CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease

Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.

Exploring the Mechanism of Blumea balsamifera(L.)DC in Preventing and Treating Alzheimer's Disease Based on HPLC-ESI-HRMS and Network Pharmacology

[Objectives]To expose the plausible mechanism of Blumea balsamifera(L.)DC.against Alzheimer s disease via network pharmacology and HPLC-ESI-HRMS technology.[Methods]To begin with,HPLC-ESI-HRMS was employed to identify the components of B.balsamifera.Secondly,the potential targets of the components were identified and predicted based on chemical similarity and online databases.Thirdly,by way of topological analysis of a component-disease target interaction network,the primary candidate targets and potential active components were identified.Lastly,molecular docking analysis was used to confirm the interaction between active components and therapeutic targets.[Results]According to the final results,HPLC-ESI-HRMS identified 70 components.Out of these,20 components were potentially biologically active,and most of them were sesquiterpenoids.According to the molecular docking results,the primary active components were appropriately coordinated with the core targets,indicating a high level of pharmacodynamic activity.Thus,the sesquiterpenes present in B.balsamifera are considered potential active ingredients having multi-target and multi-pathway effects for treating Alzheimer s disease.[Conclusions]This research will provide a scientific reference for the future pharmacological activity and clinical application of B.balsamifera.

聚丙烯接枝4-乙酰氧基苯乙烯的制备及电性能

为了研究聚丙烯材料的制备工艺及电性能,采用熔融法制备了聚丙烯(PP)接枝4-乙酰氧基苯乙烯(AOS),研究了制备工艺对接枝率的影响及接枝率对空间电荷、介电性能的影响。结果表明,当PP用量为50 g时,过氧化二异丙苯(DCP)用量对产物接枝率呈不同的影响规律。在DCP用量为0.12 g时,随AOS用量的增加,接枝率逐渐增大,后趋于平稳;而当DCP用量为0.04 g和0.08 g时,AOS用量的增加,接枝率先增加,后反而降低。随着温度、转速的增加和时间的延长,接枝率呈先上升后下降的趋势。因此,PP-g-AOS接枝材料的最佳工艺为m(PP)∶m(AOS)∶m(DCP)=50∶1.4∶0.08,温度190℃、转速80 r/min、时间8 min,接枝率1.14%。接枝产物抑制内部空间电荷的能力、击穿强度、体积电阻率随着接枝率的增加先上升后下降,而介电常数和介电损耗变化不大;当接枝率为1.14%时,接枝材料的电性能最佳,此时,PP-g-AOS接枝材料抑制空间电荷的效果最好,体积电阻率为5.1×10^15Ω·m,比纯PP提高了3.25倍,击穿强度为48.7 kV/mm,是纯PP的2倍。

Measuring Method of Radius of Curvature Based on Dual-Frequency Laser Interferometer

In order to achieve high-accuracy measurement of radius of curvature of optical sphere, ultra-high accuracy radius of curvature testing device is developed by dual-frequency laser interferometer and Fizeau interferometer based on cat’s eye and confocal method. Through analyzing the error source models of radius of curvature testing, optical configuration of the testing device has been optimized. Precise environment control and real-time monitoring system is also established to reduce the errors caused by environment. Through the above processes, the radius of curvature measurement relative accuracy is better than 2 ppm. One optical sphere, R88.5 mm, test aperture 59 mm, has been tested. Testing result is 88499.465 ± 0.176 μm, meeting the design requirement. The method has high accuracy and practical advantages.

Facile fabrication of MoP nanodots embedded in porous carbon as excellent anode material for potassium-ion batteries

Molybdenum phosphide(MoP),owing to its abundant reserve and high theoretical capacity,is regarded as a promising anode material for potassium-ion batteries.However,it still suffers from the problems of acute volume expansion and weak diffusion kinetics.This study reports a simple method to synthesize a composite of molybdenum phosphide and porous carbon(MoP@PC)through simple mixing and annealing treatment.In the MoP@PC,lots of MoP nanodots with an average diameter of about 4 nm uniformly embedded in the petal-like porous carbon.The MoP@PC shows reversible capacities of 330 mAh g^(-1) at100 mA g^(-1) after 100 cycles,and ultra-long cycling stability with a capacity of 240 mAh g^(-1) after 1000 cycles at 1 A g^(-1) and 161 mAh g^(-1) after 1000 cycles at 5 A g^(-1).The structure of MoP@PC after charging-discharging cycles is also investigated by high resolution transmission electron microscope(HRTEM)and the result shows that MoP can still maintain the nanodot morphology without any agglomeration after 1000 cycles at 5 A g^(-1).The storage mechanism of potassium ions was studied as well,which reveals that MoP and potassium ion have a conversion reaction.

3D hierarchical microspheres constructed by ultrathin MoS2-C nanosheets as high-performance anode material for sodium-ion batteries

MoS2/C composites are considered to have great application potential in sodium-ion batteries(SIBs).It is a challenging and meaningful subject that developing high-performance anode materials via combining MoS2 and carbon effectively to give free rein to their advantages in sodium ion storage.In this work,a novel MoS2-C material was designed by using cellulose nanocrystals(CNCs)as low-cost and green carbon source.3 D hierarchical microspheres(200-250 nm)constructed by ultrathin MoS2-C nanosheets were synthesized by synchronizing the pre-carbonization of CNCs with the formation of MoS2 in hydrothermal reaction and subsequent pyrolysis process.It is found that the ultrathin MoS2-C nanosheets were composed of CNCs-derived short-range ordered carbon and few-layered MoS2.Benefiting from the unique structure and robust combination of MoS2 and CNCs-derived carbon,the ultrathin MoS2-C nanosheets composite was proved to have excellent cycling stability and superior rate performance in sodium-ion half-cell test and have high first reversible specific capacity of 397.9 m Ah/g in full-cell test.This work provides a significant and effective pathway to prepare MoS2-C materials with excellent electrochemical performance for the application in large-scale energy storage systems.

Optics‑guided Robotic System for Dental Implant Surgery

At present,dental implant surgery mainly relies on the clinical experience of the doctor and the assistance of preoperative medical imaging.However,there are some problems in dental implant surgery,such as narrow space,sight obstruction,inaccurate positioning,and high requirements of doctors’proficiency.Therefore,a dental implant robot system(DIRS)guided by optical navigation is developed in this study,with an x-shaped tool and an irregular pentagonal tracer are designed for spatial registration and needle tip positioning strategy respectively.The coordinate system of each unit in DIRS is unified through system calibration,spatial registration,and needle tip positioning strategy.Then the surgical path is planned on the computed tomography(CT)images in the navigation software before operation.The automatic positioning method and the auxiliary positioning method can be used in the operation to achieve accurate positioning and assist doctors to complete the operation.The errors of spatial registration,needle tip positioning strategy,and the overall accuracy of the system were evaluated respectively,and the results showed that they all met the needs of clinical surgery.This study preliminarily verified the feasibility of the precise positioning method for dental surgery robots and provided certain ideas for subsequent related research.

Clinical data analysis reveals the role of OGR1 (GPR68) in head and neck squamous cancer

Background:Head and neck squamous cancer(HNSC)frequently occurs in the clinic.Revealing the role of the genes that correlate with cancer cell outgrowth will contribute to potential treatment target identification and tumor inhibition.Methods:The gene expression profiles and gene ontology of the proton-sensing G-protein-coupled receptor OGR1 were analyzed using the TCGA(The Cancer Genome Atlas)database.The effects of sex,age,race,and degree of malignancy on HNSC were investigated,and the survival times of HNSC patients with high or low/medium expression levels of OGR1 were compared.Methylation of the OGR1 promoter CpG sites was also investigated and OGR1-related genes were analyzed using gene set enrichment analysis.Results:OGR1 is overexpressed in HNSC patients.However,compared with the low/median expression group,the high OGR1 expression group did not have different survival rates.The OGR1 expression level differed across sex,age,race,and degree of malignancy,while the methylation of the OGR1 promoter CpG sites was maintained at a similar level.Gene set enrichment analysis revealed that OGR1 was positively correlated with head and neck cancer,cisplatin resistance,hypoxia,angiogenesis,cell migration,and TGF-β.Conclusion:The expression of OGR1 correlated with HNSC progression and survival and thus can serve as a potential treatment target and prognostic marker.

Novel spontaneous myelodysplastic syndrome mouse model

Background:Myelodysplastic syndrome(MDS)is a group of disorders involving he-mopoietic dysfunction leading to leukemia.Although recently progress has been made in identifying underlying genetic mutations,many questions still remain.Animal models of MDS have been produced by introduction of specific mutations.However,there is no spontaneous mouse model of MDS,and an animal model to simulate natu-ral MDS pathogenesis is urgently needed.Methods:In characterizing the genetically diverse mouse strains of the Collaborative Cross(CC)we observed that one,designated JUN,had abnormal hematological traits.This strain was thus further analyzed for phenotypic and pathological iden-tification,comparing the changes in each cell population in peripheral blood and in bone marrow.Results:In a specific-pathogen free environment,mice of the JUN strain are rela-tively thin,with healthy appearance.However,in a conventional environment,they become lethargic,develop wrinkled yellow hair,have loose and light stools,and are prone to infections.We found that the mice were cytopenic,which was due to abnor-mal differentiation of multipotent bone marrow progenitor cells.These are common characteristics of MDS.Conclusions:A mouse strain,JUN,was found displaying spontaneous myelodysplas-tic syndrome.This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models.JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.

Downregulation of HNRNPK in human cancer cells inhibits lung metastasis

Background: Lung cancer frequently occurs in the clinic, leading to poor prognosis and high mortality. Markers for early diagnosis of lung cancer are scarce, and further potential therapeutic targets are also urgently needed.Method: We established a new mouse model in which the specific gene HNRNPK(heterogeneous nuclear ribonucleoprotein K) was downregulated after administration of doxycycline. The lung metastatic nodules were investigated using bioluminescence imaging, micro-CT, and autopsy quantification.Results: Compared with the short hairpin negative control group, less lung metastatic nodules were formed in the short hairpin RNA group.Conclusion: Downregulation of HNRNPK in cancer cells can inhibit lung metastasis.

A Downsampled SAR-BM3D Despeckling Approach for Single-Look SAR Images in High Resolution

SAR-BM3D is one of the state of the art despeckling algorithms for SAR images. However, when tackling with high resolution SAR images, it often has an unsatisfying despeckling performance in the homogeneous smooth regions, together with a high time complexity. In this paper, a novel downsampled SAR-BM3D despeckling approach combined with edge compensation is proposed. The proposed algorithm consists of two steps. First, despeckle the image which is a downsampled version of original image with SAR-BM3D. Then, compensate edges in each level when upsampling. This approach not only utilizes the good ability of feature preservation, but also improves performance of smoothing homogenous regions. When it comes to high resolution SAR images, the efficiency can be raised by six to seven times, compared to original SAR-BM3D. Experiments on simulated and real SAR images show that the proposed method reaches a high level in terms of visual quality and act more efficiently.

On the Development and Maintenance of Cigarettes Exported to North Korea

According to the requirements of " going out" strategy of Jilin Tobacco Industry Co. Ltd.,in order to further expand the Changbaishan series brand in the market of North Korea,this paper elaborates the product development and maintenance ideas and measures for three cigarette companies in North Korea based on the actual work being done,so as to determine the development and maintenance focus of export cigarettes and provide strong technical support for accelerating the pace of localization of production while achieving homogenization of production.

Summary of animal models of myelodysplastic syndrome

Myelodysplastic syndrome(MDS)is a malignant tumor of the hematological system characterized by long-term,progressive refractory hemocytopenia.In addition,the risk of leukemia is high,and once it develops,the course of acute leukemia is short with poor curative effect.Animal models are powerful tools for studying human diseases and are highly effective preclinical platforms.Animal models of MDS can accurately show genetic aberrations and hematopoietic clone phenotypes with similar cellular features(such as impaired differentiation and increased apoptosis),and symptoms can be used to assess existing treatments.Animal models are also helpful for understanding the pathogenesis of MDS and its relationship with acute leukemia,which helps with the identification of candidate genes related to the MDS phenotype.This review summarizes the current status of animal models used to research myelodysplastic syndrome(MDS).

Direct reprogramming of fibroblasts into functional hepatocytes via CRISPRa activation of endogenous Gata4 and Foxa3

Background:The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease treatments.Clustered regularly interspaced short palindromic repeats(CRISPR)activator(CRISPRa)is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously,providing a new strategy for cell fate determination.The main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver fibrosis.Method:The differentiation of mouse embryonic fibroblasts(MEFs)into functional induced hepatocyte-like cells(iHeps)was achieved by utilizing the CRISPRa synergistic activation mediator(SAM)system,which drove the combined expression of three endogenous transcription factors-Gata4,Foxa3,and Hnf1a-or alternatively,the expression of two transcription factors,Gata4 and Foxa3.In vivo,we injected adeno-associated virus serotype 6(AAV6)carrying the CRISPRa SAM system into liver fibrotic Col1a1-Cre^(ER);Cas9^(fl/fl)mice,effectively activating the expression of endogenous Gata4 and Foxa3 in fibroblasts.The endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction(RT-qPCR)and RNA-seq,and the morphology and characteristics of the induced hepatocytes were observed through microscopy.The level of hepatocyte reprogramming in vivo is detected by immunofluorescence staining,while the improvement of liver fibrosis is evaluated through Sirius red staining,alpha-smooth muscle actin(α-SMA)immunofluorescence staining,and blood alanine aminotransferase(ALT)examination.Results:Activation of only two factors,Gata4 and Foxa3,via CRISPRa was sufficient to successfully induce the transformation of MEFs into iHeps.These iHeps could be expanded in vitro and displayed functional characteristics similar to those of mature hepatocytes,such as drug metabolism and glycogen storage.Additionally,AAV6-based delivery of the CRISPRa SAM system effectively induced the hepatic reprogramming from fibroblasts in mice with live fibrosis.After 8 weeks of induction,the reprogrammed hepatocytes comprised 0.87%of the total hepatocyte population in the mice,significantly reducing liver fibrosis.Conclusion:CRISPRa-induced hepatocyte reprogramming may be a promising strategy for generating functional hepatocytes and treating liver fibrosis caused by hepatic diseases.

Preparation and characterization of M_(1)-N_(x)-C_(y)based single atom catalysts for environmental applications

Single atom catalysts(SACs)have become the frontier research fields in catalysis.The M_(1)-N_(x)-C_(y)based SACs,wherein single metal atoms(M1)are stabilized by N-doped carbonaceous materials,have provided new opportunities for catalysis due to their high reactivity,maximized atomic utilization,and high selectivity.In this review,the fabrication methods of M_(1)-N_(x)-C_(y)based SACs via support anchoring strategy and coordination design strategy are summarized to help the readers understand the interaction mechanism of single atoms and support.Then,characterization technologies for identifying single metal atoms are presented.Besides,the environmental applications including management of harmful gases,water purification are discussed.Finally,future opportunities and challenges for preparation strategies,mechanisms and applications are concluded.We conclude this review by emphasizing the fact that M_(1)-N_(x)-C_(y)based SACs has the potential to become an important candidate for solving current and future environmental pollution problems.

Early-Life Gut Microbiota Governs Susceptibility to Colitis via Microbial-Derived Ether Lipids

Localized intestine inflammation could induce short-term increases in colonic oxygenation and leads to increases in the aerobic bacteria population and reduction in the anaerobic bacteria population by changing the intestinal environment.However,the mechanisms involved and the associated functions of intestinal anaerobes in gut health still remain unclear.Here,we found that early-life depletion of gut microbiota exacerbated later colitis,while mid-life microbiota depletion showed partially reduced colitis.Notably,we observed that early-life gut microbiota depletion confers susceptibility to ferroptosis in colitis.In contrast,restitution of early-life microbiota conferred protection against colitis and inhibited ferroptosis triggered by gut microbiota dysbiosis.Similarly,colonization with anaerobic microbiota from young mice suppressed colitis.These results may attribute to high abundance of plasmalogen-positive(plasmalogen synthase[PlsA/R]-positive)anaerobes and plasmalogens(one of the common ether lipids)in young mice but reduced abundance in the development of inflammatory bowel disease.Early-life anaerobic bacteria elimination also resulted in the aggravation of colitis,while this aggravation phenotype was reverted by plasmalogen administration.Interestingly,plasmalogens inhibited ferroptosis triggered by microbiota dysbiosis.We further find that the alkenyl-ether group of plasmalogens was critical to colitis prevention and ferroptosis inhibition.These data point to one of the mechanisms by which the gut microbiota controls susceptibility to colitis and ferroptosis early in life via microbial-derived ether lipids.

The pore structure and fractal characteristics of shales with low thermal maturity from the Yuqia Coalfield, northern Qaidam Basin, northwestern China

The continental shales from the Middle Jurassic Shimengou Formation of the northern Qaidam Basin, northwestern China, have been investigated in recent years because of their shale gas potential. In this study, a total of twenty-two shale samples were collected from the YQ-1 borehole in the Yuqia Coalfield, northern Qaidam Basin. The total organic carbon （TOC） contents, pore structure parameters, and fractal characteristics of the samples were investigated using TOC analysis, lowtemperature nitrogen adsorption experiments, and fractal analysis. The results show that the average pore size of the Shimengou shales varied from 8.149 nm to 20.635 nm with a mean value of 10.74 nm, which is considered mesopore-sized. The pores of the shales are mainly inkbottle- and slit-shaped. The sedimentary environment plays an essential role in controlling the TOC contents of the low maturity shales, with the TOC values of shales from deep to semi-deep lake facies （mean： 5.23%） being notably higher than those of the shore-shallow lake facies （mean： 0.65%）. The fractal dimensions range from 2.4639 to 2.6857 with a mean of 2.6122, higher than those of marine shales, which indicates that the pore surface was rougher and the pore structure more complex in these continental shales. The fraetal dimensions increase with increasing total pore volume and total specific surface area, and with decreasing average pore size. With increasing TOC contents in shales, the fractal dimensions increase first and then decrease, with the highest value occurring at 2% of TOC content, which is in accordance with the trends between the TOC and both total specific surface area and total pore volume. The pore structure complexity and pore surface roughness of these low-maturity shales would be controlled by the combined effects of both sedimentary environments and the TOC contents.

Hydrophilic bismuth sulfur nanoflower superstructures with an improved photothermal efficiency for ablation of cancer cells

Nanomaterials with intense near-infrared （NIR） absorption exhibit effective photon-to-thermal energy transfer capabilities and can generate heat to ablate cancer cells, thus playing a pivotal role in photothermal cancer therapeutics. Herein, hydrophilic flower-like bismuth sulfur （Bi2S3） superstructures with uniform size and improved NIR absorption were controllably synthesized via a facile solvothermal procedure assisted by polyvinylpyrrolidone （PVP）, which could adjust the product morphology. Induced by an 808-nm laser, the as-prepared Bi2S3 nanoflowers exhibited much higher photothermal conversion efficiency （64.3%） than that of Bi2S3 nanobelts （36.5%） prepared in the absence of PVP. This can be attributed not only to the Bi2S3 nanoflower superstructures assembled by 3-dimensional crumpled-paper-like nanosheets serving as many laser-cavity mirrors with improved reflectivity and absorption of NIR light but also to the amorphous structures with a lower band gap. Thus, to achieve the same temperature increase, the concentration or laser power density could be greatly reduced when using Bi2S3 nanoflowers compared to when using Bi2S3 nanobelts, which makes them more favorable for use in therapy due to decreased toxicity. Furthermore, these Bi2S3 nanoflowers effectively achieved photothermal ablation of cancer ceils in vitro and in vivo. These results not only supported the Bi2S3 nanoflowers as a promising photothermal agent for cancer therapy but also paved an approach to exploit new agents with improved photothermal efficiency.

Recent progress in advanced core-shell metal-based catalysts for electrochemical carbon dioxide reduction

Electrochemical carbon dioxide reduction(CO_(2)RR)plays an important role in solving the problem of high concentration of CO_(2)in the atmosphere and realizing carbon cycle.Core-shell structure has many unique features including tandem catalysis,lattice strain effect,defect engineering,which exhibit great potential in electrocatalysis.In this review,we focus on the advanced core-shell metal-based catalysts(CMCs)for electrochemical CO_(2)RR.The recent progress of CMCs in electrocatalytic CO_(2)RR is described as the follow-ing aspects:(1)The mechanism of electrochemical CO_(2)RR and evaluation parameters of electrocatalyst performance,(2)preparation methods of core-shell metal catalysts and core-shell structural advantages and(3)advanced CMCs towards electrochemical CO_(2)RR.Finally,we make a brief conclusion and propose the opportunities and challenges in the field of electrochemical CO_(2)RR.

A Case Study on the Rapid Rain-to-Snow Transition in Late Spring 2018 over Northern China:Effects of Return Flows and Topography

Phase changes in the precipitation processes of early winter and late spring in midlatitude regions represent challenges when forecasting the timing and magnitude of snowfall.On 4 April 2018,a heavy snow process occurred in Beijing and northwestern Hebei Province,becoming the most delayed occurrence of heavy spring snow ever recorded over Beijing in the last 30 years.This paper uses observational and numerical simulation data to investigate the causes for the rapid rain-to-snow(RRTS)phase transition during this process.The following results are obtained.(1)Return flows(RFs),an interesting type of easterly wind,including those at 1000,925,and 800 hPa,played an important role in this heavy snow process and presented a characteristic"sandwich"structure.The RFs,complex topography,and snow particles that dominated the clouds,were the three key factors for the RRTS transition.(2)The RRTS transition in the plains was directly related to the RF at 925 hPa,which brought about advective cooling initiated approximately 4-6 h before the onset of precipitation.Then,the RF played a role of diabatic cooling when snow particles began to fall at the onset of precipitation.(3)The RRTS transition in the northern part of the Taihang Mountains was closely related to the relatively high altitude that led to a lower surface temperature owing to the vertical temperature lapse rate.Both immediately before and after the onset of precipitation,the snow particles in clouds entrained the middle-level cold air downward,causing the melting layer(from surface to the 0℃-isotherm level)to become very thin;and thus the snow particles did not have adequate time to melt before falling to the ground.(4)The rapid RRTS over the Yanqing mountainous area in the northwest of Beijing could have involved all the three concurrent mechanisms:the advective cooling of RF,the melting cooling of cloud snow particles,and the high-altitude effect.Compared with that in the plain area with less urbanization the duration of the RRTS in the plain area with significant urbanization was extended by approximately 2 h.