Regulated dynamic subcellular GLUT4 localization revealed by proximal proteome mapping in human muscle cells.

Regulation of glucose transport, which is central for control of whole-body metabolism, is determined by the amount of GLUT4 glucose transporter (also known as SLC2A4) in the plasma membrane (PM) of fat and muscle cells. Physiologic signals [such as activated insulin receptor or AMP-activated protein kinase (AMPK)] increase PM GLUT4. Here, we show that the distribution of GLUT4 between the PM and interior of human muscle cells is dynamically maintained, and that AMPK promotes PM redistribution of GLUT4 by regulating exocytosis and endocytosis. Stimulation of exocytosis by AMPK is mediated by Rab10 and the Rab GTPase-activating protein TBC1D4. APEX2 proximity mapping reveals that GLUT4 traverses both PM-proximal and PM-distal compartments in unstimulated muscle cells, further supporting retention of GLUT4 by a constitutive retrieval mechanism. AMPK-stimulated translocation involves GLUT4 redistribution among the same compartments traversed in unstimulated cells, with a significant recruitment of GLUT4 from the Golgi and trans-Golgi network compartments. Our comprehensive proximal protein mapping provides an integrated, high-density, whole-cell accounting of the localization of GLUT4 at a resolution of ∼20 nm that serves as a structural framework for understanding the molecular mechanisms regulating GLUT4 trafficking downstream of different signaling inputs in a physiologically relevant cell type.

Suppression of frequency-mixing effect for pm-level heterodyne interferometers based on "zero coupling" optical path length control.

Optical path length (OPL) noise resulting from stray light significantly constrains interferometry displacement measurements in the low-frequency band. This paper presents an analytical model considering the presence of stray light in heterodyne laser interferometers. Due to the cyclic nonlinear coupling effect, there will be some special OPLs of stray light, minimizing the frequency-mixing impact to zero. Consequently, we propose a noise suppression scheme that locks the OPL of stray light at the zero coupling point. Therefore, we significantly enhanced the interference displacement measurement noise within the low-frequency band. Experimental results show that the interferometer achieves a displacement noise level lower than 6 pm/Hz1/2 covering 1 mHz.

The impact of grazing activities and environmental conditions on the stability of alpine grassland ecosystems.

Globally, grazing activities have profound impacts on the structure and function of ecosystems. This study, based on a 20-year MODIS time series dataset, employs remote sensing techniques and the Seasonal-Trend decomposition using Loess (STL) algorithm to quantitatively assess the stability of alpine grassland ecosystems from multiple dimensions, and to reveal the characteristics of grazing activities and environmental conditions on ecosystem stability. The results indicate that only 5.77% of the area remains undisturbed, with most areas experiencing varying degrees of disturbance. Further analysis shows that grazing activities in high vegetation coverage areas are the main source of interference. In areas with concentrated interference, elevation and slope have a positive correlation with resistance stability, but a negative correlation with recovery stability. Precipitation and landscape diversity have positive effects on both resistance stability and recovery stability. Vegetation coverage and grazing intensity have a negative correlation with resistance stability, but a positive correlation with recovery stability. This highlights the complex interactions between human activities, environmental factors, and ecosystem stability. The findings emphasize the need for targeted conservation and management strategies to mitigate disturbances to ecosystems affected by human activities and enhance their stability.

Improving accelerated MRI by deep learning with sparsified complex data.

PURPOSE: To obtain high-quality accelerated MR images with complex-valued reconstruction from undersampled k-space data. METHODS: The MRI scans from human subjects were retrospectively undersampled with a regular pattern using skipped phase encoding, leading to ghosts in zero-filling reconstruction. A complex difference transform along the phase-encoding direction was applied in image domain to yield sparsified complex-valued edge maps. These sparse edge maps were used to train a complex-valued U-type convolutional neural network (SCU-Net) for deghosting. A k-space inverse filtering was performed on the predicted deghosted complex edge maps from SCU-Net to obtain final complex images. The SCU-Net was compared with other algorithms including zero-filling, GRAPPA, RAKI, finite difference complex U-type convolutional neural network (FDCU-Net), and CU-Net, both qualitatively and quantitatively, using such metrics as structural similarity index, peak SNR, and normalized mean square error. RESULTS: The SCU-Net was found to be effective in deghosting aliased edge maps even at high acceleration factors. High-quality complex images were obtained by performing an inverse filtering on deghosted edge maps. The SCU-Net compared favorably with other algorithms. CONCLUSION: Using sparsified complex data, SCU-Net offers higher reconstruction quality for regularly undersampled k-space data. The proposed method is especially useful for phase-sensitive MRI applications.

Motion resilience of the balanced steady-state free precession geometric solution.

PURPOSE: Many MRI sequences are sensitive to motion and its associated artifacts. The linearized geometric solution (LGS), a balanced steady-state free precession (bSSFP) off-resonance signal demodulation technique, is evaluated with respect to motion artifact resilience. THEORY AND METHODS: The mechanism and extent of LGS motion artifact resilience is examined in simulated, flow phantom, and in vivo clinical imaging. Motion artifact correction capabilities are decoupled from susceptibility artifact correction when feasible to permit controlled analysis of motion artifact correction when comparing the LGS with standard and phase-cycle-averaged (complex sum) bSSFP imaging. RESULTS: Simulations reveal that the LGS demonstrates motion artifact reduction capabilities similar to standard clinical bSSFP imaging techniques, with slightly greater resilience in high SNR regions and for shorter-duration motion. Flow phantom experiments assert that the LGS reduces shorter-duration motion artifact error by ∼24%-65% relative to the complex sum, whereas reconstructions exhibit similar error reduction for constant motion. In vivo analysis demonstrates that in the internal auditory canal/orbits, the LGS was deemed to have less artifact in 24%/49% and similar artifact in 76%/51% of radiological assessments relative to the complex sum, and the LGS had less artifact in 97%/81% and similar artifact in 3%/16% of assessments relative to standard bSSFP. Only 2 of 63 assessments deemed the LGS inferior to either complex sum or standard bSSFP in terms of artifact reduction. CONCLUSION: The LGS provides sufficient bSSFP motion artifact resilience to permit robust elimination of susceptibility artifacts, inspiring its use in a wide variety of applications.

Effects of Exercise Training Under Hypoxia versus Normoxia on Cognitive Function in Clinical and Non-Clinical Populations: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare the effects of exercise training under hypoxia versus normoxia on cognitive function in clinical and non-clinical populations. DATA SOURCES: From inception to June 13th, 2022, a systematic search was performed on PubMed, Web of Science, Embase, Scopus, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials comparing the effects of exercise under hypoxic vs normoxic on cognition in clinical and non-clinical populations were included. The systematic search generated 14,894 relevant studies, of which 12 were finally included. DATA EXTRACTION: Two reviewers independently extracted data from included studies. Results were expressed as standardized mean difference (SMD). Each included study was assessed using the Cochrane Risk of Bias 1.0 (RoB1.0) tool. Finally, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to rate the certainty of evidence for each outcome. DATA SYNTHESIS: Overall, 12 studies with a total of 338 participants met the inclusion criteria. The pooled results suggested that hypoxia exercise had a small but not statistically significant positive effect on overall cognitive function (SMD=0.064, 95% confidence interval (CI): -0.156-0.284, P=.567, very low-certainty evidence), when compared with normoxic exercise. Regarding the domain-specific cognitive functions, there was a medium and significant positive effect on memory (SMD=0.594, 95% CI: 0.068 to 1.120, P=.027, very low-certainty evidence), while effects on visuospatial function (SMD=0.490, 95% CI: -0.030 to 1.010, P=.065, very low-certainty evidence), attention (SMD=0.037, 95% CI: -0.340 to 0.414, P=.847, very low-certainty evidence), executive function (SMD=0.096, 95% CI: -0.268 to 0.460, P=.605, very low-certainty evidence), and processing speed (SMD=-0.145, 95% CI: -0.528 to 0.239, P=.459, very low-certainty evidence) were not statistically significant. CONCLUSIONS: The current pooled results revealed that hypoxic exercise was related to improved cognitive performance. Nevertheless, exercise under hypoxia did not have a significant advantage in cognitive promotion when compared with exercise under normoxia.

The Association Between Vitamin D Levels and the 10-Year Risk of Atherosclerotic Cardiovascular Disease: A Population-Based Study.

BACKGROUND: The association between vitamin D levels and atherosclerotic cardiovascular disease (ASCVD) risk remains unclear. In this study, the association between serum 25(OH)D and 10-year ASCVD risk was examined in a national sample of middle-aged and older adults. METHODS: Cross-sectional data from the 2009-2014 National Health and Nutrition Examination Survey were analyzed. The Pooled Cohort Equations were used to estimate the risk of a first ASCVD event in 10 years. An adjusted multiple linear regression model was used to investigate the association between serum 25(OH)D and ASCVD risk. In addition, we performed sensitivity analysis and interactive analysis to assess the robustness of associations across different subgroups. RESULTS: A total of 3354 participants were included in this study. The linear regression model indicated that the risk of ASCVD decreased with the increase in serum 25(OH)D. When analyzed as a continuous variable, serum 25(OH)D was significantly associated with the estimated 10-year risk of ASCVD. In the fully adjusted model, each 10-nmol/L increase in serum 25(OH)D reduced the estimated 10-year ASCVD risk by 0.172% ( P < .001). Individuals in the moderate, insufficient, and sufficient vitamin D deficiency groups had a 0.449% ( P = .362), 0.957% ( P = .046), 1.475% ( P = .003) decrease in ASCVD risk, respectively, when a severe vitamin D deficiency group was set as a reference in the fully adjusted model. CONCLUSION: Our data suggest a negative association between vitamin D levels and the predicted 10-year risk of ASCVD. Further studies are required to investigate whether vitamin D supplements could reduce the risk of ASCVD.

Effects of enhance recovery after surgery nursing program on the surgical site wound infection in patients undergoing laparoscopic hepatectomy for hepatocellular carcinoma: A meta-analysis.

Our study aimed to investigate the effects of an enhanced recovery after surgery (ERAS) nursing program on surgical site wound infections (SSWI) and postoperative complications in patients undergoing laparoscopic hepatectomy (LH) for hepatocellular carcinoma. Computer searches of the PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure and Wanfang databases were conducted to gather randomised controlled trials (RCTs) that were published from inception to September 2023. The target studies evaluated the effects of the ERAS nursing program in patients undergoing LH for hepatocellular carcinoma. Two independent authors screened the literature, extracted the data and performed quality assessments. Dichotomous variables were analysed using odds ratios (ORs) and 95% confidence intervals (CIs), as effect analysis statistics. Stata software (version 17.0) was used for data analysis. Eleven RCTs with 765 patients were included, with 383 patients in the ERAS group and 382 in the control group. The results revealed that the incidence of SSWI (OR = 0.32, 95%CI:0.15-0.71, p = 0.004) and postoperative complications (OR = 0.23, 95%CI:0.15-0.34, p < 0.001) were both significantly reduced in the ERAS group, compared with the control group. The ERAS nursing program, when applied to patients undergoing laparoscopic hepatic cancer resection, can effectively reduce the incidence of SSWI and postoperative complications, thus promoting postoperative recovery.

Metabonomics Analysis of Brain Stem Tissue in Rats with Primary Brain Stem Injury Caused Death.

OBJECTIVES: To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death. METHODS: PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis. RESULTS: Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine). CONCLUSIONS: GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.

Research Progress on Microbial Community Succession in the Postmortem Interval Estimation.

The postmortem interval (PMI) estimation is a key and difficult point in the practice of forensic medicine, and forensic scientists at home and abroad have been searching for objective, quantifiable and accurate methods of PMI estimation. With the development and combination of high-throughput sequencing technology and artificial intelligence technology, the establishment of PMI model based on the succession of the microbial community on corpses has become a research focus in the field of forensic medicine. This paper reviews the technical methods, research applications and influencing factors of microbial community in PMI estimation explored by using high-throughput sequencing technology, to provide a reference for the related research on the use of microbial community to estimate PMI.

The Euscaphis japonica genome and the evolution of malvids.

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the γ event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.

A data-driven T2 relaxation analysis approach for myelin water imaging: Spectrum analysis for multiple exponentials via experimental condition oriented simulation (SAME-ECOS).

PURPOSE: The decomposition of multi-exponential decay data into a T2 spectrum poses substantial challenges for conventional fitting algorithms, including non-negative least squares (NNLS). Based on a combination of the resolution limit constraint and machine learning neural network algorithm, a data-driven and highly tailorable analysis method named spectrum analysis for multiple exponentials via experimental condition oriented simulation (SAME-ECOS) was proposed. THEORY AND METHODS: The theory of SAME-ECOS was derived. Then, a paradigm was presented to demonstrate the SAME-ECOS workflow, consisting of a series of calculation, simulation, and model training operations. The performance of the trained SAME-ECOS model was evaluated using simulations and six in vivo brain datasets. The code is available at https://github.com/hanwencat/SAME-ECOS. RESULTS: Using NNLS as the baseline, SAME-ECOS achieved over 15% higher overall cosine similarity scores in producing the T2 spectrum, and more than 10% lower mean absolute error in calculating the myelin water fraction (MWF), as well as demonstrated better robustness to noise in the simulation tests. Applying to in vivo data, MWF from SAME-ECOS and NNLS was highly correlated among all study participants. However, a distinct separation of the myelin water peak and the intra/extra-cellular water peak was only observed in the mean T2 spectra determined using SAME-ECOS. In terms of data processing speed, SAME-ECOS is approximately 30 times faster than NNLS, achieving a whole-brain analysis in 3 min. CONCLUSION: Compared with NNLS, the SAME-ECOS method yields much more reliable T2 spectra in a dramatically shorter time, increasing the feasibility of multi-component T2 decay analysis in clinical settings.

Lack of tumorigenesis and protumorigenic activity of human umbilical cord mesenchymal stem cells in NOD SCID mice.

BACKGROUND: The tumorigenesis of infused umbilical cord mesenchymal stem cells (UC-MSCs) is being preclinically evaluated. METHODS: We observed tumor formation in NOD SCID mice after a single subcutaneous injection of hUC-MSCs and the effect of these cells on tumor growth in tumor-bearing mice. Three generations (P5, P7, and P10) of hUC-MSCs (1 × 107) from two donors (hUC-MSC1 and hUC-MSC2) were inoculated subcutaneously into NOD SCID mice. Subcutaneous transplantation models were established in NOD SCID mice with human cervical cancer HeLa cells (solid tumor) and human B cell lymphoma Raji cells (hematological tumor). Then, the animals were euthanized, gross dissection was performed, and tissues were collected. Various organs were observed microscopically to identify pathological changes and tumor metastasis. RESULTS: In the tumorigenesis experiment, no general anatomical abnormalities were observed. In the tumor promotion experiment, some animals in the HeLa groups experienced tumor rupture, and one animal died in each of the low- and medium-dose hUC-MSC groups. The results may have occurred due to the longer feeding time, and the tumor may have caused spontaneous infection and death. Pathological examination revealed no metastasis to distant organs in any group. In the Raji tumor model, some animals in each group experienced tumor rupture, and one animal in the medium-dose hUC-MSC group died, perhaps due to increased tumor malignancy. Thus, hUC-MSCs neither promoted nor inhibited tumor growth. No cancer cell metastasis was observed in the heart, liver, spleen, lungs, kidneys or other important organs, except that pulmonary venule metastasis was observed in 1 animal in the model group. CONCLUSIONS: Injected hUC-MSCs were not tumorigenic and did not significantly promote or inhibit solid or hematological tumor growth or metastasis in NOD SCID mice.

A Resting-State Functional Magnetic Resonance Imaging Study of Abnormal Frontoparietal Network Function in Migraine without Aura.

BACKGROUND This study aimed to investigate frontoparietal network (FPN) dysfunction in participants with migraine without aura (MwoA). MATERIAL AND METHODS We selected 48 age-, sex-, and education level-matched graduate students (24 participants with MwoA [MwoA group] and 24 healthy controls). RS-fMRI and independent component analysis were used to examine the FPN and to compare abnormal encephalic regional homogeneity values. The Mindful Attention Awareness Scale (MAAS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Self-Rating Scale of Sleep (SRSS) were used to evaluate attention, anxiety, depression, and sleep, respectively. Pearson's correlation was applied to evaluate the association between abnormal brain areas and the scores for each scale. RESULTS Neural function activity in encephalic regions of FPN showed abnormal changes in the MwoA group. The MwoA group had significantly lower MAAS scores (P<0.001), higher SAS scores (P<0.001), and higher SDS (P=0.06) and SRSS scores (P=0.26). In the MwoA group, functional activity of the right parietal lobule in the left FPN was positively correlated with MAAS scores (P=0.01) and negatively correlated with SAS (P=0.02). The orbital part of left inferior frontal gyrus activity in the right FPN was positively correlated with SDS (P=0.04) and SRSS (P<0.001). Right superior marginal gyrus activity in the right FPN was positively correlated with SDS (P=0.02). CONCLUSIONS Abnormal FPN function was correlated with attention, anxiety, depression, and sleep status in the MwoA group. These results offer further insights into the evaluation and treatment of MwoA.

Endobronchial Ultrasound-Guided Transbronchial Incision and Drainage in the Treatment of Mediastinal Abscess.

Mediastinal abscess, mostly resulting from esophageal perforation or cardiothoracic surgery, is a serious condition carrying high morbidity and mortality. Antibiotic therapy alone normally did not achieve a satisfactory outcome, due to poor circulation of abscess that hampers drug delivery. Surgical intervention for debridement and drainage is recommended, but it poses a high risk in patients with poor health status and could lead to various complications. Recent studies proposed endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as an effective alternative to surgery; however, repeated TBNA procedures are usually needed for complete clearance of the lesion, thus causing increased patient suffering and medical expenses. Here, we present the first case of successful application of EBUS-guided transbronchial incision and drainage, which provides a novel, safe, and effective treatment for patient with mediastinal abscess unwilling or unsuitable to undergo surgical intervention.

Effect of Electroacupuncture on Short-Chain Fatty Acids in Peripheral Blood after Middle Cerebral Artery Occlusion/Reperfusion in Rats Based on Gas Chromatography-Mass Spectrometry.

Previous fundamental and clinical research has shown that electroacupuncture (EA) at the acupoints of Quchi (LI11) and Zusanli (ST36) can successfully alleviate motor dysfunction following stroke. Additionally, it has been discovered that gut microbiota and their metabolites play an essential role in stroke. However, the relationship between the metabolites of gut microbiota and the efficacy of EA is still unclear. Therefore, the aim of this study was to evaluate the mechanism of EA at LI11 and ST36 in the treatment of motor dysfunction after middle cerebral artery occlusion/reperfusion (MCAO/R) in model rats by comparing the differences and correlation between different short-chain fatty acids (SCFAs) and the recovery of motor function. The results indicated that EA at LI11 and ST36 acupoints enhanced the neurological function, motor function, and infarct volume of MCAO/R rats. The levels of acetic acid, propionic acid, and total SCFAs were considerably lower in the MCAO/R group than in the sham group (P < 0.05). Acetic acid, propionic acid, and total SCFA concentrations were substantially higher in the MCAO/R + EA group than in the MCAO/R group (P < 0.05). Finally, Pearson correlation analysis revealed that the propionic acid concentration was substantially favorably connected with the duration on the rotarod (r = 0.633 and P < 0.05) and highly negatively correlated with the modified neurological severity score (mNSS) (r = -0.698 and P < 0.05) and the percentage of cerebral infarct volume (r = -0.729 and P < 0.05). Taken together, these findings indicate that the increase in propionic acid may be one of the mechanisms and targets of EA at LI11 and ST36 acupoints to improve poststroke motor dysfunction in MCAO/R rats.

Tenuivirus utilizes its glycoprotein as a helper component to overcome insect midgut barriers for its circulative and propagative transmission.

Many persistent transmitted plant viruses, including rice stripe virus (RSV), cause serious damage to crop production worldwide. Although many reports have indicated that a successful insect-mediated virus transmission depends on a proper interaction between the virus and its insect vector, the mechanism(s) controlling this interaction remained poorly understood. In this study, we used RSV and its small brown planthopper (SBPH) vector as a working model to elucidate the molecular mechanisms underlying the entrance of RSV virions into SBPH midgut cells for virus circulative and propagative transmission. We have determined that this non-enveloped tenuivirus uses its non-structural glycoprotein NSvc2 as a helper component to overcome the midgut barrier(s) for RSV replication and transmission. In the absence of this glycoprotein, purified RSV virions were unable to enter SBPH midgut cells. In the RSV-infected cells, this glycoprotein was processed into two mature proteins: an amino-terminal protein (NSvc2-N) and a carboxyl-terminal protein (NSvc2-C). Both NSvc2-N and NSvc2-C interact with RSV virions. Our results showed that the NSvc2-N could bind directly to the surface of midgut lumen via its N-glycosylation sites. Upon recognition, the midgut cells underwent endocytosis followed by compartmentalization of RSV virions and NSvc2 into early and then late endosomes. The NSvc2-C triggered cell membrane fusion via its highly conserved fusion loop motifs under the acidic condition inside the late endosomes, leading to the release of RSV virions from endosomes into cytosol. In summary, our results showed for the first time that a rice tenuivirus utilized its glycoprotein NSvc2 as a helper component to ensure a proper interaction between its virions and SBPH midgut cells for its circulative and propagative transmission.

LncRNA NEAT1 accelerates renal tubular epithelial cell damage by modulating mitophagy via miR-150-5p-DRP1 axis in diabetic nephropathy.

NEW FINDINGS: What is the central question of this study? Diabetic nephropathy (DN) is a severe complication of diabetes correlated with a higher mortality rate in diabetic patients. Renal tubular injury participates in the pathogenesis of DN. We aimed to uncover the biological function of the NEAT1-miR-150-5p-DRP1 axis in an in vitro model of DN and elaborate the potential mechanisms. What is the main finding and its importance? NEAT1 facilitated high glucose-induced damage in HK-2 cells by reducing mitophagy via the miR-150-5p-DRP1 axis, which sheds light on DN pathogenesis and reveals a potential treatment for DN. ABSTRACT: Diabetic nephropathy (DN) is a severe complication in diabetic patients, with a high mortality rate. Renal tubular injury is involved in the pathogenesis of DN. In this study, we aimed to uncover the regulatory roles of the NEAT1-miR-150-5p-DRP1 axis in an in vitro model of DN and its possible mechanisms. High glucose-challenged HK-2 cells were used as an in vitro DN model. NEAT1, miR-150-5p and DRP1 levels were assessed by RT-qPCR. Cell viability was determined by the MTT assay. MitoSOX Red and JC-1 were used to evaluate intracellular production of reactive oxygen species and mitochondrial membrane potential, respectively. Lactate dehydrogenase release and superoxide dismutase activity were assessed with commercial kits. The protein levels of DRP1, p62, BECN1(beclin 1) and BNIP3 were determined by western blotting. The interaction between NEAT1 (DRP1) and miR-150-5p was verified by a dual-luciferase reporter assay and an RNA immunoprecipitation assay. Our results showed that in response to high glucose the NEAT1 and DRP1 levels were upregulated, whereas the miR-150-5p level was downregulated in HK-2 cells. Knockdown of NEAT1 or DRP1 in high glucose-challenged HK-2 cells inhibited excessive reactive oxygen species production and lactate dehydrogenase release, increased cell viability, mitochondrial membrane potential and superoxide dismutase activity and enhanced mitophagy. Inhibition of miR-150-5p resulted in the opposite results. Mechanistically, NEAT1 sponged miR-150-5p to increase the DRP1 level. Moreover, silencing of NEAT1 or DRP1 could counteract miR-150-5p inhibition-induced deleterious effects. Collectively, our findings indicate that NEAT1 facilitates high glucose-induced damage in HK-2 cells by suppressing mitophagy via the miR-150-5p-DRP 1 axis, which sheds light on a novel mechanism of DN.

Myelin water imaging data analysis in less than one minute.

PURPOSE: Based on a deep learning neural network (NN) algorithm, a super fast and easy to implement data analysis method was proposed for myelin water imaging (MWI) to calculate the myelin water fraction (MWF). METHODS: A NN was constructed and trained on MWI data acquired by a 32-echo 3D gradient and spin echo (GRASE) sequence. Ground truth labels were created by regularized non-negative least squares (NNLS) with stimulated echo corrections. Voxel-wise GRASE data from 5 brains (4 healthy, 1 multiple sclerosis (MS)) were used for NN training. The trained NN was tested on 2 healthy brains, 1 MS brain with segmented lesions, 1 healthy spinal cord, and 1 healthy brain acquired from a different scanner. RESULTS: Production of whole brain MWF maps in approximately 33 â€‹s can be achieved by a trained NN without graphics card acceleration. For all testing regions, no visual differences between NN and NNLS MWF maps were observed, and no obvious regional biases were found. Quantitatively, all voxels exhibited excellent agreement between NN and NNLS (all R2>0.98, p â€‹< â€‹0.001, mean absolute error <0.01). CONCLUSION: The time for accurate MWF calculation can be dramatically reduced to less than 1 â€‹min by the proposed NN, addressing one of the barriers facing future clinical feasibility of MWI.

The image quality, lesion detectability, and acquisition time of 18F-FDG total-body PET/CT in oncological patients.

PURPOSE: The purpose was to investigate the effects of short acquisition time on the image quality and the lesion detectability of oncological 18F-FDG total-body PET/CT. METHODS: Nineteen oncological patients (6/13 women/men, age 65.6 ± 9.4 years) underwent total-body PET/CT on uEXPLORER scanner using 3D list mode. The administration of 18F-FDG was weight-based (4.4 MBq/kg). The acquisition time was 900 s, and PET data were reconstructed into 900-, 180-, 120-, 60-, 30-, and 18-s duration groups. The subjective PET image quality was scored using a 5-point scale (5, excellent; 1, poor) in 3 perspectives: overall quality, noise, and lesion conspicuity. The objective image quality was evaluated by SUVmax and standard deviation (SD) of the liver, SUVmax of the tumor, and tumor-to-background ratio (TBR). The lesion detectability was the percentage of identifiable lesions in the groups of 180 to 18 s using the group 900 s as reference. RESULTS: Our results showed that sufficient and acceptable subjective image quality could be achieved with 60- and 30-s groups, and good image quality scores were given to 180- and 120-s groups without significant difference. For shortened acquisition time, SD was increased, while SUVmax of tumor and TBR remained unchanged. The lesion detectability was decreased with shorter acquisition time, but the detection performance could be maintained until the 60-s group compared with the 900-s group, although the image quality degraded. CONCLUSION: The total-body PET/CT can significantly shorten the acquisition time with maintained lesion detectability and image quality.