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中国科学:生命科学（英文版）
中国科学:生命科学（英文版）

周光召

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1674-7305

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北京东黄城根北街16号

中国科学:生命科学（英文版）/Journal Science China(Life Sciences)CSCDCSTPCDSCI
查看更多>>《中国科学》是中国科学院主办、中国科学杂志社出版的自然科学专业性学术刊物。《中国科学》任务是反映中国自然科学各学科中的最新科研成果，以促进国内外的学术交流。《中国科学》以论文形式报道中国基础研究和应用研究方面具有创造性的、高水平的和有重要意义的科研成果。在国际学术界，《中国科学》作为代表中国最高水平的学术刊物也受到高度重视。国际上最具有权威的检索刊物SCI，多年来一直收录《中国科学》的论文。1999年《中国科学》夺得国家期刊奖的第一名。
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    Complicated target recognition by archaeal box C/D guide RNAs

    Jiayin WangSonglin WuKeqiong Ye
    631-644页
    查看更多>>摘要：Box C/D RNAs guide the site-specific formation of 2'-O-methylated nucleotides(Nm)of RNAs in eukaryotes and archaea.Although C/D RNAs have been profiled in several archaea,their targets have not been experimentally determined.Here,we mapped Nm in rRNAs,tRNAs,and abundant small RNAs(sRNAs)and profiled C/D RNAs in the crenarchaeon Sulfolobus islandicus.The targets of C/D RNAs were assigned by analysis of base-pairing interactions,in vitro modification assays,and gene deletion experiments,revealing a complicated landscape of C/D RNA-target interactions.C/D RNAs widely use dual antisense elements to target adjacent sites in rRNAs,enhancing modification at weakly bound sites.Two consecutive sites can be guided with the same antisense element upstream of box D or D',a phenomenon known as double-specificity that is exclusive to internal box D'in eukaryotic C/D RNAs.Several C/D RNAs guide modification at a single non-canonical site.This study reveals the global landscape of RNA-guided 2'-O-methylation in an archaeon and unexpected targeting rules employed by C/D RNA.
      原文链接:
    • 万方数据
    • 维普

    B cell development and antibody responses in human immune system mice:current status and future perspective

    Tao ZhangWentao LiuYong-Guang Yang
    645-652页
    查看更多>>摘要：Humanized immune system(HIS)mice have been developed and used as a small surrogate model to study human immune function under normal or disease conditions.Although variations are found between models,most HIS mice show robust human T cell responses.However,there has been unsuccessful in constructing HIS mice that produce high-affinity human antibodies,primarily due to defects in terminal B cell differentiation,antibody affinity maturation,and development of primary follicles and germinal centers.In this review,we elaborate on the current knowledge about and previous attempts to improve human B cell development in HIS mice,and propose a potential strategy for constructing HIS mice with improved humoral immunity by transplantation of human follicular dendritic cells(FDCs)to facilitate the development of secondary follicles.
      原文链接:
    • 万方数据
    • 维普

    The burgeoning importance of PIWI-interacting RNAs in cancer progression

    Xinpei DengTianle LiaoJindong XieDa Kang...
    653-662页
    查看更多>>摘要：PIWI-interacting RNAs(piRNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that piRNAs,as tissue-specific molecules,both play oncogenic and tumor suppressive roles in cancer progression,including cancer cell proliferation,metastasis,chemoresistance and stemness.Additionally,the atypical manifestation of piRNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors.Nonetheless,the precise functions of piRNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended.This review aims to examine current research on the biogenesis and functions of piRNA and its burgeoning importance in cancer progression,thereby offering novel perspectives on the potential utilization of piRNAs and piwi proteins in the management and treatment of advanced cancer.
      原文链接:
    • 万方数据
    • 维普

    Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

    Yanfang LiuYan WangBing LiuWenzhong Liu...
    663-679页
    查看更多>>摘要：Chemoresistance is a significant barrier to effective cancer treatment.Potential mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting genes.Here,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of chemoresistance.By analyzing the serum levels of lncRNA16 in a cohort of 3 5 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive iden-tification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based chemotherapy.The expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of chemoresistance.LncRNA16 binds to HBB and promotes HBB accumulation by inhibiting autophagy.LncRNA16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the mitochondria.Importantly,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in vivo.Overall,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.
      原文链接:
    • 万方数据
    • 维普

    Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy:a novel delivery system candidate for tumor vaccines

    Nan LiYun ZhangMiaomiao HanTian Liu...
    680-697页
    查看更多>>摘要：The study of tumor nanovaccines(NVs)has gained interest because they specifically recognize and eliminate tumor cells.However,the poor recognition and internalization by dendritic cells(DCs)and insufficient immunogenicity restricted the vaccine efficacy.Herein,we extracted two molecular-weight Astragalus polysaccharides(APS,12.19 kD;APSHMw,135.67 kD)from Radix Astragali and made them self-assemble with OVA257-264 directly forming OVA/APS integrated nanocomplexes through the microfluidic method.The nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve stability.APS in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor immunotherapy.The optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline solution.The FITC-OVA in APS-NVs could be effectively taken up by DCs,and APS-NVs could stimulate the maturation of DCs,improving the antigen cross-presentation efficiency in vitro.The possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and 4.Enhanced accumulation of APS-NVs both in draining and distal lymph nodes were observed following s.c.injection.Smaller APS-NVs could easily access the lymph nodes.Furthermore,APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T cells.In addition,APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment group.The antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor region.Subsequently,the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by NVs.Therefore,this study de-veloped a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.
      原文链接:
    • 万方数据
    • 维普

    Ultrasound-responsive spherical nucleic acid against c-Myc/PD-L1 to enhance anti-tumoral macrophages in triple-negative breast cancer progression

    Runtian WangGaigai LiFangyan GaoFeng Xu...
    698-710页
    查看更多>>摘要：Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited ther-apeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an"undruggable"target due to its disordered structure.Herein,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in TNBC.It is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(siRNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a sonosensitizer.We accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and physiotherapy.Our study demonstrated significant anti-tumoral effects in vitro and in vivo.Mass cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were trans-formed into the anti-tumoral population.Our finding offers a novel therapeutic strategy against the"undruggable"c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.
      原文链接:
    • 万方数据
    • 维普

    Cancer statistics for young adults aged 20 to 49 years in China from 2000 to 2017:a population-based registry study

    Yi TengChangfa XiaHe LiMaomao Cao...
    711-719页
    查看更多>>摘要：An increasing cancer incidence among adults younger than 50 years has been reported for several types of cancer in multiple countries.We aimed to report cancer profiles and trends among young adults in China.Data from the China Cancer Registry Annual Report were used to estimate incidence and mortality among young adults(ages 20-49 years)in China in 2017,and an age-period-cohort model was employed to estimate the average annual percent change(AAPC)in incidence and mortality from 2000 to 2017.All 25 cancer types were grouped into obesity-or overweight-associated cancers(12 cancer types)and additional cancers(13 cancer types).In 2017,there were 681,178 new cases and 214,591 cancer deaths among young adults in China.Among young adults,the most common cancers were thyroid,breast,cervical,liver,lung,and colorectal cancer,and the leading causes of cancer deaths were liver,lung,cervical,stomach,breast,and colorectal cancer.From 2000 to 2017,the cancer incidence increased for all cancers combined among young adults,with the highest AAPC(1.46％)for adults aged 20-24 years,while cancer mortality decreased,with the highest AAPC(-1.63％)for those aged 35-39 years.In conclusion,the cancer incidence in China has increased among young adults,while cancer mortality has decreased for nearly all ages.Cancer control measures,such as obesity control and appropriate screening,may contribute to reducing the increasing cancer burden among young adults.
      原文链接:
    • 万方数据
    • 维普

    The spatial transcriptomic landscape of human gingiva in health and periodontitis

    Zongshan ShenRan ZhangYunjia HuangJiayao Chen...
    720-732页
    查看更多>>摘要：The gingiva is a key oral barrier that protects oral tissues from various stimuli.A loss of gingival tissue homeostasis causes periodontitis,one of the most prevalent inflammatory diseases in humans.The human gingiva exists as a complex cell network comprising specialized structures.To understand the tissue-specific pathophysiology of the gingiva,we applied a recently developed spatial enhanced resolution omics-sequencing(Stereo-seq)technique to obtain a spatial transcriptome(ST)atlas of the gingiva in healthy individuals and periodontitis patients.By utilizing Stereo-seq,we identified the major cell types present in the gingiva,which included epithelial cells,fibroblasts,endothelial cells,and immune cells,as well as subgroups of epithelial cells and immune cells.We further observed that inflammation-related signalling pathways,such as the JAK-STAT and NF-κB signalling pathways,were significantly upregulated in the endothelial cells of the gingiva of periodontitis patients compared with those of healthy individuals.Additionally,we characterized the spatial distribution of periodontitis risk genes in the gingiva and found that the expression of IFI16 was significantly increased in endothelial cells of inflamed gingiva.In conclusion,our Stereo-seq findings may facilitate the development of innovative therapeutic strategies for periodontitis by mapping periodontitis-relevant genes and pathways and effector cells.
      原文链接:
    • 万方数据
    • 维普

    Slc43a2+T cell metastasis from spleen to brain in RGNNV infected teleost

    Qing WangYali LiuMinlin ZhangMin Yang...
    733-744页
    查看更多>>摘要：The origin of T cells in the teleost's brain is unclear.While viewing the central nervous system(CNS)as immune privileged has been widely accepted,previous studies suggest that T cells residing in the thymus but not in the spleen of the teleost play an essential role in communicating with the peripheral organs.Here,we identified nine T cell subpopulations in the thymus and spleen of orange-spotted grouper(Epinephelus coioices)through single-cell RNA-sequencing analysis.After viral CNS infection with red-spotted grouper nervous necrosis virus(RGNNV),the number of slc43a2+T cells synchronously increased in the spleen and brain.During the infection tests in asplenic zebrafish(tlx1▲ zebrafish model),no increase in the number of slc43a2+T cells was observed in the brain.Single-cell tran-scriptomic analysis indicated that slc43a2+T cells mature and functionally differentiate within the spleen and then migrate into the brain to trigger an immune response.This study suggests a novel route for T cell migration from the spleen to the brain during viral infection in fish.
      原文链接:
    • 万方数据

    Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

    Shujie ChenLiujing HuangBingdong LiuHuimin Duan...
    745-764页
    查看更多>>摘要：The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle system.However,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains elusive.We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging process.Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total number.Furthermore,employing multi-omics(e.g.,RNA-seq,16S rRNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging.Meanwhile,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/myoblasts.The butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and myoblasts.As a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging.Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.
      原文链接:
    • 万方数据
    • 维普