SAHS和夜间低血压与非动脉炎性前部缺血性视神经病变的相关性

目的:探讨睡眠呼吸暂停低通气综合征(SAHS)及夜间低血压(NHP)与非动脉炎性前部缺血性视神经病变(NAION)发病的相关性。方法:回顾性分析2016-10/2018-12我院就诊的NAION患者,其中NAION组31例,对照组31例为健康体检者。对NAION患者和对照组行24h动态血压监测明确夜间血压情况,用Berlin调查问卷评估SAHS患病风险,用多导睡眠呼吸记录仪(Polysomnography)行夜间呼吸暂停低通气指数(AHI)、最小氧饱和度(MOS)监测。根据AHI对SAHS进行诊断和分级。结果:NAION组有23例患者(74%)出现NHP,对照组中NHP患者为14例(45%),NAION组中NHP的患病率显著高于对照组(P=0.020)。NAION组有22例(71%)伴有SAHS,而对照组SAHS患者为13例(42%)。Logistic回归分析显示,NHP(OR=2.762,95%CI:1.275~3.746)、AHI(OR=2.959,95%CI:1.478~6.432)及MOS(OR=3.058,95%CI:1.734~7.743)是NAION发生的危险因素。结论:SAHS和NHP与NAION的发生密切相关,预防SAHS和NHP的发生与进展可能有助于防治NAION。

The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models

Targeted genome editing technology has been widely used in biomedical studies. The CRISPR- associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio- medicine.

Multiplicity dependence of charged particle,? meson, and multistrange particle productions in p + p collisions at s^(1/2) = 200 GeV from PYTHIA simulation

We report the multiplicity dependence of charged particle production for the n~±, K~±, p, , and ? mesons at |y|<1:0 in p + p collisions at s^(1/2) = 200 GeV from a PYTHIA simulation. The impact of multiple parton interactions and gluon contributions is studied and found to be a possible source of the splitting of the particle yields as a function of p_T with respect to the multiplicity. No obvious particle species dependence of the splitting is observed.The multiplicity dependence of the ratios Kˉ/πˉ, K^+/π^+,/πˉ, p/π^+, and K_s^0 at mid-rapidity in p+ p collisions is found to follow a tendency similar to that in Au t Au collisions at (s_(NN))^(1/2) = 200 GeV at the Relativistic Heavy Ion Collider, indicating similar underlying initial production mechanisms despite the differences in the initial colliding systems.

Extraction of inclusive photon production at mid-rapidity in p+p and Au+Au collisions at√SNN=200GeV

We present a comprehensive study on the individual sources of an inclusive photon production during high-energy hadronic collisions.The cross section and invariant yields of inclusive photons are obtained as a function of pT at mid-rapidity(|y|<0.5)in p+p and Au+Au collisions at√SNN=200GeVrespectively.These results provide crucial inputs to separate measurements of open bottom and charm hadron yield suppression in heavyion collisions,which are used to test the mass hierarchy of the parton energy loss in the quark gluon plasma created during these collisions.The procedure developed in this study can also be applied to other measurements of electrons from an open heavy-flavor hadron decay,such as the collective flow in the RHIC beam energy scan program.

Effects of Volcanic Activity on Organic Matter Sources and the Paleoenvironment:Geochemical Evidence from Upper Carboniferous Source Rocks(Batamayineishan Formation)in Eastern Junggar,NW China

The mudstone,gray tuffite and carbonaceous shale in the Upper Carboniferous Batamayineishan Formation(Bashan Formation)are essential source rocks for the volcanic reservoir in eastern Junggar,northwestern China.The kerogen components,vitrinite reflectance,Rock-Eval pyrolysis,lipid biomarkers and isotope compositions were measured to understand the provenance and depositional environment of Bashan Formation under the background of volcanic activities.There were 10 and 4 periods of volcanic eruptions identified in the wells CS and DZ,respectively.The source rocks developed in the late or intermittent phase of volcanic activity.The original island arcs of the Early Carboniferous evolved into the Wucaiwan sag and the Dishuiquan sag in the Bashan Formation.The Wucaiwan sag inherited the restricted,closed residual sea,which had a slightly anoxic and hypersaline environment.The Dishuiquan sag was generally an oxidizing lacustrine environment,influenced by a marine transgression that may have occurred at the end of the DZ_(Ⅲ)period during the Late Carboniferous.Although the total organic matter decreased due to the volcanic eruption,ash could cause an increase of aquatic organisms,coinciding with increases in salinity and reducibility in the Dishuiquan sag.

CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer

CYP3A5 is a cytochrome P450(CYP)enzyme that metabolizes drugs and contributes to drug resistance in cancer.However,it remains unclear whether CYP3A5 directly influences cancer progression.In this report,we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal adenocarcinoma.Multi-omics analysis showed that CYP3A5 knockdown re-sults in a decrease in various glucose-related metabolites through its effect on glucose trans-port.A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP,a negative regulator of GLUT1.Notably,CYP3A5-generated reactive oxygen species were proved to be responsible for atten-uating the AKT-4EBP1-TXNIP signaling pathway.CYP3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic cancer.Taken together,our results,for the first time,reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

Switching On/Off of Guide RNA by Photoinduced Strand Displacement for Functional Control of CRISPR/Cas9

Functional control of CRISPR/Cas9 is essential for precise gene manipulation.Chemical engineering of guide RNA(gRNA)provides diverse approaches for conditional control of CRISPR/Cas9 function with a variety of chemical reactive groups.However,previous investigations into chemically engineering gRNA only unidirectionally regulated the CRISPR/Cas9 function via stimuli-induced caging/decaging processes.Herein,we propose a combinatory strategy to engineer the dynamics of gRNA in which photocontrolled strand-displacement reactions coupled with sequence designs of gRNA can achieve lightinduced switching-on/off control of CRISPR/Cas9 function.Biochemical analysis and cellular gene regulation indicate this approach is capable of both activating and deactivating CRISPR/Cas9 activities using light irradiation.Moreover,photocontrolled multiplex modulations of gene expression for opposite regulatory effects have also been achieved simultaneously under the same cellular context.This work establishes an essential principle for construction of stimuli-induced switching-on/off modulations of gRNA that can greatly enrich the versatility of conditional control for a variety of CRISPR/Cas9-based applications.

Properties of the QCD matter:review of selected results from the relativistic heavy ion collider beam energy scan(RHIC BES)program

In the paper,we discuss the development of the multigap resistive plate chamber time-of-fight(TOF)technology and the production of the solenoidal tracker at RHIC(STAR)TOF detector in China at the beginning of the twenty-frst century.Subsequently,recent experimental results from the frst beam energy scan program(BES-I)at the Relativistic Heavy Ion Collider(RHIC)pertaining to measurements of collectivity,chirality,criticality,global polarization,strangeness,heavy favor,dilepton and light nuclei productions are reviewed.

The recommendations of Chinese Parkinson’s disease and movement disorder society consensus on therapeutic management of Parkinson’s disease

Background:Parkinson’s disease(PD)is a chronic,progressive and debilitating disease,which affects over 2.5 million people in China.PD is characterized clinically by resting tremor,muscular rigidity,bradykinesia and postural instability.As the disease progresses,additional complications can arise such as non-motor and neurobehavioral symptoms.Pharmacological treatment and surgical intervention for PD have been implemented in China.Until 10 years ago,there was lack of standardization for the management of PD in different regions and among different physicians,leading to different treatment levels in different regions and different physicians.Since then,the Chinese Parkinson’s Disease and Movement Disorder Society have published three versions of guidelines for the management of PD in China,in 2006,2009 and 2014,respectively.Correspondingly,the overall level of treatment for PD in China improved.Objectives:To update the treatment guidelines based on current foreign and domestic practice guidelines and clinical evidence,and to improve the treatment options available to physicians in the management of PD.Summary:A variety of treatment recommendations in the treatment guidelines have been proposed,including physical activity and disease-modifying medication,which should be initiated at the early-stage of the disease.The principles of dosage titration should be followed to avoid acute adverse reactions to the drugs,to achieve a satisfactory clinical effect with a low dose and to reduce the incidence of long-term motor complications.Moreover,different treatment strategies should be considered at different stages of the disease.Importantly,treatment guidelines and personalized treatments should be valued equally.A set of treatment recommendations has been developed to assist physicians to improve and optimize clinical outcomes for patients with PD in China.

Prevalence of wearing-off and dyskinesia among the patients with Parkinson’s disease on levodopa therapy: a multi-center registry survey in China's Mainland

Objective:Chronic levodopa(L-dopa)treatment in Parkinson’s disease(PD)is often associated with the development of motor complications,but the corresponding epidemiological data is rare in Chinese PD patients.The present survey was to investigate the prevalence rate of wearing-off(WO)and dyskinesia among the patients with PD in China.Methods:From May 2012 to October 2012,a 3-step registry survey for wearing off(WO)and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China.Results:There were 1,558 PD patients fulfilling the inclusion criteria.Among them,1,051 had at least one positive response of 9-item wearing off questionnaire(WOQ-9),724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists,respectively.The overall prevalence rates of WO and dyskinesia were 46.5%(95%CI 44.0%-48.9%)and 10.3%(95%CI 8.8%-11.8%),respectively.The mean score of WOQ-9 for those with WO was 3.8(SD=1.8),with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms.Better improvement of motor symptoms(n=354,87.8%)and long-term disease control and drug selection(n=288,71.5%)were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO.Conclusions:This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from China's Mainland.WO prevalence rate among Chinese PD patients was in line with,while dyskinesia prevalence rate was lower than previous reports from other Countries.

Conceptual design of the HIRFL-CSR external-target experiment

One of the main purposes of heavy-ion collisions over a wide range of beam energy is to study the bulk properties of strong interaction matter and understand the Quantum Chromo Dy- namics （QCD） phase diagram, which carries wealth of infor- mation of the phase transition and the possibly existing criti- cal point of the strongly interacting system [1]. Such system exists as hadron gases at lower temperature and low baryon density. By increasing the temperature or density, the bound- ary of the hadrons disappears and the confined quarks move freely in the whole system.

Efficacy and safety of rasagiline in Chinese patients with early Parkinson’s disease:a randomized, double-blind,parallel,placebo-controlled,fixed-dose study

Background:Rasagiline is a monoamine oxidase-B inhibitor used for Parkinson’s disease(PD)treatment,but its effectiveness on Chinese patients is unclear.This study aimed to evaluate the efficacy and safety of rasagiline monotherapy in Chinese patients with early PD.Methods:A 26-weeks,randomized,double-blind,placebo-controlled study has been performed at 15 sites in China and enrolled outpatients(≥35 years old)with idiopathic PD without a history of using any dopaminergic drugs.Participants were randomized 1:1 to receive rasagiline 1 mg once daily or placebo.The primary endpoint was the change of the Unified Parkinson’s Disease Rating Scale(UPDRS)total score from baseline to 26 weeks treatment.Secondary endpoints included changes in UPDRS subscale scores from part Ⅰ to Ⅲ.Health status was assessed with the PD Questionnaire(PDQ)-39 and EuroQol-Five-Dimension(EQ-5D)questionnaire.Safety profile was collected until 30 weeks after randomization.Results:A total of 130 patients(n=65/group)were recruited,and 127(rasagiline,n=64;placebo,n=63)were included in the full analysis set.Baseline characteristics were comparable between the two groups.The decrease in the mean UPDRS total score was greater in the rasagiline group than in the placebo group(−3.18±0.95 vs.−0.18±0.98,P=0.025),and the mean UPDRS part I non-motor symptoms score(−0.54±0.15 vs.-0.08±0.15,P=0.003)were significantly decreased in the rasagiline group compared with placebo treated patients.An improvement trend was observed in the active treatment group for the subscales evaluation with parts Ⅱ and Ⅲ,while the difference to placebo was not statistically significant.Life quality assessed by the EQ-5D visual analog scale improved in the rasagiline group but worsened in placebo treated patients.The overall incidence of treatment-emergent adverse events(AEs)was slightly lower in the rasagiline group(41.5%)than in the placebo group(46.2%).Conclusions:Rasagiline is effective,safe,and well tolerated as monotherapy for the treatment of Chinese PD patients.

Binding between Prion Protein and Aβ Oligomers Contributes to the Pathogenesis of Alzheimer’s Disease

A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases,such as prion diseases and Alzheimer's disease(AD).Like prion diseases,AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential.Although it remains elusive how protein aggregation leads to AD,it is becoming clear that cellular prion protein(PrP^c)plays an important role in AD pathogenesis.Here,we briefly reviewed AD pathogenesis and focused on recent progresses how PrP^c contributed to AD development.In addition,we proposed a potential mechanism to explain why infectious agents,such as viruses,conduce AD pathogenesis.Microbe infections cause AD deposition and upregulation of PrP^c,which lead to high affinity binding between AD oligomers and PrP^c.The interaction between PrP^c and AP oligomers in turn activates the Fyn signaling cascade,resulting in neuron death in the central nervous system(CNS).Thus,silencing PrP^c expression may turn out be an effective treatment for PrP^c dependent AD.

Living cell synthesis of CdSe quantum dots： Manipulation based on the transformation mechanism of intracellular Se-precursors

Currently, the biosynthesis of nanomaterials by organisms is attracting considerable attention because of the sustainable and environmentally friendly nature of the reactions involved in this process compared with those in the conventional nanomaterial synthesis. However, the manipulation and control of nanomaterial biosynthesis remain difficult because of the lack of knowledge about the biosynthetic mechanisms. In the present study, we elucidated the selenium （Se）-precursor and Se metabolic flux in the biosynthesis of cadmium-selenium quantum dots （CdSe QDs） in Saccharomyces cerevisiae and improved the cells＇ ability to biosynthesize CdSe QDs through gene modification based on the regulation mechanism. By deleting the genes involved in Se metabolism and measuring seleno-amino acids, we identified selenocysteine （SeCys） as the primary Se-precursor in the intracellular biosynthesis of CdSe QDs. Further studies demonstrated that the selenomethionine （SeMet）-to-SeCys pathway regulates CdSe QD biosynthesis. Knowledge of the regulatory pathway allowed us to enhance SeMet synthesis by overexpression of the MET6 gene, and an increased CdSe QD yield was realized in the engineered cells. Understanding the mechanism of CdSe QD biosynthesis helped to determine the relationship between nanocrystal formation and biological processes, and offers a new perspective to manipulation of nanomaterial biosynthesis.

The PDZ-Containing Unconventional Myosin XVIIIA Regulates Embryonic Muscle Integrity in Zebrafish

Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, whether it regulates muscle function re- mains unclear. We show that the two zebrafish myo18a genes （myo18aa and myo18ab） are predominantly expressed at somite borders during early developmental stages. Knockdown of these genes or overexpression of the MYO18A PDZ domain disrupts myofiber integrity, induces myofiber lesions, and compromises the localization of dystrophin, ^-dystroglycan （^-DG） and laminin at the myotome boundaries. Cell transplantation experiments indicate that myo18a morphant myoblasts fail to form elongated myofibers in the myotomes of wild-type embryos, which can be rescued by the full-length MYO18A protein. These results suggest that MYO18A likely functions in the adhesion process that maintains the stable attachment of myofibers to ECM （extracellular matrix） and muscle integrity during early development.

Highly efficient genome editing using oocyte-specific zcas9 transgenic zebrafish

Since its first application to induce mutations in mammalian cells （Cong et al., 2013： Mall et al., 2013）, CRISPR/Cas9 has rapidly become a routine technique to perform genome editing in a variety of biological systems due to its facile, robust, and multiplexable fea- tures （Hwang et al, 2013; Wang et al., 2013; Guo et al., 2014; Liu, 2017）.

Phase segregation mechanisms of small molecule-polymer blends unraveled by varying polymer chain architecture

As phase separation between the small-molecule semiconductor and the polymer binder is the key enabler of blend-based organic field-effect transistors(OFETs)fabricated by low-cost solution processing,it is crucial to understand the underlying phase separation mechanisms that determine the phase morphology,which significantly impacts device performance.Beyond the parameter space investigated in previous work,here we investigate the formation of blends by varying the branch architecture of the polymer binder and by shortening the solvent dry time using ultrasonic spray casting.The phase morphologies of the resulting blend films have been thoroughly characterized with a variety of techniques in three dimensions over multiple length scales,including AFM,energy-filtered transmission electron microscope,and neutron reflectivity,and have been correlated with electrical transport performance.From the results,we have inferred that the phase morphology is kinetically determined,limited by the inherent slow movement of polymer macromolecules.The kinetic picture,supported by molecular dynamics modeling,not only consistently explains our observations but also resolves inconsistencies in previous works.The achieved mechanistic understanding will guide further optimization of blend-based organic electronics,such as OFETs and organic photovoltaics.

Advances in Polymethine Dyes for Near-Infrared Organic Photodiodes

Near-infrared organic photodiodes (NIR OPDs) have tremendous potential in industrial, military, and scientific applications, due to their unique features of lightweight, low toxicity, high structural flexibility, cooling-system-free, etc. However, the overall performance of currently available NIR OPDs still lags behind the commercial inorganic photodetectors, ascribed to the critical challenge of realizing organic semiconductors with sufficiently low optical bandgap and excellent optoelectronic properties simultaneously. Among various types of NIR-absorbing organic semiconductors, polymethine dyes not only possess advantages of simple synthesis and structural diversity, but also show fascinating optical and aggregation features in the solid state, making them attractive material candidates for NIR OPDs. In this review, after a brief introduction of NIR OPDs and polymethine dyes, we comprehensively summarize the advances of polymethine dyes for broadband and narrowband NIR OPDs, and further introduce their applications in all-organic optical upconversion devices and photoplethysmography sensors. In particular, the relationship between the chemical structure and the aggregation behaviors of polymethine dyes and the device performance is carefully discussed, providing some important molecular insights for developing high performance NIR OPDs.

Tumor Necrosis Factor a Reduces SNAP29 Dependent Autolysosome Formation to Increase Prion Protein Level and Promote Tumor Cell Migration

Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely understood. In a human melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFα up-regulates prion protein(PrP) level, and promotes tumor cell migration in a PrP dependent manner. Silencing PRNP abrogates TNFα induced tumor cell migration;this phenotype is reversed when PRNP is re-introduced. Treatment with TNFα activates nuclear factor kappa B(NF-κB)signaling, which then mitigates autophagy by reducing the expression of Forkhead Box P3(FOXP3). Down regulation of FOXP3 reduces the transcription of synaptosome associated protein 29(SNAP29), which is essential in the fusion of autophagosome and lysosome creating autolysosome. FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also up-regulates PrP, and promotes tumor cell migration without TNFα treatment. But, when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to TNFα. Thus, a reduction in autophagy is the underlying mechanism by which expression of PrP is up-regulated,and tumor cell migration is enhanced upon TNFα treatment. Disrupting the TNFα-NF-κB-FOXP3-SNAP29 signaling axis may provide a therapeutic approach to mitigate tumor cell migration.

Adjunct rasagiline to treat Parkinson’s disease with motor fluctuations:a randomized,double-blind study in China

Background:The use of adjunct rasagiline in levodopa-treated patients with Parkinson’s disease and motor fluctuations is supported by findings from large-scale clinical studies.This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson’s disease,as a product registration study.Methods:This 16-week,randomized,double-blind,parallel-group,multicenter,placebo-controlled study of rasagiline 1 mg/day included levodopa-treated patients with Parkinson’s disease and motor fluctuations.The primary efficacy endpoint was mean change from baseline in total daily OFF time over 16 weeks.Secondary endpoints were Clinical Global Impressions–Improvement(CGI-I),and change in Unified Parkinson’s Disease Rating Scale(UPDRS)Activities of daily living(ADL)and Motor scores.Patient well-being(EQ-5D),and the frequency of adverse events were also assessed.Results:In total,324 levodopa-treated patients were randomized to rasagiline 1 mg/day(n=165)or placebo(n=159).Over 16 weeks,rasagiline statistically significantly reduced the mean[95% confidence interval]total daily OFF time versus placebo(−0.5 h[−0.92,−0.07];p=0.023).There were also statistically significant improvements versus placebo in CGI-I(−0.4 points[−0.61,−0.22];p<0.001),UPDRS-ADL OFF(−1.0 points[−1.75,−0.27];p=0.008),and UPDRS-Motor ON(−1.6 points[−3.05,−0.14];p=0.032)scores,as well as the EQ-5D utility index(p<0.05).Rasagiline was safe and well tolerated.Conclusions:In levodopa-treated Chinese patients with Parkinson’s disease and motor fluctuations,adjunct rasagiline 1 mg/day statistically significantly reduced OFF time,and improved daily function and overall well-being,versus placebo.Consistent with findings in other countries,adjunct rasagiline was proven efficacious and well tolerated in Chinese patients.