RESUMO
Background: The association of Remnant cholesterol (RC) with renal function and its progression in patients with Type 2 diabetes (T2DM) related chronic kidney disease (CKD) remains unclear. Methods: 8,678 patients with T2DM-related CKD were included in cross-sectional analysis, and 6,165 patients were enrolled in longitudinal analysis and followed up for a median of 36.0 months. The outcomes were renal composite endpoint event and rapid progression of renal function. Results: 24.54% developed a renal composite endpoint event, and 27.64% rapid progression of renal function. RC levels above 0.56 mmol/L independently increased the risk of both renal composite endpoint (HR, 1.17; 95% CIs, 1.03-1.33) and rapid progression of renal function (OR, 1.17; 95% CIs, 1.01- 1.37). TG levels above 1.65 mmol/L only increased the risk of renal composite endpoint (HR, 1.16; 95% CIs, 1.02 -1.32). TC levels above 5.21 mmol/L increased the risk of renal composite endpoint (HR, 1.14; 95% CIs, 1.01-1.29) only in patients with proteinuria≥0.5g/d. Conversely, HDL-C levels below 1.20 mmol/L or above 1.84 mmol/L increased the risk of rapid progression of renal function (OR, 0.88; 95% CIs, 0.70 -0.99) in patients with proteinuria<0.5g/d (all P<0.05). Conclusion: In patients with T2DM-related CKD, RC was an independent risk factor for progression of renal function, and maintaining it below 0.56 mmol/L could reduce the risk of renal function progression.
Assuntos
Colesterol , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Progressão da Doença , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/metabolismo , Pessoa de Meia-Idade , Colesterol/sangue , Estudos Transversais , Idoso , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Taxa de Filtração Glomerular , Estudos Longitudinais , Seguimentos , Rim/fisiopatologia , Rim/metabolismo , Fatores de RiscoRESUMO
The development of temperature-sensitive sensors upgraded by poly(N-isopropylacrylamide) (PNIPAM) represents a significant stride in enhancing performance and tailoring thermoresponsiveness. In this study, an array of temperature-responsive electrochemical sensors modified with different PNIPAM-based copolymer films were fabricated via a "coating and grafting" two-step film-forming technique on screen-printed platinum electrodes (SPPEs). Chemical composition, grafting density, equilibrium swelling, surface wettability, surface morphology, amperometric response, cyclic voltammograms, and other properties were evaluated for the modified SPPEs, successively. The modified SPPEs exhibited significant changes in their properties depending on the preparation concentrations, but all the resulting sensors showed excellent stability and repeatability. The modified sensors demonstrated favorable sensitivity to hydrogen peroxide and L-ascorbic acid. Furthermore, notable temperature-induced variations in electrical signals were observed as the electrodes were subjected to temperature fluctuations above and below the lower critical solution temperature (LCST). The ability to reversibly respond to temperature variations, coupled with the tunability of PNIPAM's thermoresponsive properties, opens up new possibilities for the design of sensors that can adapt to changing environments and optimize their performance accordingly.
RESUMO
In order to study the multi-mode damage and fracture mechanisms of thin-walled tubular parts with cross inner ribs (longitudinal and transverse inner ribs, LTIRs), the Gurson-Tvergaard-Needleman (GTN) model was modified with a newly proposed stress state function. Thus, tension damage and shear damage were unified by the new stress state function, which was asymmetric with respect to stress triaxiality. Tension damage dominated the modification, which coupled with the shear damage variable, ensured the optimal prediction of fractures of thin-walled tubular parts with LTIRs by the modified GTN model. This included fractures occurring at the non-rib zone (NRZ), the longitudinal rib (LIR) and the interface between the transverse rib (TIR) and the NRZ. Among them, the stripping of material from the outer surface of the tubular part was mainly caused by the shearing of built-up material in front of the rollers under a large wall thickness reduction (ΔT). Shear and tension deformation were the causes of fractures occurring at the NRZ, while axial tension under a large TIR interval (l) mainly resulted in fractures on LIRs. Fractures at the interface between the TIR and NRZ were due to the shearing applied by rib grooves and radial tension during the formation of ribs. This study can provide guidance for the manufacturing of high-performance aluminum alloy thin-walled tubular components with complex inner ribs.
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Pseudouridine is the most abundant modified nucleoside found in non-coding RNA and is widely used in biological and pharmaceutical fields. However, current methods for pseudouridine production suffer from drawbacks such as complex procedures, low efficiency and high costs. This study presents a novel enzymatic cascade reaction route in Escherichia coli, enabling the whole-cell catalytic synthesis of pseudouridine from uridine. Initially, a metabolic pathway was established through plasmid-mediated overexpression of endogenous pseudouridine-5-phosphase glycosidase, ribokinase, and ribonucleoside hydrolase, resulting in the accumulation of pseudouridine. Subsequently, highly active endogenous ribonucleoside hydrolase was screened to enhance uridine hydrolysis and provide more precursors for pseudouridine synthesis. Furthermore, modifications were made to the substrates and products transport pathways to increase the pseudouridine yield while avoiding the accumulation of by-product uridine. The resulting recombinant strain Ψ-7 catalyzed the conversion of 30 g/L uridine into 27.24 g/L pseudouridine in 24 h, achieving a conversion rate of 90.8% and a production efficiency of 1.135 g/(L·h). These values represent the highest reported yield and production efficiency achieved by enzymatic catalysis methods to date.
Assuntos
Escherichia coli , Pseudouridina , Pseudouridina/genética , Pseudouridina/química , Pseudouridina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Uridina/genética , Uridina/química , Uridina/metabolismo , Catálise , Hidrolases/metabolismoRESUMO
BACKGROUND: This study aimed to investigate the expression and clinical value of microRNA miR-486-5p in diagnosing lumbar spinal stenosis (LSS) patients and predicting the clinical outcomes after minimally invasive spinal surgery (MISS) in LSS patients, and the correlation of miR-486-5p with inflammatory responses in LSS patients. METHODS: This study included 52 LSS patients, 46 patients with lumbar intervertebral disk herniation (LDH) and 42 healthy controls. Reverse transcription quantitative PCR was used to detect miR-486-5p expression. The ability of miR-486-5p to discriminate between different groups was evaluated by receiver-operating characteristic analysis. The visual analogue scale (VAS), Oswestry Disability Index (ODI) and Japanese Orthopaedic Association (JOA) scores at 6 months postoperatively were used to reflect the clinical outcomes of LSS patients. Enzyme-linked immunosorbent assay was used to measure the levels of inflammatory factor [interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α)]. The correlation of miR-486-5p with continuous variables in LSS patients was evaluated by the Pearson correlation coefficient. RESULTS: Expression of serum miR-486-5p was upregulated in LSS patients and had high diagnostic value to screen LSS patients. In addition, serum miR-486-5p could predict the 6-month clinical outcomes after MISS therapy in LSS patients. Moreover, serum miR-486-5p was found to be positively correlated with the levels of IL-1ß and TNF-α in patients with LSS. CONCLUSION: miR-486-5p, increased in LSS patients, can function as an indicator to diagnose LSS and a predictive indicator for the clinical outcomes after MISS therapy in LSS patients. In addition, miR-486-5p may regulate LSS progression by modulating inflammatory responses.
Assuntos
Vértebras Lombares , MicroRNAs , Procedimentos Cirúrgicos Minimamente Invasivos , Estenose Espinal , Humanos , Estenose Espinal/cirurgia , Estenose Espinal/genética , Estenose Espinal/sangue , MicroRNAs/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Vértebras Lombares/cirurgia , Idoso , Prognóstico , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adulto , Interleucina-1beta/sangue , Interleucina-1beta/genéticaRESUMO
Osteoporotic vertebral compression fracture (OVCF) is a serious complication of osteoporosis, and percutaneous vertebroplasty (PVP) is a major therapeutic method for OVCF. This study aimed to evaluate the clinical efficacy and postoperative complications of robot-assisted targeted PVP for the treatment of OVCF. The data from 202 OVCF patients were analyzed in this study, including 72 cases received traditional PVP (PVP group), 68 cases received robot-assisted PVP (R-PVP group), and 62 cases underwent robot-assisted PVP combined with targeted plugging (R-PVP + TP group). The fluoroscopic exposure conditions, operative duration, lengths of stay, postoperative bone cement leakage, refracture, Visual Analog Scale (VAS) score, and Oswestry Disability Index (ODI) score were obtained and compared between the three groups. The Kaplan-Meier method and logistic regression model were adopted to screen the risk factors related with postoperative refracture. R-PVP and R-PVP + TP group had significantly reduced fluoroscopic frequency and radiation dose, and reduced cement leakage compared with PVP group. R-PVP + TP not only showed more obvious advantages in these aspects, but also had a lower probability of postoperative refracture. In addition, BMD, fracture vertebral distribution, cement leakage, and surgery methods were independent related with refracture. All the results demonstrated robot assistance could improve the application of PVP in the treatment of OVCF, and robot-assisted PVP combined with targeted plugging showed significantly reduced fluoroscopic exposure, bone cement leakage, and rate of postoperative refracture. BMD, fracture vertebral distribution, cement leakage, and operation methods were identified as four risk factors for the onset of refracture after PVP.
Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Procedimentos Cirúrgicos Robóticos , Robótica , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Fraturas por Compressão/cirurgia , Fraturas por Compressão/complicações , Fraturas por Compressão/tratamento farmacológico , Cimentos Ósseos/uso terapêutico , Vertebroplastia/efeitos adversos , Vertebroplastia/métodos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/tratamento farmacológico , Cifoplastia/efeitos adversos , Cifoplastia/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/complicações , Fraturas por Osteoporose/tratamento farmacológico , Resultado do Tratamento , Fatores de RiscoRESUMO
BACKGROUND: The determination of glycosylated hemoglobin (HbA1c) is crucial for diabetes diagnosis and can provide more substantial results than the simple measurement of glycemia. While there is a lack of simple methods for the determination of HbA1c using a point-of-care test (POCT) compared to glycemia measurement. In particular, high-performance liquid chromatography (HPLC) is considered the current gold standard for determining HbA1c levels. However, commercial HPLC systems usually have some sort of disadvantages such as bulky size, high-cost and need for qualified operators. Therefore, there is an urgent demand to develop a portable, and fast HbA1c detection system consuming fewer reagents. RESULTS: We present a novel microchip that integrates a micromixer, passive injector, packed column and detection cell. The integrated microchip, in which all the microstructures were formed in the CNC machining center through micro-milling, is small in size (30 mm × 70 mm × 10 mm), and can withstand 1600 psi of liquid pressure. The integrated design is beneficial to reduce the band broadening caused by dead volume. Based on the microchip, a microchip liquid chromatography (LC) system was built and applied to the analysis of HbA1c. The separation conditions of HbA1c in blood calibrator samples were optimized using the microchip LC system. Samples containing four levels of HbA1c were completely separated within 2 min in optimal gradient conditions, with an inaccuracy (<3.2 %), a coefficient of variation (c.v. < 2.1 %) and a correlation coefficient (R2 = 0.993), indicating excellent separation efficiency and reproducibility. SIGNIFICANCE: The POCT of HbA1c is critical for diabetes diagnosis. The microchip chromatography system was developed for HbA1c determination, which contains an integrated microchip and works under a gradient elution. It surpasses existing chip technology in terms of separation performance and detection speed, providing a competitive advantage for POCT of HbA1c. It is considered one important step for realizing efficient portable systems for timely and accurate diabetes diagnosis.