essential for improving the anchoring and catalytic capabilities of catalysts in lithium-sulfur batteries (LSBs). This study delves into the modulation of d-orbitals in transition metal dual-atom catalysts (DACs) supported by boron nitride and graphene (BNC) hybrid sheets for LSBs. This study reveals that the d-band center of the DACs, a key determinant of material chemical properties, is primarily determined by the electronic configuration of the dyz and dx2-y2 orbitals. Furthermore, the interaction between dz2 of transition metals and S_3 p orbitals is critical for the binding strength of LiPSs. By understanding these interactions, the functionality of DACs can be customized for optimal performance in LSBs. For example, the MnCrBNC catalyst with 10 d-electrons exhibits the optimal d-band center and demonstrates exceptional LiPSs binding capability, the lowest Li2S decomposition energy barrier, and the lowest Gibbs free energy of reaction for the rate-determining step of sulfur reduction. This study elucidates the fundamental mechanisms for designing high-performance LSB catalysts through electronic structure modulation.
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BACKGROUND: Air pollution and genetic risk have been found to contribute to both onset and development of psoriasis. However, the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of incident psoriasis remains unknown. OBJECTIVES: Our study aimed to assess the association between joint exposure to multiple air pollutants and the risk of psoriasis and the modification by the genetic susceptibility. METHODS: This prospective study included 451,064 participants with complete air pollution data and free of psoriasis at baseline from the UK Biobank. All participants were enrolled from 2006 to 2010 and followed up to 2022. The air pollution score (APS) was calculated to assess the joint exposure to multiple air pollutants, including particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), between 2.5 and 10 µm (PM2.5-10), and ≤ 10 µm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). To evaluate the genetic risk, the polygenic risk score (PRS) for psoriasis was constructed. The Cox proportional hazard models were used to assess the association of air pollution and genetic susceptibility with the risk of psoriasis. Stratified analyses were conducted based on the individual characteristics. RESULTS: During a median follow-up of 13.79 years, 4414 psoriasis events were recorded. The hazard ratios (HRs) [95% confidence intervals (CIs)] for psoriasis were 1.036 (0.936-1.147), 1.091 (0.987-1.206), 1.159 (1.048-1.283), and 1.163 (1.052-1.286) in higher quintile groups compared with the lowest quintile of APS (P trend <0.05). When considering genetic susceptibility, participants with high PRS and high APS had the greatest risk of incident psoriasis [HR (95% CI): 1.962 (1.630-2.362)] than those with low PRS and low APS. The HRs (95% CIs) for PM2.5-10, NOx, PM2.5 absorbance, PM2.5, NO2, and PM10 in the group with high exposure level and genetic risk were 1.831 (1.537-2.181), 1.722 (1.431-2.073), 1.698 (1.416-2.037), 1.619 (1.353-1.938), 1.504 (1.252-1.806), and 1.425 (1.192-1.704), respectively. CONCLUSIONS: Long-term exposure to various air pollutants is positively associated with an increased risk of incident psoriasis, particularly in individuals with high genetic risk. More comprehensive measures are needed to reduce the air pollution levels for better prevention of psoriasis.
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BACKGROUND: Although there has been some amount of research into the use of platelet-rich plasma (PRP) after arthroscopic rotator cuff repair, most studies have not fully demonstrated its benefits. In addition, PRP formulations containing different concentrations of leukocytes have not been directly compared for rotator cuff repair. PURPOSE/HYPOTHESIS: The purpose of this article was to determine whether arthroscopic rotator cuff repair combined with PRP injection, either leukocyte-rich PRP (LR-PRP) or leukocyte-poor PRP (LP-PRP), is superior to the control. The null hypothesis was that the addition of any PRP formulation would not result in outcomes superior to the control group. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients with full-thickness rotator cuff tears who underwent arthroscopic repair were assessed for eligibility. The included patients were randomized to 3 treatment groups: the LR-PRP, LP-PRP, and standard-care control groups. After the rotator cuff suture was fixed firmly, different groups of liquid PRP preparations prepared by centrifugation were injected into the tendon-to-bone interface. The functional outcomes were assessed using the University of California, Los Angeles (UCLA) score, the Constant score, the American Shoulder and Elbow Surgeons (ASES) score, the visual analog scale for pain during sleep and activity, and active range of motion at 3, 6, and 12 months after surgery. In addition, the visual analog scale score was obtained at weeks 2 and 6. Postoperative structural integrity was assessed by magnetic resonance imaging at 12 months using the Sugaya classification. Type III was considered partial retear, and types IV and V were considered complete retears. The safety of surgery was compared by the incidence of complications. The main analyses were performed in accordance with the intention-to-treat principle. RESULTS: Of 150 patients initially randomized, the functional outcomes in 142 (46 LR-PRP, 47 LP-PRP, 49 control) and the structural integrity in 133 (40 LR-PRP, 46 LP-PRP, 47 control) were analyzed. There was no significant difference in the primary outcome of the UCLA score among the 3 groups (P = .169). The trends in functional outcomes and range of motion were similar for the 3 groups, with no significant differences among the groups at 12 months. However, within 6 months after surgery, the ASES score was better in the LR-PRP group than in the control group (3 months: 85.8 ± 4.1 vs 81.6 ± 8.7; P = .011; 6 months: 90.0 ± 5.4 vs 86.2 ± 6.8; P = .003). At 12 months after surgery, the overall retear rate, including partial and complete retears, was 8%. There were no significant differences in the rates of overall retear (P = .755) or complete retear (P = .633) among the 3 groups. The only surgical complication was postoperative stiffness, which occurred in 3% of patients, and the incidence did not significantly differ among the groups (P = .790). CONCLUSION: The study did not reveal that shoulders treated with the LR-PRP or LP-PRP formulations had any superior functional or structural outcomes at 12 months compared with those of the control group. However, LR-PRP may offer better ASES scores than the control group up to 6 months after surgery, and its clinical benefit remains to be proven. REGISTRATION: ChiCTR2100045039 (Chinese Clinical Trial Register).
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Cumulus granulosa cells (CGCs) are somatic cells surrounding the oocyte that play an important role in oocyte growth, meiotic maturation, ovulation, and fertilization in mammals. Therefore, revealing the molecular mechanisms related to the development and function of CGCs is essential for further understanding the regulatory network in female reproduction. MSX2 belongs to the highly conserved msh homeobox gene family and plays diverse roles in different biological processes. This study cloned the coding sequence (CDS) of the yak MSX2 gene and detected the abundance and localization of MSX2 in the major female reproductive organs. The results indicated that the CDS of this gene included 747 base pairs and encoded 248 amino acids. The abundance of MSX2 mRNA was highly expressed in the luteal phase of the yak ovary during the estrous cycle, and MSX2 protein was widely expressed in different female reproductive organs, including the ovary, corpus luteum, uterus, and oviduct. Repressing MSX2 abundance in yak CGCs declined the cell viability and defective steroidogenesis. Several genes abundances related to cell proliferation, apoptosis, and sterogenesis also changed after MSX2 knockdown. MSX2 overexpression had the opposite effect on cell viability in yak CGCs. These results reveal the specific mechanism by which MSX2 regulates the development and function of yak CGCs and give novel and valuable insights into the mechanisms involved in yak reproduction.
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BACKGROUND: Temperature prediction is crucial in the clinical ablation treatment of liver cancer, as it can be used to estimate the coagulation zone of microwave ablation. METHODS: Experiments were conducted on 83 fresh ex vivo porcine liver tissues at two ablation powers of 15 W and 20 W. Ultrasound grayscale images and temperature data from multiple sampling points were collected. The machine learning method of random forests was used to train the selected texture features, obtaining temperature prediction models for sampling points and the entire ultrasound imaging area. The accuracy of the algorithm was assessed by measuring the area of the hyperechoic area in the porcine liver tissue cross-section and ultrasound grayscale images. RESULTS: The model exhibited a high degree of accuracy in temperature prediction and the identification of coagulation zone. Within the test sets for the 15 W and 20 W power groups, the average absolute error for temperature prediction was 1.14°C and 4.73°C, respectively. Notably, the model's accuracy in measuring the area of coagulation was higher than that of traditional ultrasonic grey-scale imaging, with error ratios of 0.402 and 0.182 for the respective power groups. Additionally, the model can filter out texture features with a high correlation to temperature, providing a certain degree of interpretability. CONCLUSION: The temperature prediction model proposed in this study can be applied to temperature monitoring and coagulation zone range assessment in microwave ablation.
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Hígado , Aprendizaje Automático , Microondas , Temperatura , Ultrasonografía , Animales , Porcinos , Ultrasonografía/métodos , Hígado/diagnóstico por imagen , Hígado/cirugía , Algoritmos , Técnicas de Ablación/métodos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagenRESUMEN
Objectives: This study aimed to develop an efficient tool for assessing children's fundamental motor skills, the "Track style" Children's Fundamental Movement Skills Test (TCFMST), based on theories of motor development integrated with Chinese cultural context and physical education teaching situations. Methods: Starting from a literature analysis, the study selected items from existing fundamental movement skill (FMS) assessments, textbooks, physical education and health standards, and children's movement guidelines to construct a pool of test items. Subsequently, the items were screened and optimized using the Delphi method. Finally, the feasibility, discrimination, difficulty, reliability, and validity of the constructed test were examined using testing methods. Results: The TCFMST includes three dimensions: locomotive skills, body control skills, and manipulative skills, with a total of 10 items. The difficulty and discrimination of each item are appropriate; the correlation coefficients for retest reliability range from 0.789 to 0.943 (p < 0.01). The results of exploratory factor analysis indicate that the common factors align with the hypothesized three dimensions, indicating good structural validity of the test. The concurrent validity results show a correlation coefficient of -0.510 (p < 0.01) between the TCFMST and the total score of TGMD-3, indicating a moderate correlation between the two tests. Conclusion: The TCFMST developed in this study has good difficulty, discrimination, reliability, and validity. It also features strong operability, a short duration, and high interest. It can serve as an important tool for monitoring children's fundamental motor skill levels.
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Destreza Motora , Humanos , Destreza Motora/fisiología , Niño , Reproducibilidad de los Resultados , Femenino , Masculino , Técnica Delphi , China , Desarrollo Infantil/fisiologíaRESUMEN
Valvular heart disease (VHD) is a major cause of loss of physical function, quality of life and longevity, and its prevalence is growing worldwide due to increased survival rates and an aging population. The most common treatment for VHD is surgical heart valve replacement with mechanical heart valves (MHVs) and bioprosthetic heart valves (BHVs), but with different limitations. Polymeric heart valves (PHVs) exhibit promising material properties, valve dynamics and biocompatibility, representing the most feasible alternative to existing artificial heart valves. However, inadequate fatigue performance remains a critical obstacle to their clinical translation. In this case, geometry and material design are essential to obtain the best mechanical properties of the PHV. In this study, we summarized the effects of optimal design of PHVs from geometrical configuration optimization (valve height, thickness and design curve) and structural material optimization (anisotropy, fiber reinforcement, variable thickness, microstructure and asymmetric optimization), and selected the parameters including Effective Orifice Area (EOA), Regurgitant fraction (RF), and Stress Distribution to compare the performance of valves. It would provide the theoretical support for the optimal design of PHVs.
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BACKGROUND: The effect of proprotein convertase subtilisin kexin type (PCSK9) inhibitors on blood lipids and major adverse cardiovascular events (MACEs) is still controversial for acute coronary syndrome (ACS) patients. This study aimed to evaluate the efficacy and safety of PCSK9 inhibitors for ACS patients. METHODS: We searched the following databases until March 2023: PubMed, Embase, Cochrane, Web of Science, CNKI, Chongqing VIP Database and Wan Fang Database. Finally, all randomized controlled trials, retrospective studies and prospective studies were included in the analysis. RESULTS: A total of 20 studies involving 48,621 patients were included in this meta-analysis. The results demonstrated that PCSK9 inhibitors group was more beneficial for ACS patients compared to control group (receiving statins alone or placebo). The meta-analysis showed: there was no significant difference in high density lipoprotein cholesterol between PCSK9 inhibitors group and control group (standard mean differenceâ =â 0.17, 95% confidence interval [CI]: -0.02 to 0.36, Pâ =â .08), while the level of low density lipoprotein cholesterol in PCSK9 inhibitors group was lower than that in control group (standard mean differenceâ =â -2.32, 95% CI: -2.81 to -1.83, Pâ <â .00001). Compared with the control group, the PCSK9 inhibitors group also decreased the levels of total cholesterol and triglycerides (mean differenceâ =â -1.24, 95% CI: -1.40 to -1.09, Pâ <â .00001, mean differenceâ =â -0.36, 95% CI: -0.56 to -0.16, Pâ =â .0004). Moreover, compared with the control group, PCSK9 inhibitors group could reduce the incidence of MACEs (relative risk [RR]â =â 0.87, 95% CI: 0.83-0.91; Pâ <â .00001). However, this study showed that the incidence of drug-induced adverse events in PCSK9 inhibitors group was higher than that in the control group (RRâ =â 1.15, 95% CI: 1.05-1.25, Pâ <â .0001). CONCLUSION: Although this study demonstrates that PCSK9 inhibitors have higher drug-induced adverse events, they can not only reduce low-density lipoprotein cholesterol levels but also reduce the incidence of MACEs simultaneously. However, these findings needed to be further verified through large sample, multicenter, double-blind randomized controlled trials.
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Síndrome Coronario Agudo , Inhibidores de PCSK9 , Humanos , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , LDL-Colesterol/sangre , LDL-Colesterol/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de PCSK9/administración & dosificación , Inhibidores de PCSK9/efectos adversos , Proproteína Convertasa 9/metabolismoRESUMEN
Deoxynojirimycin (DNJ) is an α-glucosidase inhibitor with high food values. However, the complex and costly enrichment processes have greatly prevented its application. Herein, this study aimed to propose a simple and efficient enrichment process for DNJ from Morus alba L. extracts using cation exchange resins. The LSI and D113 resins were chosen due to their excellent adsorption and desorption properties. The adsorption characteristics agreed with the pseudo-first-order kinetic model and the Langmuir isotherm model. This adsorption was chemisorption, spontaneous, endothermic and entropy-driven. Furthermore, the concentration and pH of the extracts, desorption solvent, breakthrough and elution curves, sample loading and elution rate were investigated to optimize the enrichment process by resin column chromatography. The results also showed that the purity of DNJ was improved to 44.00 % with a total recovery of 78.21 % using the LSI-D113 combination strategy. This research demonstrated the industrial feasibility of DNJ enrichment using cation exchange resins.
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OBJECTIVES: The type of ligamentous tear and the degree of knee laxity have important guiding significance for the diagnosis and management of anterior cruciate ligament (ACL) tears. Instrumental measurement is necessary for ACL tears since physical examination and magnetic resonance imaging (MRI) cannot provide an objective and quantitative assessment of knee laxity. This study aimed to compare the application of a novel knee arthrometer and simultaneous stress radiography in differentiating between complete and partial acute ACL tears, and further assess the correlation between the two measurements. METHODS: A total of 106 patients with complete acute ACL tears and 52 patients with partial acute ACL tears were included in the study. Preoperative arthrometry and simultaneous stress radiography were performed using the Ligs arthrometer at 90, 120, and 150 N to assess side-to-side difference (SSD) in anterior knee laxity. The optimal threshold was determined using the receiver operating characteristic (ROC) curve. The area under the ROC curve (AUC) was used to assess the diagnostic value of the measurement. Pearson's correlation coefficient was used to assess the correlation between the two measurements. RESULTS: The optimal differential SSD thresholds in the Ligs arthrometer were 2.7 mm at 90 N, 3.8 mm at 120 N, and 4.6 mm at 150 N. Similarly, the optimal differential SSD thresholds in simultaneous stress radiography were 3.8 mm at 90 N, 5.1 mm at 120 N, and 5.6 mm at 150 N. The AUC analysis revealed that the Ligs arthrometer was fairly informative at 90 N (AUC = 0.851), 120 N (AUC = 0.878), and 150 N (AUC = 0.884), and simultaneous stress radiography was highly informative at 90 N (AUC = 0.910), 120 N (AUC = 0.925), and 150 N (AUC = 0.948). Moreover, the AUC of the combined measurements was 0.914 at 90 N, 0.931 at 120 N, and 0.951 at 150 N. A significantly strong correlation was found between the two measurements at 90 N (r = 0.743, p < 0.001), 120 N (r = 0.802, p < 0.001), and 150 N (r = 0.823, p < 0.001). CONCLUSIONS: The Ligs arthrometer and simultaneous stress radiography proved to be valid diagnostic tools to differentiate between complete and partial acute ACL tears, with a strong correlation between the two measurements in SSD values. Compared with single instrumental measurement, the combination of the two measurements can further improve the diagnostic value in this regard.
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Zearalenone (ZEN), a mycotoxin from Fusarium fungi, impairs fertility and milk production in female animals; however, the mechanisms remain poorly understood. Using the bovine mammary epithelial cells (MAC-T) as the model, this study investigated the impacts of ZEN on programmed cell death (PCD) and milk fat synthesis and explored the underlying mechanism. We found that 10 ng/mL prolactin (PRL) notably enhanced the differentiation of MAC-T cells, promoting the expression of genes related to the synthesis of milk fat, protein, and lactose. Next, the toxic effects of different doses of ZEN on the differentiated MAC-T with PRL treatment were determined. 10 and 20 µM ZEN significantly reduced cell viability, induced oxidative stress, and triggered PCD (e.g., apoptosis and necrosis). Notably, ZEN exposure downregulated the mRNA/protein levels of critical factors involved in milk fat synthesis by disrupting the AKT-mTOR-PPARγ-ACSL4 pathway. Interestingly, melatonin (MT), known for its antioxidant properties, protected against the above ZEN-induced effects by enhancing the binding of PPARγ to the promoter regions of ACSL4, which led to the upregulated expression of the ACSL4 gene. These results underscored the potential of MT to mitigate the adverse effects of ZEN on mammary cells, highlighting a way for potential therapeutic intervention.
Mycotoxin (e.g., Zearalenone, ZEN) widely exists in contaminated animal feeds and affects health. This study investigated the impacts of ZEN on programmed cell death (PCD, e.g., apoptosis and necrosis) and milk fat synthesis in MAC-T cells. ZEN exposure led to decreased cell viability, increased oxidative stress, and induced PCD. Additionally, ZEN disrupted the AKT-mTOR-PPARγ-ACSL4 pathway, resulting in the inhibition of milk fat synthesis. Melatonin (MT) partially mitigated ZEN-induced adverse effects by enhancing PPARγ binding to ACSL4 promoter regions. Overall, ZEN exposure resulted in PCD and impaired milk fat synthesis via repressing the AKT-mTOR-PPARγ-ACSL4 pathway in MAC-T cells, while MT potentially offered detoxification against ZEN-induced mammary toxicity.
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Apoptosis , Células Epiteliales , Glándulas Mamarias Animales , Leche , PPAR gamma , Proteínas Proto-Oncogénicas c-akt , Zearalenona , Animales , Bovinos , Zearalenona/toxicidad , Femenino , PPAR gamma/metabolismo , PPAR gamma/genética , Células Epiteliales/efectos de los fármacos , Glándulas Mamarias Animales/efectos de los fármacos , Leche/química , Apoptosis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Transducción de Señal/efectos de los fármacos , Línea CelularRESUMEN
The aim of this study was to elucidate the effect of FAM13A on the differentiation of goat intramuscular precursor adipocytes and its mechanism of action. Here, we cloned the CDS region 2094 bp of the goat FAM13A gene, encoding a total of 697 amino acid residues. Functionally, overexpression of FAM13A inhibited the differentiation of goat intramuscular adipocytes with a concomitant reduction in lipid droplets, whereas interference with FAM13A expression promoted the differentiation of goat intramuscular adipocytes. To further investigate the mechanism of FAM13A inhibiting adipocyte differentiation, 104 differentially expressed genes were screened by RNA-seq, including 95 up-regulated genes and 9 down-regulated genes. KEGG analysis found that the RIG-I receptor signaling pathway, NOD receptor signaling pathway and toll-like receptor signaling pathway may affect adipogenesis. We selected the RIG-I receptor signaling pathway enriched with more differential genes as a potential adipocyte differentiation signaling pathway for verification. Convincingly, the RIG-I like receptor signaling pathway inhibitor (HY-P1934A) blocked this pathway to save the phenotype observed in intramuscular adipocyte with FAM13A overexpression. Finally, the upstream miRNA of FAM13A was predicted, and the targeted inhibition of miR-21-5p on the expression of FAM13A gene was confirmed. In this study, it was found that FAM13A inhibited the differentiation of goat intramuscular adipocytes through the RIG-I receptor signaling pathway, and the upstream miRNA of FAM13A (miR-21-5p) promoted the differentiation of goat intramuscular adipocytes. This work extends the genetic regulatory network of IMF deposits and provides theoretical support for improving human health and meat quality from the perspective of IMF deposits.
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Adipocitos , Diferenciación Celular , Cabras , Transducción de Señal , Animales , Cabras/genética , Cabras/metabolismo , Adipocitos/metabolismo , Adipocitos/citología , Diferenciación Celular/genética , MicroARNs/genética , Adipogénesis/genética , Proteína 58 DEAD Box/genética , Proteína 58 DEAD Box/metabolismoRESUMEN
RATIONALE: The use of transvenous pacing leads is associated with the risk of tricuspid valve dysfunction, mainly due to the continuous presence of the leads can have an impact on subsequent tricuspid function and possible operation injury of the tricuspid valve during implantation or operation. PATIENT CONCERNS: A 69-year-old female with a history of syncope for 9 months was admitted to the hospital. The electrocardiogram showed sinus bradycardia, junctional escape rhythm, and a heart rate of 44â bpm. Echocardiography suggested a downward displacement and severe insufficiency of the tricuspid valve and atrial septal defect. DIAGNOSES: The cause of syncope was considered to be sick sinus syndrome. The patient was diagnosed with Ebstein anomaly and is considered a candidate for surgical intervention. INTERVENTIONS: To avoid aggravating tricuspid insufficiency by pacing leads crossing the tricuspid valve and hindering subsequent tricuspid valve surgery, a single-chamber pacing mode with atrial pacing (AAI) lead and Micra AV was chosen for maintaining atrioventricular synchrony after multidisciplinary discussion. OUTCOMES: The patient had stable parameters and was in good general condition at 1- and 3-month outpatient follow-ups after discharge. LESSONS: This is the first case of new implantation of single-chamber atrial pacing + leadless ventricular pacing with Micra AV, an alternative strategy to epicardial or coronary sinus system for tricuspid valve displacement and severe tricuspid regurgitation.
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Síndrome del Seno Enfermo , Insuficiencia de la Válvula Tricúspide , Humanos , Femenino , Anciano , Síndrome del Seno Enfermo/terapia , Estimulación Cardíaca Artificial/métodos , Anomalía de Ebstein/cirugía , Marcapaso Artificial , Síncope/etiología , Síncope/terapia , Electrocardiografía , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatologíaRESUMEN
BACKGROUND: Adipose tissue affects not only the meat quality of domestic animals, but also human health. Adipocyte differentiation is regulated by a series of regulatory genes and cyclins. Four and half-LIM protein (FHL2) is positively correlated with the hypertrophy of adipocytes and can cause symptoms such as obesity and diabetes. RESULT: In the transcriptome sequencing analysis of intramuscular adipocytes after three days of differentiation, the differentially expressed gene FHL2 was found. To further explore the biological significance of the differentially expressed gene FHL2, which was downregulated in the mature adipocytes. We revealed the function of FHL2 in adipogenesis through the acquisition and loss of function of FHL2. The results showed that the overexpression of FHL2 significantly increased the expression of adipogenic genes (PPARγ, C/EBPß) and the differentiation of intramuscular and subcutaneous adipocytes. However, silencing FHL2 significantly inhibited adipocyte differentiation. The overexpression of FHL2 increased the number of adipocytes stained with crystal violet and increased the mRNA expression of proliferation marker genes such as CCNE, PCNA, CCND and CDK2. In addition, it significantly increased the rate of EdU positive cells. In terms of apoptosis, overexpression of FHL2 significantly inhibited the expression of P53 and BAX in both intramuscular and subcutaneous adipocytes, which are involved in cell apoptosis. However, overexpression of FHL2 promoted the expression of BCL, but was rescued by the silencing of FHL2. CONCLUSIONS: In summary, FHL2 may be a positive regulator of intramuscular and subcutaneous adipocyte differentiation and proliferation, and acts as a negative regulator of intramuscular and subcutaneous adipocyte apoptosis. These findings provide a theoretical basis for the subsequent elucidation of FHL2 in adipocytes.
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Adipocitos , Adipogénesis , Cabras , Proteínas con Homeodominio LIM , Proteínas Musculares , Animales , Cabras/genética , Adipocitos/metabolismo , Adipocitos/citología , Adipogénesis/genética , Proteínas con Homeodominio LIM/genética , Proteínas con Homeodominio LIM/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Apoptosis/genética , Diferenciación Celular/genética , Proliferación Celular , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Grasa Subcutánea/metabolismo , Grasa Subcutánea/citología , Perfilación de la Expresión GénicaRESUMEN
Objective: The goal of this study was to further validate the effect of multimorbidity on cognitive performance in older adults after controlling for confounders using propensity score matching (PSM). Methods: A cross-sectional survey of older adult people aged 60 years or older selected by convenience sampling was conducted in seven medical institutions, three communities, and five nursing homes in Zunyi City, Guizhou Province. The data collected included general information, health-related information, and Mini-Mental State Examination (MMSE) scores. Variables were controlled for confounders by PSM to analyze differences in cognitive ability between multimorbidity and nonmultimorbidity older adults. Logistic regression and multivariate-adjusted restricted cubic spline (RCS) curves for matched samples were used to assess the relationship between multimorbidity and cognitive decline. Results: A total of 14,175 respondents were enrolled, and the mean age of the participants included in this study was 71.26 ± 7.1 years, including 7,170 (50. 58%) of the participants were males, 7,005 (49.42%) were females, and 5,482 participants (38.67%) were screened for cognitive decline. After PSM, logistic regression analysis revealed that multimorbidity was a risk factor for cognitive decline (OR = 1.392, 95% CI = 1.271-1.525, p < 0.001). The RCS show that the risk of cognitive decline is always greater in older adults with multimorbidity than in older adults without multimorbidity at the same age. Age, sex, marital status, educational level, monthly income, drinking status, participation in social activities, and exercise were influential factors for cognitive decline in older adults (p < 0.05). The incidence of cognitive decline in older adults with multimorbidity was also greater than that in older adults with one chronic disease (p < 0.001). Conclusion: The risk of cognitive decline in older adults with multimorbidity is greater than that in older adults without multimorbidity; therefore, the government should strengthen the prevention and treatment of multimorbidity in older adults to further protect their cognitive abilities.
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Disfunción Cognitiva , Multimorbilidad , Puntaje de Propensión , Humanos , Masculino , Femenino , Anciano , Estudios Transversales , China/epidemiología , Disfunción Cognitiva/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Cognición/fisiología , Anciano de 80 o más Años , Modelos Logísticos , Pruebas de Estado Mental y Demencia/estadística & datos numéricos , Pueblos del Este de AsiaRESUMEN
BACKGROUND: The triglyceride-glucose (TyG) index performs better at reflecting insulin resistance when combined with waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHtR) than when used alone. This study aimed to prospectively examine the relationships between TyG, TyG-BMI, TyG-WC, and TyG-WHtR with the incidence of myocardial infarction (MI) and its subtypes. METHODS: This cohort study included 370,390 participants from the UK Biobank. The Cox proportional hazards model and restricted cubic spline regression model were used to assess the associations of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with MI, ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI). The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were employed to examine the predictive value of four indicators. RESULTS: The hazard ratios (HRs) and 95% confidence intervals (CIs) of MI in the highest quartiles for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.36 (1.28-1.44), 1.47 (1.39-1.56), 1.53 (1.43-1.64), and 1.58 (1.48-1.68) in the fully-adjusted model. Comparable findings were observed when the outcomes were reclassified as STEMI or NSTEMI. However, the associations of TyG-BMI, TyG-WC, and TyG-WHtR with the risk of STEMI were weaker than MI and NSTEMI. A linear dose-response association between TyG and the risk of MI and NSTEMI were demonstrated. TyG-BMI, TyG-WC, and TyG-WHtR all showed nonlinear patterns in their associations with the risk of MI, STEMI, and NSTEMI. TyG-WC was most effective in diagnosing MI (AUC: 0.648, 95% CI: 0.644-0.653), STEMI (AUC: 0.631, 95% CI: 0.622-0.639), and NSTEMI (AUC: 0.647, 95% CI: 0.641-0.654). CONCLUSION: The TyG index was linearly associated with increased risk of MI and NSTEMI, whereas TyG-BMI, TyG-WC, and TyG-WHtR were nonlinearly associated with increased risk of MI and NSTEMI. There were distinct patterns in the relationships between these indicators with STEMI. TyG-WC provided the best diagnostic effectiveness for MI, STEMI, and NSTEMI.