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Traditionally, fresh S. japonicum flowers (SJF) and S. japonicum flowers buds (SJFB) are dried prior to further processing and use. Here, we investigated the ways in which drying techniques, including sun drying (SD), steam drying (STD), microwave drying (MD), hot air drying (HAD, 40 °C, 60 °C, 80 °C, 100 °C), and freeze drying (FD), alter the flavonoid composition of freshly-harvested SJF and SJFB. The flavonoid content of dried samples was determined by Ultra High Performance Liquid Chromatography-Diode Array Detector (UPLC-DAD). Overall, different drying techniques had significantly different effects on the RU content, ranging from 10.63 % (HAD-80 °C) to 34.13 % (HAD-100 °C) in SJF and from 18.91 % (HAD-100 °C) to 29.16 % (HAD-40 °C) and 30.53 % (SD) in SJFB. To clarify the mechanism by which drying affects the RU content of S. japonicum flowers, we studied the activity of a rutin-hydrolyzing enzyme (RHE) isolated from SJF and SJFB using multiple separation and assay methods. According to the Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) results, the apparent molecular weight of the purified RHE was approximately 38 kDa. According to UPLC-DAD, RHE catalyzes the production of quercetin (QU) from rutin (RU), but not from other flavonoid glycosides. Drying fresh SJF and SJFB at low and high temperatures can inhibit RHE activity and prevent RU hydrolysis. Therefore, subjecting freshly-harvest SJF to HAD-100 °C, and freshly-harvest SJFB to SD or HAD-40 °C, can greatly increase the RU content. In particular, HAD is viable for large-scale application due to its simplicity and industrial feasibility.
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In complex anal fistula, the patient's anus has multiple internal or external openings. The closure of the external opening can be broken again in other trips and another external opening. It is one of the refractory diseases in the field of anorectal surgery. In the treatment of a high recurrence rate, poor functional protection and other problems, surgical treatment such as incision and retention of sphincter hanging line, incision and suture internal opening drainage, fistula removal, and suture were used for different situations. After the failure of surgical treatment, it becomes chronic anal fistula or become cancerous tumor. In this case, the patient had a long time of illness, the mass was huge, the color was black, and it was suspected to be a secondary malignant tumor. This situation is extremely rare in clinical treatment. In our hospital, a case of complex anal fistula secondary to perianal huge tumor was found, and good therapeutic effect was achieved after complex anal fistula resection and tumor resection. In this case, the patient had complex anal fistula for about 5 years without timely treatment, and the perianal mass was rare and huge. It is shown by ultrasonography the secondary malignant tumor, which was extremely rare in clinical treatment. During the operation, it was found that three fistulas at the root of the tumor were connected with one of the anal fistulas. From the appearance, the tumor seems to have a malignant tendency. After surgical resection, the pathology was suppurative inflammation and granulation tissue hyperplasia. The patients recovered well after follow-up and did not relapse. This case report provides case reference and reference for clinical treatment of anorectal diseases.
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Aging is a known independent risk factor for several cardiovascular diseases. Here, we evaluated potential effects and possible mechanisms through which alginate oligosaccharides (AOS) affect hydrogen peroxide (H2O2)-induced senescence in H9C2 cardiomyocytes. A series of AOS molecules, including oligoM, oligoG, M-5, and G-5, were investigated. AOS significantly decreased SA-ß-gal and DAPI-stained positive cells, downregulated p53 and p21 (aging-related markers) expression, and eventually protected H9C2 cells from H2O2-induced senescence. AOS decreased reactive oxygen species and malondialdehyde production, recovered mitochondrial function, and alleviated the oxidative stress state by regulating PGC-1α and NADPH oxidase subunit expression. Furthermore, AOS treatment restored the expression of antioxidant enzymes in senescent H9C2 cells. Thus, our results show in vitro evidence that AOS alleviate senescence in H9C2 cells by regulating the redox state; thus, AOS may be an effective therapeutic agent that could protect against cardiomyocyte senescence.
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Background: Cancers arise from genetic and epigenetic abnormalities that affect oncogenes and tumor suppressor genes, compounded by gene mutations. The N6-methyladenosine (m6A) RNA modification, regulated by methylation regulators, has been implicated in tumor proliferation, differentiation, tumorigenesis, invasion, and metastasis. However, the role of m6A modification patterns in the tumor microenvironment of gastric cancer (GC) remains poorly understood. Materials and methods: In this study, we analyzed m6A modification patterns in 267 GC samples utilizing 31 m6A regulators. Using consensus clustering, we identified two unique subgroups of GC. Patients with GC were segregated into high- and low-infiltration cohorts to evaluate the infiltration proportions of the five prognostically significant immune cell types. Leveraging the differential genes in GC, we identified a "green" module via Weighted Gene Co-expression Network Analysis. A risk prediction model was established using the LASSO regression method. Results: The "green" module was connected to both the m6A RNA methylation cluster and immune infiltration patterns. Based on "Module Membership" and "Gene Significance", 37 hub genes were identified, and a risk prediction model incorporating nine hub genes was established. Furthermore, methylated RNA immunoprecipitation and RNA Immunoprecipitation assays revealed that YTHDF1 elevated the expression of DNMT3B, which synergistically promoted the initiation and development of GC. We elucidated the molecular mechanism underlying the regulation of DNMT3B by YTHDF1 and explored the crosstalk between m6A and 5mC modification. Conclusion: m6A RNA methylation regulators are instrumental in malignant progression and the dynamics of tumor microenvironment infiltration of GC. Assessing m6A modification patterns and tumor microenvironment infiltration characteristics in patients with GC holds promise as a valuable prognostic biomarker.
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Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.
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Cardiotónicos , Histona Desacetilasa 6 , Inhibidores de Histona Desacetilasas , Piridinas , Humanos , Animales , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Piridinas/uso terapéutico , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/uso terapéutico , Histona Desacetilasa 6/antagonistas & inhibidores , Histona Desacetilasa 6/metabolismo , Relación Estructura-Actividad , Cardiotónicos/farmacología , Cardiotónicos/química , Cardiotónicos/síntesis química , Cardiotónicos/uso terapéutico , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Masculino , Imidazoles/farmacología , Imidazoles/química , Imidazoles/síntesis química , Imidazoles/uso terapéutico , Ratones Desnudos , Descubrimiento de DrogasRESUMEN
Checkpoint blockades have emerged as a frontline approach in cancer management, designed to enhance the adaptive immune response against tumors. However, its clinical efficacy is limited to a narrow range of tumor types, which necessitates the exploration of novel strategies that target another main branch of the immune system. One such potential strategy is the therapeutic modulation of pattern recognition receptors (PRRs) pathways in innate immune cells, which have shown promise in tumor eradication. Previously, a ß-1,3/1,6-glucan with high purity from Durvillaea antarctica (BG136) was reported by our group to exhibit pan-antitumor effects. In the current study, we systemically studied the antitumor activity of BG136 in combination with anti-PD1 antibody in MC38 syngeneic tumor model in vivo. Integrated transcriptomic and metabolomic analyses suggested that BG136 enhances the antitumor immunity of anti-PD1 antibody by reprogramming the tumor microenvironment to become more proinflammatory. In addition, an increase in innate and adaptive immune cell infiltration and activation, enhanced lipid metabolism, and a decreased in ascorbate and aldarate metabolism were also found. These findings provide mechanistic insights that support the potent antitumor efficacy of BG136 when combined with immune checkpoint inhibitor antibodies.
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Deregulation of E3 ubiquitin ligases drives the proliferation and metastasis of various cancers; however, the underlying mechanisms remain unknown. This study aimed to investigate the role of tripartite motif-containing 22 (TRIM22), a poorly investigated E3 ubiquitin ligase in the TRIM family, as a tumor suppressor in breast cancer. High expression of TRIM22 in breast cancer correlated with better prognosis. Functional experiments demonstrated that TRIM22 significantly inhibited the proliferation and invasion of breast cancer cells. Label-free proteomics and biochemical analyses revealed that the copper chaperone for superoxide dismutase (CCS), an oncoprotein that is upregulated in breast cancer and promotes the growth and invasion of breast cancer cells, was a target of TRIM22 for degradation via K27-linked ubiquitination. Notably, the ability of the coiled-coil domain-defective mutants of TRIM22 to induce CCS ubiquitination and degradation diminished, with lysine 76 of the CCS serving as the ubiquitination site. Moreover, the TRIM22-mediated inhibition of the proliferation and invasion of breast cancer cells was restored by ectopic CCS expression. RNA-sequencing experiments using Gene Set Enrichment Analysis demonstrated that TRIM22 is involved in the JAK-STAT signaling pathway. TRIM22 overexpression also improved reactive oxygen species levels in breast cancer cells and inhibited STAT3 phosphorylation, which was restored via CCS overexpression or N-acetyl-l-cysteine treatment. Chromatin immunoprecipitation-quantitative polymerase chain reaction results showed that TRIM22 overexpression decreased the enrichment of phosphorylated STAT3 in FN1, VIM and JARID2 promoters. Clinically, low TRIM22 expression correlated with high CCS expression and decreased survival rates in patients with breast cancer. Moreover, TRIM22 upregulation was associated with a better prognosis in patients with breast cancer who received classical therapy. TRIM22 expression was downregulated in many cancer types, including colon, kidney, lung, and prostate cancers. To the best of our knowledge, the E3 ubiquitin ligase TRIM22 was first reported as a tumor suppressor that inhibits the proliferation and invasion of breast cancer cells through CCS ubiquitination and degradation. TRIM22 is a potential prognostic biomarker in patients with breast cancer.
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Integrating anodic biomass valorization with carbon dioxide electroreduction (CO2RR) can produce value-added chemicals on both the cathode and anode; however, anodic oxidation still suffers from high overpotential. Herein, a photothermal-assisted method was developed to reduce the potential of 5-hydroxymethyl furfural (HMF) electrooxidation. Capitalizing on the copious oxygen vacancies, defective Co3O4 (D-Co3O4) exhibited a stronger photothermal effect, delivering a local temperature of 175.47 oC under near infrared light illumination. The photothermal assistance decreased the oxidation potential of HMF from 1.7 V over pristine Co3O4 to 1.37 V over D-Co3O4 to achieve a target current density of 30 mA cm-2, with 2,5-furandicarboxylic acid as the primary product. Mechanistic analysis disclosed that the photothermal effect did not change the HMF oxidation route but greatly enhanced the adsorption capacity of HMF. Meanwhile, faster electron transfer for direct HMF oxidation and the surface conversion to cobalt (oxy)hydroxide, which contributed to indirect HMF oxidation, was observed. Thus, rapid HMF conversion was realized, as evidenced by in situ surface-enhanced infrared spectroscopy. Upon coupling cathodic CO2RR with an atomically dispersed Ni-N/C catalyst, the Faradaic efficiencies of CO (cathode) and 2,5-furandicarboxylic acid (FDCA, anode) exceeded 90.0% under a low cell potential of 1.77 V.
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The urban heat island (UHI) effect in arid cities can be small or even negative, the latter known as the urban cool island (UCI) effect. Differences in defining urban and rural areas can introduce uncertainties in detecting UHI or UCI, especially when the UHI signal is small. Here, we compared the surface UHI intensity (SUHII) estimated by a dozen different methods (with multiple urban and/or rural definitions) across 104 arid cities globally, providing a comprehensive evaluation of the uncertainty in SUHII estimates. Results show that the absolute difference in annual average SUHII (∆SUHII) among methods exceeded 1 °C in about half of the arid cities during both daytime and nighttime. The overall annual mean ∆SUHII for all arid cities was 1.35 °C during daytime and 1.03 °C at night. The uncertainty arising from simultaneous variations in urban and rural definitions was generally higher than that resulting from their individual changes. It was observed that, with varying definitions of urban and rural areas, nearly 50 % of arid cities experienced a sign reversal in daytime SUHII estimates, while approximately 15 % exhibited a sign reversal in nighttime SUHII. Variations in urban-rural differences in surface properties, such as vegetation index and albedo, due to differing urban and rural definitions, contributed strongly to the observed SUHII uncertainties. Overall, our results offer new insights into the ongoing debate on heat and cold islands in arid cities, emphasizing a critical need to standardize SUHII estimation frameworks.
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The metastasis-associated protein (MTA) family plays a crucial role in the development of breast cancer, a common malignancy with a high incidence rate among women. However, the mechanism by which each member of the MTA family contributes to breast cancer progression is poorly understood. In this study, we aimed to investigate the roles of MTA1, MTA3, and tripartite motif-containing 21 (TRIM21) in the proliferation, invasion, epithelial-mesenchymal transition (EMT), and stem cell-like properties of breast cancer cells in vivo and in vitro. The molecular mechanisms of the feedback loop between MTA1 and MTA3/TRIM21 regulated by estrogen were explored using Chromatin immunoprecipitation (ChIP), luciferase reporter, immunoprecipitation (IP), and ubiquitination assays. These findings demonstrated that MTA1 acts as a driver to promote the progression of breast cancer by repressing the transcription of tumor suppressor genes, including TRIM21 and MTA3. Conversely, MTA3 inhibited MTA1 transcription and TRIM21 regulated MTA1 protein stability in breast cancer. Estrogen disrupted the balance between MTA1 and MTA3, as well as between MTA1 and TRIM21, thereby affecting stemness and the EMT processes in breast cancer. These findings suggest that MTA1 plays a vital role in stem cell fate and the hierarchical regulatory network of EMT through negative feedback loops with MTA3 or TRIM21 in response to estrogen, supporting MTA1, MTA3, and TRIM21 as potential prognostic biomarkers and MTA1 as a treatment target for future breast cancer therapies.
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Neoplasias de la Mama , Transición Epitelial-Mesenquimal , Estrógenos , Histona Desacetilasas , Células Madre Neoplásicas , Proteínas Represoras , Transactivadores , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Transactivadores/metabolismo , Transactivadores/genética , Estrógenos/farmacología , Estrógenos/metabolismo , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Animales , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Retroalimentación Fisiológica/efectos de los fármacos , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Ratones Desnudos , Células MCF-7 , Ratones Endogámicos BALB C , Proteínas de NeoplasiasRESUMEN
BACKGROUND: This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3. METHODS: A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated. RESULTS: Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence. CONCLUSIONS: The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3.
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Selenium (Se) is a beneficial trace element for plants, while zinc (Zn) is a vital micronutrient. Bletilla striata (Thunb.) Reichb. F. is widely recognized as a medicinal herb. In this study, Se and Zn were introduced to determine the medicinal properties of B. striata. The plant's biomass, polysaccharides, Se and Zn contents, and the antioxidant properties of polysaccharide solutions were all examined. A notable increase in polysaccharide synthesis in B. striata tubers was observed following the application of 0.2 kg ha-1 of Se, and 1.0 kg ha-1 of Zn, either individually or in combination. Se and Zn content in polysaccharides were 3.33 to 3.77 mg kg-1 and 82.82 to 121.78 mg kg-1, at 1.0 kg ha-1 Se and 10.0 kg ha-1 Zn treatments, respectively. These values were 2.1-3.1 times and 1.8-2.8 times higher than those observed in control samples. Polysaccharide antioxidation has resulted in an increase in antioxidant activity as the concentration of polysaccharide solutions increased. The largest scavenging of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radicals and the most excellent reducing power of the polysaccharide solutions were observed when a mixture of Se and Zn was applied at a rate of 1.0 kg ha-1 and 10.0 kg ha-1. The individual application of Se at 1.0 kg ha-1 and Zn at 10.0 kg ha-1 also resulted in significant DPPH radicals scavenging and reduced power. These data suggested that Se-Zn enriched B. striata is a new source of Se and Zn supplementation and an antioxidant resource.
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Mendelian randomization method is a powerful tool in epidemiological research. The core idea is to use genetic variation as a tool to assess the causal relationship between risk factors and specific diseases. Confounding factors are important interference factors for causal inference in epidemiological studies, and genetic variation in Mendelian randomization studies follows the principle of random distribution of alleles to offspring, which is similar to randomized controlled trials. Mendel 's randomization method can effectively avoid the confounding factors, reverse causality in observational studies and the representativeness and feasibility of randomized controlled trials. Previous observational studies have reported a relationship between negative emotions and upper gastrointestinal disease. However, whether this relationship is causal remains unclear. We aimed to evaluate the causal relationship between negative emotions and upper gastrointestinal diseases using two-sample Mendelian randomization (MR). Three sets of genetic instruments from the database were obtained for analysis, including 12 anxiety-related single nucleotide polymorphisms (SNPs), 46 depression-related SNPs, and 58 nervous-related SNPs. SNPs were filtered using the Phenoscanner website, and the inverse variance weighted method, weighted median method, MR-Egger regression, MR pleiotropy residual sum, and outlier test were used for analysis. In inverse variance weighted analysis, anxiety and depression had an effect on gastroduodenal ulcer (p = 2.849×10-3, ß = 4.908, 95% CI = 1.684-8.132; and p = 6.457×10-4, ß = 1.767, 95% CI = 0.752-2.782, respectively). Additionally, depression had an effect on diseases of the esophagus, stomach, and duodenum (p = 3.498×10-5, ß = 0.926, 95% CI = 0.487-1.364). Cochran's Q-derived p-values were 0.457, 0.603, and 0.643, and MR-Egger intercept-derived p-values were 0.697, 0.294, and 0.362, respectively. Here, we show that anxiety and depression have a causal relationship with gastroduodenal ulcers, and depression has a causal relationship with diseases of the esophagus, stomach, and duodenum.
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Emociones , Enfermedades Gastrointestinales , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Enfermedades Gastrointestinales/psicología , Enfermedades Gastrointestinales/genética , Depresión/genética , Ansiedad , Predisposición Genética a la EnfermedadRESUMEN
Pseudomonas species are known for their diverse metabolic abilities and broad ecological distribution. They are fundamental components of bacterial communities and perform essential ecological functions in the environment. A psychrotrophic Pseudomonas sp. IT1137 was isolated from intertidal sediment in the coastal region of the Fildes Peninsula, King George Island, Antarctica. The strain contained a circular chromosome of 5,346,697 bp with a G + C content of 61.66 mol% and one plasmid of 4481 bp with a G + C content of 64.61 mol%. A total of 4848 protein-coding genes, 65 tRNA genes and 15 rRNA genes were obtained. Genome sequence analysis revealed that strain IT1137 not only is a potentially novel species of the genus Pseudomonas but also harbors functional genes related to nitrogen, sulfur and phosphorus cycling. In addition, genes involved in alkane degradation, ectoine synthesis and cyclic lipopeptide (CLP) production were detected in the bacterial genome. The results indicate the potential of the strain Pseudomonas sp. IT1137 for biotechnological applications such as bioremediation and secondary metabolite production and are helpful for understanding bacterial adaptability and ecological function in cold coastal environments.
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Alcanos , Frío , Genoma Bacteriano , Sedimentos Geológicos , Pseudomonas , Pseudomonas/genética , Regiones Antárticas , Sedimentos Geológicos/microbiología , Alcanos/metabolismo , Secuenciación Completa del Genoma , Biodegradación AmbientalRESUMEN
OBJECTIVE: Currently, the most commonly used methods for linkage analysis of pre-implantation genetic testing for monogenic disorders (PGT-M) are next generation sequencing (NGS) and SNP array. We aim to investigate whether the application efficacy of Asian screening array (ASA) in PGT-M preclinical workup for the Chinese population is superior to NGS based single nucleotide polymorphism (SNP) panels. METHODS: We conducted a retrospective analysis by reviewing 294 couples from a single center over the past 4 years and compared the detection results between NGS-based SNP panels and ASA. Using the numbers of informative SNPs upstream and downstream flanking of variants, we assessed the detection efficiency of both methods in monogenic diseases, chromosomal microdeletion syndrome and males with de novo variants, among other scenarios. RESULTS: Results indicate that ASA offers a greater number of informative SNPs compared with NGS-based SNP panels. Additionally, data analysis for ASA is generally more straightforward and may require less computational resources. While ASA can address most PGT-M challenges, we have also identified certain genes in previous tests that are not suitable for PGT-M using ASA. CONCLUSION: The application of ASA in PGT-M preclinical workup for Chinese populations has good practical value as it can perform linkage analysis for most genetic variants. However, for certain variants, NGS or other testing methods, such as mutated allele revealed by sequencing with aneuploidy and linkage analysis (MARSALA), may still be necessary for completion.
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Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease worldwide. Caspase 8 and FADD-like apoptosis regulator (CFLAR) has been identified as a potent factor in mitigating non-alcoholic steatohepatitis (NASH) by inhibiting the N-terminal dimerization of apoptosis signal-regulating kinase 1 (ASK1). While arginine methyltransferase 1 (PRMT1) was previously reported to be associated with increased hepatic glucose production, its involvement in hepatic lipid metabolism remains largely unexplored. The interaction between PRMT1 and CFLAR and the methylation of CFLAR were verified by Co-IP and immunoblotting assays. Recombinant adenoviruses were generated for overexpression or knockdown of PRMT1 in hepatocytes. The role of PRMT1 in NAFLD was investigated in normal and high-fat diet-induced obese mice. In this study, we found a significant upregulation of PRMT1 and downregulation of CFLAR after 48h of fasting, while the latter significantly rebounded after 12h of refeeding. The expression of PRMT1 increased in the livers of mice fed a methionine choline-deficient (MCD) diet and in hepatocytes challenged with oleic acid (OA)/palmitic acid (PA). Overexpression of PRMT1 not only inhibited the expression of genes involved in fatty acid oxidation (FAO) and promoted the expression of genes involved in fatty acid synthesis (FAS), resulting in increased triglyceride accumulation in primary hepatocytes, but also enhanced the gluconeogenesis of primary hepatocytes. Conversely, knockdown of hepatic PRMT1 significantly alleviated MCD diet-induced hepatic lipid metabolism abnormalities and liver injury in vivo, possibly through the upregulation of CFLAR protein levels. Knockdown of PRMT1 suppressed the expression of genes related to FAS and enhanced the expression of genes involved in FAO, causing decreased triglyceride accumulation in OA/PA-treated primary hepatocytes in vitro. Although short-term overexpression of PRMT1 had no significant effect on hepatic triglyceride levels under physiological conditions, it resulted in increased serum triglyceride and fasting blood glucose levels in normal C57BL/6J mice. More importantly, PRMT1 was observed to interact with and methylate CFLAR, ultimately leading to its ubiquitination-mediated protein degradation. This process subsequently triggered the activation of c-Jun N-terminal kinase 1 (JNK1) and lipid deposition in primary hepatocytes. Together, these results suggested that PRMT1-mediated methylation of CFLAR plays a critical role in hepatic lipid metabolism. Targeting PRMT1 for drug design may represent a promising strategy for the treatment of NAFLD.
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Hepatocitos , Metabolismo de los Lípidos , Hígado , Enfermedad del Hígado Graso no Alcohólico , Proteína-Arginina N-Metiltransferasas , Animales , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Hígado/metabolismo , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Hepatocitos/metabolismo , Metilación , Masculino , Dieta Alta en Grasa/efectos adversos , Humanos , Ratones Endogámicos C57BL , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genéticaRESUMEN
BACKGROUND Previous studies on professional identity, self-directed learning competence, and self-efficacy among central sterile supply department (CSSD) nurses are rare. We investigated the status of these 3 characteristics among CSSD nurses and offered suggestions, to provide a reference for CSSD talent development. MATERIAL AND METHODS CSSD nurses working in 45 hospitals in southwest China were invited to participate in a questionnaire survey in August 2021. The survey comprised a general information questionnaire, a self-directed learning competence rating scale, a professional identity scale, and a general self-efficacy scale. RESULTS The CSSD nurses' scores for professional identity, self-directed learning competence, and self-efficacy were 109.92±17.161, 125.77±21.316, and 26.92±6.633, respectively. For professional identity, statistically significant differences were identified (P≤0.05) for 3 factors: monthly income, reason for studying nursing, and reason for working in the CSSD. For self-directed learning competence, statistically significant differences (P≤0.05) were identified for 5 factors: age, hospital grade, type of employee, monthly income, and reason for working in the CSSD. For self-efficacy, statistically significant differences were identified (P≤0.05) for 3 factors: age, reason for studying nursing and working in the CSSD, and whether the CSSD nurses wished their children to become nurses. CONCLUSIONS The professional identity, self-directed learning competence, and self-efficacy of the CSSD nurses in this study were at the medium level. More attention should be paid to career planning of young nurses and improvement of their professional identity and self-directed learning competence.
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Enfermeras y Enfermeros , Autoeficacia , Humanos , Adulto , Femenino , Encuestas y Cuestionarios , Masculino , China , Enfermeras y Enfermeros/psicología , Persona de Mediana Edad , Aprendizaje , Competencia Clínica , Personal de Enfermería en Hospital/psicologíaRESUMEN
Inorganic hydrated salt phase change materials (PCMs) hold promise for improving the energy conversion efficiency of thermal systems and facilitating the exploration of renewable thermal energy. Hydrated salts, however, often suffer from low thermal conductivity, supercooling, phase separation, leakage and poor solar absorptance. In recent years, compounding hydrated salts with functional carbon materials has emerged as a promising way to overcome these shortcomings and meet the application demands. This work reviews the recent progress in preparing carbon-enhanced hydrated salt phase change composites for thermal management applications. The intrinsic properties of hydrated salts and their shortcomings are firstly introduced. Then, the advantages of various carbon materials and general approaches for preparing carbon-enhanced hydrated salt PCM composites are briefly described. By introducing representative PCM composites loaded with carbon nanotubes, carbon fibers, graphene oxide, graphene, expanded graphite, biochar, activated carbon and multifunctional carbon, the ways that one-dimensional, two-dimensional, three-dimensional and hybrid carbon materials enhance the comprehensive thermophysical properties of hydrated salts and affect their phase change behavior is systematically discussed. Through analyzing the enhancement effects of different carbon fillers, the rationale for achieving the optimal performance of the PCM composites, including both thermal conductivity and phase change stability, is summarized. Regarding the applications of carbon-enhanced hydrate salt composites, their use for the thermal management of electronic devices, buildings and the human body is highlighted. Finally, research challenges for further improving the overall thermophysical properties of carbon-enhanced hydrated salt PCMs and pushing towards practical applications and potential research directions are discussed. It is expected that this timely review could provide valuable guidelines for the further development of carbon-enhanced hydrated salt composites and stimulate concerted research efforts from diverse communities to promote the widespread applications of high-performance PCM composites.
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Managing chronic non-healing wounds presents a significant clinical challenge due to their frequent bacterial infections. Mesoporous silica-based materials possess robust wound-healing capabilities attributed to their renowned antimicrobial properties. The current study details the advancement of mesoporous silicon-loaded MnO and CaO molecules (HMn-Ca) against bacterial infections and chronic non-healing wounds. HMn-Ca was synthesized by reducing manganese chloride and calcium chloride by urotropine solution with mesoporous silicon as the template, thereby transforming the manganese and calcium ions on the framework of mesoporous silicon. The developed HMn-Ca was investigated using scanning electron microscopy (SEM), transmission electron microscope (TEM), ultraviolet-visible (UV-visible), and visible spectrophotometry, followed by the determination of Zeta potential. The production of reactive oxygen species (ROS) was determined by using the 3,3,5,5-tetramethylbenzidine (TMB) oxidation reaction. The wound healing effectiveness of the synthesized HMn-Ca is evaluated in a bacterial-infected mouse model. The loading of MnO and CaO inside mesoporous silicon enhanced the generation of ROS and the capacity of bacterial capture, subsequently decomposing the bacterial membrane, leading to the puncturing of the bacterial membrane, followed by cellular demise. As a result, treatment with HMn-Ca could improve the healing of the bacterial-infected wound, illustrating a straightforward yet potent method for engineering nanozymes tailored for antibacterial therapy.