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Beryllium-containing sludge (BCS) is a byproduct of the physicochemical treatment of beryllium smelting wastewater. The pollutant element beryllium within BCS is highly unstable and extremely toxic, characterized by its small ionic radius and low charge density, resulting in a high risk of leaching and migration. This study is the first to investigate the leaching behavior, influencing mechanisms, and kinetic processes of beryllium in BCS under various environmental conditions. The results indicate that, under national standard conditions, beryllium exhibits a rapid leaching phase within the first 5 h, which then stabilizes after 10 h, with the total leached content significantly exceeding the leaching toxicity identification standards. Under mildly acidic (pH ≤ 5) or highly alkaline (pH = 14) conditions, beryllium demonstrates pronounced leaching and migration behaviors. Notably, in acidic conditions, the leaching rate exceeds 80% within 5 h. Combining the treatment process of beryllium-containing wastewater with analytical methods such as SEM, XPS, ToF-SIMS, and FTIR, it is revealed that due to the heterogeneous nature of BCS, the particle aggregates dissociate over time under acidic conditions. The particle surfaces become increasingly rough, leading to dissolution and the emergence of more reactive sites, resulting in a high proportion of beryllium leaching. Under these conditions, the gradual reaction of Be(OH)2 in BCS to form soluble Be2+ and its hydrolytic complexes is identified as the primary mechanism for extensive beryllium migration. The process encounters minimal diffusion resistance and is classified as reaction-controlled. In acidic conditions with pH = 4, the leaching rate of beryllium significantly increases with rising temperature. The leaching kinetics equation is [(1-x)-0.44]=e(18.26-53050RT)·t, with an apparent activation energy of 53.05 kJ mol-1.
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Background: Intervertebral disc degeneration (IVDD) is the main cause of low back pain (LBP), but the specific regulatory factors, pathways and specific molecular mechanisms remain unclear. Methods: We identified and quantitatively analyzed Pfirrmann Grade II (n=3) and Pfirrmann Grade IV (n=3) pulposus samples via MRI. The differential abundance of proteins in the samples was determined and quantitatively analyzed by relative and absolute quantitative analysis of the isotope marker levels combined with the liquid chromatography-tandem mass spectrometry (LCâMSMS/MS). Results: A total of 70 proteins (30 significantly increased proteins (> 1.2-fold change) and 40 significantly decreased proteins (< 0.8-fold change)) showed different levels among the groups. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO) enrichment analyses and Western blot analysis showed that CYCS, RAC1, and PSMD14 may play important roles in IVDD and that EpsteinâBarr virus infection, viral myocarditis, colorectal cancer, nonalcoholic fatty liver disease (NAFLD) and amyotrophic lateral sclerosis (ALS) are the main pathways involved in IVDD. Conclusion: CYCS, RAC1 and PSMD14 may play important roles in IVDD, and EpsteinâBarr virus infection, viral myocarditis, colorectal cancer, NAFLD and ALS may be the main pathways involved in IVDD.
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Appropriate Ca2+ concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca2+ signal, serves significant roles in physiological function of pancreatic ß cells. To maintaining ER homeostasis, Ca2+ movement across the ER membrane is always accompanied by a simultaneous K+ flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca2+ influx. Meanwhile, the specific function of KCNH6 in pancreatic ß-cells remains unclear. In this study, we found that KCNH6 exhibited mainly ER localization and Kcnh6 ß-cell-specific knockout (ßKO) mice suffered from abnormal glucose tolerance and impaired insulin secretion in adulthood. ER Ca2+ store was overloaded in islets of ßKO mice, which contributed to ER stress and ER stress-induced apoptosis in ß cells. Next, we verified that ethanol treatment induced increases in ER Ca2+ store and apoptosis in pancreatic ß cells, whereas adenovirus-mediated KCNH6 overexpression in islets attenuated ethanol-induced ER stress and apoptosis. In addition, tail-vein injections of KCNH6 lentivirus rescued KCNH6 expression in ßKO mice, restored ER Ca2+ overload and attenuated ER stress in ß cells, which further confirms that KCNH6 protects islets from ER stress and apoptosis. These data suggest that KCNH6 on the ER membrane may help to stabilize intracellular ER Ca2+ stores and protect ß cells from ER stress and apoptosis. In conclusion, our study reveals the protective potential of KCNH6-targeting drugs in ER stress-induced diabetes.
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Diabetes Mellitus , Células Secretoras de Insulina , Camundongos , Animais , Secreção de Insulina , Diabetes Mellitus/metabolismo , Células Secretoras de Insulina/metabolismo , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Cálcio/metabolismo , Etanol , Insulina/metabolismoRESUMO
OBJECTIVE: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of KATP depolarization and K+ repolarization. It is well known that glucose stimulates insulin secretion from pancreatic ß-cells, mainly via the KATP depolarization channel, but whether other nutrients directly regulate the repolarization K+ channel to promote insulin secretion is unknown. METHODS: We used a system involving CRISPR-Cas9-mediated knockout of all 83 K+ channels and scRNA-seq in a pancreatic ß cell line to identify genes associated with insulin secretion. RESULTS: The expression levels of insulin genes were significantly increased after all-K+ channel knockout. Furthermore, Kcnb1 and Kcnh6 were the two most important repolarization K+ channels for the increase in high-glucose-dependent insulin secretion that occurred upon application of specific inhibitors of the channels. Kcnh6 currents, but not Kcnb1 currents, were reduced by one of the amino acids, lysine, in both transfected cells, primary cells and mice with ß-cell-specific deletion of Kcnh6. CONCLUSIONS: Our function-related CRISPR screen with scRNA-seq identifies Kcnh6 as a lysine-specific channel.
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Insulina , Lisina , Camundongos , Animais , Secreção de Insulina , Lisina/metabolismo , Insulina/metabolismo , Glucose/farmacologia , Trifosfato de Adenosina/metabolismoRESUMO
Due to the intervention of human activities, the background values of riverbed sediment exhibit spatiotemporal variability, which can affect the accuracy of risk assessment results. Using risk assessment that do not rely on background values is an executable alternative to avoid such problems. In this study, a relative pollution level assessment (RPLA) method which was based on the statistical results of relevant literatures was proposed. This method includes a four-step data processing procedure to extract the evaluation indexes of relative pollution degree of pollutants in environment and a series of relative pollution status assessment methods to evaluate the overall relative pollution level and regional difference of world-wide rivers. To demonstrate how to use RPLA method, 310 relevant literatures covering world-wide rivers were selected. And the ambient background value (xÌ ), the world-wide threshold values (WWTV) and the relative pollution grades (LEVEL I â¼ IV) of 9 target metals (Cr, Ni, Cu, Zn, As, Cd, Pb, Sb and Tl) in riverbed surface sediments of world-wide rivers were extracted and used for evaluation. Moreover, the stability and applicability of RPLA method were evaluated. Results show that the evaluation results of RPLA method are robust and comparable with traditional evaluation method.
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To explore the groundwater recharge rate and soybean growth dynamics under different groundwater depths, we conducted a field experiment with four groundwater depth treatments (1 m, D1; 2 m, D2; 3 m, D3; 4 m, D4) through the groundwater simulation system in 2021 and 2022 and explored the relationships between groundwater depth and groundwater recharge, irrigation, growth dynamics of soybean plants, and yield. We used the Logistic regression model to simulate the dynamics of soybean growth indices, including plant height, leaf area index, and dry matter accumulation. The results showed that compared with D1 treatment, the amount of groundwater recharge under D2, D3, and D4 treatments decreased by 81.1%, 96.8%, 97.5% and 80.7%, 96.7%, 97.3% in the two years, respectively. The groundwater in D1 treatment could meet water needs of soybean throughout the whole growth period, except that irrigation was needed in the sowing stage. The amount of irrigation under D1 treatment was decreased by 91.7%, 93.0%, 94.2%, and 90.9%, 92.9%, 94.0% in the two years, respectively, compared with D2, D3, D4 treatments. Among the four treatments, D1 treatment took the shortest time for entering the rapid growth stage and reach the maximum growth rate, which had the highest maximum growth rate. At the mature stage of soybean, the dry matter distribution ratio of stem in D1 treatment was the highest. D1 treatment promoted the translocation of post-flowering assimilates in soybean, and its post-flowering assimilate contribution to seeds increased by 15.5%, 16.2%, 32.6% and 45.5%, 48.7%, 63.3% in the two years, respectively, compared with D2, D3, D4 treatments. D1 treatment had the highest plant height, leaf area index, and dry matter accumulation, follo-wed by D4 treatment, while D3 treatment had the lowest. Soybean yield, number of pods per plant, number of grains per plant, and 100-grain weight all decreased and then increased with increasing groundwater depth, following an order of D1>D4>D2>D3. Soybean yield was significantly positively correlated with groundwater recharge, which was positively correlated with plant height, leaf area index, and dry matter accumulation. Our results indicated that the D1 treatment with adequate groundwater recharge increased plant height, leaf area index, and dry matter accumulation, coordinated the distribution and translocation of dry matter among all plant parts in the late soybean growth period, and ultimately achieved the highest yield. When groundwater depth was deep (D4), groundwater recharge was small. In such case, the growth and development status and yield of soybean could also reach a high level if there was sufficient water supply.
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Glycine max , Água Subterrânea , Abastecimento de Água , China , Simulação por ComputadorRESUMO
OBJECTIVE: To investigate the clinical efficacy of acrylic cement (PMMA) mixed with calcium sulfate combined with percutaneous kyphoplasty (PKP) in the treatment of osteoporotic fracture (OVCF). METHODS: The clinical data of 191 patients with OVCF treated with PKP from January 2020 to March 2021 were retrospectively analyzed. Among them, 82 patients with 94 vertebral bodies were treated with PMMA mixed with calcium sulfate as the observation group, and 109 patients with 125 vertebral bodies were treated with pure PMMA as the control group. Among the 82 patients in the observation group, there were 16 males and 66 females, with a mean age of (75.35±11.22) years old, including 36 thoracic vertebrae and 58 lumbar vertebrae. In the control group, there were 109 patients, 22 males and 87 females, with an average age of (74.51±9.21) years old, including 63 thoracic vertebrae and 62 lumbar vertebrae. The visual analog scale (VAS) before operation and 1 day, 3 months and 1 year after operation were calculated. The Oswestry disability index (ODI), Cobb's angle, vertebral body height and the probability of postoperative bone cement leakage were used to analyze the efficacy of the two groups. RESULTS: All the patients were followed up for more than one year. Compared with the control group, there was no significant difference in operation time, bleeding volume and bone cement injection volume between the two groups(P>0.05), while the leakage rate of bone cement was significantly lower in the observation group (P<0.05). In addition, there was no significant difference in VAS, ODI, Cobb angle, and vertebral body height between the two groups before operation, and 1 day, 3 months, and 1 year after operation (P>0.05), but each index was improved compared with that before operation (P<0.05). CONCLUSION: PMMA mixed with calcium sulfate has equivalent efficacy in treating OVCF than PMMA alone, but can effectively reduce the probability of cement leakage.
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Cifoplastia , Fraturas por Osteoporose , Feminino , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Polimetil Metacrilato , Sulfato de Cálcio/uso terapêutico , Fraturas por Osteoporose/cirurgia , Cimentos Ósseos/uso terapêutico , Estudos Retrospectivos , Vértebras Lombares/cirurgiaRESUMO
Background: At present, the phenomenon of patients with mental disorders not seeking mental help is very serious, and the mental help-seeking attitude is the central structure of the help process. However, there is no consensus on which patient-reported outcome measure (PROM) should be used to assess mental help-seeking attitudes. Objective: The systematic review aims to critically appraise, compare, and summarize the measurement quality of the all-available PROMs about mental help-seeking attitudes to provide evidence-based guidance and reference for clinical researchers. Methods: A systematic search was conducted in 9 databases (PubMed, Embase, Web of Science, Medline, APA, CINAHL, Sinomed, CNKI, and WanFang) since the establishment of the database until November 30, 2022 to identify articles on the PROMs of mental help-seeking attitudes. We used the COSMIN guidelines to evaluate the methodological quality and measurement properties of all-available PROMs, and a modified Grading, Recommendation, Assessment, Development, and Evaluation (GRADE) system to evaluate the level of evidence supporting each rating. Finally, the recommendation level is given according to the overall quality of each PROM. Results: We identified 29 studies representing 13 PROMs out of 2,828 screening studies. The overall quality of the included PROMs varied, with 6 rated as class B, 6 as class C, and only the Mental Help Seeking Attitudes Scale (MHSAS) as class A. Conclusion: The measurement characteristics of MHSAS have been the most comprehensive evaluation, and it has good reliability and validity, and high feasibility for clinical application, so it can be temporarily recommended for use, but the above conclusions still need to be supported by more high-quality evidence.
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Background: The most common disorder of the intracellular cobalamin metabolism pathway is the combined methylmalonic acidemia and homocysteinemia, cblC type (cblC). There is a variation in its clinical spectrum ranging from severe neonatal-onset forms that are highly fatal to later-onset forms which are milder. In this study, the first case of an asymptomatic Chinese woman with a defect in congenital cobalamin (cblC type) metabolism at prenatal diagnosis due to elevated homocysteine level is identified. Case presentation: The proband, a male child born to a 29-year-old G1P0 mother, admitted to local hospital with feeding disorder, intellectual disability, seizures, microcephaly, as well as heterophthalmos. The level of the urine methylmalonic was elevated. Equally found were increased blood propionylcarnitine (C3) and propionylcarnitine/free carnitine ratio (C3/C0) and decreased methionine levels. The plasma total homocysteine level was elevated at 101.04 µmol/L (normal < 15 µmol/L). The clinical diagnosis of combined methylmalonic acidemia and homocysteinemia was supported. Four years later, the mother of the boy married again and came to us for prenatal diagnosis exactly 15 weeks after her last menstrual period. Subsequently, there is an increase in the amniotic fluid methylmalonate. The level of the amniotic fluid total homocysteine was marginally high. A considerably elevated amniotic fluid C3 was equally observed. In addition, there is a respective significant increase in the plasma and urine total homocysteine at 31.96 and 39.35 µmol/L. After the sequencing of MMACHC genes, it is found that the boy, a proband carried a homozygous mutation of the MMACHC at c.658_660delAAG. While the boy's mother, she carries two mutations in MMACHC: c.658_660delAAG and c.617G>A. The fetus is a carrier of the MMACHC gene. Following the administration of routine treatment, the mother remained symptom-free in the course of pregnancy, and she gave birth to a healthy boy. Conclusion: Variable and nonspecific symptoms characterized the cblC type of methylmalonic acidemia combined with homocysteinemia. Both biochemical assays and mutation analysis are recommended as crucial complementary techniques.
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The release of highly toxic beryllium in sludge (BCS) produced by physico-chemical treatment of beryllium-containing wastewater from Be smelting production has become a growing concern with the widespread use of Be in the defense industry. This work investigated the potential mobility of Be in BCS. The toxicity characteristic leaching procedure (TCLP) of BCS showed that the amount of leached Be was up to 202 mg L-1, which exceeded the regulated limit by nearly 10,000 times. The chemical fractionation analysis further revealed that the excessive amount of Be leached from BCS was contributed to the high content of acid-soluble fraction and reducible fraction of Be, which accounted for over 70% of the Be content. The results obtained from mineralogical automatic analyzer (MLA) showed that gypsum (23.23%) and epidote (19.55%) were the two major mineralogical phases of BCS. Both were small and loosely structured agglomerated particles with a D50 of 6.61 µm and 3.31 µm. ToF-SIMS results revealed that the Be distribution on the surface of BCS particles was relatively dispersed, with no aggregation or encapsulation. Be co-precipitated with gypsum and chlorite in the form of unstable Be(OH)2, which attached to the surface of these small particles. The unstable state of Be and the small size, loose structure and high liberation of the host material phases are the main reasons for the high leaching mobility of Be. The results of the risk assessment indicated that BCS posed an extremely high potential ecological risk, with Be being the most significant contributor.
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Metais Pesados , Esgotos , Esgotos/química , Águas Residuárias , Metais Pesados/análise , Berílio , Sulfato de CálcioRESUMO
OBJECTIVE: To explore the clinical outcomes of anteromedial combined with lateral locking plate for complex proximal humeral fractures in the eldery. METHODS: From June 2018 to October 2020, 30 patients who underwent surgical treatment for Neer grade 3 to 4 proximal humeral fractures, including 8 males and 22 females, aged from 51 to 78 years old with an average of (61.5±7.5) years old. Of them, 15 patients had fractures fixed with anteromedial combined with lateral locking plate(ALLP group), whereas 15 received internal fixation with proximal humerus locking plate only(PHLP group). The clinical data, simple shoulder test (SST), humeral head height loss, varus angle and shoulder range of motion were compared between the two groups. RESULTS: All fractures were healed. The follow-up time ranged from 12 to 24 months, with an average of(14.3±2.9) months. The operation time of ALLP group was longer than that of PHLP group (P<0.05). There was no significant difference in intraoperative blood loss between the two groups (P>0.05). There was no significant difference in SST score between the two groups at 1, 3 and 12 months after operation (P>0.05). In terms of radiographic measurement, there was no significant difference in humeral head height loss and varus angle between the two groups at 1 and 3 months after operation (P>0.05). At 12 months after operation, the height loss and varus angle of humeral head in ALLP group were lower than those in PHLP group (P<0.05). In shoulder range of motion, the range of forward elevation in ALLP group was larger than that in PHLP group 1 year after operation(P<0.05). There was no significant difference in external rotation between the two groups. CONCLUSION: Anteromedial combined with lateral locking plate in the treatment of complex proximal humeral fractures in the elderly can increase the stability of the medial column and obtain a good fracture prognosis. But there are also disadvantages such as longer operation time, so it should be individualized according to the fracture type of the patient.
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Fraturas do Úmero , Fraturas do Ombro , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Fixação Interna de Fraturas , Ombro , Cabeça do Úmero , Placas Ósseas , Fraturas do Úmero/cirurgiaRESUMO
Graves' ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves' disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves' ophthalmopathy are still unclear. We aimed to isolate exosomes and analyze the different exosomal proteins. Tear fluids were collected from twenty-four GO patients, twenty-four GD patients and sixteen control subjects. The numbers of tear exosomes were assayed using nanoparticle tracking analysis. A Luminex 200 kit and ELISA kit were used to confirm the different cytokine concentrations in serum. Extraocular muscle from GO patients and controls was extracted, and western blotting was used to assay the levels of Caspase-3 and complement C4A. Our study demonstrated that the number of tear exosomes differ from GD patients and control. The expression levels of cytokines, including IL-1 and IL-18, were significantly increased in the tear exosomes and serum from GO patients compared with GD patients and controls. The levels of the exosomal proteins Caspase-3, complement C4A and APOA-IV were significantly increased in GO patients compared to GD patients and controls. Orbital fibroblasts from GO patients showed significantly higher levels of Caspase-3 and complement C4A than those from controls. The levels of serum APOA-IV in GO patients were significantly higher than those in GD patients and controls. Specific proteins showed elevated expression in tear exosomes from GO patients, indicating that they may play important roles in GO pathogenesis.
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Exossomos , Oftalmopatia de Graves , Lágrimas , Humanos , Biomarcadores/análise , Caspase 3/análise , Complemento C4a/análise , Citocinas/análise , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/metabolismo , Qualidade de Vida , Lágrimas/química , Lágrimas/metabolismo , Exossomos/química , Exossomos/metabolismoRESUMO
Mutations in KCNH6 has been proved to cause hypoinsulinemia and diabetes in human and mice. Cisapride is a stomach-intestinal motility drug used to treat gastrointestinal dysfunction. Cisapride has been reported to be a potential inhibitor of the KCNH family, but it remained unclear whether cisapride inhibited KCNH6. Here, we discovered the role of cisapride on glucose metabolism, focusing on the KCNH6 potassium channel protein. Cisapride reduced blood glucose level and increased serum insulin secretion in wild-type (WT) mice fed standard normal chow/a high-fat diet or in db/db mice, especially when combined with tolbutamide. This effect was much stronger after 4 weeks of intraperitoneal injection. Whole-cell patch-clamp showed that cisapride inhibited KCNH6 currents in transfected HEK293 cells in a concentration-dependent manner. Cisapride induced an increased insulin secretion through the disruption of intracellular calcium homeostasis in a rat pancreatic ß-cell line, INS-1E. Further experiments revealed that cisapride did not decrease blood glucose or increase serum insulin in KCNH6 ß-cell knockout (Kcnh6-ß-KO) mice when compared with WT mice. Cisapride also ameliorated glucose-stimulated insulin secretion (GSIS) in response to high glucose in WT but not Kcnh6-ß-KO mice. Thus, our data reveal a novel way for the effect of KCNH6 in cisapride-induced hypoglycemia.
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Glicemia , Hipoglicemia , Humanos , Ratos , Camundongos , Animais , Glicemia/metabolismo , Cisaprida , Insulina/metabolismo , Canais de Potássio , Células HEK293 , Glucose/metabolismo , Canais de Potássio Éter-A-Go-Go/genética , Canais de Potássio Éter-A-Go-Go/metabolismoRESUMO
The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved in the regulation of genome stability and transcription. Telomeric-repeat containing RNA (TERRA) is capable of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures at TERRA target and non-target sites in mouse embryonic stem cells. TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation. G4 ChIP-seq reveals that G4 abundance decreases at accessible chromatin regions, particularly at transcription start sites (TSS) after TERRA depletion; such G4 reduction at TSS is associated with elevated ATRX occupancy and differentially expressed genes. Loss of ATRX alleviates the effect of gene repression caused by TERRA depletion. Immunostaining analyses demonstrate that knockdown of TERRA diminishes DNA G4 signals, whereas silencing ATRX elevates G4 formation. Our results uncover an epigenetic regulation by TERRA that sequesters ATRX and preserves DNA G4 structures.
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Quadruplex G , RNA Longo não Codificante , Animais , Camundongos , Cromatina/genética , Epigênese Genética , Telômero/genética , Telômero/metabolismo , RNA Longo não Codificante/metabolismo , DNA , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/metabolismoRESUMO
KCNH6 has been proven to affect glucose metabolism and insulin secretion both in humans and mice. Further study revealed that Kcnh6 knockout (KO) mice showed impaired glucose tolerance. However, the precise function of KCNH6 in the liver remains unknown. Mitochondria have been suggested to maintain intracellular Ca2+ homeostasis; ROS generation and defective mitochondria can cause glucose metabolism disorders, including type 2 diabetes (T2D). Here, we found that Kcnh6 attenuated glucose metabolism disorders by decreasing PEPCK and G6pase abundance and induced Glut2 and IRS2 expression. Overexpression of Kcnh6 increased hepatic glucose uptake and glycogen synthesis. Kcnh6 attenuated intracellular and mitochondrial calcium levels in primary hepatocytes and reduced intracellular ROS and mitochondrial superoxide production. Kcnh6 suppressed oxidative stress by inhibiting mitochondrial pathway activation and NADPH oxidase expression. Experiments demonstrated that Kcnh6 expression improved hepatic glucose metabolism disorder through the c-Jun N-terminal kinase and p38MAPK signaling pathways. These results were confirmed by experiments evaluating the extent to which forced Kcnh6 expression rescued metabolic disorder in KO mice. In conclusion, KCNH6 enhanced hepatic glucose metabolism by regulating mitochondrial Ca2+ levels and inhibiting oxidative stress. As liver glucose metabolism is key to T2D, understanding KCNH6 functions may provide new insights into the causes of diabetes.
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Diabetes Mellitus Tipo 2 , Canais de Potássio Éter-A-Go-Go , Glucose , Mitocôndrias , Estresse Oxidativo , Animais , Cálcio/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Canais de Potássio Éter-A-Go-Go/metabolismo , Glucose/metabolismo , Glicogênio/metabolismo , Humanos , Insulina/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismoRESUMO
Objective: Chronic low back pain (CLBP) after percutaneous endoscopic transforaminal discectomy (PTED) surgery may be caused by preoperative lumbar microinstability (MI). However, there is a paucity of research on the relationship between lumbar microinstability and chronic low back pain. The purpose of this article is to assess the preoperative radiographic characteristics of patients and evaluate the effects of lumbar microinstability on patient-reported outcomes among single-level lumbar disc herniation (LDH) patients who underwent PTED. Methods: This study retrospectively reviewed the radiographic characteristics of a consecutive series of 127 patients with low back pain and leg pain caused by single-level LDH underwent PTED from August 2018 to March 2021. They were divided into three groups according to the radiographic parameters: the stable group (Group S), the dysfunctional group (Group D), and the microinstability group (Group M). The visual analogue scale (VAS) scores for leg and low back pain and Oswestry Disability Index (ODI) were evaluated preoperatively and postoperatively. Logistic regression analysis was used to identify independent risk factors for CLBP. Results: Compared with Group D and Group S, Group M had the highest ODI scores (P < 0.01) and VAS scores (low back pain) (P < 0.01) after 1 year, while there were no significant differences in the VAS scores for leg pain at different time points after surgery (P > 0.05). In addition, the logistic regression analysis results regarding CLBP revealed that muscle fatty degeneration on MRI (95% CI, 1.20-8.51, P = 0.02), and facet tropism (95% CI, 1.39 -11.37, P = 0.01) may be independent risk factors. Conclusion: Patients with lumbar microinstability may have CLBP after PTED, so patients with lumbar microinstability may need to take internal fixation surgery to solve their symptoms.
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Pyrite affects the adsorption of tylosin (TYL) due to their coexistence in the lake system. As well as the reactivity groups of S-S-H, S-OH, and Fe-OH, defects also have the possibilities to influence the adsorption of organic contaminants. However, the role of these active sites in antibiotic adsorption on pyrite has not been deeply studied. Besides, pH, N, P, dissolved oxygen, and dissolved organic matter (DOM) fluctuate greatly in lake at different seasons, which may change the surface characteristics of pyrite. Hence, the adsorption of TYL on natural pyrite considered solution chemistry and DOM in lake water was explored in this study. The fitting results of the kinetic and isotherm models showed that the adsorption included physical and chemical interactions. The neutral initial solution pH was conductive to TYL adsorption owing to the combined result of electrostatic and cover of Fe-oxyhydroxide. NO3- and NH4+ had no effect on TYL adsorption, whereas H2PO4- promoted adsorption by forming flocculent Fe(H2PO4)3 precipitates. The dissolved oxygen increased adsorption. This is due to the co-promotion of the pyrite oxidation by oxygen and sulfur defects. The Fe(II)-DOM complex caused by pyrite surface oxidation reduced the concentration of TYL in solution by gathering. Except for the surface charge, reactivity groups on pyrite significantly influenced the adsorption of TYL. The bond fracture of S-S resulted in sulfur defects that contributed to pyrite oxidation. As a result, Fe(III)/Fe(II) on the surface of pyrite or in solution produced a complex Fe(III)/Fe(II) with anions and DOM. In addition, Fe(III)-S on sulfur defects interacted with the O-H of TYL through hydrogen bonding. Furthermore, the Fe-O-C bond is formed by the interaction of C-OH on TYL and Fe(III) (hydr)oxides on the surface of pyrite. The study provides a deep insight into the effect of pyrite surface active sites on amphoteric antibiotic adsorption. It helps to understand antibiotic migration and interactions with widespread pyrite in the real environment.
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Óxidos , Tilosina , Matéria Orgânica Dissolvida , Compostos Férricos , Enxofre , Antibacterianos , Oxigênio , Compostos Ferrosos , ÁguaRESUMO
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important target for vaccine and drug development. However, the rapid emergence of variant strains with mutated S proteins has rendered many treatments ineffective. Cleavage of the S protein by host proteases is essential for viral infection. Here, we discovered that the S protein contains two previously unidentified Cathepsin L (CTSL) cleavage sites (CS-1 and CS-2). Both sites are highly conserved among all known SARS-CoV-2 variants. Our structural studies revealed that CTSL cleavage promoted S to adopt receptor-binding domain (RBD) "up" activated conformations, facilitating receptor-binding and membrane fusion. We confirmed that CTSL cleavage is essential during infection of all emerged SARS-CoV-2 variants (including the recently emerged Omicron variant) by pseudovirus (PsV) infection experiment. Furthermore, we found CTSL-specific inhibitors not only blocked infection of PsV/live virus in cells but also reduced live virus infection of ex vivo lung tissues of both human donors and human ACE2-transgenic mice. Finally, we showed that two CTSL-specific inhibitors exhibited excellent In vivo effects to prevent live virus infection in human ACE2-transgenic mice. Our work demonstrated that inhibition of CTSL cleavage of SARS-CoV-2 S protein is a promising approach for the development of future mutation-resistant therapy.
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Antimonene (Sb) is a novel kind of two-dimensional (2D) material that is predicted to be promising for various applications, such as water splitting and semiconductor devices. Several methods have been reported to prepare Sb nanoflakes/nanofilms; however, it is still relatively difficult to prepare Sb nanofilms. In this work, a method of low-power magnetron sputtering deposition was used for the preparation of Sb nanofilms with lateral dimensions on the centimeter scale and controllable film thickness. It was found that the control of the deposition temperature is important for the final crystalline structure of the nanofilms. Furthermore, the application of the nanofilms as a catalyst for water splitting (hydrogen evolution reaction (HER) and oxygen evolution reaction (OER)) was demonstrated.