Seabuckthorn juice alleviates allergic symptoms in shrimp-induced food allergy mice

Tropomyosin(TM)in shrimp is one of the predominant causes of food allergy around the world.In the present study,the effect of seabuckthorn juice against TM-induced shrimp allergy was investigated in BALB/c mice.Allergic symptoms,spleen index,intestinal section and diarrhea were measured in shrimp allergy mice.As the results,seabuckthorn juice suppressed the lesions in jejunum tissue,diarrhea and allergic symptoms in shrimp allergy mice.Seabuckthorn juice also reduced serum concentrations of tumor necrosis factor-a(TNF-α)as well as immunoglobulin E(IgE)and stimulated the secretion of interleukin-10(IL-10)in mice with shrimp allergy.Taken together,our findings suggest that increased IL-10 by seabuckthorn juice inhibits Th2 cytokine production to suppress shrimp allergic symptoms.Furthermore,seabuckthorn juice also regulates shrimp allergy by reducing jejunum lesions,inhibiting levels of TNF-αand IgE.

Changes in the global cryosphere and their impacts:A review and new perspective

As one of the five components of Earth's climatic system,the cryosphere has been undergoing rapid shrinking due to global warming.Studies on the formation,evolution,distribution and dynamics of cryospheric components and their interactions with the human system are of increasing importance to society.In recent decades,the mass loss of glaciers,including the Greenland and Antarctic ice sheets,has accelerated.The extent of sea ice and snow cover has been shrinking,and permafrost has been degrading.The main sustainable development goals in cryospheric regions have been impacted.The shrinking of the cryosphere results in sea-level rise,which is currently affecting,or is soon expected to affect,17 coastal megacities and some small island countries.In East Asia,South Asia and North America,climate anomalies are closely related to the extent of Arctic sea ice and snow cover in the Northern Hemisphere.Increasing freshwater melting from the ice sheets and sea ice may be one reason for the slowdown in Atlantic meridional overturning circulation in the Arctic and Southern Oceans.The foundations of ports and infrastructure in the circum-Arctic permafrost regions suffer from the consequences of permafrost degradation.In high plateaus and mountainous regions,the cryosphere's shrinking has led to fluctuations in river runoff,caused water shortages and increased flooding risks in certain areas.These changes in cryospheric components have shown significant heterogeneity at different temporal and spatial scales.Our results suggest that the quantitative evaluation of future changes in the cryosphere still needs to be improved by enhancing existing observations and model simulations.Theoretical and methodological innovations are required to strengthen social economies'resilience to the impact of cryospheric change.

A Homozygotic Mutation in KDSR may Cause Keratinization Disorders and Thrombocytopenia: A Case Report

Pathogenic mutations in 3-keto-dihydrosphingosine reductase(KDSR)gene are associated with keratinization disorders and impaired platelet function.However,no case with both homozygotic mutation of KDSR and hepatic hemangioendothelioma has ever been reported due to its low prevalence.Here we report a seven months old Chinese boy with a homozygotic missense mutation in KDSR and both of his parents carry a same heterozygous mutation.He was born with thick plate-like scales overlying erythrodermic skin,but the skin symptoms were resolved spontaneously over the first month of his birth.He was also diagnosed with hepatic hemangioendothelioma at birth and accepted a resection surgery at 2 months old.At birth,his platelet count was severely low(10-20×10~9/L)with recurrent skin and gingival bleeding.Meanwhile,he suffered a mild normocytic,normochromic anemia with normal iron and hematinic levels.The anemia spontaneously recovered over the first 6 months,while the platelet count keeped at a low level(4-20×10~9/L).Treatment with corticosteroids,immunoglobulin or thrombopoietin was all suboptimal.

Primitive Neuroectodermal Tumor as the Second Malignant Neoplasm in a Long-Term Survivor Child of Acute Lymphoblastic Leukemia: A Case Report

Acute lymphoblastic leukemia(ALL)is a common pediatric cancer.The second malignant neoplasms(SMNs)in long-term survivors of pediatric ALL are relatively rare.Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor(PNET)5 years after the initial diagnosis of ALL with radiotherapy・free treatment.PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL.It is predisposed to be misdiagnosed and the pathogenesis is unclear.The outcome is poor.Long-term follow-up is necessary for the survival children of ALL.

An investigation of long-term outcome of rabbit anti-thymocyte globulin and cyclosporine therapy for pediatric severe aplastic anemia

Children with severe aplastic anemia(SAA)face heterogeneous prognoses after immunosuppressive therapy(IST).There are few models that can predict the long-term outcomes of IST for these patients.The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA.In the early stage,a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques.Among the indicators related to long-term efficacy,white blood cell count,lymphocyte count,absolute reticulocyte count,lymphocyte ratio in bone-marrow smears,C-reactive protein,and the level of IL-6,IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy(P<.05).Taken together,we analyzed the long-term outcomes of rabbit antithymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques,which may shorten the observation period of therapeutic effects and reduce treatment costs and time.

Investigation of the genetic etiology in male infertility with apparently balanced chromosomal structural rearrangements by genome sequencing

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1%of azoospermia or severe oligospermia.However,the underlying mechanisms of pathogenesis and etiologies are still largely unknown.Herein,we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants.In addition,high read-depth genome sequencing(GS)(30-fold)was performed to investigate point mutations causative of male infertility.Mate-pair GS(4-fold)revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements.Overall,the breakpoints caused truncations of 30 RefSeq genes,five of which were associated with spermatogenesis.Furthermore,the breakpoints disrupted 43 topological-associated domains.Direct disruptions or potential dysregulations of genes,which play potential roles in male germ cell development,apoptosis,and spermatogenesis,were found in all cases(n=6).In addition,high read-depth GS detected dual molecular findings in case MI6,involving a complex rearrangement and two point mutations in the gene DNAH1.Overall,our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility.We demonstrated the complexity of chromosomal structural rearrangements,potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.

Transcriptome Analysis of Monozygotic Twin Brothers with Childhood Primary Myelofibrosis

Primary myelofibrosis （PMF） is a chronic myeloproliferative disorder in human bone marrow. Over 50% of patients with myelofibrosis have mutations in JAK2, MPL, or CALR. However, these mutations are rarely detected in children, suggesting a difference in the pathogenesis of childhood PMF. In this study, we investigated the response to drug treatment of a monozygotic twin pair with typical childhood PMF. The twin exhibited different clinical outcomes despite following

Highly efficient gene editing and single cell analysis of hematopoietic stem/progenitor cells from X-linked sideroblastic anemia patients

Dear Editor,X-linked sideroblastic anemia(XLSA),which is the most common genetic form of congenital sideroblastic anemia,is typically characterized by reduced heme synthesis and the presence of bone marrow(BM)ring sideroblasts containing pathologic iron deposits in the mitochondria.

Novel diagnostic approaches for Fanconi anemia (FA) by single-cell sequencing and capillary nano-immunoassay

Next-generation sequencing technology has been widely utilized for the diagnosis of Fanconi anemia(FA).However,mixed cell sequencing and chimerism of FA patients may lead to unconfirmed genetic subtypes.Herein,we introduced two novel diagnostic methods,including single-cell sequencing and capillary nano-immunoassay.One FA case with FANCM c.4931G>A p.R1644Q and FANCD1 c.6325G>A p.V2109I was studied.The DNA of 28 cells was amplified and eight types of cells were observed after Sanger sequencing.There were two homozygous mutations(FANCM/FANCD1).Furthermore,the capillary nano-immunoassay was conducted to analyze the expression profile of FA-associated proteins.Abnormal FANCM and FANCD1 expressions simultaneously existed.This case was thus diagnosed as FA-D1/FA-M dual subtype.Compared with mixed cell sequencing,single-cell sequencing data shows more accuracy for the FA subtype evaluation,while the capillary nano-immunoassay is a good method to detect the expression profile of abnormal or modified FA protein.

Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia

T cell acute lymphoblastic leukemia(T-ALL)is an aggressive hematologic malignancy often associated with poor outcomes.To identify high-risk factors and potential actionable targets for T-ALL,we perform integrated genomic and transcriptomic analyses on samples from 165 Chinese pediatric and adult T-ALL patients,of whom 85%have outcome information.The genomic mutation landscape of this Chinese cohort is very similar to the Western cohort published previously,except that the rate of NOTCH1 mutations is significant lower in the Chinese T-ALL patients.Among 47 recurrently mutated genes in 7 functional categories,we identify RAS pathway and PTEN mutations as poor survival factors for non-TAL and TAL subtypes,respectively.Mutations in the PI3K pathway are mutually exclusive with mutations in the RAS and NOTCH1 pathways as well as transcription factors.Further analysis demonstrates that approximately 43%of the high-risk patients harbor at least one potential actionable alteration identified in this study,and T-ALLs with RAS pathway mutations are hypersensitive to MEKi in vitro and in vivo.Thus,our integrated genomic analyses not only systematically identify high-risk factors but suggest that these high-risk factors are promising targets for T-ALL therapies.

DNAH2 facilitates the homologous recombination repair of Fanconi anemia pathway through modulating FANCD2 ubiquitination

Fanconi anemia(FA),an X-linked genetic or autosomal recessive disease,exhibits complicated pathogenesis.Previously,we detected the mutated Dynein Axonemal Heavy Chain 2(DNAH2)gene in 2 FA cases.Herein,we further investigated the potential association between DNAH2 and the homologous recombination repair pathway of FA.The assays of homologous recombination repair,mitomycin C(MMC)sensitivity,immunofluorescence,and ubiquitination modification were performed in U2OS and DR-U2OS cell lines.In MMC-treated U2OS cells,the downregulation of the DNAH2 gene increased the sensitivity of cells to DNA inter-strand crosslinks.We also observed the reduced enrichment of FANCD2 protein to DNA damage sites.Furthermore,the ubiquitination modification level of FANCD2 was influenced by the deficiency of DNAH2.Thus,our results suggest that DNAH2 may modulate the cell homologous recombination repair partially by increasing the ubiquitination and the enrichment to DNA damage sites of FANCD2.DNAH2 may act as a novel co-pathogenic gene of FA patients.