Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve ...Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.展开更多
A series of graphitic-C3N4/ZnS（g-C3N4/ZnS） supercapacitor electrode materials have been prepared via a one-step calcination process of zinc acetate/thiourea with different mass ratios under nitrogen atmosphere. The ...A series of graphitic-C3N4/ZnS（g-C3N4/ZnS） supercapacitor electrode materials have been prepared via a one-step calcination process of zinc acetate/thiourea with different mass ratios under nitrogen atmosphere. The optimized g-C3N4/ZnS composite shows a highest specific capacitance of 497.7 F/g at 1 A/g and good cycling stability with capacitance retention of 80.4% at 5 A/g after 1000 cycles. Moreover, gC3N4/ZnS composites display an improved supercapacitor performance in terms of specific capacitance compared to the pure g-C3N4 and ZnS. In addition, our designed symmetric supercapacitor device based on g-C3N4/ZnS composite electrodes can exhibit an energy density of 10.4 Wh/kg at a power density of 187.3 W/kg. As a result, g-C3N4/ZnS composites are expected to be a prospective material for supercapacitors and other energy storage applications.展开更多
It is difficult for physicians to identify patients with metastatic nasopharyngeal carcinoma(NPC)who are sensitive to local treatment of metastases.Here,we aimed to establish a prognostic model for survival and indivi...It is difficult for physicians to identify patients with metastatic nasopharyngeal carcinoma(NPC)who are sensitive to local treatment of metastases.Here,we aimed to establish a prognostic model for survival and individualize treatments for patients with metastatic NPC.Data were collated from 240 NPC patients diagnosed with metachronous metastasis between 2006 and 2020 who received palliative chemotherapy with or without local treatment.Multivariable Cox regression was implemented to construct a nomogram which had a concordance index of 0.764 when predicting 1-,3-,and 5-year overall survival(OS).We then classified patients according to risk,creating low-and high-risk groups using the nomogram.Differences in OS between the two groups were significant(P<0.001).In the low-risk group,the OS for patients who received local treatment was longer than those without(P=0.009).This novel nomogram shows good performance in classifying patients according to risk and may also be a promising tool for determining who responds best to local treatment.Further validation using external center data is warranted.展开更多
N-glycans in many proteins are of great concern because of their strong association with food allergies. Triticum aestivum(bread wheat), a major food crop, is known as one of the “Big Eight” allergenic groups. Howev...N-glycans in many proteins are of great concern because of their strong association with food allergies. Triticum aestivum(bread wheat), a major food crop, is known as one of the “Big Eight” allergenic groups. However, little research has been done about N-glycans in wheat glycoproteins. In this study, a soluble wheat glycoprotein was purified from wheat and further identified as globulin-1 S allele(GSA). The wheat GSA displayed significant IgE-binding activity. Moreover, one N-glycosylation site and 6 kinds of N-glycans were identified by mass spectrometry, including 3 high mannose types and 3 complex types. Furthermore, the IgE-binding activity of wheat GSA is proved to be reduced by the removal of N-glycan, thermal treatment(temperatures > 80 ℃), and strong acidic treatment(pH 3.0). These findings would provide a better understanding of the effects of N-glycosylation, thermal treatment, and acidic treatment on the molecular characteristics of GSA, and further provide new insights into the development of hypoallergenic wheat products.展开更多
In this paper, we propose a novel seismic blind deconvolution approach based on the Spearman’s rho in the case of band-limited seismic data with a low dominant frequency and short data records. The Spearman’s rho is...In this paper, we propose a novel seismic blind deconvolution approach based on the Spearman’s rho in the case of band-limited seismic data with a low dominant frequency and short data records. The Spearman’s rho is a measure of the dependence between two continuous random variables without the influence of the marginal distributions, by which a new criterion for blind deconvolution is constructed. The optimization program for new criterion of blind deconvolution is performed by applying Neidell’s wavelet model to the inverse filter. The noise-free and noisy synthetic data, onshore seismic trace in the Ordos Basin, and offshore stacked section in the Bohai Bay Basin examples show good results of the method.展开更多
Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resul...Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.展开更多
Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechani...Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechanism for ART resistance are under way,no effective therapeutic targets for reversing resistance have been applied.Here,we explore glutathione(GSH)as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor(L-buthionine sulfoximine,BSO)in a sustained manner,effectively reversing ART resistance in vivo.By combining with BSO,ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration(IC50)by 7.43-fold in ART-resistant strains.This work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance,paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.展开更多
Hereditary spherocytosis （HS）, the most common cause of congenital hemolytic anemia, is caused by deficiency of the ery- throcyte membrane proteins. Five causative genes （ANK1, SPTB, SPTA1, SLC4AI, and EPB42） have...Hereditary spherocytosis （HS）, the most common cause of congenital hemolytic anemia, is caused by deficiency of the ery- throcyte membrane proteins. Five causative genes （ANK1, SPTB, SPTA1, SLC4AI, and EPB42） have been identified. To date, molecular genetic studies have been performed in different populations, including the American, European, Brazilian, Japanese and Korean populations, whereas only a few studies have been described in the Chinese population. Here, by reanalysis of the exome data, we revealed causative mutations and established a definitive diagnosis of HS in all 38 Chinese families. We found 34 novel mutations and four reported mutations in three known HS-causing genes--17 in ANK1, 17 in SPTB and four in SLC4A1, suggesting that ANK1 and SPTB are the major genes in Chinese patients with HS. All of the ANK1 or SPTB mutations, scattered throughout the entire genes, are non-recurrent; and most of them are null mutations, which might cause HS via a hap-loinsufficiency mechanism. De novo mutations in ANK1 or SPTB often occur with an unexpected high frequency （87.5% and 64.2%, respectively）. Our study updates our knowledge about the genetic profile of HS in Chinese and shows that family-based, especially parent-offspring trio, sequencing analysis can help to increase the diagnostic power and improve diagnostic efficiency.展开更多
We present a method based on least-squares reverse time migration with plane-wave encoding （P-LSRTM） for rugged topography. Instead of modifying the wave field before migration, we modify the plane-wave encoding fun...We present a method based on least-squares reverse time migration with plane-wave encoding （P-LSRTM） for rugged topography. Instead of modifying the wave field before migration, we modify the plane-wave encoding function and fill constant velocity to the area above rugged topography in the model so that P-LSRTM can be directly performed from rugged surface in the way same to shot domain reverse time migration. In order to improve efficiency and reduce I/O （input/output） cost, the dynamic en- coding strategy and hybrid encoding strategy are implemented. Numerical test on SEG rugged topography model show that P-LSRTM can suppress migration artifacts in the migration image, and compensate am- plitude in the middle-deep part efficiently. Without data correction, P-LSRTM can produce a satisfying image of near-surface if we could get an accurate near-surface velocity model. Moreover, the pre-stack P- LSRTM is more robust than conventional RTM in the presence of migration velocity errors.展开更多
Marfan syndrome(MFS) is a systemic connective tissue disease principally affecting the ocular, skeletal and cardiovascular systems. This autosomal dominant disorder carries a prevalence of 1:3,000 to 1:5,000. This stu...Marfan syndrome(MFS) is a systemic connective tissue disease principally affecting the ocular, skeletal and cardiovascular systems. This autosomal dominant disorder carries a prevalence of 1:3,000 to 1:5,000. This study aims to define the mutational spectrum of MFS related genes in Chinese patients and to establish genotype-phenotype correlations in MFS. Panel-based targeted next-generation sequencing was used to analyze the FBN1, TGFBR1 and TGFBR2 genes in 123 unrelated Chinese individuals with MFS or a related disease. Genotype-phenotype correlation analyses were performed in mutation-positive patients. The results showed that 97 cases/families(78.9%;97/123) harbor at least one(likely) pathogenic mutation, most of which were in FBN1;four patients had TGFBR1/2 mutations;and one patient harbored a SMAD3 mutation. Three patients had two FBN1 mutations, and all patients showed classical MFS phenotypes. Patients with a dominant negative-FBN1 mutation had a higher prevalence of ectopia lentis(EL). Patients carrying a haploinsufficiency-FBN1 mutation tended to have aortic dissection without EL. This study extends the spectrum of genetic backgrounds of MFS and enriches our knowledge of genotype-phenotype correlations.展开更多
A phytochemical investigation on the leaves of Cistus parviflorus led to the isolation of 18 compounds.The structures of the isolated compounds were elucidated as kaempferol 3-O-（3′′,6′′-di-O-E-p-coumaroyl）-β-D...A phytochemical investigation on the leaves of Cistus parviflorus led to the isolation of 18 compounds.The structures of the isolated compounds were elucidated as kaempferol 3-O-（3′′,6′′-di-O-E-p-coumaroyl）-β-D-glucopyranoside（1）,scopoletin（2）,kaempferol 3-O-（3′′-O-E-p-coumaroyl）-β-D-glucopyranoside（3）,kaempferol 3-O-（6′′-O-E-p-coumaroyl）-β-D-glucopyranoside（4）,kaempferol 3-O-β-D-glucopyranoside（5）,kaempferol 3-O-α-L-rhamnopyranosyl-（1→2）-（6′-O-E-p-coumaroyl）-β-D-glucopyranoside（6）,methyl flavogallonate（7）,quercetin 3-O-β-D-glucopyranoside（8）,quercetin 3-O-β-D-galactopyranoside（9）,hydroquinone（10）,arbutin（11）,methyl β-glucopyranoside（12）,shikimic acid（13）,（S）-1,2-propandiol-1-O-β-D-glucopyranoside（14）,benzyl-O-α-L-rhamnopyranosyl-（1→6）-β-D-glucopyranoside（15）,2-phenethyl-O-α-L-rhamnopyranosyl-（1→6）-β-D-glucopyranoside（16）,corchoionoside C（17）,kaempferol 3-O-α-L-rhamnopyranosyl-（1→2）-β-D-glucopyranoside（18） by the analysis of the MS and NMR spectroscopic data and comparison with the literature.Compounds 1–2,6–7,10–12,and 14–16 were isolated from Cistus genus for the first time.展开更多
Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component genes.We and other researchers showed that nicastrin (NCSTN) ...Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component genes.We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI.In this study,we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice.We determined that this mutant recapitulated the major phenotypes of AI,including hyperkeratosis of hair follicles and inflammation.In Ncstnflox/flox;K5-Cre mice,the IL-36a expression level markedly increased starting from postnatal day 0 (P0),and this increase occurred much earlier than those of TNF-α,IL-23A,IL-1 3,and TLR4.RNA-Seq analysis indicated that Sprr2d,a member of the small proline-rich protein 2 family,in the skin tissues of the Ncstnflox/flox,;K5-Cre mice was also upregulated on P0.Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern.Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and implicate malfunction of the skin barrier in the pathogenesis of AI.展开更多
Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB...Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB,and eight variants including a novel nonsense variant(c.47G>A,p.W16*)in LAMA3,a known recurrent variant(c.74C>T,p.P25L)in KRT5,2 novel(c.2531T>A,p.V844E;c.6811_6814del,p.R2271fs)and 4 known(c.6187C>T,p.R2063W;c.7097G>A,p.G2366D;c.8569G>T,p.E2857*;c.3625_3635del,p.S1209fs)variants in COL7A1 were detected.Notably,this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay.Our study expands the mutation spectra of Chinese patients with EB.展开更多
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-Co V-2) has occasioned worldwide alarm. Globally, the number of reported confirmed cases has exceeded 84...The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-Co V-2) has occasioned worldwide alarm. Globally, the number of reported confirmed cases has exceeded 84.3 million as of this writing(January 2, 2021). Since there are no targeted therapies for COVID-19。展开更多
Dear Editor,Neurofibromatosis type 1(NF1;von Recklinghausen neurofibromatosis;OMIM 162200)is a neurocutaneous genetic disorder that affects approximately one in 2,500 people worldwide(Huson et al.,1989).NF1 is charact...Dear Editor,Neurofibromatosis type 1(NF1;von Recklinghausen neurofibromatosis;OMIM 162200)is a neurocutaneous genetic disorder that affects approximately one in 2,500 people worldwide(Huson et al.,1989).NF1 is characterized by wide clinical variability,including multiple café-au-lait macules(CALMs),fibromatous tumors,axillary or inguinal freckling,Lisch nodules(iris hamartomas),skeletal anomalies,and cognitive impairments(Monroe et al.,2017).展开更多
Since the new round of health system reform,the annual average growth rate of health expenditure in real term in China was 10.5%,which is much faster than that of any other Asian countries.The aim of this study is to ...Since the new round of health system reform,the annual average growth rate of health expenditure in real term in China was 10.5%,which is much faster than that of any other Asian countries.The aim of this study is to analyze major effect-ing factors include population ageing’s contribution to health expenditure growth,as population ageing is accelerating and considered as a major driver of health expenditure growth in China.A component based health expenditure model was developed in this study and five major factors were employed,namely popula-tion size,population structure,disease prevalence rate,excess health price infla-tion(EHPI)and expenditure per prevalent case.Then Das Gupta’s decomposition method was applied to decompose the health expenditure growth into the five factors.Results shows that expenditure per prevalent case was the major factor,which accounted for 59.6%of the health expenditure growth.21.2%of the health expenditure growth was driven by population ageing,followed by EHPI(11.2%),population growth(5.4%)and disease prevalence rate(2.6%).Population age-ing affected circulatory diseases the most,which caused 5.2%of the difference in health expenditure,followed by neoplasms(2.9%),respiratory diseases(2.0%),digestive diseases(1.8%),and endocrine(1.5%).Our work highlights that meas-ures should be taken to reduce risk factors of major non-communicable disease to promote healthy ageing,and it is fundamental to address growth in expenditure per case,especially for circulatory,respiratory,digestive,genitourinary diseases,and endocrine,nutritional and metabolic to contain the rapid health expenditure growth in China.展开更多
基金supported by Key Project of China Rehabilitation Research Center,Nos.2022ZX-05,2018ZX-08(both to JB)。
文摘Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.
基金supported by the National Nature Science Foundations of China (Grant no. 51372212)
文摘A series of graphitic-C3N4/ZnS（g-C3N4/ZnS） supercapacitor electrode materials have been prepared via a one-step calcination process of zinc acetate/thiourea with different mass ratios under nitrogen atmosphere. The optimized g-C3N4/ZnS composite shows a highest specific capacitance of 497.7 F/g at 1 A/g and good cycling stability with capacitance retention of 80.4% at 5 A/g after 1000 cycles. Moreover, gC3N4/ZnS composites display an improved supercapacitor performance in terms of specific capacitance compared to the pure g-C3N4 and ZnS. In addition, our designed symmetric supercapacitor device based on g-C3N4/ZnS composite electrodes can exhibit an energy density of 10.4 Wh/kg at a power density of 187.3 W/kg. As a result, g-C3N4/ZnS composites are expected to be a prospective material for supercapacitors and other energy storage applications.
基金supported by the National Natural Science Foundation of China(Grant No.81872192)China International Medical Foundation(Grant No.Z-2014-06-19392).
文摘It is difficult for physicians to identify patients with metastatic nasopharyngeal carcinoma(NPC)who are sensitive to local treatment of metastases.Here,we aimed to establish a prognostic model for survival and individualize treatments for patients with metastatic NPC.Data were collated from 240 NPC patients diagnosed with metachronous metastasis between 2006 and 2020 who received palliative chemotherapy with or without local treatment.Multivariable Cox regression was implemented to construct a nomogram which had a concordance index of 0.764 when predicting 1-,3-,and 5-year overall survival(OS).We then classified patients according to risk,creating low-and high-risk groups using the nomogram.Differences in OS between the two groups were significant(P<0.001).In the low-risk group,the OS for patients who received local treatment was longer than those without(P=0.009).This novel nomogram shows good performance in classifying patients according to risk and may also be a promising tool for determining who responds best to local treatment.Further validation using external center data is warranted.
基金financially supported by the National Natural Science Foundation of China (31871735)。
文摘N-glycans in many proteins are of great concern because of their strong association with food allergies. Triticum aestivum(bread wheat), a major food crop, is known as one of the “Big Eight” allergenic groups. However, little research has been done about N-glycans in wheat glycoproteins. In this study, a soluble wheat glycoprotein was purified from wheat and further identified as globulin-1 S allele(GSA). The wheat GSA displayed significant IgE-binding activity. Moreover, one N-glycosylation site and 6 kinds of N-glycans were identified by mass spectrometry, including 3 high mannose types and 3 complex types. Furthermore, the IgE-binding activity of wheat GSA is proved to be reduced by the removal of N-glycan, thermal treatment(temperatures > 80 ℃), and strong acidic treatment(pH 3.0). These findings would provide a better understanding of the effects of N-glycosylation, thermal treatment, and acidic treatment on the molecular characteristics of GSA, and further provide new insights into the development of hypoallergenic wheat products.
文摘In this paper, we propose a novel seismic blind deconvolution approach based on the Spearman’s rho in the case of band-limited seismic data with a low dominant frequency and short data records. The Spearman’s rho is a measure of the dependence between two continuous random variables without the influence of the marginal distributions, by which a new criterion for blind deconvolution is constructed. The optimization program for new criterion of blind deconvolution is performed by applying Neidell’s wavelet model to the inverse filter. The noise-free and noisy synthetic data, onshore seismic trace in the Ordos Basin, and offshore stacked section in the Bohai Bay Basin examples show good results of the method.
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.82001221 and 81788101)the National Key Research and Development Program of China(Nos.2022YFC2703900 and 2022YFC2703903)the CAMS Innovation Fund for Medical Sciences(CIFMS)(Nos.2021-I2M-1-018,2022-I2M-JB-004 and 2017-I2M-B&R-05).
文摘Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.
基金supported by the National Natural Science Foundation of China(Nos.81803470 and 82173767)。
文摘Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechanism for ART resistance are under way,no effective therapeutic targets for reversing resistance have been applied.Here,we explore glutathione(GSH)as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor(L-buthionine sulfoximine,BSO)in a sustained manner,effectively reversing ART resistance in vivo.By combining with BSO,ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration(IC50)by 7.43-fold in ART-resistant strains.This work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance,paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.
基金supported by the National Key Research and Development Program of China (2016YFC0905100)the CAMS Innovation Fund for Medical Sciences (2016-I2M-1-002)+3 种基金the National Natural Science Foundation of China (NSFC) (81230015)the Beijing Municipal Science and Technology Commission (Z151100003915078)the Medical Science and Technology Research Projects of Henan Provincial Health Bureau (201601019)the Scientific and Technological Projects of the Technology Bureau of Henan Provincial Technology (172102410010)
文摘Hereditary spherocytosis （HS）, the most common cause of congenital hemolytic anemia, is caused by deficiency of the ery- throcyte membrane proteins. Five causative genes （ANK1, SPTB, SPTA1, SLC4AI, and EPB42） have been identified. To date, molecular genetic studies have been performed in different populations, including the American, European, Brazilian, Japanese and Korean populations, whereas only a few studies have been described in the Chinese population. Here, by reanalysis of the exome data, we revealed causative mutations and established a definitive diagnosis of HS in all 38 Chinese families. We found 34 novel mutations and four reported mutations in three known HS-causing genes--17 in ANK1, 17 in SPTB and four in SLC4A1, suggesting that ANK1 and SPTB are the major genes in Chinese patients with HS. All of the ANK1 or SPTB mutations, scattered throughout the entire genes, are non-recurrent; and most of them are null mutations, which might cause HS via a hap-loinsufficiency mechanism. De novo mutations in ANK1 or SPTB often occur with an unexpected high frequency （87.5% and 64.2%, respectively）. Our study updates our knowledge about the genetic profile of HS in Chinese and shows that family-based, especially parent-offspring trio, sequencing analysis can help to increase the diagnostic power and improve diagnostic efficiency.
基金jointly financial support of the National 973 Project of China(Nos.2014CB239006,2011CB202402)the National Natural Science Foundation of China(Nos.41104069,41274124)+1 种基金the Shandong Natural Science Foundation of China(No.ZR2011DQ016)the Fundamental Research Funds for the Central Universities of China(No.R1401005A)
文摘We present a method based on least-squares reverse time migration with plane-wave encoding （P-LSRTM） for rugged topography. Instead of modifying the wave field before migration, we modify the plane-wave encoding function and fill constant velocity to the area above rugged topography in the model so that P-LSRTM can be directly performed from rugged surface in the way same to shot domain reverse time migration. In order to improve efficiency and reduce I/O （input/output） cost, the dynamic en- coding strategy and hybrid encoding strategy are implemented. Numerical test on SEG rugged topography model show that P-LSRTM can suppress migration artifacts in the migration image, and compensate am- plitude in the middle-deep part efficiently. Without data correction, P-LSRTM can produce a satisfying image of near-surface if we could get an accurate near-surface velocity model. Moreover, the pre-stack P- LSRTM is more robust than conventional RTM in the presence of migration velocity errors.
基金supported by the National Natural Science Foundation of China (81400187 and 81230015)CAMS Innovation Fund for Medical Sciences (2016-I2M-1-002)+1 种基金the Beijing Municipal Science and Technology Commission (Z151100003915078)the Special Research Fund for Central Public Scientific Research Institutes, Peking Union Medical College (2016ZX310160)
文摘Marfan syndrome(MFS) is a systemic connective tissue disease principally affecting the ocular, skeletal and cardiovascular systems. This autosomal dominant disorder carries a prevalence of 1:3,000 to 1:5,000. This study aims to define the mutational spectrum of MFS related genes in Chinese patients and to establish genotype-phenotype correlations in MFS. Panel-based targeted next-generation sequencing was used to analyze the FBN1, TGFBR1 and TGFBR2 genes in 123 unrelated Chinese individuals with MFS or a related disease. Genotype-phenotype correlation analyses were performed in mutation-positive patients. The results showed that 97 cases/families(78.9%;97/123) harbor at least one(likely) pathogenic mutation, most of which were in FBN1;four patients had TGFBR1/2 mutations;and one patient harbored a SMAD3 mutation. Three patients had two FBN1 mutations, and all patients showed classical MFS phenotypes. Patients with a dominant negative-FBN1 mutation had a higher prevalence of ectopia lentis(EL). Patients carrying a haploinsufficiency-FBN1 mutation tended to have aortic dissection without EL. This study extends the spectrum of genetic backgrounds of MFS and enriches our knowledge of genotype-phenotype correlations.
文摘A phytochemical investigation on the leaves of Cistus parviflorus led to the isolation of 18 compounds.The structures of the isolated compounds were elucidated as kaempferol 3-O-（3′′,6′′-di-O-E-p-coumaroyl）-β-D-glucopyranoside（1）,scopoletin（2）,kaempferol 3-O-（3′′-O-E-p-coumaroyl）-β-D-glucopyranoside（3）,kaempferol 3-O-（6′′-O-E-p-coumaroyl）-β-D-glucopyranoside（4）,kaempferol 3-O-β-D-glucopyranoside（5）,kaempferol 3-O-α-L-rhamnopyranosyl-（1→2）-（6′-O-E-p-coumaroyl）-β-D-glucopyranoside（6）,methyl flavogallonate（7）,quercetin 3-O-β-D-glucopyranoside（8）,quercetin 3-O-β-D-galactopyranoside（9）,hydroquinone（10）,arbutin（11）,methyl β-glucopyranoside（12）,shikimic acid（13）,（S）-1,2-propandiol-1-O-β-D-glucopyranoside（14）,benzyl-O-α-L-rhamnopyranosyl-（1→6）-β-D-glucopyranoside（15）,2-phenethyl-O-α-L-rhamnopyranosyl-（1→6）-β-D-glucopyranoside（16）,corchoionoside C（17）,kaempferol 3-O-α-L-rhamnopyranosyl-（1→2）-β-D-glucopyranoside（18） by the analysis of the MS and NMR spectroscopic data and comparison with the literature.Compounds 1–2,6–7,10–12,and 14–16 were isolated from Cistus genus for the first time.
基金This work was financially supported by the National Key Research and Development Program of China(No.2016Y FC0905100)the CAMS Innovation Fund for Medical Sciences(No.2016-I2M-1-002)+3 种基金the National Natural Science Foundation of China(NSFCNos.81788101 and 81230015)the Beijing Municipal Science and Technology Commission(No.Z151100003915078)for Xue Zhangby the National NSFC(No.31271345)for Yaping Liu.
文摘Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component genes.We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI.In this study,we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice.We determined that this mutant recapitulated the major phenotypes of AI,including hyperkeratosis of hair follicles and inflammation.In Ncstnflox/flox;K5-Cre mice,the IL-36a expression level markedly increased starting from postnatal day 0 (P0),and this increase occurred much earlier than those of TNF-α,IL-23A,IL-1 3,and TLR4.RNA-Seq analysis indicated that Sprr2d,a member of the small proline-rich protein 2 family,in the skin tissues of the Ncstnflox/flox,;K5-Cre mice was also upregulated on P0.Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern.Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and implicate malfunction of the skin barrier in the pathogenesis of AI.
基金This work was financially supported by the National Natural Science Foundation of China(No.81788101)the National Key Research and Development Program of China(No.2016YFC0905100)+1 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-1-002)the Natural Science Foundation of Beijing(No.7172167).
文摘Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB,and eight variants including a novel nonsense variant(c.47G>A,p.W16*)in LAMA3,a known recurrent variant(c.74C>T,p.P25L)in KRT5,2 novel(c.2531T>A,p.V844E;c.6811_6814del,p.R2271fs)and 4 known(c.6187C>T,p.R2063W;c.7097G>A,p.G2366D;c.8569G>T,p.E2857*;c.3625_3635del,p.S1209fs)variants in COL7A1 were detected.Notably,this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay.Our study expands the mutation spectra of Chinese patients with EB.
基金the National Natural Science Foundation of China(No.81703612)。
文摘The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-Co V-2) has occasioned worldwide alarm. Globally, the number of reported confirmed cases has exceeded 84.3 million as of this writing(January 2, 2021). Since there are no targeted therapies for COVID-19。
基金supported by the National Key Research and Development Program of China(2016YFC0905100 and 2016YFC1000504)the National Natural Science Foundation of China(81788101)+1 种基金the CAMS Innovation Fund for Medical Sciences(2016-I2M-1002)the Natural Science Foundation of Beijing(7172167)。
文摘Dear Editor,Neurofibromatosis type 1(NF1;von Recklinghausen neurofibromatosis;OMIM 162200)is a neurocutaneous genetic disorder that affects approximately one in 2,500 people worldwide(Huson et al.,1989).NF1 is characterized by wide clinical variability,including multiple café-au-lait macules(CALMs),fibromatous tumors,axillary or inguinal freckling,Lisch nodules(iris hamartomas),skeletal anomalies,and cognitive impairments(Monroe et al.,2017).
文摘Since the new round of health system reform,the annual average growth rate of health expenditure in real term in China was 10.5%,which is much faster than that of any other Asian countries.The aim of this study is to analyze major effect-ing factors include population ageing’s contribution to health expenditure growth,as population ageing is accelerating and considered as a major driver of health expenditure growth in China.A component based health expenditure model was developed in this study and five major factors were employed,namely popula-tion size,population structure,disease prevalence rate,excess health price infla-tion(EHPI)and expenditure per prevalent case.Then Das Gupta’s decomposition method was applied to decompose the health expenditure growth into the five factors.Results shows that expenditure per prevalent case was the major factor,which accounted for 59.6%of the health expenditure growth.21.2%of the health expenditure growth was driven by population ageing,followed by EHPI(11.2%),population growth(5.4%)and disease prevalence rate(2.6%).Population age-ing affected circulatory diseases the most,which caused 5.2%of the difference in health expenditure,followed by neoplasms(2.9%),respiratory diseases(2.0%),digestive diseases(1.8%),and endocrine(1.5%).Our work highlights that meas-ures should be taken to reduce risk factors of major non-communicable disease to promote healthy ageing,and it is fundamental to address growth in expenditure per case,especially for circulatory,respiratory,digestive,genitourinary diseases,and endocrine,nutritional and metabolic to contain the rapid health expenditure growth in China.
