880 research outputs found
A multi-factor analysis of revision in total hip replacement using the collarless-polished-tapered stems with different cups
Research on on-line assembly and calibration system based on laser scanning and optical fiber sensor
In order to improve the degree of assembly automation, an online assembly calibration system is designed based on laser scanning and optical fiber sensors. The optical fiber sensing module is used to obtain the stress field information, and the laser scanning module is used to obtain the point cloud information of the assembly structure. The position offset caused by the stress field can be compensated to the 3D point cloud for improving the target reconstruction accuracy. It consists of laser scanning module, optical fiber sensor module, demodulator, data analysis module, etc. Analyzing the structural characteristics of the module, the stress field distribution of the module structure is obtained through simulation analysis, and an appropriate optical fiber sensor network layout is constructed. When the force is applied in different directions, the stress field distribution of the assembly structure is simulated and analyzed. The results show that the magnitude and direction of the residual stress have an impact on the distribution of the stress field. At the same time, the stress field diffusion degree had been also analyzed in different strength conditions. In the calibration test of FBG sensor, the functional relationship between wavelength variation and stress is about 0.0011 nm/N. In the assembly test, the stress test trends of different FBGs were obtained, and the relative error was concentrated between 4.0% and 9.0%, which had good stability. After correcting the position of the point cloud for optical fiber sensing data, the position deviation between the test point and the digital analog has been significantly reduced, with the average value decreasing from 2.953. to 0.095 mm. It has good applicability in factories with large interference of working environment, and can improve the application field of intelligent assembly
Golgi-associated LC3 lipidation requires V-ATPase in noncanonical autophagy
Autophagy is an evolutionarily conserved catabolic process by which cells degrade intracellular proteins and organelles in the lysosomes. Canonical autophagy requires all autophagy proteins (ATGs), whereas noncanonical autophagy is activated by diverse agents in which some of the essential autophagy proteins are dispensable. How noncanonical autophagy is induced and/or inhibited is still largely unclear. In this study, we demonstrated that AMDE-1, a recently identified chemical that can induce canonical autophagy, was able to elicit noncanonical autophagy that is independent of the ULK1 (unc-51-like kinase 1) complex and the Beclin1 complex. AMDE-1-induced noncanonical autophagy could be specifically suppressed by various V-ATPase (vacuolar-type H(+)-ATPase) inhibitors, but not by disturbance of the lysosome function or the intracellular ion redistribution. Similar findings were applicable to a diverse group of stimuli that can induce noncanonical autophagy in a FIP200-independent manner. AMDE-1-induced LC3 lipidation was colocalized with the Golgi complex, and was inhibited by the disturbance of Golgi complex. The integrity of the Golgi complex was also required for multiple other agents to stimulate noncanonical LC3 lipidation. These results suggest that the Golgi complex may serve as a membrane platform for noncanonical autophagy where V-ATPase is a key player. V-ATPase inhibitors could be useful tools for studying noncanonical autophagy
Aberrant Brain Function in Active-Stage Ulcerative Colitis Patients: A Resting-State Functional MRI Study
Background: Patients with ulcerative colitis (UC) usually display cognitive impairments, such as memory loss, attention deficits, and declining executive functions, particularly during the active stage of the disease. However, the potential neurological mechanisms of these symptoms remain unclear.Method: Forty-one patients with mildly to moderately active UC, as well as 42 matched healthy controls, were recruited for an examination using psychological scales, cognitive function tests and resting-state functional magnetic resonance imaging (rs-fMRI). Seed points were identified via analysis of amplitude of low-frequency fluctuation (ALFF), and functional connectivity (FC) was calculated between these seed regions and other voxels in the whole brain. Correlation analyses were performed among clinical indexes, neuropsychological assessments and neuroimaging data.Result: Compared with the healthy controls, patients with UC exhibited lower ALFF values in the bilateral hippocampal/parahippocampal (HIPP/ParaHIPP) region and higher ALFF values in the left posterior cingulate cortex (PCC.L) and left middle frontal gyrus (MFG.L). With HIPP/ParaHIPP as the seed point, the strengths of the FC in the bilateral middle frontal gyri (MFG), anterior cingulate cortex (ACC), and left caudate nucleus (CAU.L) increased; using the PCC.L as the seed point, the strengths of the FC in the middle cingulate cortex (MCC) and the left angular gyrus (AUG.L) increased. These abnormal brain regions were mainly located in the limbic system. By analyzing the correlations between these brain regions and behavioral data, we observed a close correlation between decreased HIPP/ParaHIPP activity and memory loss; increased PCC activity and strength of FC with the AUG.L were related to dysfunction of executive function and attention network in patients with UC.Conclusion: Based on these results, the limbic lobe might be the core of the brain-gut axis (BGA) and play an important role in cognitive impairments, suggesting potential mechanisms for cognitive impairment in patients with UC in the active stage of the disease
Effects of ketogenic diet on the classification and functional composition of intestinal flora in children with mitochondrial epilepsy
The ketogenic diet (KD) has shown excellent performance in the treatment of refractory epilepsy, but how it works is not yet fully understood. Gut microbiota is associated with various neurological disorders through the brain-gut axis. Different dietary patterns have different effects on the composition and function of gut microbiota. Here, by analyzing fecal samples from some patients with mitochondrial epilepsy before and after KD treatment through 16SrRNA sequencing, we found that KD intervention reduced the abundance of Firmicutes in the patient’s gut, while the abundance of Bacteroidota increased in the KD group. LefSe analysis showed that Actinobacteriota, Phascolarctobacterium had significant advantages in the control group, while Bacteroides increased significantly after KD intervention, especially Bacteroides fragilis. Functional analysis showed that there were significant differences in 12 pathways in level 3. These changes suggest that KD can change the composition and diversity of the gut microbiota in patients and affect their function. Changes in specific bacterial groups in the gut may serve as biomarkers for the therapeutic effects of KD on epilepsy
A joint numerical study of multi-regime turbulent combustion
This article presents a joint numerical study on the Multi Regime Burner configuration. The burner design consists of three concentric inlet streams, which can be operated independently with different equivalence ratios, allowing the operation of stratified flames characterized by different combustion regimes, including premixed, non-premixed, and multi-regime flame zones. Simulations were performed on three LES solvers based on different numerical methods. Combustion kinetics were simplified by using tabulated or reduced chemistry methods. Finally, different turbulent combustion modeling strategies were employed, covering geometrical, statistical, and reactor based approaches. Due to this significant scattering of simulation parameters, a conclusion on specific combustion model performance is impossible. However, with ten numerical groups involved in the numerical simulations, a rough statistical analysis is conducted: the average and the standard deviation of the numerical simulation are computed and compared against experiments. This joint numerical study is therefore a partial illustration of the community's ability to model turbulent combustion. This exercise gives the average performance of current simulations and identifies physical phenomena not well captured today by most modeling strategies. Detailed comparisons between experimental and numerical data along radial profiles taken at different axial positions showed that the temperature field is fairly well captured up to 60 mm from the burner exit. The comparison reveals, however, significant discrepancies regarding CO mass fraction prediction. Three causes may explain this phenomenon. The first reason is the higher sensitivity of carbon monoxide to the simplification of detailed chemistry, especially when multiple combustion regimes are encountered. The second is the bias introduced by artificial thickening, which overestimates the species’ mass production rate. This behavior has been illustrated by manufacturing mean thickened turbulent flame brush from a random displacement of 1-D laminar flame solutions. The last one is the influence of the subgrid-scale flame wrinkling on the filtered chemical flame structure, which may be challenging to model.</p
A joint numerical study of multi-regime turbulent combustion
This article presents a joint numerical study on the Multi Regime Burner configuration. The burner design consists of three concentric inlet streams, which can be operated independently with different equivalence ratios, allowing the operation of stratified flames characterized by different combustion regimes, including premixed, non-premixed, and multi-regime flame zones. Simulations were performed on three LES solvers based on different numerical methods. Combustion kinetics were simplified by using tabulated or reduced chemistry methods. Finally, different turbulent combustion modeling strategies were employed, covering geometrical, statistical, and reactor based approaches. Due to this significant scattering of simulation parameters, a conclusion on specific combustion model performance is impossible. However, with ten numerical groups involved in the numerical simulations, a rough statistical analysis is conducted: the average and the standard deviation of the numerical simulation are computed and compared against experiments. This joint numerical study is therefore a partial illustration of the community's ability to model turbulent combustion. This exercise gives the average performance of current simulations and identifies physical phenomena not well captured today by most modeling strategies. Detailed comparisons between experimental and numerical data along radial profiles taken at different axial positions showed that the temperature field is fairly well captured up to 60 mm from the burner exit. The comparison reveals, however, significant discrepancies regarding CO mass fraction prediction. Three causes may explain this phenomenon. The first reason is the higher sensitivity of carbon monoxide to the simplification of detailed chemistry, especially when multiple combustion regimes are encountered. The second is the bias introduced by artificial thickening, which overestimates the species’ mass production rate. This behavior has been illustrated by manufacturing mean thickened turbulent flame brush from a random displacement of 1-D laminar flame solutions. The last one is the influence of the subgrid-scale flame wrinkling on the filtered chemical flame structure, which may be challenging to model.</p
SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate
共济失调是一类以运动协调性紊乱为主要特征的神经系统症状,临床表现包括步态不稳、丧失平衡、吞咽困难、眼球运动异常、肌张力受损等。厦门大学医学院神经科学研究所王鑫教授团队首次从轴突线粒体运输这一全新视角揭示了一类遗传性共济失调的发病机制,并发现抗癫痫药--丙戊酸大幅度减缓模型小鼠的疾病进程,具有较强的转化应用价值,有望为共济失调提供新的治疗手段。
该研究工作由王鑫教授指导完成,厦门大学医学院助理教授张洪峰和博士生洪育娟共同完成主要实验工作。Loss-of-function mutations in SNX14 cause autosomal recessive spinocerebellar ataxia 20, which is a form of early-onset cerebellar ataxia that lacks molecular mechanisms and mouse models. We generated Snx14-deficient mouse models and observed severe motor deficits and cell-autonomous Purkinje cell degeneration. SNX14 deficiency disrupted microtubule organization and mitochondrial transport in axons by destabilizing the microtubule-severing enzyme spastin, which is implicated in dominant hereditary spastic paraplegia with cerebellar ataxia, and compromised axonal integrity and mitochondrial function. Axonal transport disruption and mitochondrial dysfunction further led to degeneration of high-energy-demanding Purkinje cells, which resulted in the pathogenesis of cerebellar ataxia. The antiepileptic drug valproate ameliorated motor deficits and cerebellar degeneration in Snx14-deficient mice via the restoration of mitochondrial transport and function in Purkinje cells. Our study revealed an unprecedented role for SNX14-dependent axonal transport in cerebellar ataxia, demonstrated the convergence of SNX14 and spastin in mitochondrial dysfunction, and suggests valproate as a potential therapeutic agent.We thank Tim Huang for helpful discussion, Wei Mo for sharing mouse lines, Li Zhong
for sharing reagents, Aidong Han, Luming Yao, Caiming Wu, Mingxia Zhu, Qingfeng
Liu, Lin Zhu, Shuo Zhang, Haiping Zheng, and Changchuan Xie for technical
assistance, and Cui Li for providing bioinformatics software. We also thank Novogene
Co., Ltd. and PTM Biolab Co., Ltd. for technical assistance in the transcriptomic and
proteomic analyses, respectively.
厦门大学医学院许华曦、赵颖俊、张云武、杜丹教授在研究过程中给予大力帮助和支持。本研究工作得到国家重点研发计划项目、国家自然科学基金、福建省自然科学基金、厦门大学校长基金的资助和支持
The Effect of Plasma Triglyceride-Lowering Therapy on the Evolution of Organ Function in Early Hypertriglyceridemia-Induced Acute Pancreatitis Patients With Worrisome Features (PERFORM Study): Rationale and Design of a Multicenter, Prospective, Observational, Cohort Study
Background: Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease with multiple etiologies. The prevalence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has been increasing in recent years. It is reported that early triglyceride (TG) levels were associated with the severity of the disease, and TG- lowering therapies, including medical treatment and blood purification, may impact the clinical outcomes. However, there is no consensus regarding the optimal TG-lowering therapy, and clinical practice varies greatly among different centers. Our objective is to evaluate the TG-lowering effects of different therapies and their impact on clinical outcomes in HTG-AP patients with worrisome features. Methods: This is a multicenter, observational, prospective cohort study. A total of approximately 300 patients with HTG-AP with worrisome features are planned to be enrolled. The primary objective of the study is to evaluate the relationship between TG decline and the evolution of organ failure, and patients will be dichotomized depending on the rate of TG decline. The primary outcome is organ failure (OF) free days to 14 days after enrollment. Secondary outcomes include new-onset organ failure, new-onset multiple-organ failure (MOF), new-onset persistent organ failure (POF), new receipt of organ support, requirement of ICU admission, ICU free days to day 14, hospital free days to day 14, 60-day mortality, AP severity grade (Based on the Revised Atlanta Classification), and incidence of systemic and local complications. Generalized linear model (GLM), Fine and Gray competing risk regression, and propensity score matching will be used for statistical analysis. Discussion: Results of this study will reveal the current practice of TG-lowering therapy in HTG-AP and provide necessary data for future trials
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