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BACKGROUND: Research on the co-production of multiple enzymes by Bacillus velezensis as a novel species is still a topic that needs to be studied. This study aimed to investigate the fermentation characteristics of B. velezensis D6 co-producing α-amylase and protease and to explore their enzymatic properties and applications in fermentation. RESULTS: The maximum co-production of α-amylase and protease reached 13.13 ± 0.72 and 2106.63 ± 64.42 U mL-1, respectively, under the optimal fermented conditions (nutrients: 20.0 g L-1 urea, 20.0 g L-1 glucose, 0.7 g L-1 MnCl2; incubation conditions: initial pH 7.0, temperature 41 °C, 8% inoculation size and 30% working volume). Moreover, the genetic co-expression of α-amylase and protease increased from 0 to 24 h and then decreased after 36 h at the transcriptional level, which coincided with the growth trend of B. velezensis D6. The optimal reaction temperature of α-amylase was 55-60 °C, while that of protease was 35-40 °C. The activities of α-amylase and protease were retained by over 80% after thermal treatment (90 °C, 1 h), which indicated that two enzymes co-produced by B. velezensis D6 demonstrated excellent thermal stability. Moreover, the two enzymes were stable over a wide pH range (pH 4.0-8.0 for α-amylase; pH 4.0-9.0 for protease). Finally, the degrees of hydrolysis of corn, rice, sorghum and soybeans by α-amylase from B. velezensis D6 reached 44.95 ± 2.95%, 57.16 ± 2.75%, 52.53 ± 4.01% and 20.53 ± 2.42%, respectively, suggesting an excellent hydrolysis effect on starchy raw materials. The hydrolysis degrees of mackerel heads and soybeans by protease were 43.93 ± 2.19% and 26.38 ± 1.72%, respectively, which suggested that the protease from B. velezensis D6 preferentially hydrolyzed animal-based protein. CONCLUSION: This is a systematic study on the co-production of α-amylase and protease by B. velezensis D6, which is crucial in widening the understanding of this species co-producing multi-enzymes and in exploring its potential application. © 2024 Society of Chemical Industry.
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AIMS: The current recognition of mitral annular disjunction (MAD) as an anatomical abnormality potentially associated with ventricular arrhythmias has sparked controversy regarding its prevalence and clinical implications. This study aimed to investigate the prevalence and extent of MAD in individuals with no significant structural abnormalities involving the left heart using enhanced cardiac CT, while also exploring potential factors, such as age, that may be associated with MAD. METHODS: Systolic datasets of cardiac CT from 742 subjects were retrospectively included. MAD was determined by rotating orthogonal multiplanar reconstruction images around the central axis of the mitral annulus. The maximal distance of disjunction (DMAD) and segments involved (SI, 0 to 5 basal segments at left ventricular wall) was quantified to evaluate the extent of separation. RESULTS: In total, 449 (60.5%) had MAD. Subjects with MAD were significantly older (51.3 ± 19.9 years vs. 29.6 ± 20.3 years, P < 0.001). Age was found to be an independent relevant factor for MAD (OR = 1.059; 95%CI: 1.033, 1.085; P < 0.001). Subjects with MAD were then divided into 4 subgroups (G1: ≤20 years, G2: 21-40 years, G3: 41-60 years, G4: ≥61 years). DMAD and SI of each age subgroup were 1.9 ± 0.2 mm, 2.0 ± 1.2 (G1, n = 36), 2.7 ± 0.8 mm, 2.9 ± 1.3 (G2, n = 51), 3.0 ± 0.8 mm, 3.0 ± 1.3 (G3, n = 183), and 3.0 ± 1.0 mm, 3.7 ± 1.1 (G4, n = 179). Age was an independent relevant factor associated with DMAD (R2 = 0.132; ß = 0.014; 95%CI: 0.004, 0.024; P = 0.007) and SI (OR = 1.030; 95%CI: 1.005, 1.055; P = 0.016). CONCLUSIONS: MAD is a common finding on cardiac CT. Its prevalence and extent increase with age.
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Yunling cattle is a new breed of beef cattle bred in Yunnan Province, China, which has the advantages of fast growth, excellent meat quality, improved tolerance ability, and important landscape value. Copy number variation (CNV) is a significant source of gene structural variation and plays a crucial role in evolution and phenotypic diversity. Based on the latest reference genome ARS-UCD2.0, this study analyzed the genome-wide distribution of CNVs in Yunling cattle using short-read whole-genome sequencing data (n = 129) and single-molecule long-read sequencing data (n = 1), and a total of 16,507 CNVs were detected. After merging CNVs with overlapping genomic positions, 3,728 CNV regions (CNVRs) were obtained, accounting for 0.61% of the reference genome. The functional analysis indicated significant enrichment of CNVRs in 96 GO terms and 57 KEGG pathways, primarily related to cell adhesion, signal transduction, neuromodulation, and nutritional metabolism. Additionally, 111 CNVRs overlapped with 76 quantitative trait loci (QTLs), including Subcutaneous fat thickness QTL, Longissimus muscle area QTL, and Marbling score QTL. Several CNVR-overlapping genes, including BZW1, AOX1, and LOC100138449, overlap with regions associated with meat color and quality QTLs. Furthermore, Vst analysis showed that PSMB4, ERICH1, SMC2, and PPP4R3A were highly divergent between Yunling and Brahman cattle. In summary, we have constructed the genomic CNV map of Yunling cattle for the first time using whole-genome resequencing. This provides valuable genetic variation resources for the study of the Yunling cattle genome and contributes to the study of economic traits in Yunling cattle.
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BACKGROUND: Many patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC. METHODS: This retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan-Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We included 132 patients in this study, divided into RDI < 0.7 and RDI ≥ 0.7 groups using cut-off value of 0.7. RDI grade was an independent prognostic factor for OS. Baseline demographic and clinical characteristics were well balanced between the groups. There was no evidence that patients with RDI < 0.7 experienced less toxicity or those with RDI ≥ 0.7 resulted in more toxicity. However, patients with RDI < 0.7 who were given reduced doses had a worse overall survival [HR 0.49, 95% CI 0.27-0.88, P = 0.015]. The risk of a lower RDI increased with a longer dose delay time (P < 0.001). CONCLUSION: The RDI below 0.7 for avoiding chemoradiotherapy toxicity administration led to a reduction in the dose intensity of treatment and decreased overall survival.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Humanos , Femenino , Masculino , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Anciano , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Paclitaxel/administración & dosificación , Quimioradioterapia/métodos , Carboplatino/administración & dosificación , Esofagectomía , Adulto , Estimación de Kaplan-Meier , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
Under China's strict industrial control measures, the reduction of secondary pollutants (O3 and secondary organic aerosols [SOA]) and precursors (volatile organic compounds [VOCs] and NOx) caused by industrial processes has encountered bottlenecks. In this study, the net O3 formation rate (Net [O3]) in summer and the self-reaction rate between peroxy radicals (Self-Rnxs) in winter are used to characterize the formation potentials of O3 and SOA, respectively. Assuming that the precursor reduction ratio based on emission inventories is approximately equal to that based on observed concentrations, this study combines emission inventory and observation-based model (OBM) methods to indicate the potential source of secondary pollutants reduction. The findings show that strict control measures implemented by local governments, particularly those targeting industrial processes and fossil fuel combustion, are effective in reducing VOCs and NOx emissions during summer, and the two sources result in 3.8 % and 5.3 % decrease in the Net (O3), respectively. Similarly, control measures focusing on industrial processes help to significantly reduce VOCs emissions during winter, resulting in an 8.0 % decrease in Self-Rnxs. However, current measures for industrial processes are stringent and have little potential for further reduction. Therefore, additional sources with higher reduction potentials beyond industrial processes should be subject to stringent controls in industrial cities. Given the limited emission reduction potential associated with industrial processes, this study provides perspectives for sustained reduction of secondary pollutants in industrial cities.
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Our previous studies have shown that activating α7nAChRs suppresses systemic inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP) in early sepsis. Now that the medullary visceral zone (MVZ) is the center of CAP and responsible for regulating systemic inflammation, what changes will occur in MVZ's pathology and function in sepsis, especially when interfering with α7nAChRs? Does activation of MVZ's α7nAChRs contribute to the inhibition of systemic inflammation? To clarify these issues, we explored the systemic inflammation and immunity state by detecting serum levels of TNF-α, IL-6, HMGB1, sCD14, and CD4+CD25+Treg and TH17 lymphocytes percentage, meanwhile, we analyzed the apoptosis of cholinergic and catecholaminergic neurons and the expressions of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) in MVZ in sepsis and the interfering effects on α7nAChRs. In this study, we found that in sepsis, serum TNF-α, IL-6, HMGB1, sCD14, CD4+CD25+Treg, and TH17 lymphocytes significantly increased and the ratio of Treg/TH17 significantly decreased, cholinergic and catecholaminergic neurons underwent apoptosis with low expressions of TH and CHAT in MVZ; activation of α7nAChRs not only significantly decreased the levels of septic serum TNF-α, IL-6, HMGB1, sCD14, and TH17 lymphocytes (P ï¼ 0.05), but also significantly reduced cholinergic and catecholaminergic neurons' apoptosis, and promoted expressions of TH/CHAT. Our study reveals that sepsis undermines MVZ through neuroinflammation which contributes to the uncontrolled systemic inflammation. Activating central α7nAChRs is not only helpful to restore MVZ's structure and function but also beneficial to subside the inflammatory storm in sepsis. Even if MVZ is damaged in sepsis, cholinergic neurons in MVZ still regulate the systemic inflammation stably.
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OBJECTIVE: The principal aim of this report is to address the challenge of integrating prosthetic crowns with natural dentition in the esthetic zone. It highlights the utilization of a prosthetically driven treatment plan, designed to ensure predictable esthetic outcomes. CLINICAL CONSIDERATIONS: This report details a technique that utilizes three digital guides, all derived from a 3-dimensional digital smile design. The integration of a restoration guide, an implant drilling guide, and an alveoloplasty guide is described. These tools collectively facilitate the precise execution of both surgical and prosthetic procedures, enhancing treatment accuracy and esthetic integration. CONCLUSIONS: This technique considers the esthetic prosthetic crowns, implant positions, and alveoloplasty collectively. It enhances the predictability of esthetic outcomes in oral implantology and potentially provides an integrated prosthetically driven workflow in cosmetic dental treatments. CLINICAL SIGNIFICANCE: The application of multiple digital guides derived from the same prosthetically driven treatment significantly enhances the predictability of esthetic outcomes in oral implantology.
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Per- and polyfluoroalkyl substances (PFASs) in high-latitude polar regions and the Tibetan Plateau have received widespread international attention. Here, we measured 18 PFASs and 11 major isomers in the lake water, sediment, and surrounding runoff of Lake Nam Co in 2020. The concentrations of ultrashort-chain trifluoroacetic acid (TFA) and perfluoropropanoic acid (PFPrA) and major isomers of perfluoooctanoic acid (PFOA) and perfluoooctane sulfonate acid (PFOS) in water bodies in high-latitude polar regions and the Tibetan Plateau are reported for the first time. The results showed that the concentration of ∑PFASs in glacial runoff was approximately 139â¯% greater than that in nonglacial runoff. The concentrations of ∑PFASs in the lake water and sediment in the southern lake with multiple glacial runoff events were approximately 113â¯% and 108â¯% higher, respectively, than those in the northern lake. The concentrations of short-chain perfluorobutanoic acid (PFBA) and ultrashort-chain TFA and PFPrA, which may be indicators of ice and snow melt, exhibited significant spatial heterogeneity. Overall, the spatial heterogeneity of PFAS concentrations in the water, sediment and surrounding runoff of Lake Nam Co may be caused mainly by glacial melting.
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Androgenetic alopecia (AGA) is a common type of hair loss in men and efficacy and safety of current medical treatment remain limited. Therefore, the present study aimed to investigate the efficacy and safety of botulinum toxin type A (BTA) combined with Minoxidil in patients with AGA. 60 male patients were included in this study and control group received topical 5% Minoxidil and the treatment group received BTA combined with topical 5% Minoxidil. BTA injections (60-70 U) were administered at 30-35 scalp sites. Head photographs were taken at baseline, 2nd, 4th, and 6th months. Clinical descriptions recorded scalp conditions, and patient satisfaction along with Dermatology Life Quality Index scores were documented. The treatment group (TG) showed significant hair growth differences compared to the control group (CG) at the 4th month (P < 0.001) and 6th month (P = 0.0046) post-treatment. TG had improved Investigator Global Assessment (IGA) scores in the 4th month (P = 0.0001) and 6th month (P = 0.0259) compared to CG. Patient satisfaction in TG for hair growth and scalp improvement was higher than CG (all P < 0.05). TG exhibited substantial quality of life improvement at the 4-month (P = 0.0009) and 6-month (P = 0.0099). No adverse reactions were observed post-botulinum toxin injection. BTA combined with Minoxidil effectively promotes hair growth, enhances the quality of life, and alleviates scalp symptoms in male AGA patients at 4th and 6th months, with no adverse effects compared to Minoxidil alone.Trial registration number: Ethics Committee of Shanghai Tongji Hospital (ID: K-2018-026).
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Alopecia , Toxinas Botulínicas Tipo A , Minoxidil , Satisfacción del Paciente , Calidad de Vida , Humanos , Masculino , Minoxidil/administración & dosificación , Minoxidil/efectos adversos , Alopecia/tratamiento farmacológico , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/efectos adversos , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Administración Tópica , Quimioterapia Combinada/métodos , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Cuero Cabelludo , Adulto JovenRESUMEN
This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8-not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4-15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7-63.5) and 69.7% (95% CI: 55.7-87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Masculino , Femenino , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/radioterapia , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/mortalidad , Persona de Mediana Edad , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Carboplatino/uso terapéutico , Carboplatino/administración & dosificación , Supervivencia sin Progresión , Quimioradioterapia/métodos , AdultoRESUMEN
Synergistic reduction of air pollutants and carbon dioxide (CO2) emissions is currently a key environmental policy in China, yet provincial-level studies remain scarce. To fill the gap, this study developed a coupled emission inventory from 2013 to 2020 in Shanxi, a coal-dependent province critical to China's energy security. This facilitated the investigation of emission trends, primary sources, synergistic effects, and spatial distribution. The results show that, while air pollutant emissions decreased significantly during the study period, CO2 emissions increased slightly. The main emitters of SO2, NOx, and CO2 were identified as power, heating, industrial boilers, and residential coal combustion. The iron and steel industry contributed significantly to PM2.5 emissions, coke production to VOCs, and vehicles to NOx and VOCs. NH3 emissions were mainly attributed to fertilizer use and livestock. Synergistic reductions were evident in coal-related sources, especially industrial boilers and residential coal combustion, underlining the importance of optimizing the energy structure. Anthropogenic emissions were concentrated in basins with poor dispersion conditions. Taiyuan, Yuncheng, and Linfen emerged as key areas for synergistic reduction efforts. This study provides important insights for environmental policy development in Shanxi and other coal-dependent regions.
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Flavonoids are found in the roots, stems, leaves, and fruits of many plant taxa. They are related to plant growth and development, pigment formation, and protection against environmental stress. Flavonoids function as antioxidants and exert anti-inflammatory effects in the cardiovascular system by modulating classical inflammatory response pathways, such as the TLR4-NF-ĸB, PI3K-AKT, and Nrf2/HO-1 signalling pathways. There is increasing evidence for the therapeutic effects of flavonoids on hypertension, atherosclerosis, and other diseases. The potential clinical value of flavonoids for diseases of the cardiovascular system has been widely explored. For example, studies have evaluated the roles of flavonoids in the regulation of blood pressure via endothelium-dependent and non-endothelium-dependent pathways and in the regulation of myocardial systolic and diastolic functions by influencing calcium homeostasis and smooth muscle-related protein expression. Flavonoids also have hypoglycaemic, hypolipidemic, anti-platelet, autophagy, and antibacterial effects. In this paper, the role and mechanism of flavonoids in cardiovascular diseases were reviewed in order to provide reference for the clinical application of flavonoids in the future.
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CASE: A 12-year-old boy with Klippel-Trenaunay-Weber syndrome underwent surgery for unstable slipped capital femoral epiphysis who developed pulmonary embolism postoperatively. CONCLUSION: It is important to be vigilant about pulmonary embolism in children because it is rare but potentially fatal, especially in the presence of risk factors. Early diagnosis and treatment of unstable slipped capital femoral epiphysis are crucial to minimize immobility. Close monitoring of femoral head osteonecrosis is also necessary.
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Síndrome de Klippel-Trenaunay-Weber , Embolia Pulmonar , Epífisis Desprendida de Cabeza Femoral , Humanos , Masculino , Embolia Pulmonar/etiología , Niño , Síndrome de Klippel-Trenaunay-Weber/complicaciones , Epífisis Desprendida de Cabeza Femoral/cirugía , Epífisis Desprendida de Cabeza Femoral/complicaciones , Epífisis Desprendida de Cabeza Femoral/diagnóstico por imagen , Complicaciones Posoperatorias/etiologíaRESUMEN
Applying chemical enhanced oil recovery (EOR) to shale and tight formations is expected to accelerate China's Shale Revolution as it did in conventional reservoirs. However, its screening and modeling are more complex. EOR operations are faced with choices of chemicals including traditional surfactant solutions, surfactant solutions in the form of micro-emulsions (nano-emulsions), and nano-fluids, which have similar effects to surfactant solutions. This study presents a systematic comparative analysis composed of laboratory screening and numerical modeling. It was conducted on three scales: tests of chemical morphology and properties, analysis of micro-oil-displacing performance, and simulation of macro-oil-increasing effect. The results showed that although all surfactant solutions had the effects of reducing interfacial tension, altering wettability, and enhancing imbibition, the nano-emulsion with the lowest hydrodynamic radius is the optimal selection. This is attributed to the fact that the properties of the nano-emulsion match well with the characteristics of these shale and tight reservoirs. The nano-emulsion is capable of integrating into the tight matrix, interacting with the oil and rock, and supplying the energy for oil to flow out. This study provides a comprehensive understanding of the role that surfactant solutions could play in the EOR of unconventional reservoirs.
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OBJECTIVES: Obesity related glomerulopathy (ORG) is induced by obesity, but the pathogenesis remains unclear. This study aims to investigate the expression of early growth response protein 3 (EGR3) in the renal cortex tissues of ORG patients and high-fat diet-induced obese mice, and to further explore the molecular mechanism of EGR3 in inhibiting palmitic acid (PA) induced human podocyte inflammatory damage. METHODS: Renal cortex tissues were collected from ORG patients (n=6) who have been excluded from kidney damage caused by other diseases and confirmed by histopathology, and from obese mice induced by high-fat diet (n=10). Human and mouse podocytes were intervened with 150 µmol/L PA for 48 hours. EGR3 was overexpressed or silenced in human podocytes. Enzyme linked immunosorbent assay (ELISA) was used to detcet the levels of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). Real-time RT-PCR was used to detect the mRNA expressions of EGR3, podocytes molecular markers nephrosis 1 (NPHS1), nephrosis 2 (NPHS2), podocalyxin (PODXL), and podoplanin (PDPN). RNA-seq was performed to detect differentially expressed genes (DEGs) after human podocytes overexpressing EGR3 and treated with 150 µmol/L PA compared with the control group. Co-immunoprecipitation (Co-IP) combined with liquid chromatography tandem mass spectrometry (LC-MS) was used to detect potential interacting proteins of EGR3 and the intersected with the RNA-seq results. Co-IP confirmed the interaction between EGR3 and protein arginine methyltransferases 1 (PRMT1), after silencing EGR3 and PRMT1 inhibitor intervention, the secretion of IL-6 and IL-1ß in PA-induced podocytes was detected. Western blotting was used to detect the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) after overexpression or silencing of EGR3. RESULTS: EGR3 was significantly upregulated in renal cortex tissues of ORG patients and high-fat diet-induced obese mice (both P<0.01). In addition, after treating with 150 µmol/L PA for 48 hours, the expression of EGR3 in human and mouse podocytes was significantly upregulated (both P<0.05). Overexpression or silencing of EGR3 in human podocytes inhibited or promoted the secretion of IL-6 and IL-1ß in the cell culture supernatant after PA intervention, respectively, and upregulated or downregulated the expression of NPHS1, PODXL, NPHS2,and PDPN (all P<0.05). RNA-seq showed a total of 988 DEGs, and Co-IP+LC-MS identified a total of 238 proteins that may interact with EGR3. Co-IP confirmed that PRMT1 was an interacting protein with EGR3. Furthermore, PRMT1 inhibitors could partially reduce PA-induced IL-6 and IL-1ß secretion after EGR3 silencing in human podocytes (both P<0.05). Overexpression or silencing of EGR3 negatively regulated the expression of PRMT1 and p-STAT3. CONCLUSIONS: EGR3 may reduce ORG podocyte inflammatory damage by inhibiting the PRMT1/p-STAT3 pathway.
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Proteína 3 de la Respuesta de Crecimiento Precoz , Obesidad , Podocitos , Proteína-Arginina N-Metiltransferasas , Proteínas Represoras , Factor de Transcripción STAT3 , Animales , Humanos , Masculino , Ratones , Dieta Alta en Grasa/efectos adversos , Proteína 3 de la Respuesta de Crecimiento Precoz/metabolismo , Proteína 3 de la Respuesta de Crecimiento Precoz/genética , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-6/genética , Corteza Renal/metabolismo , Corteza Renal/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/etiología , Enfermedades Renales/patología , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/complicaciones , Obesidad/metabolismo , Ácido Palmítico/farmacología , Podocitos/metabolismo , Podocitos/patología , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Transducción de Señal , Factor de Transcripción STAT3/metabolismoRESUMEN
Autoimmunity is a normal physiological state that requires immunological homeostasis and surveillance, whereas necroptosis is a type of inflammatory cell death. When necroptosis occurs, various immune system cells must perform their appropriate duties to preserve immunological homeostasis, whether the consequence is expanding or limiting the inflammatory response and the pathological condition is cleared or progresses to the autoimmune disease stage. This article discusses necroptosis based on RIP homotypic interaction motif (RHIM) interaction under various physiological and pathological situations, with the RIPK1-RIPK3-MLKL necrosome serving as the regulatory core. In addition, the cell biology of necroptosis involved in autoimmunity and its application in autoimmune diseases were also reviewed.
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Enfermedades Autoinmunes , Autoinmunidad , Necroptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Humanos , Necroptosis/inmunología , Autoinmunidad/inmunología , Animales , Proteína Serina-Treonina Quinasas de Interacción con Receptores/inmunología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Enfermedades Autoinmunes/inmunología , Proteínas Quinasas/inmunología , Proteínas Quinasas/metabolismoRESUMEN
To achieve rapid preparation of hydrogels without using conventional chemical initiators, a stable suspension of eutectic gallium indium (EGaIn) liquid metal nanoparticles is explored by probe-sonicating the metal in an aqueous solution. Liquid metal suspension was sonicated to serve as a photo-initiator for acrylamide polymerization and produce hydrogels. The initiation effect comes from the fact that liquid metal suspension after sonication can produce a large number of free radicals when exposed to ultraviolet (UV) radiation, leading to initiation. The changes of liquid metal nanodroplets under UV light irradiation have been systematically investigated. Further, the liquid metal colloidal solutions were used to prepare hydrogels with the same transparency and adjustable mechanical properties as the samples initiated by commercial photo-initiators. This work shows the great application potential of liquid metal in the preparation of hydrogels and provides a new technical idea for the design of multifunctional hydrogels.
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OBJECTIVE: Systemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is still challenging due to the side effects of the different drugs used. Receptor-interacting protein kinase 1 (RIPK1) is a kinase involved in T cell homeostasis and autoinflammation. Although clinical trials have shown that RIPK1 inhibition exhibits significant efficacy in different autoimmune diseases, its role in SLE remains unclear. METHODS: MRL/lpr lupus-prone mice received RIPK1 inhibitor ZJU37 or vehicle intraperitoneally for 10 weeks. A BM12-induced chronic graft-versus-host-disease (cGVHD) lupus-like model was introduced in RIPK1 D138N mice or C57BL/6 mice. Nephritis, serum autoantibody levels, dysregulation of adaptive immune response and cytokines were compared in treated and untreated mice. RESULTS: ZJU37 alleviated the clinical features of the MRL/lpr mice including nephritis and anti-dsDNA antibody production. In addition, ZJU37 treatment reduced the proportion of double-negative T cells in the spleen and the cytokines of TNFα, IFN-γ, IL-6, IL-17 and IL-1ß in the serum. Moreover, RIPK1 D138N mice were able to prevent the cGVHD lupus-like model from SLE attack, manifesting as anti-dsDNA antibody production, the proliferation of germinal centre B cells, plasma cells, and T follicular helper cells as well as IgG and C3 deposits in kidneys. CONCLUSION: RIPK1 inhibition has a protective effect in the mouse model of SLE and can potentially become a new therapeutic target for SLE in humans.