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The development of efficient and stable catalysts for oxygen evolution reaction (OER) in seawater presents a major challenge for hydrogen production through water electrolysis. In this work, we present a stable NiFe foam catalyst with a Se-doped Ni/Fe oxide surface prepared through a combination of chemical vapor deposition and electrochemical exfoliation. This method effectively modifies the surface of the commercial NiFe foam to a rough and stable Se-doped Ni/Fe oxide surface, displaying exceptional OER performance in both freshwater and seawater with more than 54 days stability in natural seawater. Characterizations reveal Ni-Se doped Fe oxide surface, with subsurface layers consisting of Ni alloyed with a moderate concentration of Fe, optimizes the adsorption free energy of oxygen-containing intermediates. Our results demonstrate a surface engineering approach to activate NiFe foam as a robust OER catalyst for seawater electrolysis, which is beneficial for the hydrogen economy and for the environment.
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With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion.
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Piel , Streptomyces , Pez Cebra , Animales , Streptomyces/metabolismo , Streptomyces/química , Piel/metabolismo , Humanos , Pez Cebra/metabolismo , Tilapia/metabolismo , Fermentación , Colágeno/metabolismo , Colágeno/química , Fibroblastos/metabolismoRESUMEN
HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. However, the mechanisms underlying HOTAIR-mediated TMZ resistance remains poorly understood. HOTAIR expression in glioma-related public datasets and drug response estimation were analyzed using bioinformatics. These findings were verified by overexpressing HOTAIR in TMZ-sensitive U251 cells and/or silencing HOTAIR in resistant U251 cells (U251R). The cytotoxic effects were evaluated using cell viability assay and flow cytometry analysis of cell cycle and apoptosis. In this study, we found that HOTAIR was upregulated in TMZ-resistant GBM cell lines and patients with high HOTAIR expression responded poorly to TMZ therapy. HOTAIR knockdown restored TMZ sensitivity in U251R cells, while HOTAIR overexpression conferred TMZ resistance in U251 cells. Wnt/ß-catenin signaling was enriched in patients with high HOTAIR expression; consistently, HOTAIR positively regulated ß-catenin expression in U251 cells. Moreover, HOTAIR-mediated TMZ resistance was associated with increased MGMT protein level, which resulted from the HOTAIR/miR-214-3p/ß-catenin network. Besides, GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and ß-catenin. Thus, we conlcude that HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.
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Metilasas de Modificación del ADN , Enzimas Reparadoras del ADN , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Glioblastoma , MicroARNs , ARN Largo no Codificante , Temozolomida , Proteínas Supresoras de Tumor , beta Catenina , Humanos , Temozolomida/farmacología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Glioblastoma/genética , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Resistencia a Antineoplásicos/genética , MicroARNs/genética , MicroARNs/metabolismo , beta Catenina/metabolismo , beta Catenina/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Metilasas de Modificación del ADN/metabolismo , Metilasas de Modificación del ADN/genética , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Antineoplásicos Alquilantes/farmacología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Factores de Riesgo , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/genética , Apoptosis/efectos de los fármacos , Apoptosis/genéticaRESUMEN
Objectives: This study describes the detection and tracking of emergency neurosurgical cross-transmission infections with carbapenem-resistant Klebsiella oxytoca (CRKO). Methods: We conducted an epidemiological investigation and a rapid screening of 66 surveillance samples using the chromogenic selective medium. Two CRKO isolates from infected patients and three from the preoperative shaving razors had similar resistance profiles identified by the clinical laboratory. Results: The whole genome sequencing (WGS) results identified all isolates as Klebsiella michiganensis (a species in the K. oxytoca complex) with sequence type 29 (ST29) and carrying resistance genes bla KPC-2 and bla OXY-5, as well as IncF plasmids. The pairwise average nucleotide identity values of 5 isolates ranged from 99.993% to 99.999%. Moreover, these isolates displayed a maximum genetic difference of 3 among 5,229 targets in the core genome multilocus sequence typing scheme, and the razors were confirmed as the contamination source. After the implementation of controls and standardized shaving procedures, no new CRKO infections occurred. Conclusion: Contaminated razors can be sources of neurosurgical site infections with CRKO, and standard shaving procedures need to be established. Chromogenic selective medium can help rapidly identify targeted pathogens, and WGS technologies are effective mean in tracking the transmission source in an epidemic or outbreak investigation. Our findings increase the understanding of microbial transmission in surgery to improve patient care quality.
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Infecciones por Klebsiella , Klebsiella oxytoca , Tipificación de Secuencias Multilocus , Secuenciación Completa del Genoma , Humanos , Klebsiella oxytoca/genética , Klebsiella oxytoca/aislamiento & purificación , Klebsiella oxytoca/efectos de los fármacos , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/transmisión , Carbapenémicos/farmacología , Antibacterianos/farmacología , Infección Hospitalaria/microbiología , beta-Lactamasas/genética , Pruebas de Sensibilidad Microbiana , Plásmidos/genética , Compuestos Cromogénicos , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Genoma Bacteriano/genética , Procedimientos Neuroquirúrgicos/efectos adversos , Masculino , FemeninoRESUMEN
At present, the problem of global warming is becoming increasingly serious, and one of the main culprits is the increasing amount of carbon dioxide emissions. Although the traditional carbon capture technologies can reduce the concentration of CO2 in the atmosphere, it has a series of problems such as high energy consumption, high cost, low efficiency or unfriendly environment. Hydrate-based carbon dioxide separation are considered to be a technology with great application and development prospects. Compared with the traditional method of carbon dioxide separation, the hydrate method has the advantages of simple process, low energy consumption and environmental friendliness. This review introduces the advantages of hydrate method compared with traditional carbon capture technologies, expounds the theory of carbon dioxide capture by hydrate, and the strengthening and improvement techniques of hydrate method, including thermodynamic promoter, kinetic promoter and mechanical reinforcement, and introduces the practical application of hydrate method in various fields.
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Background: The relationship between negative emotions and atrial fibrillation (AF) has garnered significant attention, yet observational studies have yielded contradictory findings regarding the causal associations between the two. Our study sought to provide genetic evidence for a causal relationship between negative emotions and AF through Mendelian randomization (MR) study. Methods: Utilizing genetic variations associated with negative emotions and AF as instrumental variables (IVs), a two-sample MR study was implemented. The potential causality between the two was initially assessed by using negative emotions as exposure and AF as outcome. Subsequently, potential reverse causality was evaluated by using AF as exposure and negative emotions as outcome. The inverse variance weighted (IVW) method served as the primary analysis for the two-sample MR, supplemented by weighted median method, MR-Egger regression, Simple mode method, and Weighted mode method. Sensitivity analyses were performed using the MR pleiotropy residual sum and outlier test (MR-PRESSO), Cochran Q test, and leave-one-out analysis to ensure the robustness of the results. Results: The two-sample MR analyses revealed that genetic susceptibility to AF had no potential causal effect on negative emotions (p > 0.05). Conversely, genetic susceptibility to negative emotions was positively correlated with an increased relative risk of AF [odds ratio (OR), 1.173, 95% confidence interval (CI): 1.115-1.235, p = 8.475 × 10-10]. Furthermore, neither horizontal pleiotropy nor heterogeneity was detected in the analysis. Conclusions: Genetic evidence from the study supports a potential causal link between negative emotions and AF. The study suggests that negative emotions may elevate the risk of AF, and the escalation of negative emotions in AF patients is more likely attributable to modifiable factors rather than genetically related factors.
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BACKGROUND: The ecosystems of marine ranching have enhanced marine biodiversity and ecological balance and have promoted the natural recovery and enhancement of fishery resources. The microbial communities of these ecosystems, including bacteria, fungi, protists, and viruses, are the drivers of biogeochemical cycles. Although seasonal changes in microbial communities are critical for ecosystem functioning, the current understanding of microbial-driven metabolic properties and their viral communities in marine sediments remains limited. Here, we employed amplicon (16S and 18S) and metagenomic approaches aiming to reveal the seasonal patterns of microbial communities, bacterial-eukaryotic interactions, whole metabolic potential, and their coupling mechanisms with carbon (C), nitrogen (N), and sulfur (S) cycling in marine ranching sediments. Additionally, the characterization and diversity of viral communities in different seasons were explored in marine ranching sediments. RESULTS: The current study demonstrated that seasonal variations dramatically affected the diversity of microbial communities in marine ranching sediments and the bacterial-eukaryotic interkingdom co-occurrence networks. Metabolic reconstruction of the 113 medium to high-quality metagenome-assembled genomes (MAGs) was conducted, and a total of 8 MAGs involved in key metabolic genes and pathways (methane oxidation - denitrification - S oxidation), suggesting a possible coupling effect between the C, N, and S cycles. In total, 338 viral operational taxonomic units (vOTUs) were identified, all possessing specific ecological characteristics in different seasons and primarily belonging to Caudoviricetes, revealing their widespread distribution and variety in marine sediment ecosystems. In addition, predicted virus-host linkages showed that high host specificity was observed, with few viruses associated with specific hosts. CONCLUSIONS: This finding deepens our knowledge of element cycling and viral diversity in fisheries enrichment ecosystems, providing insights into microbial-virus interactions in marine sediments and their effects on biogeochemical cycling. These findings have potential applications in marine ranching management and ecological conservation. Video Abstract.
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Bacterias , Biodiversidad , Explotaciones Pesqueras , Sedimentos Geológicos , Microbiota , Estaciones del Año , Virus , Sedimentos Geológicos/microbiología , Sedimentos Geológicos/virología , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Virus/clasificación , Virus/genética , Virus/aislamiento & purificación , Ecosistema , Metagenoma , Azufre/metabolismo , Metagenómica , Carbono/metabolismo , Nitrógeno/metabolismoRESUMEN
Background: Low-intensity pulsed ultrasound (LIPUS) is an effective and safe treatment for mild to moderate erectile dysfunction (ED). This study aimed to investigate the efficacy and safety of combining LIPUS with tadalafil in treating severe ED. Methods: The data from 27 patients treated with LIPUS alone (group A) and 21 patients treated with a combination of LIPUS and daily 10 mg tadalafil (group B) were retrospectively analyzed. The LIPUS regimen consisted of twice-weekly treatments for 4 consecutive weeks. The treatment was considered effective if the change in International Index of Erectile Function-Erectile Function Domain (IIEF-EF) score after treatment was greater than or equal to the minimal clinically important difference (MCID) (the MCID for severe ED is 7 points). The effectiveness, IIEF-EF score, erectile hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), and adverse events were evaluated before treatment, 4 weeks after treatment, and 12 weeks after treatment. Results: Compared to pre-treatment, both groups showed significant improvement in IIEF-EF score and EHS at 4 and 12 weeks after treatment (P<0.001), with no statistically significant difference between the two time points (P>0.05). The effective rate did not significantly differ between group A (9/27, 33.3%) and group B (10/21, 47.62%) at 4 weeks or between group A (9/27, 33.3%) and group B (12/21, 57.14%) at 12 weeks after treatment (P=0.32, P=0.10). However, in patients without comorbidities, the effective rate of group B (12/18, 66.67%) was higher than that of group A (9/25, 36.00%) at 12 weeks after treatment (P=0.047). After LIPUS treatment, the PSV level significantly increased and the EDV level significantly decreased compared with before treatment (P<0.05). No adverse events were reported. Conclusions: The study suggests that LIPUS has a therapeutic effect on severe ED patients, especially those without comorbidities. It may have a synergistic or overlapping effect with phosphodiesterase type 5 inhibitors (PDE5Is) on severe ED patients without comorbidities.
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Sulfoquinovose (SQ), the polar head group of sulfolipids essential for photosynthesis, is naturally abundant. Anaerobic Firmicutes degrade SQ through a transaldolase-dependent (sulfo-TAL) pathway, producing dihydroxypropanesulfonate (DHPS). Some bacteria extend this pathway by the sequential action of HpfG and HpfD converting DHPS to 3-hydroxypropanesulfonate (3-HPS) via 3-sulfopropionaldehyde (3-SPA). Here, we report a variant sulfo-TAL pathway in Enterococcus gilvus, involving additional enzymes, a NAD+-dependent 3-SPA dehydrogenase HpfX, and a 3-sulfopropionyl-CoA synthetase HpfYZ, which oxidize 3-SPA to 3-sulfopropionate (3-SP) coupled with ATP formation. E. gilvus grown on SQ or DHPS produced a mixture of 3-HPS and 3-SP, indicating the bifurcated pathway. Similar genes are found in various Firmicutes, including gut bacteria. Importantly, 3-SP, but not 3-HPS, can serve as a respiratory terminal electron acceptor for Bilophila wadsworthia, a common intestinal pathobiont, resulting in the production of toxic H2S. This research expands our understanding of sulfonate metabolism and reveals cross-feeding in the anaerobic microbiome.
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Background: Increasing evidence indicates that clinicopathologic phenotypes and ANCA serotypes may differ ethnically and geographically. This review highlights the progress in the prevalence, pathogenesis, management, and outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in China. Summary: AAV is not rare in China. Cumulative evidence has demonstrated a significant preponderance of microscopic polyangiitis (MPA) and myeloperoxidase (MPO)-ANCA AAV in China. Even in patients with granulomatosis with polyangiitis (GPA), there is a predominance of MPO-ANCA over proteinase 3 (PR3)-ANCA, presenting a unique subset. The pathogenesis of AAV is multifactorial, with the role of complement activation being highlighted during recent years. Treatment strategies for AAV in China have also been refined recently. A rapid tapering of glucocorticoids to minimize exposure has been recommended by the Chinese guidelines. Along with a better understanding of the disease, B cell-targeted therapy and complement-targeted therapy are developing. A considerable number of patients in China received rituximab treatment and achieved remission. However, infection risk and associated mortality still remain concerns. Therefore, less rituximab exposure should be considered and evaluated in Chinese AAV patients. Prognostic factors have been reviewed. Of note, along with improved outcomes, there is an increase of cardiovascular and malignant-related death, warranting specific care. Recently, a modified renal risk score model has been validated for early risk prediction in Chinese AAV patients. Moreover, emerging biomarkers for AAV, including complement components, have been identified in Chinese patients. Key Messages: There is a preponderance of MPA and MPO-ANCA in China. Treatment strategies for Chinese AAV patients generally align with those in western countries, and to some extent, less aggressive. Prognostic factors and emerging biomarkers for AAV in China have been identified. Further challenges include optimizing interventions, minimizing treatment-related comorbidities, improving disease monitoring, and enhancing life qualities of AAV patients.
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INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.
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BACKGROUND: Toxocara canis, the most prevalent helminth in dogs and other canines, is one of the socioeconomically important zoonotic parasites, particularly affecting pediatric and adolescent populations in impoverished communities. However, limited information is available regarding the proteomes of female and male adult T. canis. To address this knowledge gap, we performed a comprehensive proteomic analysis to identify the proteins with differential abundance (PDAs) and gender-specifically expressed proteins between the two sexes adult T. canis. METHODS: The comparative proteomic analysis was carried out by the Orbitrap mass spectrometry (MS) with asymmetric track lossless (Astral) analyzer. The difference analysis was conducted using t-test and the proteins verification was achieved through parallel reaction monitoring (PRM). The potential biological functions of identified adult T. canis proteins and PDAs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The domain, transcription factor and subcellular localization of the identified proteins and PDAs were analyzed by InterPro, AnimalTFDB 4.0 and Cell-mPLOC 2.0 databases, respectively. RESULTS: A total of 8565 somatic proteins of adult T. canis were identified. Compared to male adult, 682 up-regulated PDAs and 844 down-regulated PDAs were identified in female adult with P-values < 0.05 and |log2FC| > 1, including 139 proteins exclusively expressed in female and 272 proteins exclusively expressed in male. The GO annotation analysis using all PDAs revealed that the main biological processes, cellular components and molecular functions corresponded to aminoglycan metabolic process, extracellular region and protein tyrosine phosphatase activity, respectively. The KEGG analysis using all PDAs showed that the pathways were mainly associated with adipocytokine signaling pathway, proximal tubule bicarbonate reclamation and PPAR signaling pathway. CONCLUSIONS: This study reveals the differential protein expression between female and male adult T. canis, providing valuable resource for developing the novel intervention strategies against T. canis infection in humans and animals, especially from the perspective of sexual development and reproduction.
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Proteínas del Helminto , Proteómica , Toxocara canis , Animales , Femenino , Masculino , Proteómica/métodos , Proteínas del Helminto/metabolismo , Proteínas del Helminto/genética , Proteínas del Helminto/análisis , Proteoma , Perros , Toxocariasis/parasitología , Espectrometría de Masas , Factores Sexuales , Enfermedades de los Perros/parasitologíaRESUMEN
Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.
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The present study investigated the effect of connexin 43 (Cx43) on the regulation of osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) using low-frequency-pulsed electromagnetic fields (LPEMF). The BMSCs were isolated and cultured in vitro using adherent whole-bone marrow cultures. CCK-8 assay was used to detect the effects of LPEMF on the proliferation ability of BMSCs and alkaline phosphatase (ALP) activity and the levels of osteogenic marker genes were detected to evaluate the osteogenic ability change following LPEMF treatment. Lentiviral vector-mediated RNA interference was transfected into BMSCs to inhibit the expression of Cx43 and western blotting was used to detect Cx43 expression. The BMSCs showed the highest proliferation following LPEMF treatment at 80 Hz for 1 h. The results of ALP activity, osteogenic marker genes and Alizarin Red S staining showed that the osteogenic ability was notably increased following LPEMF treatment at 80 Hz for 1 h. Cx43 expression increased during the osteogenic differentiation of BMSCs following LPEMF treatment at 80 Hz. The enhanced osteogenic differentiation of the LPEMF-treated BMSCs were partially reversed when Cx43 expression was inhibited. LPEMF may promote the osteogenic differentiation of BMSCs by regulating Cx43 expression and enhancing osteogenic ability.
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Importance: Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential. Objective: To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC. Design, Setting, and Participants: This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9). Main Outcomes and Measures: The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping. Results: Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects. Conclusion and Relevance: The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.
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Sepsis-associated encephalopathy (SAE) is a serious neurological complication accompanied with acute and long-term cognitive dysfunction. Ferroptosis is a newly discovered type of cell death that is produced by iron-dependent lipid peroxidation. Emerging evidence suggests that ferroptosis is involved in SAE. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a mitochondria related gene involved in ferroptosis. However, the role of Nrf2 in SAE and the mechanisms remains elusive. In this study, we found that Nrf2 knockout aggravated cognitive and emotional dysfunction and promoted caecal ligation and puncture (CLP)-induced brain injury and hippocampus ferroptosis as indicated by the increase of ROS, Fe2+ and the levels of proinflammatory cytokines. Meanwhile, the levels of glutathione peroxidase 4 (GPX4), SLC7A11 and glutathionewere downregulatedin Nrf2 knockout group. In vitro experiments showed that mitochondrial ROS, Fe2+ and the expression of Fis1 and Drp1 decreased, and the level of Mfn1 and Opa-1 increased after Nrf2 overexpression. The silence of Nrf2 increased the expression of ROS, MDA and Fe2+, while decreased glutathione, mitochondrial membrane potential (MMP) and cell viability in vitro, indicating Nrf2 improved LPS-induced mitochondrial dysfunction and mitigated hippocampal cells ferroptosis. These results suggest that Nrf2 could inhibit ferroptosis and neuroinflammation in hippocampus and reduce cognitive dysfunction in SAE mice, making it a potential therapeutic target in the treatment of SAE. The protective effects of Nrf2 on the brain may be mediated by maintaining mitochondrial dynamic homeostasis.
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Metal-organic frameworks (MOFs) are crystalline porous materials for storage and energy conversion applications with three-dimensional pore structure, high porosity, and specific surface area, which are widely utilized in electrocatalysis. Herein, MoSe2/NiSe composites were synthesized by selenization reaction using NiMOF as the precursor. The composites were hollow nanoflower structures with a synergistic effect between MoSe2 and NiSe to promote rapid electron transfer, which exhibited good hydrogen evolution reaction performance in an alkaline medium. At a current density of 10 mA/cm2, the HER overpotential reaches 80 mV, the Tafel slope is 33.86 mV/dec, and the material has good stability, with polarization curves remaining essentially unchanged after 3000 cycles. These results indicate that the method has a promising application in the preparation of efficient and sustainable catalysts for hydrogen production in alkaline medium.
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Sugar beets account for 30% of global sugar production each year, and their byproducts are an important source of bioethanol and animal feed. Sugar beet is an important cash crop in Inner Mongolia, China. To achieve high yields and sugar content, it is essential to supply nitrogen fertilizer in accordance with the growth characteristics of sugar beet, thereby enhancing the efficiency of nitrogen fertilizer utilization. A two-year experiment was carried out in the experimental field of the Inner Mongolia Academy of Agricultural & Animal Husbandry Sciences. The impact of varying ratios of nitrogen-based fertilizer to topdressing on nitrate nitrogen and ammonium nitrogen levels in the 20-60 cm soil layer, as well as the activities of protease, urease, catalase, and sucrose in the 20-40 cm soil layer were investigated during the rapid leaf growth period and root and sugar growth period. Results indicated that different ratios of nitrogen-based fertilizer to topdressing significantly influenced the levels of nitrate nitrogen and ammonium nitrogen, and the activities of protease and urease in the 0-20 cm soil layer, with these effects diminishing as soil depth increased. The activities of catalase and sucrose were minimally impacted. Nitrogen was applied at 150 kg/ha during the growth period of sugar beet, according to the growth characteristics of sugar beet to maximize nitrogen utilization efficiency. Topdressing was completed with irrigation at the rapid growth stage. The nitrogen-based fertilizer to topdressing ratio of 6:4 resulted in optimal crop yield and sugar yield of sugar beet under shallow drip irrigation. Additionally, the activities of protease and urease in different soil treatments were significantly different, and the activities of protease and urease in the 0-40 cm soil layer were identified as useful soil physiological indicators for nitrogen utilization in sugar beet.
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Riego Agrícola , Beta vulgaris , Fertilizantes , Nitrógeno , Suelo , Ureasa , Fertilizantes/análisis , Beta vulgaris/crecimiento & desarrollo , Nitrógeno/metabolismo , Suelo/química , Riego Agrícola/métodos , China , Ureasa/metabolismo , Catalasa/metabolismo , Péptido Hidrolasas/metabolismoRESUMEN
INTRODUCTION: Stroke survivors often face motor dysfunction, increasing fall risk. Lower extremity muscle weakness is a key factor affecting walking ability. Tai chi (TC) has been shown to improve muscle strength and mobility in patients with stroke more effectively than traditional walking training. However, existing TC programmes for stroke rehabilitation are often too simplified and fail to fully use TC's benefits. Additionally, subjective assessment scales are time-consuming and prone to bias. This study proposes integrating TC's early movement features with neurodevelopmental therapy, using surface electromyography and inertial measurement unit (IMU) sensors to thoroughly analyse diverse TC movements. Tailored exercises, based on stroke-induced impairments, will be objectively assessed through biomechanical analysis. METHODS AND ANALYSIS: The study unfolds in two phases. The initial phase employs the IMU sensor and electromyography to objectively analyse TC's biomechanics, informing personalised rehabilitation plans aligned with distinct movement impairments. The second phase adopts a randomised, single-blind, parallel controlled trial design involving 60 patients with stroke randomly assigned to either the intervention or control group. The intervention group undergoes biomechanics-based TC training alongside routine rehabilitation for 12 weeks, practicing the 24-form TC three times weekly. The control group engages in routine rehabilitation thrice weekly for the same duration. Primary and secondary outcomes, including kinematic/dynamic data, surface electromyography, motion analysis, comprehensive the international classification of functioning, disability and health Core Set for Stroke, Modified Barthel Index and Fugl-Meyer Assessment, will be evaluated at baseline and post-intervention. ETHICS AND DISSEMINATION: The study has received approval from the Ethics Committee of Zhongda Hospital Southeast University (2023ZDSYLL378-P01). All prospective participants will receive comprehensive information regarding the study protocol, and their informed consent will be obtained before their participation. Additionally, the trial will be registered with the Chinese Clinical Trial Registry to ensure transparency and compliance with research regulations. Results from this study will be disseminated through peer-reviewed journals, conference presentations and public databases to ensure wide accessibility and to contribute to the advancement of medical knowledge. PROTOCOL VERSION: 2.0 (14 June 2024). TRIAL REGISTRATION NUMBER: www.chictr.org.cn, identifier ChiCTR2400080158.