5-aminolevulinic acid-based photodynamic therapy in combination with antifungal agents for adult kerion and facial ulcer caused by Trichophyton rubrum.

Dermatophytosis is the most common fungal infectious disease in the world, which is commonly caused by Trichophyton rubrum in China. The traditional therapies for treating dermatophytosis include topical and oral antifungal agents like terbinafine, griseofulvin, and azole antifungal drugs. However, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) as a new alternative therapy avoids the side effects and drug resistance of traditional antifungal agents. We report two cases diagnosed as kerion and tinea faciei secondary to ulcers with CARD 9 deficiency, both of whom were infected by T.rubrum. They were both successfully treated by ALA-PDT combined with antifungal drugs, providing a feasible strategy for therapeutic choice for adult kerion and ulcer treatment.

Imaging signs and the qualitative diagnosis of solitary rib lesions using 99mtechnetium-methylene diphosphonate whole-body bone imaging in patients with a malignant tumor.

Background: The aim of this study was to summarize the valuable information for qualitative diagnosis by investigating the imaging signs from the whole-body bone imaging of solitary rib lesions. Methods: A retrospective analysis was conducted of the data from 313 patients with malignant tumors and solitary rib lesions identified using whole-body bone imaging in Department of Nuclear Medicine of Central South University Xiangya School Affiliated Haikou Hospital between January 2015 and December 2017. Based on the final comprehensive diagnosis of the rib lesions, the patients were divided into a bone metastasis group, fracture group, other benign lesions group, and an uncertain group, and the characteristic imaging changes in rib lesions in each group were explored. Results: (I) Significant differences were identified among the 4 groups (P<0.001) in the distribution of lesions in the anterior, posterior, and lateral ribs and proximal costal cartilage. The fracture group had the highest proportion of lesions in the anterior ribs (99/121, 81.8%) and proximal costal cartilage (74.4%, 90/121). (II) Significant differences were detected in morphology, concentration, boundaries, and radioactivity distribution among the 4 groups of patients (P<0.001). The bone metastasis group had the highest proportion of lesions appearing as stripes (35/67, 52.2%), and the fracture group had the highest proportion of lesions appearing as spots (94.2%, 114/121) and the lowest proportion appearing as stripes (3/121, 2.5%). (III) Significant differences were found in the longitudinal diameter, transverse diameter, aspect ratio, and tumor-to-normal tissue ratio between the 4 groups (P<0.001). The longitudinal diameter (27.8±16.0 mm) and aspect ratio (1.9±1.0) of the bone metastasis group were the highest, whereas the longitudinal diameter (15.2±3.9 mm) and aspect ratio (1.0±0.2) of the fracture group were the smallest. Conclusions: This study revealed that different types of solitary rib lesions had relatively characteristic imaging signs in whole-body bone imaging.

The SphK1/S1P Axis Regulates Synaptic Vesicle Endocytosis via TRPC5 Channels.

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid concentrated in the brain, is essential for normal brain functions, such as learning and memory and feeding behaviors. Sphingosine kinase 1 (SphK1), the primary kinase responsible for S1P production in the brain, is abundant within presynaptic terminals, indicating a potential role of the SphK1/S1P axis in presynaptic physiology. Altered S1P levels have been highlighted in many neurologic diseases with endocytic malfunctions. However, it remains unknown whether the SphK1/S1P axis may regulate synaptic vesicle endocytosis in neurons. The present study evaluates potential functions of the SphK1/S1P axis in synaptic vesicle endocytosis by determining effects of a dominant negative catalytically inactive SphK1. Our data for the first time identify a critical role of the SphK1/S1P axis in endocytosis in both neuroendocrine chromaffin cells and neurons from mice of both sexes. Furthermore, our Ca2+ imaging data indicate that the SphK1/S1P axis may be important for presynaptic Ca2+ increases during prolonged stimulations by regulating the Ca2+ permeable TRPC5 channels, which per se regulate synaptic vesicle endocytosis. Collectively, our data point out a critical role of the regulation of TRPC5 by the SphK1/S1P axis in synaptic vesicle endocytosis.SIGNIFICANCE STATEMENT Sphingosine kinase 1 (SphK1), the primary kinase responsible for brain sphingosine-1-phosphate (S1P) production, is abundant within presynaptic terminals. Altered SphK1/S1P metabolisms has been highlighted in many neurologic disorders with defective synaptic vesicle endocytosis. However, whether the SphK1/S1P axis may regulate synaptic vesicle endocytosis is unknown. Here, we identify that the SphK1/S1P axis regulates the kinetics of synaptic vesicle endocytosis in neurons, in addition to controlling fission-pore duration during single vesicle endocytosis in neuroendocrine chromaffin cells. The regulation of the SphK1/S1P axis in synaptic vesicle endocytosis is specific since it has a distinguished signaling pathway, which involves regulation of Ca2+ influx via TRPC5 channels. This discovery may provide novel mechanistic implications for the SphK1/S1P axis in brain functions under physiological and pathologic conditions.

The influencing factors of infectious complications after percutaneous nephrolithotomy: a systematic review and meta-analysis.

Infection is the most common complications of percutaneous nephrolithotomy (PCNL) in treating urinary calculi. However, the risk factors for developing infectious complications after surgery have not been clarified, and the predictive value of some factors is controversial. This study aimed to assess the risk factors for postoperative infectious complications of PCNL. We performed a systematic search of PubMed, Web of Science, Cochrane Library, and EMBASE to obtain studies reporting risk factors for postoperative infection complications after PCNL. In this review, demographic factors, laboratory test factors, and perioperative factors were evaluated. The odds ratio (OR) or mean difference (MD) with a 95% confidence interval (CI) was calculated to assess the risk factors. A total of 18 studies were included, with a total of 7161 study patients with a mean age of 46.4 to 55.5 years and an incidence of infectious complications after PCNL ranging from 2.4% to 40.4%. Twelve factors were identified as independent risk factors for post-PCNL infection complications (P < 0.05), female (OR = 1.60, 95% CI 1.23-2.07), positive urine culture (UC) (OR = 3.16, 95% CI 2.11-4.74), positive renal pelvis urine culture (RPUC) (OR = 5.81, 95% CI 1.75-19.32), positive stone culture (SC) (OR = 5.11, 95% CI 1.46-17.89), positive urine leukocyte (OR = 3.61, 95% CI 2.45-5.34), infected stones (OR = 7.00, 95% CI 1.27-38.55), elevated blood leukocyte (MD = 0.71, 95% CI 0.31-1.10), elevated neutrophil-to-lymphocyte ratio (NLR) (MD = 0.55, 95% CI 0.43-0.66), preoperative stenting (OR = 1.55, 95% CI 1.10-2.20), multiple puncture access (OR = 2.58, 95% CI 1.75-3.82), prolonged operative time (MD = 10 20, 95% CI 4.80-15.60), and postoperative residual stone (OR = 1.56, 95% CI 1.24-1.98). Female, UC positivity, RPUC positivity, SC positivity, urine leukocyte positivity, infected stones, elevated peripheral blood leukocytes, elevated NLR, preoperative stent implantation, multiple puncture channels, prolonged operation time, and postoperative residual stones were identified as independent risk factors for infection complications after PCNL.

Comparison of postoperative outcomes of mini percutaneous nephrolithotomy and standard percutaneous nephrolithotomy: a meta-analysis.

Our study was aimed to evaluate the postoperative outcomes of Mini Percutaneous Nephrolithotomy (Mini-PCNL) and Standard Percutaneous Nephrolithotomy (Standard-PCNL) to determine the optimum option for patients with renal calculi. For publications published between January 2010 and April 2021, a comprehensive search of the PubMed, Cochrane Library, Web of Science, and EMBASE databases was done. The literatures were chosen based on the criteria for inclusion and exclusion. After the data were retrieved and the quality was assessed, the meta-analysis was performed using Review Manager Software (RevMan 5.4.1, Cochrane Collaboration, Oxford, UK). We selected 20 trials with a total of 4953 people out of 322 studies. There were 2567 patients treated with Mini-PCNL and 2386 patients treated with Standard-PCNL. Meta-analysis results showed no difference in stone-free rates (SFR, P = 0.93), fever (P = 0.83), and postoperative pain (VAS score) (P = 0.21) between Mini-PCNL and Standard-PCNL. Patients in the Mini-PCNL group experienced shorter hospital stay (P < 0.0001), less hemoglobin drop (P < 0.00001), less blood transfusion (P < 0.00001), higher postoperative tubeless (P = 0.0002), and fewer complications including bleeding (P = 0.01), perforation (P = 0.03), and leakage (P = 0.01). Compared with Standard-PCNL, operative time was longer in the Mini-PCNL group (P = 0.0005). Mini-PCNL had a shorter hospital stay, less hemoglobin drop, less blood transfusion, greater postoperative tubeless, fewer complications, and a longer operational time when compared to Standard-PCNL. SFR, fever, and postoperative pain were similar in both of them. Mini-PCNL may be a superior option for patients with proper size renal calculi.

Virus-virus interactions of febrile respiratory syndrome among patients in China based on surveillance data from February 2011 to December 2020.

The burden of acute respiratory infections is still considerable, and virus-virus interactions may affect their epidemics, but previous evidence is inconclusive. To quantitatively investigate the interactions among respiratory viruses at both the population and individual levels, we use data from the pathogen surveillance for febrile respiratory syndrome (FRS) in China from February 2011 to December 2020. Cases tested for influenza virus (IV), respiratory syncytial virus (RSV), human parainfluenza virus (PIV), human Adenovirus (AdV), human coronavirus (CoV), human bocavirus (BoV), and rhinovirus (RV) were collected. We used spearman's rank correlation coefficients and binary logistic regression models to analyze the interactions between any two of the viruses at the population and individual levels, respectively. Among 120 237 cases, 4.5% were coinfected with two or more viruses. Correlation coefficients showed seven virus pairs were positively correlated, namely: IV and RSV, PIV and AdV, PIV and CoV, PIV and BoV, PIV and RV, AdV and BoV, and CoV and RV. Regression models showed positive interactions for all virus pairs, except for the negative interaction between IV and RV (odds ratio = 0.70, 95% confidence interval: 0.61-0.81). Most of the respiratory viruses interact positively, while IV and RV interact negatively.

Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones.

Intrarenal calcium oxalate (CaOx) crystals induce renal tubular epithelial cell (TEC) inflammatory and oxidative injury. This study is aimed at exploring potential therapeutic lipid components in kidney stones because lipids are involved in the development of several diseases and indicate the risk of kidney stones. Serum specimens were collected from 35 kidney stone patients and 35 normal controls. The lipid components in serum were measured, and differences were analyzed. The documented biological importance was comprehensively reviewed to identify lipids that differed significantly between the two groups to find potential agents associated with kidney stones. CaOx nephrocalcinosis mouse model was established to examine the therapeutic effects of specific lipids on CaOx deposition and CaOx-induced oxidative renal injury. Several lipids with significantly different levels were present in the serum of patients with stones and normal controls. Resolvin D1 (RvD1) (4.93-fold change, P < 0.001) and protectin D1 (PD1) (5.06-fold change, P < 0.001) were significantly decreased in the serum of patients with kidney stones, and an integrative review suggested that these factors might be associated with inflammatory responses, which is a crucial mechanism associated with stone damage. The administration of RvD1 and PD1 significantly inhibited kidney CaOx deposition and suppressed CaOx-induced renal tubular cell inflammatory injury and necrosis in a CaOx nephrocalcinosis mouse model. Furthermore, RvD1 and PD1 facilitated the expression of the oxidative indicator superoxide dismutase 2 (SOD2), inhibited NADPH oxidase 2 (NOX2) expression, and diminished intracellular reactive oxygen species (ROS) levels. This study preliminarily elucidated the role of lipids in kidney stones. The inhibitory effects of RvD1 and PD1 on oxidative damage induced by CaOx deposition provide a promising perspective for kidney stone treatment strategies.

Does obesity mediate the relationship between diabetes and osteoporosis in Chinese elderly population?

OBJECTIVES: Diabetes mellitus (DM), osteoporosis (OP), and obesity (OB) are three complex diseases. OB is associated with both DM and OP, but it is unclear whether OB mediates association between DM and OP. The study aimed to investigate the potential mediation effects of OB on association between DM and bone mineral density (BMD) by the causal inference tests (CIT). METHODS: A total of 5682 Chinese aged over 65 years were enrolled in an ongoing cohort: Osteoporosis Preventive Project (OPP). Obesity-related indexes, including body mass index (BMI), waist circumference, and waist circumference-hip circumference-ratio (WHR), and BMD at total hip (TH) and femur neck (FN) were measured. RESULTS: Subjects with DM had significant greater values of age, weight, BMI, waist circumference, WHR, and BMD than non-DM subjects. BMD at TH and FN was significantly associated with DM (p < 0.05) with adjustment of age both in males and females. Further CIT showed that OB-related indexes (BMI, waist circumference, and WHR) are significantly mediators in the associations between DM and BMD in females, but not in males. Furthermore, the mediation effects of waist circumference were detected on DM and TH BMD in the females of normal-weight group. CONCLUSIONS: Obesity-related indexes, especially waist circumference, serve as significant mediator(s) between DM and OP in Chinese female elderly. Diabetes increases BMD by increasing obesity-related indexes. The findings established the intermediate role of OB underlying the association between DM and OP in human population.

Mechanism of Cordyceps Cicadae in Treating Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking Analysis.

OBJECTIVE: To systematically study the mechanism of cordyceps cicadae in the treatment of diabetic nephropathy (DN) with the method of network pharmacology and molecular docking analysis, so as to provide theoretical basis for the development of new drugs for the treatment of DN. METHODS: TCMSP, Symmap, PubChem, PubMed, and CTD database were used to predict and screen the active components and therapeutic targets for DN. The network of active components and targets was drawn by Cytoscape 3.6.0, the protein-protein interaction (PPI) was analyzed by the STRING database, and the DAVID database was used for the enrichment analysis of intersection targets. Molecular docking studies were finished by Discovery Studio 3.5. RESULTS: A total of 36 active compounds, including myriocin, guanosine, and inosine, and 378 potential targets of cordyceps cicadae were obtained. PPI network analysis showed that AKT1, MAPK8, and TP53 and other targets were related to both cordyceps cicadae and DN. GO and KEGG pathway analysis showed that these targets were mostly involved in R-HSA-450341, 157.14-3-3 cell cycle, and PDGF pathways. Docking studies suggested that myriocin can fit in the binding pocket of two target proteins (AKT1 and MAPK8). CONCLUSION: Active ingredients of cordyceps cicadae such as myriocin may act on DN through different targets such as AKT1, MAPK8, and TP53 and other targets, which can help to develop innovative drugs for effective treatment of DN.

TRPM7 is critical for short-term synaptic depression by regulating synaptic vesicle endocytosis.

Transient receptor potential melastatin 7 (TRPM7) contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in central nervous system (CNS) neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+ imaging detects a defect in presynaptic Ca2+ dynamics in TRPM7 KO neuron, suggesting an importance of Ca2+ influx via TRPM7 in synaptic vesicle endocytosis. Moreover, the short-term depression is enhanced in both excitatory and inhibitory synaptic transmissions from TRPM7 KO mice. Taken together, our data suggests that Ca2+ influx via TRPM7 may be critical for short-term plasticity of synaptic strength by regulating synaptic vesicle endocytosis in neurons.

The current status of preventive measures for urinary calculi in children.

Urological calculus is a common disease in urology. Urological calculi are generally more common in adults but have become more common in children in recent years. Most existing studies focus on the prevention of urinary calculi in adults; there are relatively few articles on calculi in children. Reported preventive measures are not comprehensive enough, while the latest research progress has not been updated. The pathogenesis and preventive measures associated with urinary calculi have been the focus of research, but many preventive measures still need further clarification. This article reviews the progress on preventive measures for urinary calculi in children.

Effects of aerobic exercise on TC, HDL-C, LDL-C and TG in patients with hyperlipidemia: A protocol of systematic review and meta-analysis.

BACKGROUND: With the development of the social level and the improvement of living standards, people's dietary structure changes in the direction of high blood fat, high sugar and high fever, which leads to the occurrence of many diseases.Long-term increase in blood lipids can easily cause cholesterol to invade the walls of large blood vessels, deposit and accumulate, and promote the proliferation of smooth muscle cells and fibroblasts in the arterial intima, leading to coronary heart disease and atherosclerosis (AS) and other cardiovascular and cerebrovascular diseases. METHODS: Electronic databases including Google Scholar, PubMed, Web of Science(WOS), the Cochrane Library, EMBASE and VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang. These databases will be searched to identify randomized controlled trials published January 1, 1980, and January 20, 2021. Language is limited with English and Chinese. We will use the standards provided in Cochrane Handbook 5.3.0 for quality assessment and risk assessment, and use Revman 5.3 software for meta-analysis. The primary outcomes are mainly evaluated by total cholesterol and triglyceride. CONCLUSION: The results of this study can provide a beneficial basis for the improvement of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and triglyceride in patients with hyperlipidemia.

Altered spontaneous brain activity in essential tremor with and without resting tremor: a resting-state fMRI study.

OBJECTIVES: Essential tremor with resting tremor (rET) often exhibits severer clinical features and more extensive functional impairment than essential tremor without resting tremor (ETwr). However, the pathophysiology of rET is still unclear. This study aims to use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the alterations of brain activity between the drug-naïve patients of rET and ETwr. METHODS: We recruited 19 patients with rET, 31 patients with ETwr and 25 healthy controls (HCs) to undergo a 3.0-T rs-fMRI examination. The differences of regional brain spontaneous activity between the rET, ETwr and HCs, as well as between total ET (rET + ETwr) and HCs were measured by amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). The relationships between the altered brain measurements and the clinical scores were analyzed. RESULTS: Compared with HCs, both ET subgroups showed significantly decreased ALFF or fALFF values in the basal ganglia, inferior orbitofrontal gyrus and insula. The rET group specifically showed decreased ALFF values in the hippocampus and motor cortices, while the ETwr group specifically evidenced increased ALFF and fALFF values in the cerebellum. DISCUSSION: Regional spontaneous activity in rET and ETwr share common changes and have differences, which may suggest that the functional activities in the limbic system and cerebellum are different between the two subtypes. Improved insights into rET and ETwr subtypes and the different brain spontaneous activity will be valuable for improving our understanding of the pathophysiology of the disease.

LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-ĸB pathway in diabetic nephropathy.

BACKGROUND: It has been reported that long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). Our study aims to research the function of lncRNA KCNQ1OT1 in DN cells and the molecular mechanism. METHODS: Human glomerular mesangial cells (HGMCs) and human renal glomerular endothelial cells (HRGECs) were cultured in high glucose (30 mM) condition as models of DN cells. KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and miR-18b-5p levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mRNA and protein levels of Sorbin and SH3 domain-containing protein 2 (SORBS2), Type IV collagen (Col-4), fibronectin (FN), transcriptional regulatory factor-beta 1 (TGF-ß1), Twist, NF-κB and STAT3 were measured by qRT-PCR and western blot. Cell viability was detected by cell counting kit-8 (CCK-8) assay for selecting the proper concentration of glucose treatment. Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry assay were employed to determine cell proliferation and apoptosis, respectively. The targets of KCNQ1OT1 was predicted by online software and confirmed by dual-luciferase reporter assay. RESULTS: KCNQ1OT1 and SORBS2 were elevated in DN. Both knockdown of KCNQ1OT1 and silencing of SORBS2 restrained proliferation and fibrosis and induced apoptosis in DN cells. Besides, Overexpression of SORBS2 restored the KCNQ1OT1 knockdown-mediate effects on proliferation, apoptosis and fibrosis in DN cells. In addition, miR-18b-5p served as a target of KCNQ1OT1 as well as targeted SORBS2. KCNQ1OT1 knockdown repressed NF-ĸB pathway. CONCLUSION: KCNQ1OT1 regulated DN cells proliferation, apoptosis and fibrosis via KCNQ1OT1/miR-18b-5p/SORBS2 axis and NF-ĸB pathway.

[Responses of potential suitable area of Paris verticillata to climate change and its dominant climate factors]. / åŒ—é‡æ¥¼æ½œåœ¨é€‚ç”ŸåŒºå¯¹æ°”å€™å˜åŒ–çš„å“åº”åŠå ¶ä¸»å¯¼æ°”å€™å› å­.

Prediction of the potential distribution of species based on the data of its current distribution in combination with climatic variables is important for understanding species evolution and reasonable conservation. Based on 220 distribution sites in China and 12 low-correlation climatic variables, we analyzed the potential distribution of Paris verticillata at present and future (2050s and 2070s) using the MaxEnt model and ArcGIS program. Further, we analyzed the dominant driving factors for its geographic distribution. The results showed that the area under the curve indices (AUC) was 0.940, with high prediction accuracy. The potential suitable regions of P. verticillata were mainly distributed in the Greater Xing'an Mountains, the Xiao Xing'an Mountains, the Changbai Mountains, the Qinling-Daba Mountains, Hebei, Shanxi and north Shandong under current climate scenario. Those regions accounted for 18.1% of the total suitable area in the country, of which the highly suitable areas accounted for 7.0% and the lowly suitable area 11.1%. The total suitable areas of P. verticillata in the 2050s and 2070s would decline under the climate change scenarios of RCP 2.6, RCP 4.5, RCP 6.0 and RCP 8.5. The highly suitable area would decline, but the lowly suitable area would increase. With the global climate change, both the range and the geometric center of its distribution would gradually spread to higher altitude in the northeast. The cumulative contributions of four dominant factors reached as high as 89.2%, namely, precipitation of wettest month, mean annual temperature, isothermality, and precipitation of January. Their appropriate ranges were 100-275 mm, -0.1-16 ℃, 21-35 and 3-14 mm, respectively.

Patterns of intrinsic brain activity in essential tremor with resting tremor and tremor-dominant Parkinson's disease.

The clinical pictures of essential tremor (ET) with resting tremor (rET) and tremor-dominant Parkinson's disease (tPD) are often quite mimic at the early stage, current approaches to the diagnosis and treatment therefore remain challenging. The regional homogeneity (ReHo) method under resting-state functional magnetic resonance imaging (rs-fMRI) would help exhibit the patterns in neural activity, which further contribute to differentiate these disorders and explore the relationship between symptoms and regional functional abnormalities. Sixty-eight Chinese participants were recruited, including 19 rET patients, 24 tPD patients and 25 age- and gender-matched healthy controls (HCs). All participants underwent clinical assessment and rs-fMRI with a ReHo method to investigate the alterations of neural activity, and the correlation between them. Differences were compared by two-sample t-test (corrected with AlphaSim, p < 0.05). Compared with HCs, patients' groups both displayed decreased ReHo in the default mode network (DMN), bilateral putamen and bilateral cerebellum. While tPD patients specifically exihibited decreased ReHo in the bilateral supplementary motor area (SMA) and precentral gyrus (M1). The correlation analysis revealed that ReHo in the bilateral putamen, right SMA and left cerebellum_crus I were negatively correlated with the UPDRS-III score, respectively, in tPD group. Our results indicated the rET patients may share part of the pathophysiological mechanism of tPD patients. In addition, we found disorder-specific involvement of the SMA and M1 in tPD. Such a distinction may lend itself to use as a potential biomarker for differentiating between these two diseases.

Phosphatidylserine is critical for vesicle fission during clathrin-mediated endocytosis.

Phosphatidylserine (PS), a negatively charged phospholipid present predominantly at the inner leaflet of the plasma membrane, has been widely implicated in many cellular processes including membrane trafficking. Along this line, PS has been demonstrated to be important for endocytosis, however, the involved mechanisms remain uncertain. By monitoring clathrin-mediated endocytosis (CME) of single vesicles in mouse chromaffin cells using cell-attached capacitance measurements that offer millisecond time resolution, we demonstrate in the present study that the fission-pore duration is reduced by PS addition, indicating a stimulatory role of PS in regulating the dynamics of vesicle fission during CME. Furthermore, our results show that the PS-mediated effect on the fission-pore duration is Ca2+ -dependent and abolished in the absence of synaptotagmin 1 (Syt1), implying that Syt1 is necessary for the stimulatory role of PS in vesicle fission during CME. Consistently, a Syt1 mutant with a defective PS-Syt1 interaction increases the fission-pore duration. Taken together, our study suggests that PS-Syt1 interaction may be critical in regulating fission dynamics during CME.

Screening and survival analysis of differentially expressed genes in papillary thyroid carcinoma / 解剖学报

Objective Bioinformatics method was used to analyze gene expression microarrays of papillary thyroid cancer (PTC) and adjacent tissues. The key genes of PTC and their signal pathways were screened to understand their carcinogenic mechanisms. Methods Data on PTC and paracancerous tissue samples were obtained from seven GSE series on two sequencing platforms in the Gene Expression Omnibus Database ( GEO ). Firstly, the differential genes of the two sequencing platform samples were screened by R language. Then biological function, signal pathway analysis and protein-protein interaction analysis were performed on differential genes by Metascape and STRING. Finally, the key gene were selcected by Cytoscape 3. 5. 1 software. Results A total of 302 differential genes were obtained from the intersection of the two sequencing platform samples, of which 149 genes were up-regulated and 153 genes were down-regulated. Using the Cytoscape 3. 5. 1 software to screen out 15 key genes, 12 of them are involved in the extracellular matrix receptor interaction signal pathway. Survival analysis of 15 key genes was performed using the UALCAN database, and the changes in the expression levels of 4 genes were closely related to the survival time of patients. Conclusion This study uses bioinformatics technology to analyze the data from seven PTC gene chips, making up for the inconsistency of small sample result and improving the reliability and stability of the result . In addition, 15 key genes are screened out and found that the matrice extracellulaire receptor interactions pathway plays an important role in the development of thyroid cancer. The result of this experiment provides guidance for the further study of PTC molecular mechanism, diagnosis and screening of prognostic molecular markers.

Extracellular and intracellular sphingosine-1-phosphate distinctly regulates exocytosis in chromaffin cells.

Sphingosine-1-phosphate (S1P) is an essential bioactive sphingosine lipid involved in many neurological disorders. Sphingosine kinase 1 (SphK1), a key enzyme for S1P production, is concentrated in presynaptic terminals. However, the role of S1P/SphK1 signaling in exocytosis remains elusive. By detecting catecholamine release from single vesicles in chromaffin cells, we show that a dominant negative SphK1 (SphK1DN ) reduces the number of amperometric spikes and increases the duration of foot, which reflects release through a fusion pore, implying critical roles for S1P in regulating the rate of exocytosis and fusion pore expansion. Similar phenotypes were observed in chromaffin cells obtained from SphK1 knockout mice compared to those from wild-type mice. In addition, extracellular S1P treatment increased the number of amperometric spikes, and this increase, in turn, was inhibited by a selective S1P3 receptor blocker, suggesting extracellular S1P may regulate the rate of exocytosis via activation of S1P3. Furthermore, intracellular S1P application induced a decrease in foot duration of amperometric spikes in control cells, indicating intracellular S1P may regulate fusion pore expansion during exocytosis. Taken together, our study represents the first demonstration that S1P regulates exocytosis through distinct mechanisms: extracellular S1P may modulate the rate of exocytosis via activation of S1P receptors while intracellular S1P may directly control fusion pore expansion during exocytosis. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

Association of three candidate genetic variants in ACMSD/TMEM163, GPNMB and BCKDK /STX1B with sporadic Parkinson's disease in Han Chinese.

Large-scale meta-analyses of genome-wide association studies have identified that polymorphisms ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 to be the risk loci for Parkinson's disease (PD) in a Caucasian population. However, the role of these three polymorphisms in a Han Chinese population from mainland China still remains to be clarified. We conducted a large sample study to examine genetic associations of rs6430538, rs199347 and rs14235 with PD in a Han Chinese population of 989 sporadic PD patients and 1058 healthy controls. All subjects were genotyped for these loci using the Sequenom iPLEX Assay. In addition, we conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. However, no significant differences were found in genotype and allele frequency distribution between PD patients and controls for the three loci, even after being stratified by age at onset. Moreover, we demonstrated that minor allele carriers cannot be distinguished from non-carriers based on their clinical features. Our study is the first to demonstrate that ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 do not confer a significant risk for sporadic PD in mainland China. Therefore, more replication studies in additional Chinese population and other cohorts and functional studies are warranted to further clarify the role of the three loci in PD susceptibility.