Neuroprotective effects of chaperone-mediated autophagy in neurodegenerative diseases

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins.Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis,while providing nutrients and support for cell survival.Chaperone-mediated autophagy activity can be detected in almost all cells,including neurons.Owing to the extreme sensitivity of neurons to their environmental changes,maintaining neuronal homeostasis is critical for neuronal growth and survival.Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases.It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction.Under certain conditions,regulation of chaperone-mediated autophagy activity attenuates neurotoxicity.In this paper,we review the changes in chaperone-mediated autophagy in neurodegenerative diseases,brain injury,glioma,and autoimmune diseases.We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

Preliminary Study on Overseas Applicability of Chinese Architectural Design Standards:Taking China-Aided Construction Projects in Asia Since the Belt and Road Initiative as Examples

This research takes China-aided construction projects in Asia since the Belt and Road Initiative as examples to explore the applicability of Chinese architectural design standards in other Asian countries.So far,the standards demonstrated the highest applicability in South Asia is the best followed by Southeast Asia.Chinese architectural design standards for educational buildings showed the highest applicability,followed by office,medical,and sports buildings.This study puts forward some strategies to improve the applicability of Chinese architectural design standards.These strategies include integrating regionalism and local cultural traditions,optimizing energy efficiency,and aligning designs with local usage habits.This study serves as a reference for similar projects in the future.

一例ISPD基因复合杂合变异所致的肢带型肌营养不良症2U型的诊断和基因检测分析

肢带型肌营养不良症(limb-girdle muscular dystrophy,LGMD)是一组罕见的非先天性遗传性肌肉疾病,主要表现为四肢近端肌张力及肌力进行性减退,其临床表现及遗传模式具有异质性。本研究报道了1例肢带型肌营养不良症2U型10岁男性患者,运动后出现双下肢肌肉无力,入院查肌酸激酶明显升高,经水化碱化治疗后无效。利用高通量测序方法对患者及其父母、妹妹进行肌营养不良相关基因检测,该患者存在ISPD基因外显子9杂合缺失以及c.1231C>T(p.Leu411Phe)的杂合错义变异,其父亲携带ISPD基因c.1231C>T(p.Leu411Phe)的杂合错义变异,母亲及妹妹携带ISPD基因外显子9杂合缺失,上述变异在现有的数据库及文献中均未见报道。对变异位点的保守性分析和蛋白结构预测分析表明,上述位点保守性高,且均位于ISPD蛋白C端结构域,可能对蛋白功能产生影响。综合以上结果并结合相关临床资料,可明确诊断该患者为肢带型肌营养不良症2U型。本文通过总结该患者临床特点及对ISPD基因新变异进行分析,丰富了ISPD基因变异谱,有助于该病早期诊断及遗传咨询。

长链非编码RNA SNHG3在食管鳞状细胞癌中的表达及其对ECA-109细胞迁移和侵袭的影响

目的:探究长链非编码RNA SNHG3在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织中的表达及其对ECA-109细胞迁移和侵袭的影响。方法:收集安阳市肿瘤医院2011年6月到2014年6月收治的60例ESCC患者癌及对应癌旁组织样本,采用qRT-PCR检测ESCC癌与癌旁组织、ESCC细胞ECA-109和人正常食管上皮细胞HEEC中lncRNA SNHG3的表达水平,分析ESCC患者组织中lncRNA SNHG3的表达与ESCC患者临床特征的关系。采用siRNA-SNHG3质粒转染ECA-109细胞,以敲降lncRNA SNHG3的表达水平。采用Kaplan-Meier法分析lncRNA SNHG3表达与患者预后的关系。采用Transwell实验检测ECA-109细胞的迁移和侵袭能力。采用qRT-PCR和Western blot实验检测ECA-109细胞中SNAIL和TWIST的mRNA及蛋白的表达水平。结果:ESCC肿瘤组织中lncRNA SNHG3的表达水平显著高于癌旁组织(P<0.05),ECA-109细胞中lncRNA SNHG3的表达水平显著高于人正常食管上皮细胞HEEC(P<0.05)。ESCC患者组织中lncRNA SNHG3的表达水平与肿瘤分化程度、TNM分期及淋巴结转移情况显著相关(P<0.05)。siRNA-SNHG3质粒转染ECA-109细胞后,lncRNA SNHG3的表达水平显著降低(P<0.05)。lncRNA SNHG3的高表达与ESCC患者预后不良显著相关。敲降lncRNA SNHG3后,ECA-109细胞的迁移和侵袭能力显著降低(P<0.05),SNAIL和TWIST的mRNA及蛋白的表达水平显著降低(P<0.05)。结论:lncRNA SNHG3在ESCC肿瘤组织和细胞中高表达,通过调控SNAIL和TWIST蛋白的表达,促进ECA-109细胞的迁移和侵袭。

Cognitive effects of atypical antipsychotic drugs in first-episode drug-nave schizophrenic patients

Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-naTve patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.

On Graphs with Same Distance Distribution

In the present paper we investigate the relationship between Wiener number W, hyper-Wiener number R, Wiener vectors WV, hyper-Wiener vectors HWV, Wiener polynomial H, hyper-Wiener polynomial HH and distance distribution DD of a (molecular) graph. It is shown that for connected graphs G and G*, the following five statements are equivalent:?;and if G and G* have same distance distribution DD then they have same W and R but the contrary is not true. Therefore, we further investigate the graphs with same distance distribution. Some construction methods for finding graphs with same distance distribution are given.

Simulation of structural design with high coupling efficiency in external cavity semiconductor laser

For external cavity semiconductor lasers(ECSLs),high coupling efficiency is critical to reducing the linewidth.In this paper,the coupling efficiency between the laser diode and the waveguide grating has been improved,with proposals for its improvement presented,including adding spot-size conversion(SSC)and using a silicon-on-insulator(SOI)waveguide.The results indicate an increase of coupling efficiency from 41.5%to 93.1%,which exhibits an improvement of approximately 51.6%over conventional schemes.The relationship between coupling efficiency and SOI waveguide structures is mainly concerned in this article.These findings provide a new way for the future research of the narrow linewidth of ECSL.

Regional climate response to global warming in the source region of the Yellow River and its impact on runoff

The source region of the Yellow River has experienced obvious climate and discharge changes in recent decades due to global warming, which largely affects the water resources and ecological and environmental security in the Yellow River basin. This study analyzed the changes in runoff and several climate factors in the source region of the Yellow River based on the observed discharges at the Tangnag hydrological station, routine meteorological data from China Meteorological Administration(CMA) stations within and near this source region, and several evaporation datasets. The results indicate that the runoff in the source region was relatively abundant from 1960 to 1989 and then declined sharply afterward. It recovered slightly after 2005 but was still below normal—10% less than that during 1960–1989. Similarly, the precipitation amounts in the source region were relatively low in the 1990s, but they increased significantly after 2003, with an average increase of 31.4 mm or 6% more when compared to that in 1960–1989. In addition, the temperatures in the source region continued to rise from 1960 to 2017, and the evaporation levels also showed an upward trend after 1990. The influences of the spatial and temporal variations in climatic factors on runoff in the source region were then further analyzed. The results indicate that the decreases in precipitation and the number of days of heavy rainfall in the source region from 1990 to 2002 were important reasons for the lower runoff during this period. After 2003, the precipitation in the southeastern part of the source region, which is a key area for runoff generation,increased only to a limited extent, but the evaporation in the entire source region generally increased with increasing temperature,which might have led to the low capacity for actual runoff production in each subbasin and persistent low runoff in the source region. Therefore, such a climate response to global warming in the source region might be unfavorable for increased runoff in the future. The above analysis provides a valuable reference for the future planning and management of water resources in the source region of the Yellow River and the entire Yellow River Basin in the context of warming.

Pt_(1)/Ni_(6)Co_(1)layered double hydroxides/N-doped graphene for electrochemical non-enzymatic glucose sensing by synergistic enhancement of single atoms and doping

The development of novel single-atom catalysts is important for highly efficient electrochemical catalysis and sensing.In this work,a novel Pt single atoms(SAs)supported on Ni_(6)Co_(1)layered double hydroxides/nitrogen-doped graphene(Pt_(1)/Ni_(6)Co_(1)LDHs/NG)was constructed for electrochemical enzyme-free catalysis and sensing towards glucose.The loading of Pt single atoms increases with doping of Co atoms that generate more anchoring sites for Pt SAs.The resulting Pt_(1)/Ni_(6)Co_(1)LDHs/NG exhibits low oxidative potential of 0.440 V with high sensitivity of 273.78μA·mM^(−1)·cm^(−2)toward glucose,which are 85 mV lower and 15 times higher than those of Ni(OH)_(2),respectively.Pt_(1)/Ni_(6)Co_(1)LDHs/NG also shows excellent selectivity and great stability during 5-week testing.Theoretical and experimental results show that the boosted performance of Pt_(1)/Ni_(6)Co_(1)LDHs/NG originates from its stronger binding energy with glucose and the synergistic effect of Pt SAs,Co doping,and NG.This work provides a general strategy of designing highly active SACs for extending their application in electrochemical sensing.

RAFT链转移剂的选用原则及通用型RAFT链转移剂

可逆加成-断裂链转移聚合(RAFT Polymerization)是目前最为常用的活性可控自由基聚合方法之一,因其产物分子量分布较窄、适用单体范围广、反应条件温和等优势得到了不同领域科学家的广泛应用。然而,科学家们在选择RAFT链转移剂(也称RAFT试剂)时,经常会忽略RAFT链转移剂与单体活性的匹配原则,导致在制备高活单体与低活单体的嵌段共聚物方面存在产物分子量分布宽、聚合速率慢,甚至反应无法成功进行的问题。基于此,本文首先综述聚合中RAFT链转移剂的选用原则,随后介绍近几年开发的一类同时适用于高/低活性单体聚合的通用型RAFT链转移剂(Universal/Switchable RAFT agent)的作用原理及适用条件,并着重探讨了基于通用型RAFT链转移剂制备高/低活性单体的嵌段共聚物的最新进展及应用。

Short and long-term efficacy of combining Fuzhengliqi mixture with acupuncture in treatment of functional constipation

OBJECTIVE: To explore the short and long-term efficacy of combining Fuzhengliqi mixture (FLM) with acupuncture in treating functional constipation (FC). METHODS: The 560 patients with confirmed diagnosis of FC were randomly assigned to four groups: FLM group, acupuncture group, combined therapy group, and control group. There were 140 cases in each group. The FLM group was administered FLM 60 mL twice a day, while the acupuncture group was treated with acupuncture at acupoints Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Dachangshu (BL 25), and Zhigou (TE 6) twice a day, the combined therapy group with FLM and acupuncture, and the control group was administered mosapride (5 mg thrice a day) and Macrogol 4000 (10 g twice a day). The treatment lasted 6 weeks. The defecation interval, stool property, constipation symptoms, and accompanying symptomswere recorded, graded, and scored.The gastrointestinal transit time (GITT) and motilin (MTL) level in serum and life quality score were detected at three time points (pre-treatment, at the end of treatment, and 60 weeks post-treatment). Moreover, the adverse reactions were also observed. RESULTS: In the FLM group 2 cases were eliminated for not taking medication strictly according to the research plan and 1 case was lost to follow-up, while 2 cases in the acupuncture group and 2 cases in the combined therapy group were lost to follow-up. Compared with those detected pre-treat- ment, the defecation interval, stool property, consti- pation symptom grade, accompanying symptom grade, and GITT were all decreased markedly at the end of treatment in every group, while the MTL levels in serum and life quality score were increased markedly (P<0.01), the above-mentioned detecting indices were better in the combined therapy group than those in other groups (P<0.05). Compared with the end of treatment, above-mentioned detecting indices all recurred significantly in the FLM group and control group 60 weeks post-treatment (P>0.05), but these indices recurred insignificantly in the acupuncture and combined therapy groups (P>0.05). The short and long-term total effective rates in the combined therapy group were significantly different from those in other groups (P<0.05 or P<0.01). No serious adverse reactions were found in four groups. CONCLUSION: Both FLM and acupuncture can significantly shorten the defecation interval and GITT, increase MTL levels in serum, decrease the scores of stool property, constipation symptoms, and accompanying symptoms in patients with FC to increase their life quality. The combined therapy is much better in long-term efficacy and the safety is also good, worth spreading in clinical practice.

Clinical curative effect of electroacupuncture combined with Zhizhukuanzhong Capsules for treating gastroesophageal reflux disease

OBJECTIVE：To study the clinical curative effect,safety and mechanism of action of electroacupuncture combined with Zhizhukuanzhong capsules（ZZKZC） in treating gastroesophageal reflux disease（GERD）.METHODS：A total of 480 patients with confirmed GERD were randomly divided into four groups：the electroacupuncture group,the ZZKZC group,the combined therapy group,and the control group,with 120 cases in each group.Each case in the electroacupuncture group was treated with electroacupuncture on Zusanli（ST36）,Zhongwan（CV12）,Neiguan（PC6）,Taichong（LR3）and Gongsun（SP 4）once daily for 6 weeks.Each case in the ZZKZC group was treated with oral administration of 1.29 g ZZKZC three times daily.The combined therapy group had electroacupuncture and ZZKZC.The control group was given oral administration of 5 mg mosapride three times and 20 mg pantoprazole twice daily.The 24-hour intraesophageal total number of reflux episodes with pH 0.05）;however,these indices all significantly deteriorated in the ZZKZC and control groups（P〉0.05）.The short and long-term total efficacy rates in the combined therapy group showed significant superiority to those in the other groups（P〈0.05 or P〈0.01）.No serious adverse reactions were found in the four groups.CONCLUSION：Electroacupuncture and ZZKZC play an important role in inhibiting intraesophageal acid and bile reflux,decreasing the endoscopic grading score,and alleviating the symptoms of gastroesophageal reflux to improve the quality of life.However,the effect of combined treatment is more effective,with better security and long-term efficacy,and therefore,this combination treatment is appropriate for clinicaluse.

Effects of flow parameters on thermal performance of an inner-liner anti-icing system with jets impingement heat transfer

The multiple jets impingement heat transfer is widely applied in the wing anti-icing system.It is challenging to apply the similarity criterion to carry out the anti-icing experiments due to the complex flow and heat transfer behavior.In the present study,the full-scale slat model is used to carry out anti-icing experimental researches in a 2 m×3 m icing wind tunnel of China Aerodynamics Research and Development Center.The effects of icing parameters Liquid Water Content(LWC)and Median Volume Diameter(MVD)and hot air parameters(mass flow rate and temperature)on the thermal performance of an inner-liner anti-icing system with jets impingement heat transfer are studied.The effects of the experimental parameters are analyzed in detail by combining impingement and evaporation heat transfer mechanisms.The impingement hot air mass flow rate dramatically affects the heat transfer performance of the impingement stagnation region within the range of the experimental parameters.The temperature of impingement hot air and that of wing skin are approximately linear correlated.The experimental results show the effects of LWC and MVD on water film formation and runback ice accretion.The formation of water film is analyzed by an analytical method based on the wing skin temperature difference of dry and wet air conditions.

Artesunate and Dihydroartemisinin Inhibit Rabies Virus Replication

Rabies is caused by infection of rabies virus(RABV)and remains a serious threat to the global public health.Except for the requirement for cold chain and high cost of human rabies immune globulin,no small molecule drugs are currently available for clinical treatment of rabies.So,it is of great importance to identify novel compounds that can effectively inhibit RABV infection.Artesunate(ART)and dihydroartemisinin(DHA),two derivatives of artemisinin,are widely used for treatment of malaria in adults and children,showing high safety.In this study,we found that both ART and DHA were able to inhibit RABV replication in host cells at a low concentration(0.1μmol/L).The antiviral effects of ART and DHA were independent of viral strains and cell lines.Pre-treatment with ART or DHA for 2 h in vitro did not affect the viral replication in host cells,implying that ART and DHA neither reduced the viability of RABV directly nor inhibited the binding and entrance of the virus to host cells.Further studies revealed that ART and DHA inhibited RABV genomic RNA synthesis and viral gene transcription.Treatment with ART or DHA(5 mg/kg)by intramuscular injection improved,to some extent,the survival rate of RABV-challenged mice.Combination treatment with derivatives of artemisinin and mannitol significantly improved the survival rate of RABV-challenged mice.The results suggest that ART and DHA have a great potential to be explored as new anti-rabies agents for treatment of rabies.

REMOVABLE EARS OF 1-EXTENDABLE GRAPHS

Carvalho, Lucchesi and Murty proved that any 1-extendable graph G different from K2 and C2n has at least A（G） edge-disjoint removable ears, and any brick G distinct from K4 and C6 has at least A（G） - 2 removable edges, where A（G） denotes the maximum degree of G. In this paper, we improve the lower bounds for numbers of removable ears and removable edges of 1-extendable graphs. It is proved that any 1-extendable graph G different from K2 and C2n has at least x′（G） edge-disjoint removable ears, and any brick G distinct from Ka and Ce has at least x′（G） - 2 removable edges, where x′（G） denotes the edge-chromatic number of G. Key words 1-extendable graphs, removable ear, removable edge.