Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Objective:To investigate the protective effect and potential mechanisms of microRNA-26a-5p (miR-26a-5p) on podocyte injury in diabetic kidney disease (DKD).Methods:(1) In vivo experiment: Four-week-old db/db mice were divided into db/db group, db/db+agomir-NC group and db/db+miR-26a-5p agomir group according to random number table method, with 10 mice in each group, and 10 db/m mice of the same week-old were set as normal control group. At the age of 10 weeks, pathological changes were observed through light and electron microscopy. Kidney weight/body weight (KW/BW), urinary albumin to creatinine ratio (ACR), fasting blood glucose (FBG) and other biochemical indicators were also detected. The position and expression of miR-26a-5p in kidney tissue were determined through fluorescence in situ hybridization and quantitative real-time PCR, while the expressions of transient receptor potential cation channel-6 (TRPC6) and Nephrin in kidney tissue were determined by Western blotting and immunohistochemistry. (2) In vitro experiment: The immortalized mouse podocytes (MPC5) were divided into 5 groups: normal glucose group, high mannitol group, high glucose group, high glucose+miR-26a-5p mimic group, and high glucose+mimic-NC group. The expressions of miR-26a-5p, TRPC6 and Nephrin were detected. Luciferase reporter assay was conducted to research the relationship of miR-26a-5p and TRPC6. Results:(1) In vivo experiment: Compared with db/m group, db/db mice exhibited lower KW/BW and disrupted conditions of ACR, FBG, total cholesterol, triglycerides and low density lipoprotein cholesterol (all P<0.01). Increased glomeruli volume, more extracellular matrix deposition, thicker basement membrane and more foot process fusion were observed by light and electron microscope. Increased expression of TRPC6 protein as well as decreased expression of Nephrin protein and miR-26a-5p were detected in kidney tissues of db/db mice ( P<0.05). Compared with db/db+agomir-NC group, db/db mice transfected by miR-26a-5p agomir exhibited less albuminuria, with less protein expression of TRPC6 and more Nephrin in kidney tissue (all P<0.05). (2) In vitro experiment: Compared with normal glucose group, high glucose-treated podocytes exhibited increased expression of TRPC6 ( P<0.05), as well as decreased expression of Nephrin ( P<0.05) and miR-26a-5p ( P<0.01). Compared with high glucose+mimic-NC group, lower expression of TRPC6 and higher expression of Nephrin were detected in podocytes transfected by miR-26a-5p mimic (both P<0.05). Luciferase reporter assay confirmed that miR-26a-5p could regulate the expression of TRPC6 precisely. Conclusions:The expression of miR-26a-5p in podocytes is down-regulated in the context of high glucose and miR-26a-5p protects podocytes from injury via inhibiting the expression of TRPC6 in DKD.

The Genome Warehouse (GWH) is a public repository housing genome assembly data for a wide range of species and delivering a series of web services for genome data submission, storage, release, and sharing. As one of the core resources in the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB;https://ngdc.cncb.ac.cn), GWH accepts both full and partial (chloroplast, mitochondrion, and plasmid) genome sequences with different assembly levels, as well as an update of existing genome assemblies. For each assembly, GWH collects detailed genome-related metadata of biological project, biological sample, and genome assembly, in addition to genome sequence and annotation. To archive high-quality genome sequences and annotations, GWH is equipped with a uniform and standardized procedure for quality control. Besides basic browse and search functionalities, all released genome sequences and annotations can be visualized with JBrowse. By May 21, 2021, GWH has received 19,124 direct submissions covering a diversity of 1108 species and has released 8772 of them. Collectively, GWH serves as an important resource for genome-scale data management and provides free and publicly accessible data to support research activities throughout the world. GWH is publicly accessible at https://ngdc.cncb.ac.cn/gwh.

Objective:To study on the effects of micro-plasma radio frequency technology on guinea pig skin pigmentation animal model induced by narrow band ultraviolet B (NB-UVB).Methods:We selected ten healthy guinea pigs (common grade), removed the brown hair of the guinea pig and established UVB to induce the skin pigmentation model of guinea pig. The pigmentation zone was randomly divided into four groups: Group A was used as blank control with no treatment and Groups B , C and D were treated with micro-plasma radio frequency technology using different energy parameters. Group B treatment parameters were as follows: output power was 10 watts, and treatment energy was 0.06J. Group C treatment parameters were as follows: output power was 20 watts, and treatment energy was 0.12J. Group D treatment parameters were as follows: output power was 30 watts, and treatment energy was 0.18J. They were compared before treatment and at 2, 4, and 6 weeks after treatment, based on melanin cell staining (epidermis separation-dopa staining) and melanin granules dyeing method (Masson-Fontana). Immunohistochemical staining (c-kit protein) was used to observe the tyrosinase activity in the melanocytes, melanin granule percentage area of the skin area, and the change in melanin cell activity. SPSS13.0 statistical software was used for statistical analysis of the experimental data. The significance of the difference ( P< 0.05) was measured. Results:The results showed that micro-plasma radio frequency (RF) technology treatment could reduce the tyrosinase activity in the melanocytes, 2, 4 and 6 weeks after the end of treatment: Groups B, C and D were lower than group A, and the difference was statistically significant ( P<0.05), and as the treatment energy increased, the speed of reduction was increased. Micro-plasma radio frequency technology could reduce skin pigmentation and decrease the amount of epidermal melanin granules, 2 and 4 weeks after the end of treatment: Groups B, C and D were lower than Group A; 6 weeks after the end of treatment, only Group D was lower than Group A, with statistically significant differences ( P< 0.05). An increase in the energy of the micro-plasma radio frequency sped up the decline in the amount of epidermal melanin granules.The number of c-kit positive cells was not increased in this experiment. Two weeks after the end of treatment, the number of c-kit positive cells was higher than those of Groups B, C and D. There were no statistically significant differences in Groups B, C and D ( P<0.05). No c-kit positive cells were found in Groups A, B, C and D at 4 and 6 weeks after the irradiation. Conclusions:Micro-plasma radio frequency technology could accelerate the fading of guinea pig skin pigmentation. It is effective to improve pigmentation of guinea pig skin after NB-UVB irradiation.

The pathogenesis of vascular cognitive impairment (VCI) remains unclear. There is a lack of specific treatment methods, and there is no unified evaluation standard for its clinical efficacy. In recent years, in addition to traditional drug therapy, the role of non-drug therapy in VCI therapy has gradually attracted attention. This article reviews the drug therapy, non-drug therapy and preventive interventions to improve the cognitive symptoms of VCI.

Objective:To study on the effects of micro-plasma radio frequency technology on guinea pig skin pigmentation animal model induced by narrow band ultraviolet B (NB-UVB).Methods:We selected ten healthy guinea pigs (common grade), removed the brown hair of the guinea pig and established UVB to induce the skin pigmentation model of guinea pig. The pigmentation zone was randomly divided into four groups: Group A was used as blank control with no treatment and Groups B , C and D were treated with micro-plasma radio frequency technology using different energy parameters. Group B treatment parameters were as follows: output power was 10 watts, and treatment energy was 0.06J. Group C treatment parameters were as follows: output power was 20 watts, and treatment energy was 0.12J. Group D treatment parameters were as follows: output power was 30 watts, and treatment energy was 0.18J. They were compared before treatment and at 2, 4, and 6 weeks after treatment, based on melanin cell staining (epidermis separation-dopa staining) and melanin granules dyeing method (Masson-Fontana). Immunohistochemical staining (c-kit protein) was used to observe the tyrosinase activity in the melanocytes, melanin granule percentage area of the skin area, and the change in melanin cell activity. SPSS13.0 statistical software was used for statistical analysis of the experimental data. The significance of the difference ( P< 0.05) was measured. Results:The results showed that micro-plasma radio frequency (RF) technology treatment could reduce the tyrosinase activity in the melanocytes, 2, 4 and 6 weeks after the end of treatment: Groups B, C and D were lower than group A, and the difference was statistically significant ( P<0.05), and as the treatment energy increased, the speed of reduction was increased. Micro-plasma radio frequency technology could reduce skin pigmentation and decrease the amount of epidermal melanin granules, 2 and 4 weeks after the end of treatment: Groups B, C and D were lower than Group A; 6 weeks after the end of treatment, only Group D was lower than Group A, with statistically significant differences ( P< 0.05). An increase in the energy of the micro-plasma radio frequency sped up the decline in the amount of epidermal melanin granules.The number of c-kit positive cells was not increased in this experiment. Two weeks after the end of treatment, the number of c-kit positive cells was higher than those of Groups B, C and D. There were no statistically significant differences in Groups B, C and D ( P<0.05). No c-kit positive cells were found in Groups A, B, C and D at 4 and 6 weeks after the irradiation. Conclusions:Micro-plasma radio frequency technology could accelerate the fading of guinea pig skin pigmentation. It is effective to improve pigmentation of guinea pig skin after NB-UVB irradiation.

Objective To understand the eco-hydraulics characteristics of Biomphalaria straminea,the intermediate host of Schistosoma mansoni. Methods The drainage method and settlement tube method were applied to measure B. straminea's den-sity and hydrostatic settling velocity respectively. Results The density of B. straminea was 1.04-1.16 g/cm3,and the average value was 1.08 g/cm3. The hydrostatic settling velocity was 2.32-12.92 cm/s. Conclusions The eco-hydraulics characteristics of B. straminea is different from Oncomelania hupensis,and more attention should be paid to the hydraulic measures for the con-trol of B. straminea.

Objective To investigate the prevalence of BPPV in patients with Meniere’s Disease(MD),and to investigate the diagnostic and predictive values of VEMP in patients with MD and BPPV.Methods A total of 1 1 6 patients previously diagnosed MD were followed up through telephone about their BPPV-like attacks.We recorded the detailed history of BPPV-like attacks,and provided them with complete Dix-Hallpike and roll tests if patients were on their BPPV-like attacks.Results In all,4 patients'histories supported BPPV,and 4 patients were found with BPPV.The prevalence of BPPV in patients with MD was 3 .4%(4/1 1 6 ).Meniere's symptoms preceded the on-set of BPPV in 8 patients.In 4 confirmed BPPV patients with Meniere's disease,BPPV was limited to the same ear as the MD in 2 cases,and 1 had contralateral BPPV,and 1 was uncertain.Six histories supported or confirmed BP-PVpatients with high abnormal oVEMP rates (5/6).Four in this 5 (80%)had abnormal oVEMP of the same MD ear.The single repositioning procedures can improve vertigo and eliminated positional nystagmus in cases of BPPV associated with MD.Conclusion In the present study,the prevalence of BPPV in patients with MD was 3 .45%.De-tailed medical histories combined with Dix-Hallpike and roll tests and VEMP tests can identify BPPV in patients with MD.

OBJECTIVE: To analyze the abnormal conditions of the affected ear and the contralateral ear of patients with unilateral Meniere's disease and the prevalence of bilateral abnormalities among these unilateral Meniere disease population, providing reference for the clinical treatment strategies for Meniére disease. METHOD: A retrospective analysis of 106 Meni6re disease cases was performed, the abnormal incidence of the affected ears, the contralateral ears and the bilateral abnormalities were calculated, and the disease characteristics were analyzed. RESULT: The bilateral ears abnormal incidence of unilateral Meniére disease was 35. 85% (38/106); the cochlear symptoms of the contralateral ears often occurred 2. 25 years later of the symptoms of Meni6re disease; contralateral cochlear symptoms included at least two symptoms of tinnitus, deafness and ear fullness; 39. 47%(15/38) patients with bilateral abnormalities would appear binaural hearing impairment. CONCLUSION This study showed that about one-third of unilateral Meniére diseases have binaural symptoms, among which about one-third would occur bilateral hearing loss. Therefore, it is necessary to consider the course of disease and the symptoms of the contralateral ear before taking damage or destructive method for treating Meniére's disease clinically.
Cochlea ; physiopathology ; Deafness ; Ear ; abnormalities ; Hearing Loss, Bilateral ; epidemiology ; Humans ; Incidence ; Meniere Disease ; epidemiology ; Prevalence ; Retrospective Studies ; Tinnitus

OBJECTIVE: To investigate the result of vestibular evoked myogenic potentials (VEMP) of primary benign paroxysmal positional vertigo(BPPV)and to identify the characteristics in VEMP examination of the primary BPPV and to observe the relevance of patients with primary BPPV and abnormal VEMP with hearing loss. METHOD: Patients with primary BPPV were tested with pure tone audiometry, videonystagmograph and VEMPs test. We analyzed the difference in the two groups with normal hearing and hearing loss, discussed the etiology and pathogenesis. RESULT: Primary BPPV comprised 23.0% with hearing lost, 77.0% hearing normal. The results of oVEMP were abnormal in 79. 7% (59/74) of the cases; and the results of cVEMP were abnormal in 66. 2% (49/74) of the cases; oVEMP and cVEMP differences to the diagnosis of primary BPPV (P<0. 05); oVEMP and cVEMP differences to the diagnosis primary BPPV with hearing lost (P<0. 05). CONCLUSION oVEMP detection positive rate of primary BPPV is higher than cVEMP,which may be due to otolithic particles falling from the utricle; positive rate of cVEMP in primary BPPV with hearing loss is higher than that of oVEMP, which may related to the cochlear and sacculus occured in the same embryonic tissue structure.
Audiometry, Pure-Tone ; Benign Paroxysmal Positional Vertigo ; physiopathology ; Cochlea ; Hearing Loss ; etiology ; Hearing Tests ; Humans ; Otolithic Membrane ; Saccule and Utricle ; Vestibular Evoked Myogenic Potentials