In the design realm of fusion power supplies,structural components play a pivotal role in ensuring the safety of fusion devices.To verify the reliability of the converter structure design at the Comprehensive Research...In the design realm of fusion power supplies,structural components play a pivotal role in ensuring the safety of fusion devices.To verify the reliability of the converter structure design at the Comprehensive Research Facility for Fusion Technology(CRAFT),meticulous analysis of the converter's dynamic impact is carefully performed based on the worst fault current(400k A),firstly.Subsequently,the thermal stress analysis based on the maximum allowable steadystate temperature is finished,and the equivalent thermal stress,thermal deformation,maximum shear stress of a single bridge arm and the whole converter are studied.Furthermore,a simple research method involving the current-sharing characteristics of a bridge arm with multithyristor parallel connection is proposed using a combination of Simplorer with Q3D in ANSYS.The results show that the current-sharing characteristics are excellent.Finally,the structural design has been meticulously tailored to meet the established requirements.展开更多
Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus patients.Methods:Clinical data of patients with scrub typhus admitted to different types...Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus patients.Methods:Clinical data of patients with scrub typhus admitted to different types of medical institutions in Guangzhou from September 2012 to December 2016 were collected using medical records.Demographic data,clinical manifestations,as well as hematological and biochemical indicators of patients infected with different genotypes were analyzed and compared.Results:A total of 192 patients were included in this study,including 121 patients with Karp genotype of O.tsutsugamushi infection(63.0%),36 patients with Gilliam genotype(19.0%),23 patients with Kato genotype(12.0%),and 12 patients with TA763 genotype(6.0%)infection.The median value of albumin in patients with Karp genotype infection was significantly lower than that of Gilliam-infected patients(P=0.032).Patients with Karp genotype infection had a significantly longer hospital stay(9 days)than those with Gilliam genotype(7 days)(P=0.009)and Kato genotype infection(6 days)(P=0.005).Karp-infected patients also represented for the largest number of patients with complicated organ involvement(88/133,66.2%).Furthermore,Karp-infected patients had higher risk of developing multiple organ dysfunction syndrome(18.2%)and requiring intensive care unit treatment(15.9%).Besides,patients with Gilliam genotype(8 days)and TA763 genotype infection(7.5 days)had shorter fever duration than those with Karp genotype(9 days)and Kato genotype(9 days)infection,respectively.Conclusions:Genotypes of Orientia tsutsugamushi were associated with varying clinical manifestations,organ involvement,and treatment outcomes,suggesting that genotypes ranged in virulence.展开更多
Lithium metal batteries(LMBs)have received increasing attention due to the high energy density.However,the practical application of LMBs is limited due to the incompatibility of ester electrolytes.Transition metal(TM)...Lithium metal batteries(LMBs)have received increasing attention due to the high energy density.However,the practical application of LMBs is limited due to the incompatibility of ester electrolytes.Transition metal(TM)nitrates have been reported as effective additives in ester electrolyte to improve the stability of lithium anode.Unfortunately,the nitrates are restricted to use due to their poor solubility.We find that the nitrates containing crystal water have high solubility in ester electrolytes.Considering that most TM nitrates contain crystal water and the crystal water can be used as a perfect solubilizer of nitrates,thus,the method is of universality and facile without introducing any solubilizing agent.Herein,In(NO_(3))_(3.6)H_(2)O is chosen as one typical case with increased solubility up to 0.2 M compared with In(NO_(3))_(3)which hardly dissolves in ester electrolyte.The additive promotes the rapid and stable formation of the solid electrolyte interface(SEI),which effectively inhibits the lithium dendrites formation.Moreover,the induced cathode electrolyte interface(CEI)maintains the structural stability of Li Ni_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811).As a result,the electrochemical performance of Li|NCM811 cell is obviously improved.Our study provides a new idea for dissolving nitrates in ester electrolytes and discloses the synergistic function of TM-ions.展开更多
In order to test the superconducting magnet performance for the Comprehensive Research Facility for Fusion Technology(CRAFT)project of China,a power supply converter needs to be designed.In this paper,short circuits u...In order to test the superconducting magnet performance for the Comprehensive Research Facility for Fusion Technology(CRAFT)project of China,a power supply converter needs to be designed.In this paper,short circuits upstream and downstream of the direct current(DC)reactor are analyzed,and the thyristor style and the parallel number are determined by the limit analysis of junction temperature and fault current I^2t.On this basis,the over current and voltage verification of fast fuse are finished to protect the thyristor at fault cases by considering the short circuit of the bridge arm.Then,the resistor and capacitor parameters of thyristor snubber are committed to decreasing the reverse over voltage.These analysis results will be used as the preliminary design of high power magnet converter for CRAFT.展开更多
结直肠癌是世界高发和高致死率的恶性肿瘤。靶向新抗原的免疫治疗已被证实可以诱导癌症患者肿瘤持续消退,但这些特异性新抗原,仅适用于个体精准治疗。随着大量的高频肿瘤基因突变被发现,这些与突变相关的高频新抗原可覆盖更多人群,具有...结直肠癌是世界高发和高致死率的恶性肿瘤。靶向新抗原的免疫治疗已被证实可以诱导癌症患者肿瘤持续消退,但这些特异性新抗原,仅适用于个体精准治疗。随着大量的高频肿瘤基因突变被发现,这些与突变相关的高频新抗原可覆盖更多人群,具有较强的临床意义。然而目前结直肠癌中是否也存在高频新抗原仍不清楚。本研究利用来源于321个结直肠癌患者的体细胞突变数据库,联合1种标准过滤和7种预测算法,筛选并获得了25个基于中国人高频分型HLA-A^*1101限制性的高频新抗原,它们均具有高亲和力(IC50<50 nmol/L)和高呈递分值(>0.90);其中,除了阳性对照多肽KRAS_G12V8-16外,11个高频新抗原能够在体外诱导细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)分泌γ干扰素(interferon gamma,IFN-γ),证实具有免疫原性。选取免疫原性最强的新抗原C1orf170_S418G413-421及阳性对照多肽KRAS_G12V8-16体外刺激T细胞,利用流式细胞分选及单细胞转录组测序技术,获得其特异性CTL的免疫组库信息,所构建的TCR-T(T-cell receptor engineered T cell)能够识别新抗原并分泌细胞因子。以上结果表明,本研究开发了一种利用体细胞数据库预测并体外筛选验证具有免疫原性高频新抗原的方法,为结直肠癌及其他癌种的多肽、DC(dendritic cells)疫苗、TCR-like抗体、TCR-T等免疫治疗提供了重要的多肽靶点和TCR信息,具有实际的临床应用价值。展开更多
In recent years,with the vigorous development of the Chinese herbal medicine market in China,the government and various circles of society pay close attention to the safety of Chinese herbal medicine production. The c...In recent years,with the vigorous development of the Chinese herbal medicine market in China,the government and various circles of society pay close attention to the safety of Chinese herbal medicine production. The cultivation and production of traditional Chinese herbal medicine already could not satisfy the current market demands. This paper summarized the forming,changing and the influencing factors of Chinese herbal medicines,and organized the research for the formation of traditional Chinese herbal medicines by modern scholars in China. It reached the following conclusion: the production of modern Chinese herbal medicines should ensure its unique properties,and the more important is to guarantee the quality and safety. With the continuous improvement of science and technology innovation ability and the appraisal method of Chinese medicines,the better management system has been applied in the process of planting. This paper summarized the six attributes of modern production of Chinese herbal medicines,to ensure genuine,safe and standardized production of traditional Chinese medicines.展开更多
Chiral high-nuclearity lanthanide(4f)clusters have shown fantastic properties in various fields.However,their synthesis is still of great challenge.Herein,we report two pairs of enantiomers of highnuclearity Dy-oxo cl...Chiral high-nuclearity lanthanide(4f)clusters have shown fantastic properties in various fields.However,their synthesis is still of great challenge.Herein,we report two pairs of enantiomers of highnuclearity Dy-oxo clusters synthesized through in situ strategy.They are[Dy18(^(R/S)Hftp)4(^(R/S)H_(2)btp)4(μ2-OH)_(8)(μ3-OH)20(μ6-O)(NO_(3))_(4)(μ-H_(2)O)_(8)]·[solvents](1R and 1S)and[Dy9(^(R/S)Hftp)2(^(R/S)H_(2)btp)_(2)(OAc)_(6)(μ3-OH)_(10)(H_(2)O)_(6)](OAc)·[solvents](2R and 2S),where^(R/S)Hftp2−and^(R/S)H_(2)btp^(3−)represent in situ formed 2-formyl-6-[N-(threonine)iminomethyl]-4-methylphenol and 2,6-bis[N-(threonine)iminomethyl]-4-methylphenol anions,respectively.These in situ formed clusters were endowed with not only homochirality via introducing^(R/S)Hftp2−and^(R/S)H_(2)btp^(3−)ligands,but also rich oxo-bridges by controlling the hydrolysis of Dy^(III)ions.Different anions from DyIII salts further induced structural variation between two sets of clusters.1R and 1S feature an unprecedent four-blade propeller shaped{Dy18}core,whose centered octahedral{Dy6}unit are surrounded by four triangular{Dy3}units.Strikingly,they represent the second largest chiral 4f cluster species so far.2R and 2S display a sandglass-like{Dy9}skeleton that consist of two square pyramid{Dy5}units sharing a Dy^(III)vertex.Magnetic investigation revealed possible antiferromagnetic interactions between the Dy^(III)centers in these clusters.展开更多
Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor prognosis.However, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demo...Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor prognosis.However, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demonstrated. We performed single-cell whole exome sequencing to detect somatic singlenucleotide variants(SNVs) and significantly mutated genes(SMGs) among 34 tumor cells and 9 normal cells from a patient with GC. The Complete Prediction for Protein Conformation(CPPC) approach directly predicting the folding conformation of the protein 3D structure with Protein Folding Shape Code, combined with functional experiments were used to confirm the characterization of mutated SMGs in GC cells. We identified 201 somatic SNVs, including 117 non-synonymous mutations in GC cells. Further analysis identified 24 significant mutated genes(SMGs) in single cells, for which a single amino acid change might affect protein conformation. Among them, two genes(CDC27 and FLG) that were mutated only in single cells but not in the corresponding tumor tissue, were recurrently present in another GC tissue cohort, and may play a potential role to promote carcinogenesis, as confirmed by functional characterization. Our findings showed a mutational landscape of GC at intra-tumor level for the first time and provided opportunities for understanding the heterogeneity and individualized target therapy for this disease.展开更多
Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell t...Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell types,which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types.Here,we report the application of single-nucleus RNA-seq on midbrain,striatum,and cerebellum of theα-syn-A53 T mouse,a well-established PD mouse model,and matched controls,generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells.Additionally,we comprehensively depicte the dysfunctions in PD pathology,covering the elevation of NF-k B activity,the alteration of ion channel components,the perturbation of protein homeostasis network,and the dysregulation of glutamatergic signaling.Notably,we identify a variety of cell types closely associated with PD risk genes.Taken together,our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution,which facilitates the development of novel approaches for diagnosis and therapies against PD.展开更多
Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased.Diseases that were once regional now have the ability to spread globally in a short amoun...Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased.Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health(Weaver et al.2018).Yellow fever virus(YFV,family Flaviviridae,genus Flavivirus)is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years(Domingo et al.2018).展开更多
The year of 2018 marks the 65th anniversary of the discovery of DNA double helix and the 15th anniversary of the successful completion of the international Human Genome Project (HGP),the two revolutions in life scienc...The year of 2018 marks the 65th anniversary of the discovery of DNA double helix and the 15th anniversary of the successful completion of the international Human Genome Project (HGP),the two revolutions in life sciences (Sharp, 2014). The year also sees the effective implementation of the "1%Program", the Chinese contribution to the reference sequence of the human genome,which coincides with the 40th anniversary of the founding of the Genetics Society of China, one of the most influential national academic organizations in China.展开更多
Circular genomes, being the largest proportion of sequenced genomes, play an important role in genome analysis. However, traditional 2D circular map only provides an overview and annotations of genome but does not off...Circular genomes, being the largest proportion of sequenced genomes, play an important role in genome analysis. However, traditional 2D circular map only provides an overview and annotations of genome but does not offer feature-based comparison. For remedying these shortcomings, we developed 3D Genome Tuner,a hybrid of circular map and comparative map tools. Its capability of viewing comparisons between multiple circular maps in a 3D space offers great benefits to the study of comparative genomics. The program is freely available （under an LGPL licence） at http：//sourceforge.net/projects/dgenometuner.展开更多
Array comparative genomic hybridization （CGH） has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patien...Array comparative genomic hybridization （CGH） has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome （2GH arrays. A number of highly frequent genomic aberrations were discovered, which may act as ＂drivers＂ of tumor progression. Meanwhile, the genomic profiles of four ＂normal＂ breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.展开更多
Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein comple...Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein complexes. Traditionally studies of heme-binding proteins have been approached on a case by case basis, thus there is a limited global view of the distribution of heme-binding proteins in different cells or tissues. The procedure described here is aimed at profiling heme-binding proteins in mouse tissues sequentially by 1) purification of heme-binding proteins by heme-agarose, an affinity chromatographic resin; 2) isolation of heme-binding proteins by SDS-PAGE or two-dimensional electrophoresis; 3) identification of heme-binding proteins by mass spectrometry. In five mouse tissues, over 600 protein spots were visualized on 2DE gel stained by Commassie blue and 154 proteins were identified by MALDI-TOF, in which most proteins belong to heme related. This methodology makes it possible to globally characterize the heme-binding proteins in a biological system.展开更多
T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-Co...T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-CoV-2.^(2) CMV-related diseases occur once the host immune system is impaired or lacks a protective repertoire of virus-specific T lymphocytes.3 Adoptive transfer of T-cell receptor(TCR)-engineered T cells(TCR-Ts)provides an encouraging alternative treatment option for patients with CMV reactivation.^(4) However,generating TCR-Ts requires the identification of epitope-specific and functional TCR pairs.Modern single-cell sequencing techniques open up the ability to unravel TCR repertoires,^(5 )which offers a potential opportunity to screen functional TCR pairs for TCR-T therapy.Here,we report an efficient approach that combines ex vivo CD8+T-cell stimulation with single-cell RNA and TCR V(D)J sequencing to identify CMV-specific TCRs for generating TCR-Ts.展开更多
CRISPR/Cas9 is an adaptive immunity system in bacteria and most archaea(Koonin and Makarova,2009;Horvath and Barrangou,2010).The CRISPR/Cas9 gene editing system is comprised of two key components,a small guide RNA(gRN...CRISPR/Cas9 is an adaptive immunity system in bacteria and most archaea(Koonin and Makarova,2009;Horvath and Barrangou,2010).The CRISPR/Cas9 gene editing system is comprised of two key components,a small guide RNA(gRNA)and a Cas9 endonuclease(Deltcheva etal.,2011;Jineketal.,2012).展开更多
基金supported by the Talent Research Fund of Hefei University(No.21-22RC09)National Natural Science Foundation of China(No.U22A20225)。
文摘In the design realm of fusion power supplies,structural components play a pivotal role in ensuring the safety of fusion devices.To verify the reliability of the converter structure design at the Comprehensive Research Facility for Fusion Technology(CRAFT),meticulous analysis of the converter's dynamic impact is carefully performed based on the worst fault current(400k A),firstly.Subsequently,the thermal stress analysis based on the maximum allowable steadystate temperature is finished,and the equivalent thermal stress,thermal deformation,maximum shear stress of a single bridge arm and the whole converter are studied.Furthermore,a simple research method involving the current-sharing characteristics of a bridge arm with multithyristor parallel connection is proposed using a combination of Simplorer with Q3D in ANSYS.The results show that the current-sharing characteristics are excellent.Finally,the structural design has been meticulously tailored to meet the established requirements.
基金supported by the Science and Technology Plan Grant of Guangzhou(grant number 202102080035)the Guangzhou Health and Family Planning Science and Technology Project Western Medicine-general Guidance Project(20221A011067)+2 种基金the Basic Research Project of Key Laboratory of Guangzhou(grant number 202102100001)the Key Project of Medicine Discipline of Guangzhou(grant number 2021-2023-12)the Guangzhou Health Science and Technology Project(grant number 20221A011066).
文摘Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus patients.Methods:Clinical data of patients with scrub typhus admitted to different types of medical institutions in Guangzhou from September 2012 to December 2016 were collected using medical records.Demographic data,clinical manifestations,as well as hematological and biochemical indicators of patients infected with different genotypes were analyzed and compared.Results:A total of 192 patients were included in this study,including 121 patients with Karp genotype of O.tsutsugamushi infection(63.0%),36 patients with Gilliam genotype(19.0%),23 patients with Kato genotype(12.0%),and 12 patients with TA763 genotype(6.0%)infection.The median value of albumin in patients with Karp genotype infection was significantly lower than that of Gilliam-infected patients(P=0.032).Patients with Karp genotype infection had a significantly longer hospital stay(9 days)than those with Gilliam genotype(7 days)(P=0.009)and Kato genotype infection(6 days)(P=0.005).Karp-infected patients also represented for the largest number of patients with complicated organ involvement(88/133,66.2%).Furthermore,Karp-infected patients had higher risk of developing multiple organ dysfunction syndrome(18.2%)and requiring intensive care unit treatment(15.9%).Besides,patients with Gilliam genotype(8 days)and TA763 genotype infection(7.5 days)had shorter fever duration than those with Karp genotype(9 days)and Kato genotype(9 days)infection,respectively.Conclusions:Genotypes of Orientia tsutsugamushi were associated with varying clinical manifestations,organ involvement,and treatment outcomes,suggesting that genotypes ranged in virulence.
基金supported by the National Natural Science Foundation of China(22005274 and 21975225)the Postdoctoral Science Foundation of China(2020M672261)。
文摘Lithium metal batteries(LMBs)have received increasing attention due to the high energy density.However,the practical application of LMBs is limited due to the incompatibility of ester electrolytes.Transition metal(TM)nitrates have been reported as effective additives in ester electrolyte to improve the stability of lithium anode.Unfortunately,the nitrates are restricted to use due to their poor solubility.We find that the nitrates containing crystal water have high solubility in ester electrolytes.Considering that most TM nitrates contain crystal water and the crystal water can be used as a perfect solubilizer of nitrates,thus,the method is of universality and facile without introducing any solubilizing agent.Herein,In(NO_(3))_(3.6)H_(2)O is chosen as one typical case with increased solubility up to 0.2 M compared with In(NO_(3))_(3)which hardly dissolves in ester electrolyte.The additive promotes the rapid and stable formation of the solid electrolyte interface(SEI),which effectively inhibits the lithium dendrites formation.Moreover,the induced cathode electrolyte interface(CEI)maintains the structural stability of Li Ni_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811).As a result,the electrochemical performance of Li|NCM811 cell is obviously improved.Our study provides a new idea for dissolving nitrates in ester electrolytes and discloses the synergistic function of TM-ions.
基金supported by the National Key R&D Program of China(No.2017YFE0300504)Comprehensive Research Facility for Fusion Technology(No.2018-00005273-01-001228).
文摘In order to test the superconducting magnet performance for the Comprehensive Research Facility for Fusion Technology(CRAFT)project of China,a power supply converter needs to be designed.In this paper,short circuits upstream and downstream of the direct current(DC)reactor are analyzed,and the thyristor style and the parallel number are determined by the limit analysis of junction temperature and fault current I^2t.On this basis,the over current and voltage verification of fast fuse are finished to protect the thyristor at fault cases by considering the short circuit of the bridge arm.Then,the resistor and capacitor parameters of thyristor snubber are committed to decreasing the reverse over voltage.These analysis results will be used as the preliminary design of high power magnet converter for CRAFT.
文摘结直肠癌是世界高发和高致死率的恶性肿瘤。靶向新抗原的免疫治疗已被证实可以诱导癌症患者肿瘤持续消退,但这些特异性新抗原,仅适用于个体精准治疗。随着大量的高频肿瘤基因突变被发现,这些与突变相关的高频新抗原可覆盖更多人群,具有较强的临床意义。然而目前结直肠癌中是否也存在高频新抗原仍不清楚。本研究利用来源于321个结直肠癌患者的体细胞突变数据库,联合1种标准过滤和7种预测算法,筛选并获得了25个基于中国人高频分型HLA-A^*1101限制性的高频新抗原,它们均具有高亲和力(IC50<50 nmol/L)和高呈递分值(>0.90);其中,除了阳性对照多肽KRAS_G12V8-16外,11个高频新抗原能够在体外诱导细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)分泌γ干扰素(interferon gamma,IFN-γ),证实具有免疫原性。选取免疫原性最强的新抗原C1orf170_S418G413-421及阳性对照多肽KRAS_G12V8-16体外刺激T细胞,利用流式细胞分选及单细胞转录组测序技术,获得其特异性CTL的免疫组库信息,所构建的TCR-T(T-cell receptor engineered T cell)能够识别新抗原并分泌细胞因子。以上结果表明,本研究开发了一种利用体细胞数据库预测并体外筛选验证具有免疫原性高频新抗原的方法,为结直肠癌及其他癌种的多肽、DC(dendritic cells)疫苗、TCR-like抗体、TCR-T等免疫治疗提供了重要的多肽靶点和TCR信息,具有实际的临床应用价值。
基金Supported by the Program of Infinitus(China)Company Ltd
文摘In recent years,with the vigorous development of the Chinese herbal medicine market in China,the government and various circles of society pay close attention to the safety of Chinese herbal medicine production. The cultivation and production of traditional Chinese herbal medicine already could not satisfy the current market demands. This paper summarized the forming,changing and the influencing factors of Chinese herbal medicines,and organized the research for the formation of traditional Chinese herbal medicines by modern scholars in China. It reached the following conclusion: the production of modern Chinese herbal medicines should ensure its unique properties,and the more important is to guarantee the quality and safety. With the continuous improvement of science and technology innovation ability and the appraisal method of Chinese medicines,the better management system has been applied in the process of planting. This paper summarized the six attributes of modern production of Chinese herbal medicines,to ensure genuine,safe and standardized production of traditional Chinese medicines.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21961008,22271068,22075058 and 22261012)Guangxi Science and Technology Base and Talents Program(No.AD21220105)Guangxi Natural Science Foundation(No.2022GXNSFBA035472).
文摘Chiral high-nuclearity lanthanide(4f)clusters have shown fantastic properties in various fields.However,their synthesis is still of great challenge.Herein,we report two pairs of enantiomers of highnuclearity Dy-oxo clusters synthesized through in situ strategy.They are[Dy18(^(R/S)Hftp)4(^(R/S)H_(2)btp)4(μ2-OH)_(8)(μ3-OH)20(μ6-O)(NO_(3))_(4)(μ-H_(2)O)_(8)]·[solvents](1R and 1S)and[Dy9(^(R/S)Hftp)2(^(R/S)H_(2)btp)_(2)(OAc)_(6)(μ3-OH)_(10)(H_(2)O)_(6)](OAc)·[solvents](2R and 2S),where^(R/S)Hftp2−and^(R/S)H_(2)btp^(3−)represent in situ formed 2-formyl-6-[N-(threonine)iminomethyl]-4-methylphenol and 2,6-bis[N-(threonine)iminomethyl]-4-methylphenol anions,respectively.These in situ formed clusters were endowed with not only homochirality via introducing^(R/S)Hftp2−and^(R/S)H_(2)btp^(3−)ligands,but also rich oxo-bridges by controlling the hydrolysis of Dy^(III)ions.Different anions from DyIII salts further induced structural variation between two sets of clusters.1R and 1S feature an unprecedent four-blade propeller shaped{Dy18}core,whose centered octahedral{Dy6}unit are surrounded by four triangular{Dy3}units.Strikingly,they represent the second largest chiral 4f cluster species so far.2R and 2S display a sandglass-like{Dy9}skeleton that consist of two square pyramid{Dy5}units sharing a Dy^(III)vertex.Magnetic investigation revealed possible antiferromagnetic interactions between the Dy^(III)centers in these clusters.
基金supported by the National Key Research and Development Program of China (2017YFC1308900)Beijing Municipal Commission of Health and Family Planning Project (PXM2018_026279_000005)+1 种基金National High-tech R&D Program of China (2012AA02A203, No.2012AA02A504)Beijing talent fund
文摘Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor prognosis.However, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demonstrated. We performed single-cell whole exome sequencing to detect somatic singlenucleotide variants(SNVs) and significantly mutated genes(SMGs) among 34 tumor cells and 9 normal cells from a patient with GC. The Complete Prediction for Protein Conformation(CPPC) approach directly predicting the folding conformation of the protein 3D structure with Protein Folding Shape Code, combined with functional experiments were used to confirm the characterization of mutated SMGs in GC cells. We identified 201 somatic SNVs, including 117 non-synonymous mutations in GC cells. Further analysis identified 24 significant mutated genes(SMGs) in single cells, for which a single amino acid change might affect protein conformation. Among them, two genes(CDC27 and FLG) that were mutated only in single cells but not in the corresponding tumor tissue, were recurrently present in another GC tissue cohort, and may play a potential role to promote carcinogenesis, as confirmed by functional characterization. Our findings showed a mutational landscape of GC at intra-tumor level for the first time and provided opportunities for understanding the heterogeneity and individualized target therapy for this disease.
基金supported by the National Natural Science Foundation of China(31702074 and 31872309)Sanming Project of Medicine in Shenzhen(SZSM202011012)Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20170412153100794)。
文摘Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell types,which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types.Here,we report the application of single-nucleus RNA-seq on midbrain,striatum,and cerebellum of theα-syn-A53 T mouse,a well-established PD mouse model,and matched controls,generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells.Additionally,we comprehensively depicte the dysfunctions in PD pathology,covering the elevation of NF-k B activity,the alteration of ion channel components,the perturbation of protein homeostasis network,and the dysregulation of glutamatergic signaling.Notably,we identify a variety of cell types closely associated with PD risk genes.Taken together,our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution,which facilitates the development of novel approaches for diagnosis and therapies against PD.
基金supported by grants from the National Science and Technology Major Project of China (2016ZX10004222 and 2016YFC1200800)Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010102)+5 种基金Sanming Project of Medicine in Shenzhen (SZSM201412003)Shenzhen Municipal Government of China (JCYJ20160427151920801)Beijing Municipal Science & Technology Commission (Z161100000116049)the National Natural Science Foundation of China (NSFC) International Cooperation and Exchange Program (816110193)supported by the NSFC Outstanding Young Scholars (31822055)Youth Innovation Promotion Association of Chinese Academy of Sciences (CAS) (2017122)
文摘Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased.Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health(Weaver et al.2018).Yellow fever virus(YFV,family Flaviviridae,genus Flavivirus)is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years(Domingo et al.2018).
文摘The year of 2018 marks the 65th anniversary of the discovery of DNA double helix and the 15th anniversary of the successful completion of the international Human Genome Project (HGP),the two revolutions in life sciences (Sharp, 2014). The year also sees the effective implementation of the "1%Program", the Chinese contribution to the reference sequence of the human genome,which coincides with the 40th anniversary of the founding of the Genetics Society of China, one of the most influential national academic organizations in China.
基金supported by the National HighTech R&D Program (863 Program) of China (Grant No. 2006AA02A301) awarded to XZ
文摘Circular genomes, being the largest proportion of sequenced genomes, play an important role in genome analysis. However, traditional 2D circular map only provides an overview and annotations of genome but does not offer feature-based comparison. For remedying these shortcomings, we developed 3D Genome Tuner,a hybrid of circular map and comparative map tools. Its capability of viewing comparisons between multiple circular maps in a 3D space offers great benefits to the study of comparative genomics. The program is freely available （under an LGPL licence） at http：//sourceforge.net/projects/dgenometuner.
基金supported by the Danish Cancer Soci-ety through the budget of the Institute of Cancer Biol-ogy and by grants from the Danish Medical Research Council, the Natural and Medical Sciences Committee of the Danish Cancer Society, Novo Nordisk, the John and Birthe Meyer Foundation, the Solar Fonden, the Stensbygaard Fonden, the Kai Langeog Gundhild Kai Lange Fond, the will of Edith Stern, and the "Race Against Breast Cancer" ProjectThe support of the Marketing Department at the Danish Cancer Society is greatly appreciatedsupported by a project grant from the Hi-Tech Research and Development Program of China (2006AA02A301)
文摘Array comparative genomic hybridization （CGH） has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome （2GH arrays. A number of highly frequent genomic aberrations were discovered, which may act as ＂drivers＂ of tumor progression. Meanwhile, the genomic profiles of four ＂normal＂ breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.
文摘Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein complexes. Traditionally studies of heme-binding proteins have been approached on a case by case basis, thus there is a limited global view of the distribution of heme-binding proteins in different cells or tissues. The procedure described here is aimed at profiling heme-binding proteins in mouse tissues sequentially by 1) purification of heme-binding proteins by heme-agarose, an affinity chromatographic resin; 2) isolation of heme-binding proteins by SDS-PAGE or two-dimensional electrophoresis; 3) identification of heme-binding proteins by mass spectrometry. In five mouse tissues, over 600 protein spots were visualized on 2DE gel stained by Commassie blue and 154 proteins were identified by MALDI-TOF, in which most proteins belong to heme related. This methodology makes it possible to globally characterize the heme-binding proteins in a biological system.
基金supported by the Science,Technology and Innovation Commission of Shenzhen Municipality under grant No.JCYJ20170303151334808 and grant No.JSGG20180508152912700The first author would like to acknowledge financial support from the China Scholarship Council(CSC)(grant No.201904910476).
文摘T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-CoV-2.^(2) CMV-related diseases occur once the host immune system is impaired or lacks a protective repertoire of virus-specific T lymphocytes.3 Adoptive transfer of T-cell receptor(TCR)-engineered T cells(TCR-Ts)provides an encouraging alternative treatment option for patients with CMV reactivation.^(4) However,generating TCR-Ts requires the identification of epitope-specific and functional TCR pairs.Modern single-cell sequencing techniques open up the ability to unravel TCR repertoires,^(5 )which offers a potential opportunity to screen functional TCR pairs for TCR-T therapy.Here,we report an efficient approach that combines ex vivo CD8+T-cell stimulation with single-cell RNA and TCR V(D)J sequencing to identify CMV-specific TCRs for generating TCR-Ts.
基金This work was supported by the Lundbeck Foundation(R219-2016-1375 and R173-2014-1105)the Danish Research Council for Independent Research(DFF-1337-00128 and 9041-00317B)+4 种基金the Sapere Aude Young Research Talent Prize(DFF-1335-00763A)the Innovation Fund Denmark(BrainStem)Aarhus University Strategic Grant(AU-iCRISPR)the Sanming Project of Medicine in Shenzhen(SZ5M201612074)BGIResearch,and Guangdong Provincial Key Laboratory of Genome Read and Write(2017B030301011)。
文摘CRISPR/Cas9 is an adaptive immunity system in bacteria and most archaea(Koonin and Makarova,2009;Horvath and Barrangou,2010).The CRISPR/Cas9 gene editing system is comprised of two key components,a small guide RNA(gRNA)and a Cas9 endonuclease(Deltcheva etal.,2011;Jineketal.,2012).
