Alpha-synuclein and Parkinson disease

OBJECTIVE： To review the recent progresses on the studies of α -synuclein in the pathogenesis of Parkinson disease （PD） and look into the perspective of α -synuclein as a new therapy target. DATA SOURCES： To search the literatures on the progresses of PD studies, especially on the structure, gene expression of α-synuclein and the pathogenesis of PD in Medline from January 1998 to February 2007. Search terms were ＂Parkinson＇s disease, α-synuclein＂ in English. STUDY SELECTION： Initial check the data and choose the original and review articles directly linked to the role of α-synuclein in PD pathogenesis and screening out indirectly discussing articles. Collect the full text and trace the quoting articles and the quoted articles. Only the latest reviews were chosen in Chinese articles. DATA EXTRACTION： There were 424 articles on α-synuclein and its role in the pathogenesis of PD and 43 articles directly related with α-synuclein were chosen among which 12 were reviews. DATA SYNTHESIS： α-synuclein is a kind of soluble protein expressed in pre-synapse in central nervous system encoded by gene in homologous chromosome 4q21. It has physiological function in modulating the stability of membrane and neural plasticity. There is a close relationship between gene mutation in α -synuclein and the pathogenesis of PD. Environmental and genetic factors can induce the misfolding of α-synuclein, and secondary structural change can result in oligomer formation which induces a series of cascade reaction to damage dopaminergic system subsequently. Cell and animal transgenic and non-transgenic models are established recently and the important role of α-synuclein in the pathogenesis both of familial and sporadic PD is confirmed. Studies reveal that inhibiting the aggregation of α-synuclein can prevent its neurotoxicity; gene parkin can intercept the cell death pathway triggered by the aggregation of α-synuclein in cytoplasm. CONCLUSION： Gene mutation ofα-synuclein and the impairment in its structure and function are important in the pathogenesis of PD. Intervention of the gene mutations and abnormal protein aggregation ofα-synuclein may be a new strategy for preventing and treating PD.

The m^(6)A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

Chronic myeloid leukemia(CML)is a common adult leukemia.Both the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor prognosis.The N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological processes.KIAA1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is unclear.In this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase CML.Notably,KIAA1429 regulated the total level of RNA m^(6)A modification in the CML cells and promoted the malignant biological behaviors of CML cells,including proliferation,migration,and imatinib resistance.Inhibiting KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis,consequently inhibiting CML proliferation and drug efflux,ultimately increasing the sensitivity of CML cells to imatinib.Moreover,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their apoptosis.Rucaparib,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell apoptosis.Rucaparib also inhibited the tumorigenesis of CML cells in vivo.The combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to imatinib.Our study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis to up-regulate RAB27B expression,thereby promoting CML progression.Rucaparib exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

Real-world Effectiveness and Tolerability of Interferonfree Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C:A Multinational Cohort Study

Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).

Greenhouse gas emissions mitigation and economic viability of sugar crops in China

Climate change mitigation is a major challenge of human society.Currently,to this end,many countries including China are committed to achieving carbon neutrality within a few decades.China is a major sugarcane and sugar beet producing country and has one of the largest carbon footprint for sugarcane and sugar beet production globally.A comprehensive study was conducted on sugarcane and sugar beet crops grown in China for greenhouse gas(GHG)emissions mitigation potential,economic crop production from a sustainable sugar production perspective.Long-term trend analysis showed that yield and GHG emissions of sugarcane and sugar beet crops increased but the ratio of income to cost declined.Structural equation model analysis revealed nitrogen fertilizer and labor as the major drivers of GHG emissions for both sugarcane and sugar beet.For sugarcane and sugar beet,the path coefficient of N fertilizer were‒0.964 and‒0.835 and that of labor were 0.771 and 0.589,respectively.By transitioning the current cropping system to an improved model with optimized labor,N input and machinery use,the GHG emissions and total annual cost of sugarcane and sugar beet production can be reduced by 32%and 24%,respectively,by 2030,compared to a business-as-usual scenario.This is the first integrated and comparative study of environmental and economic sustainability of sugarcane and sugar beet production in China.These findings will enable all stakeholders of Chinese sugarcane and sugar beet industries to transform them into environmentally and economically sustainable sugar production.

Identification of TP53 mutation-associated prognostic genes and investigation of the immune cell infiltration in patients with hepatocellular carcinoma

Primary liver cancer,which is mainly composed of hepatocellular carcinoma(HcC),is the sixth most common type of cancer worldwide and the thirdmost common cause of cancer mortality.1 The total number of mutations present in tumor specimens is called tumor mutation burden(TMB)and it is an emerging biomarker of immunotherapy response.2 TMB can predict clinical responses to immunotherapy such as ICl(immune checkpoint inhibitor)treatments and higher TMB is related to better survival.3 TP53,a gene encoding a tumor suppressor protein that triggers apoptosis and cell cycle arrest,is one of the most prevalent mutations in 25%-30%of HCC patients.4 Research shows that TP53 mutations in HCC patients are associated with advanced tumor grade and poor prognosis.5 To identify the TP53 mutation-related genes which can predict HCC patients'prognosis and explore the immune cell infiltration,we constructed a risk model based on six TP53 mutation-related genes which can accurately predict patients'prognosis.Besides,six immune cells with a similar expression pattern were identified in The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)databases.

A prognostic model of patients with pancreatic cancer based on four N^(6)-methyladenosine-related IncRNAs and analysis of related immune infiltration

Pancreatic cancer is one of the most lethal malignant tumors in the world.Despite advances in diagnosis and treatment,the five-year survival rate for pancreatic cancer patients remains only 9%.1 Pancreatic adenocarcinoma(PAAD)belongs to pancreatic cancer,which occupies 85%of the whole pancreatic cancer.2 Reversible modification of Ne-methyladenosine(m^(6)A)has been shown to be involved in cancer progression,resulting in up-regulation of oncogene expression or down-regulation of tumor-suppressing genes and may affect the prognosis of patients with pancreatic cancer.

基于多壳层Co3O4中空正十二面体的高效葡萄糖传感器

对比了多壳层Co3O4中空正十二面体与有序介孔Co3O4作为电催化剂,并应用在葡萄糖电化学催化氧化中的反应行为.多壳层中空结构促进了葡萄糖分子及相关产物的反应扩散,而壳层纳米粒子的取向排列不仅优先暴露了更多高活性(111)晶面也能促进反应电子的转移,从而有效提高了对葡萄糖电催化氧化的活性.多壳层中空正十二面体在低浓度范围对葡萄糖的灵敏度可达4075.2μA mmol/(L cm^2),优于有序大介孔Co3O4和有序小介孔Co3O4分别为3561.1和2074.3μA mmol/(L cm^2).电化学性能结果表明,多壳层Co3O4中空正十二面体是一种构筑葡萄糖传感器的优异电催化剂,为高效葡萄糖电催化剂的设计与合成提供了一定的借鉴.

Microvesicles(MIVs)secreted from adipose-derived stem cells(ADSCs)contain multiple microRNAs and promote the migration and invasion of endothelial cells

Extracellular vesicles(EVs)such as microvesicles(MIVs)play an important role in intercellular communications.MIVs are small membrane vesicles sized 100e1000 nm in diameter that are released by many types of cells,such as mesenchymal stem cells(MSCs),tumor cells and adipose-derived stem cells(ADSC).As EVs can carry out autocrine and paracrine functions by controlling multiple cell processes,it is conceivable that EVs can be used as delivery vehicles for treating several clinical conditions,such as to improve cardiac angiogenesis after myocardial infarction(MI).Here,we seek to investigate whether ADSC-derived MIVs contain microRNAs that regulate angiogenesis and affect cell migration of endothelial cells.We first characterized the ADSC-derived MIVs and found that the MIVs had a size range of 100 e300 nm,and expressed the MIV marker protein Alix.We then analyzed the microRNAs in ADSCs and ADSC-derived MIVs and demonstrated that ADSC-derived MIVs selectively released a panel of microRNAs,several of which were related to angiogenesis,including two members of the let-7 family.Furthermore,we demonstrated that ADSC-derived MIVs promoted the cell migration and invasion of the HUVEC endothelial cells.The PKH26-labeled ADSC-derived MIVs were effectively uptaken into the cytoplasm of HUVEC cells.Collectively,our results demonstrate that the ADSC-derived MIVs can promote migration and invasion abilities of endothelial cells,suggesting pro-angiogenetic potential.Future studies should focus on investigating the roles and mechanisms through which ADSC-derived MIVs regulate angiogenesis.

Baseline Characteristics and Treatment Patterns of the Patients Recruited to the China Registry of Hepatitis B

Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to the China Registry of Hepatitis B.Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data.Exclusion criteria were patients with hepatocellular car-cinoma.The baseline clinical,laboratory and treatment pro-files were analyzed.Results: Finally,40,431 patients were included.The median age was 43 years,with 65.2%being men and 51.3%being positive for hepatitis B e antigen(HBeAg).The most common initial diagnosis was chronic hep-atitis B(81.0%),followed by cirrhosis(9.3%),inactive carrier of hepatitis B surface antigen(HBsAg)(6.7%),and immune tolerant phase of hepatitis B infection(3.0%).Among the 21,228 patients who were on treatment,88.0%,10.0%and 2.0%received nucleos(t)ide analogues(NAs),interferon or combination of NAs and interferon,respectively.The propor-tion of patients who received preferred NAs(entecavir or te-nofovir disoproxil fumarate)had increased from 13.5%in 2003 to 79.7%in 2016.Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study.About half of the patients were HBeAg-positive.NAs were the most com-monly used therapy,and use of the preferred NAs had steadily increased in the past decade.

Direct-acting Antiviral Regimens for Patients with Chronic Infection of Hepatitis C Virus Genotype 3 in China

Hepatitis C virus(HCV)genotype(GT)3 infection is associated with a more rapid hepatic disease progression than the other genotypes.Hence,early HCV clearance slows down the disease progression and is important for improving prognosis in GT3-infected patients.Nevertheless,compared with other genotypes,GT3 is difficult-to-treat with direct-acting antivirals,especially in the presence of cirrhosis.Current guidelines recommend several regimens which have been proven to be effective in GT3-infected patients from the Western world(North America,Europe,and Oceania).In China,GT3 infection comprises 8.7–11.7%of the 10 million patients infected with HCV and has strikingly different characteristics from that in Western countries.Unlike the Western countries,where GT3a is the predominant subtype,GT3a and 3b each affect roughly half of Chinese GT3-infected patients,with 94–96%of the GT3b-infected patients carrying A30K+L31M double NS5A resistance-associated substitutions.Phase 3 clinical trials including GT3b-infected patients have suggested that GT3b infection is difficult to cure,making the regimen choice for GT3b-infected patients an urgent clinical gap to be filled.This review includes discussions on the epidemiology of HCV GT3 in China,recommendations from guidelines,and clinical data from both Western countries and China.The aim is to provide knowledge that will elucidate the challenges in treating Chinese GT3-infected patients and propose potential solutions and future research directions.

Correlation between acne and Northwest dryness syndrome in Xinjiang autonomous region of China

OBJECTIVE： To analyze the correlation between ac- he and Northwest dryness syndrome in the Xinji- ang region to provide an epidemiological founda- tion for the prevention and treatment of acne in the region. METHODS： The correlations among acne, clinical syndromes of Northwest dryness syndrome, and Northwest dryness syndrome were evaluated using the syndrome fitness index and canonical correla- tion analysis. RESULTS： The ache group had a Northwest drynesssyndrome rate of 24.13%, and the control group 10.34% （χ2=7.733, P〈0.01）. There was no significant difference in the fitness index for acne and for the sub-syndromes of Northwest dryness syndrome （P〉 0.05）. The first canonical correlation coefficient was 0.5656 （P〈0.01）. The acne-dependent variable group had the largest damp-heat syndrome load （0.8709）, and the independent variable had the largest lung-heart-spleen pyretic dryness load （0.6766）. CONCLUSION： Northwest dryness syndrome is a risk factor for ache in the Xinjiang region. Exoge- nous dryness and endogenous damp are frequent- ly seen as subsyndromes in Northwest dryness syn- drome in acne patients in the region. Acne was cor- related with the damp-heat and lung-heart-spleen pyretic dryness sub-syndromes of Northwest dry- ness syndrome.

Identification of inflammatory factor-related genes associated with the prognosis and immune cell infiltration in colorectal cancer patients

This study aims to identify the inflammatory factor-related genes which help to predict the prognosis of patients with colorectal cancer.GSEA(Gene Set Enrichment Analysis)was used to acquire inflammation-related genes and the corresponding expression information was collected from TCGA database to determine the DEGs(differentially-expressed genes)in CRC patients.We conducted enrichment analysis and PPI(protein–protein interaction)of these DEGs.Besides,key genes that are both differentially-expressed and prognosis-related were screened out,which were used to establish the prognostic model.We obtained 79 DEGs and 19 prognostic genes,10 prognostic-related differential genes were eventually screened.These genes were used to construct the prognostic model.We also identified that the immune infiltration score of macrophages between different risk groups was significantly different and similar distinction was witnessed in immune function score of APC(antigen-presenting cell)co-stimulation and type I IFN(interferon)response.

Ordered mesoporous NiFe_2O_4 with ultrathin framework for low-ppb toluene sensing

Highly sensitive and selective detection against specific target gases, especially at low-ppb （part per bil- lion） level, remain a great number of challenges in gas sensor applications. In this paper, we first present an ordered mesoporous NiFe204 for highly sensitive and selective detection against low-ppb toluene. A series of mesoporous NiFe204 materials were synthesized by templating from mesoporous silica KIT-6 and its framework thickness was reduced from 8.5 to 5 nm by varying the pore size of KIT-6 from 9.4 to 5.6 nm, accompanied with the increase of the specific surface area from 134 to 216 m^2 g^-1. The ordered mesoporous NiFe2O4 with both ultrathin framework of 5 nm and large specific surface area of up to 216 m^2 g^-1 exhibits a highest response （Rgas/Ralr-1 = 77.3） toward 1,000 ppb toluene at 230℃ and is nearly 7.3 and 76.7 times higher than those for the NiFe204 replica with thick framework and its bulk counter- part respectively, which also possesses a quite low limit of detection （〈2 ppb）, and good selectivity.

Overcoming the limitations of anthracene alkylation using SZ-DeAl-DFNS acid catalyst

In situ formation of composite micro-mesoporous dendritic fibrous nano-silica(DFNS) and Al-DFNS was prepared using a cetylpyridinium bromide(CPB) template synthetic system. Dealumination is induced by impregnation of zirconium with flux followed by a sulfuric acid treatment. This procedure results in a series of highly uniform nano-spheres, which exhibit stronger acid property than that of Al-MCM-41. In the selective alkylation of anthracene with tert–amyl alcohol, SO_(4)^(2-)modified Zr-contained dealuminated Al-DFNS(SZ-De Al-DFNS) shows great catalytic activity and higher conversion(60.8%). The DFNS samples were characterized with XRD, SEM, TEM, NH_(3)-TPD and other techniques. The results reveal that DFNSs consist of center-radial micro-mesopores and that the acid contribution of SZ-De Al-DFNS is much broader,as compared with amorphous aluminosilicate.

SUSTAINABLE NITROGEN MANAGEMENT FOR VEGETABLE PRODUCTION IN CHINA

Inappropriate nitrogen fertilizer management for the intensive Chinese vegetable production has caused low N use efficiency(NUE),high reactive nitrogen(Nr)losses and serious environmental risks with limited yield increase.Innovative N management strategy is an urgent need to achieve sustainable vegetable production.This paper summarizes recent studies on Nr losses and identifies the limitations from Chinese vegetable production systems and proposes three steps for sustainable N management in Chinese vegetable production.The three N management steps include,but are not limited to,(1)knowledge-based optimization of N fertilizer rate strategy,which maintains soil N supply to meet the dynamic vegetable demand in time,space and quantity;(2)innovative products and technology,which regulates the soil N forms and promotes the vegetable root growth to reduce the Nr loss;(3)integrated knowledge and products strategy(IKPS).The knowledge-based optimization of N fertilizer rate strategy and innovative products and technology,can maintain or increase vegetable yield,significantly improve NUE,and mitigate the region-specific and crop-specific Nr losses.More importantly,IKPS,based on combination of in-season root-zone N management strategy,innovative products and technology,and best crop cultivation management,is needed to produce more vegetables with lower Nr losses.

Transcriptomic analysis identifies a pan-cancer association of IL27 expression with cancer prognosis and immune microenvironment

Nowadays great progress has been made in targeted therapy and comprehensive therapy for a few cancers. But the prognosis of the vast majority of cancer patients is still weakness. It has been proven that inflammation can affect the development and treatment of cancer. Some previous studies have suggested that inflammation-related interleukins (ILs) play a significant role in the development of some cancers.1,2 ILs act as a considerable role in immunity,3 and inflammation affects the development of cancer. Therefore, the expression profile of IL gene may also be one of the vital markers of early pathological changes, occurrence and progression of cancer.4,5 Currently, studies on the expression of IL27 in cancer are still extremely limited. Our work comprehensively and systematically studied the IL27 gene expression in the generic cancer when compared with the existing IL27 gene related research experiment. We screened out cancer species linked with poor prognosis, and explored the correlation between IL27 gene expression and immune cell infiltration and immune microenvironment in these cancers further, providing an increasing number of the direct basis for subsequent studies. Our findings showed that IL27 can be used to assess prognosis and immune infiltration in patients with colon adenocarcinoma (COAD), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), skin cutaneous melanoma (SKCM) and testicular germ cell tumors (TGCT) as a biomarker.