Arabidopsis TETRASPANIN8 mediates exosome secretion and glycosyl inositol phosphoceramide sorting and trafficking.

Sphingolipids are components of plant membranes, and their heterogeneous distribution gives different membrane systems distinct properties. For example, glycosyl inositol phosphoceramides (GIPCs), 1 major type of sphingolipids, aggregate in the outer layer of the plasma membrane (PM), as well as in extracellular vesicles (EVs), including the small (30 to 100 nm) EVs termed exosomes. How these sphingolipids are sorted and trafficked is not clear. In this work, we report that Arabidopsis thaliana TETRASPANIN8 (TET8) acts as a sphingolipid carrier and thus regulates the export of GIPCs from the Golgi apparatus. TET8 recognized the coat protein complex I (COPI) subunit γ2-COPI and moved to its proper location in the PM; this recognition required the TET8 C-terminal tail. Deleting the C-terminal tail of TET8 largely restricted its roles in GIPC transport and endosomal trafficking. Further, we show that TET8 affects EV secretion in association with GIPCs. Thus, our findings shed light on GIPC transport and the molecular machinery involved in EV biogenesis.

Role of HCN channels in the functions of basal ganglia and Parkinson's disease.

Parkinson's disease (PD) is a motor disorder resulting from dopaminergic neuron degeneration in the substantia nigra caused by age, genetics, and environment. The disease severely impacts a patient's quality of life and can even be life-threatening. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a member of the HCN1-4 gene family and is widely expressed in basal ganglia nuclei. The hyperpolarization-activated current mediated by the HCN channel has a distinct impact on neuronal excitability and rhythmic activity associated with PD pathogenesis, as it affects the firing activity, including both firing rate and firing pattern, of neurons in the basal ganglia nuclei. This review aims to comprehensively understand the characteristics of HCN channels by summarizing their regulatory role in neuronal firing activity of the basal ganglia nuclei. Furthermore, the distribution and characteristics of HCN channels in each nucleus of the basal ganglia group and their effect on PD symptoms through modulating neuronal electrical activity are discussed. Since the roles of the substantia nigra pars compacta and reticulata, as well as globus pallidus externus and internus, are distinct in the basal ganglia circuit, they are individually described. Lastly, this investigation briefly highlights that the HCN channel expressed on microglia plays a role in the pathological process of PD by affecting the neuroinflammatory response.

The significance of serum SLC7A11 levels in the occurrence of vascular calcification in maintenance peritoneal dialysis patients.

AIM: This research aimed to explore the serum levels of solute carrier family 7 member 11 (SLC7A11) in patients with maintenance peritoneal dialysis (MPD) and its correlation with vascular calcification (VC) and clinical results. METHODS: This present prospective observational cohort study enrolled 189 patients with MPD who were undergoing regular peritoneal dialysis for over 3 months in our hospital from February 2020 to July 2022. The abdominal aortic calcification score was used to assess the VC condition of MPD patients. The serum SLC7A11, interleukin (IL)-6, IL-1ß and C-reactive protein levels were measured by enzyme-linked immunosorbent assay (ELISA). Demographic and clinical statistics were collected. All patients were followed up for 1 year and the overall survival time (OS) of all patients were recorded. All data used SPSS 18.0 for statistical analyses. RESULTS: Patients with moderate/severe calcification in MPD had a longer duration of dialysis, higher serum levels of phosphate (P) and calcium (Ca) and lower serum levels of SLC7A11. Spearman's analysis revealed a negative correlation between serum SLC7A11 levels and the levels of P, Ca and IL-1ß. Additionally, we observed an association between serum SLC7A11 levels and clinical prognosis as well as the extent of VC in MPD patients. Multivariate logistic regression analysis indicated that dialysis duration, SLC7A11, and P were risk factors for VC in MPD patients. CONCLUSION: The serum SLC7A11 levels decreased remarkably in MPD patients with moderate/severe calcification. This study may provide new targets and comprehensive approach to cardiovascular protection in patients with chronic kidney disease.

Correlation Analysis of Vascular Endothelial Growth Factor Level with Clinicopathological Features and Prognosis in Patients with Diabetic Nephropathy: A Biopsy-based Study.

Globally, Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases, which poses a great potential threat to the human body. Diabetic nephropathy (DN), a very common complication in T2DM, is also the main trigger for end-stage renal disease. A thorough understanding of the pathogenesis is the key as well as the breakthrough for future diagnosis and treatment of DN. This investigation aims to provide more in-depth and accurate guidance for future follow-up research by analyzing the role of vascular endothelial growth factor (VEGF) in the kidney tissue of DN patients. Seventy-nine patients with suspected DN who underwent renal needle biopsy in our hospital from January 2015 to June 2019 were selected as the research participants. After the biopsy, 36 cases were confirmed as DN, and the other 43 were T2DM with primary glomerulonephritis. Determination of VEGF mRNA and protein expression in renal tissue employed PCR and Western blot, and the connection between VEGF mRNA level and clinical pathology (such as renal function, inflammatory factors and pathological manifestations) was discussed. The disease recurrence in DN patients was recorded through the 3-year prognostic followed up, and the related influencing factors were analyzed. In kidney tissue, VEGF mRNA level and protein expression were notably higher in DN patients than in diabetic patients (P<0.05). Pearson correlation coefficient analysis identified that VEGF mRNA and protein had a positive connection with blood urea nitrogen (BUN), serum creatinine (Scr), 24-hour urine total protein (24hUTP) and C-reactive protein (CRP) (P<0.05). Among the various clinicopathological features of DN patients, age, BMI, sex, family history, smoking, drinking, exercise habits, clinical presentations and pathological changes had no significant relationship with VEGF level (P>0.05), but the course of the disease, fasting blood glucose (FBG), glycosylated hemoglobin (HBALC) and pathological stages of nephropathy had a close connection with VEGF level (P<0.05). Prognostic follow-up revealed that VEGF mRNA was noticeably higher in patients with recurrence than in those without (P<0.05). When VEGF mRNA >5.20 in kidney tissue, the sensitivity and specificity for predicting the 3-year recurrence were 85.71% and 84.00% respectively (P<0.05). Finally, Logistic regression analysis identified the independence of FBG, HBALC and VEGF levels as the influencing factors for the prognostic recurrence of DN (P<0.05).VEGF expression in kidney tissue of DN patients is closely linked to renal function and increases as the disease progresses, which is an independent risk factor associated with the prognostic recurrence of DN, with great potential significance for future DN diagnosis and treatment.

Three-Dimensional Wind Measurement Based on Ultrasonic Sensor Array and Multiple Signal Classification.

The wind power industry continues to experience rapid growth worldwide. However, the fluctuations in wind speed and direction complicate the wind turbine control process and hinder the integration of wind power into the electrical grid. To maximize wind utilization, we propose to precisely measure the wind in a three-dimensional (3D) space, thus facilitating the process of wind turbine control. Natural wind is regarded as a 3D vector, whose direction and magnitude correspond to the wind's direction and speed. A semi-conical ultrasonic sensor array is proposed to simultaneously measure the wind speed and direction in a 3D space. As the ultrasonic signal transmitted between the sensors is influenced by the wind and environment noise, a Multiple Signal Classification algorithm is adopted to estimate the wind information from the received signal. The estimate's accuracy is evaluated in terms of root mean square error and mean absolute error. The robustness of the proposed method is evaluated by the type A evaluation of standard uncertainty under a varying signal-to-noise ratio. Simulation results validate the accuracy and anti-noise performance of the proposed method, whose estimated wind speed and direction errors converge to zero when the SNR is over 15 dB.

Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease.

ABSTRACT: The globus pallidus plays a pivotal role In the basal ganglia circuit. Parkinson's disease Is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore, bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico-striato-pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease, particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia-thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity, and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

China lung cancer screening (CLUS) version 2.0 with new techniques implemented: Artificial intelligence, circulating molecular biomarkers and autofluorescence bronchoscopy.

OBJECTIVE: The present study, CLUS version 2.0, was conducted to evaluate the performance of new techniques in improving the implementation of lung cancer screening and to validate the efficacy of LDCT in reducing lung cancer-specific mortality in a high-risk Chinese population. METHODS: From July 2018 to February 2019, high-risk participants from six screening centers in Shanghai were enrolled in our study. Artificial intelligence, circulating molecular biomarkers and autofluorescencebronchoscopy were applied during screening. RESULTS: A total of 5087 eligible high-risk participants were enrolled in the study; 4490 individuals were invited, and 4395 participants (97.9%) finally underwent LDCT detection. Positive screening results were observed in 857 (19.5%) participants. Solid nodules represented 53.6% of all positive results, while multiple nodules were the most common location type (26.8%). Up to December 2020, 77 participants received lung resection or biopsy, including 70 lung cancers, 2 mediastinal tumors, 1 tracheobronchial tumor, 1 malignant pleural mesothelioma and 3 benign nodules. Lung cancer patients accounted for 1.6% of all the screened participants, and 91.4% were in the early stage (stage 0-1). CONCLUSIONS: LDCT screening can detect a high proportion of early-stage lung cancer patients in a Chinese high-risk population. The utilization of new techniques would be conducive to improving the implementation of LDCT screening.

Discrete Lorentz symmetry and discrete spacetime translational symmetry in two- and three-dimensional crystals.

As is well known, crystals have discrete space translational symmetry. It was recently noticed that one-dimensional crystals possibly have discrete Poincaré symmetry, which contains discrete Lorentz and discrete time translational symmetry as well. In this paper, we classify the discrete Poincaré groups on two- and three- dimensional Bravais lattices. They are the candidate symmetry groups of two- or three-dimensional crystals, respectively. The group is determined by an integer generator g, and it reduces to the space group of crystals at g = 2.

Lipidomic Analysis Reveals the Importance of GIPCs in Arabidopsis Leaf Extracellular Vesicles.

Plant extracellular vesicles (EVs) are membrane-enclosed nanoparticles that play diverse roles in plant development and response. Recently, impressive progress has been made in the isolation and identification of the proteins and RNAs carried in plant EVs; however, the analysis of EV lipid compositions remains rudimentary. Here, we performed lipidomic analysis of Arabidopsis rosette leaf EVs, revealing a high abundance of certain groups of lipids, in particular sphingolipids, in the EVs. Remarkably, the EV sphingolipids are composed of nearly pure glycosylinositolphosphoceramides (GIPCs), which are green lineage abundant and negatively charged. We further showed that the Arabidopsis TETRASPANIN 8 (TET8) knockout mutant has a lower amount of cellular GIPCs and secrets fewer EVs, companied with impaired reactive oxygen species (ROS) burst toward stresses. Exogenous application of GIPCs promoted the secretion of EVs and ROS burst in both the WT and tet8 mutant. The characteristic enrichment of sphingolipid GIPCs provides valuable insights into the biogenesis and function of plant EVs.

Improvement of Outcomes in Patients with Lupus Nephritis: Management Evolution in Chinese Patients from 1994 to 2010.

OBJECTIVE: To assess how the longterm outcomes have changed over the past decades in Chinese patients with lupus nephritis (LN). The trends in patient manifestation at presentation, treatment pattern, and therapeutic effects were evaluated. METHODS: A cohort of biopsy-proven patients with LN (n = 1945) from January 1994 to December 2010 was analyzed. Treatment regimens, treatment response, renal relapse, and renal outcome were compared at different time periods (1994-1998, 1999-2004, and 2005-2010). RESULTS: Patients in the later periods had shorter duration of disease, lower serum creatinine value and chronicity at biopsy, and more frequent followup. They were more likely to receive standard-of-care therapies, which included cyclophosphamide, mycophenolate mofetil, and combination therapy. Patients in the later periods had higher probabilities of achieving remission (p < 0.001) and lower probabilities of experiencing renal flare (p = 0.007). The 5-year renal survival rates were 92.6%, 90.6%, and 94.3% in 1994-1998, 1999-2004, and 2005-2010, respectively. The 5-year risk of endstage renal disease (ESRD) did not differ between 1994-1998 and 1999-2004, but was significantly lower in 2005-2010 (HR 0.40, 95% CI 0.19-0.85 vs 1999-2004). In multivariable Cox analysis, standard therapy was independently associated with lower risk of ESRD (adjusted HR 0.72, 95% CI 0.52-0.98, p = 0.04). Variables of renal damage at biopsy (renal function, activity index, and chronicity index) were independently associated with poor outcome. CONCLUSION: The outcomes of Chinese patients with LN have improved from 1994 to 2010. With the increased use of standard therapies, the remission rates have increased and renal relapse has decreased.

Changes in the Spectrum of Kidney Diseases: An Analysis of 40,759 Biopsy-Proven Cases from 2003 to 2014 in China.

OBJECTIVES: To evaluate the changing spectrum of kidney diseases over time in China using renal biopsy-proven cases. METHODS: All patients over the age of 14 years who were diagnosed with a kidney disease by renal biopsy in the Renal Biopsy Registry of the National Clinical Research Center of Kidney Diseases in Jinling Hospital, Nanjing, from 2003 to 2014 were included. RESULTS: In total, 40,759 cases of renal biopsy were analyzed. The mean age of the patients was 36.59 ± 14.12 years. 52.0$ of the patients were male. Primary glomerulonephritis (PGN), secondary glomerulonephritis, tubulointerstitial disease, and hereditary renal diseases accounted for 67.1, 26.4, 2.9, and 2.5$, respectively. IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change disease, and focal segmental glomerulosclerosis were the leading PGN diagnoses. The frequency of MN increased significantly (p < 0.001) by doubling from 2003 to 2014. An analysis by age category indicated that the frequency of MN increased significantly over time (p < 0.001) in all age categories and increased by more than 2 times in the 14-24 age category. Lupus nephritis (LN) and Henoch-Schönlein purpura nephritis (HSPN) decreased significantly (p < 0.001), diabetic nephropathy (DN) increased nearly twice (p < 0.001), monoclonal immunoglobulin deposition disease (MIDD) tripled (p < 0.001), and hypertensive nephropathy (HT) (p < 0.001) and renal amyloidosis (AMY) (p < 0.05) showed an upward trend. An analysis by age category showed that hepatitis B-related nephritis has significantly decreased in the 14-24 age category (p < 0.001). CONCLUSION: PGN continued to be the predominant kidney disease in China with IgAN being the most common PGN. The frequency of MN increased significantly, with a maximum increase in young adults. LN and HSPN decreased significantly, DN and MIDD increased significantly, and HT and AMY also showed an increasing trend. The kidney disease trends presented in this study serve as a reference point for patient care, disease prevention, and public health interventions.