Microplastics(MPs),particularly polyvinyl chloride microplastics(PVC MPs)have become a notable environmental pollutant that affect various marine organisms such as Pinctada fucata martensii.As filter feeders,these biv...Microplastics(MPs),particularly polyvinyl chloride microplastics(PVC MPs)have become a notable environmental pollutant that affect various marine organisms such as Pinctada fucata martensii.As filter feeders,these bivalves consume significant volumes of water containing MPs,leading to contact with and ingestion of MPs.Moreover,given the ecological and economic importance of P.f.martensii in artificial pearl production,investigating the effects of PVC MPs exposure is crucial.This study aimed to investigate the effects of PVC MPs exposure on nucleus retention,pearl formation,oxidative stress by examining superoxide dismutase(SOD)activity,catalase(CAT)activity,lipid peroxidation(LPO),and total antioxidant capacity(TAOC)of P.f.martensii,while also exploring transcriptomic changes at different concentrations and exposure time points,including a recovery period.The pearl oysters were exposed to PVC MPs at concentrations of 1-,2.5-,and 5-mg PVC MPs/L for 10 d followed by 6 d of recovery.After 1-,4-,10-d of exposure,and additional 6 d of recovery,samples were taken and analyzed.Findings revealed that only prolonged exposure(10 d)to PVC MPs affected SOD activity,while CAT activity,LPO,and TAOC remained unaffected throughout the experiment.Notably,SOD activity was restored during the 6-d recovery phase.Transcriptome analysis highlighted significant gene alterations linked to various pathways,affecting cellular processes,environmental information processing,genetic information processing,metabolism,and organismal systems,with an increase in pathway-related genes during recovery,implying a potential role of PVC MPs as gene inhibitors.This study provided insights into the effects of PVC MPs on P.f.martensii,shedding light on pearl retention,oxidative systems,and molecular pathways influenced by PVC MPs.Additionally,it contributed novel information on potential MPs exposure biomarkers,particularly relevant to marine organisms like P.f.martensii.展开更多
Deep-sea organisms survive in an extremely harsh environment.There must be some genetic adaptation mechanisms for them.We systematically characterized and compared the complete mitochondrial genome(mitogenome)of a dee...Deep-sea organisms survive in an extremely harsh environment.There must be some genetic adaptation mechanisms for them.We systematically characterized and compared the complete mitochondrial genome(mitogenome)of a deep-sea crab(Chaceon granulates)with those of shallow crabs.The mitogenome of the crab was 16126 bp in length,and encoded 37 genes as most of a metazoan mitogenome,including 13 protein-coding genes(PCGs),22 transfer RNA(tRNA)genes,and 2 ribosomal RNA(rRNA)genes.The gene arrangement and orientation was conserved in the crabs.However,a unique mitogenome element regulator,the origin of light-strand replication(O L),was firstly predicted in the present crab mitogenome.In addition,further positive selection analysis showed that two residues(33 S in ND3 and 502 I in ND5)in C.granulates mitogenome were positively selected,indicated the selective evolution of the deep-sea crab.Therefore,the mitogenome of deep-sea C.granulates showed a unique OL element and positive selection.These special features would influence the mitochondrial energy metabolism,and be involved in the adaptation of deepsea environment,such as oxygen deficits and low temperatures.展开更多
The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels.This is a crosssectional study conducted at Androscience,Science and Innovation Center in Andrology ...The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels.This is a crosssectional study conducted at Androscience,Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo,Brazil,with 508 male patients,aged 18-60 years,from 2007 to 2017.Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria.Patients were divided into normozoospermic group(NZG,n=124)and a group with seminal abnormalities(SAG,n=136).Evaluation included complete physical examination,past medical history,habits and lifestyle factors,two complete seminal analysis with sperm functional tests,serum levels of 25-hydroxy-vitamin D_(3)(25(OH)VD_(3)),total and free testosterone,luteinizing hormone(LH),follicle-stimulating hormone(FSH),sex hormone-binding globulin(SHBG),total cholesterol,homeostatic model assessment of insulin resistance(HOMA-IR)index,and karyotype.The mean concentration of 25(OH)VD_(3)was significantly lower in the SAG(P<0.001)and positively correlated with all baseline seminal parameters and total testosterone levels.In addition,serum vitamin D_(3)concentration was found to be positively correlated with sperm concentration(β=2.103;P<0.001),total number of spermatozoa with progressive motility(β=2.069;P=0.003),total number of motile spermatozoa(β=2.571;P=0.015),and strict morphology(β=0.056;P=0.006),regardless of other variables.This is the first comparative study to address the issue of serum vitamin D_(3)content between normozoospermic patients and those with sperm abnormalities.It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality,male reproductive potential,and testosterone levels.展开更多
Viral infections have haunted humankind since times immemorial.Overpopulation,globalization,and extensive deforestation have created an ideal environment for a viral spread with unknown and multiple shedding routes.Ma...Viral infections have haunted humankind since times immemorial.Overpopulation,globalization,and extensive deforestation have created an ideal environment for a viral spread with unknown and multiple shedding routes.Many viruses can infect the male reproductive tract,with potential adverse consequences to male reproductive health,including infertility and cancer.Moreover,some genital tract viral infections can be sexually transmitted,potentially impacting the resulting offspring's health.We have summarized the evidence concerning the presence and adverse effects of the relevant viruses on the reproductive tract(mumps virus,human immunodeficiency virus,herpes virus,human papillomavirus,hepatitis B and C viruses,Ebola virus,Zika virus,influenza virus,and coronaviruses),their routes of infection,target organs and cells,prevalence and pattern of virus shedding in semen,as well as diagnosis/testing and treatment strategies.The pathophysiological understanding in the male genital tract is essential to assess its clinical impact on male reproductive health and guide future research.展开更多
Transition-metal oxides have attracted much attention due to its abundant crystalline phases and intriguing physical properties. However, some of these compounds are difficult to be fabricated directly in film form du...Transition-metal oxides have attracted much attention due to its abundant crystalline phases and intriguing physical properties. However, some of these compounds are difficult to be fabricated directly in film form due to the ease of valence variation of transition-metal elements.In this work, we reveal the reversible structural transition between SrVO3 and Sr2V2O7 films via thermal treatment in oxygen atmosphere or in vacuum. Based on this, Sr2V2O7 epitaxial films are successfully synthesized and studied. Property characterizations show that the semitransparent and metallic SrVO3 could reversibly switch into transparent and insulating Sr2V2O7, implying potential applications in controllable electronic and optical devices.展开更多
MICAtronics, based on the functional oxide/mica heterostructures, has recently attracted much attention due to its potential applications in transparent, flexible electronics and devices. However, the weak van der Waa...MICAtronics, based on the functional oxide/mica heterostructures, has recently attracted much attention due to its potential applications in transparent, flexible electronics and devices. However, the weak van der Waals interaction decreases the tolerable lattice mismatch and thus limits the species of function oxides that are able to be epitaxially grown on mica. We successfully fabricate relatively high-quality epitaxial anatase TiO2 thin films on mica substrates. Structural analyses reveal that the carefully chosen growth temperature(650℃) and suitable crystalline phase(anatase phase) of TiO2 are the key issues for this van der Waals epitaxy. Moreover, as a buffer layer, the TiO2 layer successfully suppresses the decomposition of BiFeO3 and the difficulty of epitaxial growth of BiFeO3 is decreased. Therefore, relatively high-quality anatase TiO2 is proved to be an effective buffer layer for fabricating more functional oxides on mica.展开更多
Direct Z-scheme CdO-CdS 1-dimensional nanorod arrays were constructed through a facile and simple hydrothermal process. The structure, morphology, photoelectrochemical properties and H2 evolution activity of this cata...Direct Z-scheme CdO-CdS 1-dimensional nanorod arrays were constructed through a facile and simple hydrothermal process. The structure, morphology, photoelectrochemical properties and H2 evolution activity of this catalyst were investigated systematically. The morphology of the obtained nanorod is a regular hexagonal prism with 100-200 nm in diameter. The calcination temperature and time were optimized carefully to achieve the highest photoelectrochemical performance. The as-fabricated hybrid system achieved a photocurrent density up to 6.5 mA/cm2 and H2 evolution rate of 240 μmol·cm-2·h-1 at 0 V vs. Ag/AgCl, which is about 2-fold higher than that of the bare CdS nanorod arrays. The PEC performance exceeds those previously reported similar systems. A direct Z-scheme photocatalytic mechanism was proposed based on the structure and photoelectrochemical performance characterization results, which can well explain the high separation efficiency of photoinduced carriers and the excellent redox ability.展开更多
This study investigated the positive effect of surface modification with ozone on the photocatalytic performance of anatase TiO_(2)with dominated(001)facets for toluene degradation.The performance of photocatalyst was...This study investigated the positive effect of surface modification with ozone on the photocatalytic performance of anatase TiO_(2)with dominated(001)facets for toluene degradation.The performance of photocatalyst was tested on a home-made volatile organic compounds degradation system.The ozone modification,toluene adsorption and degradation mechanism were established by a combination of various characterization methods,in situ diffuse reflectance infrared fourier transform spectroscopy,and density functional theory calculation.The surface modification with ozone can significantly enhance the photocatalytic degradation performance for toluene.The abundant unsaturated coordinated 5 c-Ti sites on(001)facets act as the adsorption sites for ozone.The formed Ti–O bonds reacted with H_(2)O to generate a large amount of isolated Ti5 c-OH which act as the adsorption sites for toluene,and thus significantly increase the adsorption capacity for toluene.The outstanding photocatalytic performance of ozone-modified TiO2 is due to its high adsorption ability for toluene and the abundant surface hydroxyl groups,which produce very reactive OH·radicals under irradiation.Furthermore,the O_(2)generated via ozone dissociation could combine with the photogenerated electrons to form superoxide radicals which are also conductive to the toluene degradation.展开更多
The yellow-colored line of pearl oyster Pinctada fucata martensii displays a yellow prismatic layer and a white nacreous layer that can be used as an ideal model for research on shell color formation.Micro-Raman spect...The yellow-colored line of pearl oyster Pinctada fucata martensii displays a yellow prismatic layer and a white nacreous layer that can be used as an ideal model for research on shell color formation.Micro-Raman spectroscopy and transcriptome analyses were performed to explore the potential molecular mechanism underlying the phenotype differentiation.The micro-Raman spectroscopy results indicate that the prismatic layer exhibits distinct characteristic peaks of carotenoids,while these peaks are not prominent in the nacreous layer.In the transcriptome comparison of the central zone of mantle and mantle edge tissue,which function in nacreous and prismatic layer formation,respectively,935 significantly differentially expressed genes(DEGs)were identified,with 385 genes upregulated and 227 genes downregulated(|log_(2)(Fold change)|>1 and false discovery rate<0.05)in the mantle edge tissue.Among these genes,some were associated with melanoma/melanogenesis,such as tyrosinase,zinc metalloprotease,glutathione S-transferase,and ATP-binding cassette sub-family;some were associated with the carotenoid-related pathway,including scavenger receptors,cytochrome P450 and lipoprotein receptor.Genes associated with porphyrin metabolism,including porphobilinogen deaminase,and copper/zinc superoxide dismutase,and genes associated with shell matrix protein,including amorphous calcium carbonate binding protein,shematrin,PIF,and collagen,also exhibited significantly different expressions.It is speculated that the different colours between prismatic layer and nacreous layer in the yellow-colored line of P.f.martensii might be resulted from melanin,carotenoids and porphyrin metabolism,while genes related to shell structure and biomineralization might also affect coloration.Our results provide new insights to understand the mechanism of shell color formation in mollusca.展开更多
Autophagy is a central lysosomal degradation pathway required for maintaining cellular homeostasis and its dysfunction is associated with numerous human diseases. To identify players in autophagy, we tested ~ 1200 che...Autophagy is a central lysosomal degradation pathway required for maintaining cellular homeostasis and its dysfunction is associated with numerous human diseases. To identify players in autophagy, we tested ~ 1200 chemically induced mutations on the X chromosome in Drosophila fat body clones and discovered that shibire （shi） plays an essential role in starvation-induced autophagy, shi encodes a dynamin protein required for fission of clathrin-coated vesicles from the plasma membrane during endocytosis. We showed that Shi is dispensable for autophagy initiation and autophagosome--lysosome fusion, but required for lysosomal/autolysosomal acidification. We also showed that other endocytic core machinery components like clathrin and AP2 play similar but not identical roles in regulating autophagy and lysosomal function as dynamin. Previous studies suggested that dynamin directly regulates autophagosome formation and autophagic lysosome reformation （ALR） through its excision activity, Here, we provide evidence that dynamin also regulates autophagy indirectly by regulating lysosomal function.展开更多
Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcit...Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcitabine,and oxaliplatin)regimen in advanced NKTL.Nine patients underwent six 21-day cycles of anti-PD-1 antibody(day 1),pegaspargase 2000 U/m2(day 1),gemcitabine 1 g/m2(days 1 and 8)and oxaliplatin 130 mg/m2(day 1),followed by anti-PD-1 antibody maintenance every 3 weeks.Programmed death-ligand 1(PD-L1)expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing(NGS)analysis.Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography(18FDG-PET)and computed tomography or magnetic resonance imaging.Eight patients exhibited significant responses,comprising of seven complete remissions and one partial remission(overall response rate:88.9%).After a median follow-up of 10.6 months,6/9 patients(66.7%)remained in complete remission.The most common grade 3/4 adverse events were anemia(33.3%),neutropenia(33.3%),and thrombocytopenia(33.3%);all of which were manageable and resolved.Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression(5/6,83.3%).NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy.Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D,TET2,and BCORL1 might indicate a poor response to immunochemotherapy.In conclusion,the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL.PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.展开更多
As the two largest cratonic basins in China,the Ordos Basin and the Sichuan Basin are of key importance for understanding the evolutionary history of the Chinese continent.In this study,the shear-wave velocity(V_(S))s...As the two largest cratonic basins in China,the Ordos Basin and the Sichuan Basin are of key importance for understanding the evolutionary history of the Chinese continent.In this study,the shear-wave velocity(V_(S))structures of the shallow crust(depth up to 10 km)beneath the two basins are imaged based on the frequency-dependence of direct P-wave amplitudes in receiver functions.The teleseismic data used in the study came from 160 broadband seismic stations,including permanent and temporary stations.The results show that the V_(S)and the thickness of the sediments in the Ordos Basin and the Sichuan Basin are respectively lower and thicker in the west than in the east.In the Ordos Basin,the shallow crustal V_(S)increases gradually from 2.10 km s^(−1)in the northwest to 2.65 km s^(−1)in the southeast and the thickest sediments are 7–8 km in the northwest and 5 km in the east.In the Sichuan Basin,the shallow crustal V_(S)increases from 2.4 km s^(−1)in the west to 2.7 km s^(−1)in the east and the thickness of the sediments decreases from>7 km in the west to 6 km in the east.The east-west difference of the shallow crustal structures of the two basins may have been controlled by the Cenozoic India-Eurasia collision.The western parts of the basins near the collision have a higher deposition rate,while in the parts inside the basins far from the collision,the V_(S)slowly increases with depth,indicating that these areas have experienced a more uniform deposition process.In addition,both basins are characterized by velocity structures that are higher along the edges and lower inside of the basins.The edges of the basins suffered strong denudation due to the uplifting and deformation influenced by tectonic evolution.The downward gradient of the shear-wave velocity beneath the Ordos Basin is twice that of the Sichuan Basin,which may be caused by the different deposition and denudation rates of the two basins resulting from differences in structural evolution and thermal events.In addition,the northern Ordos Basin exhibits a strong structural horizontal stratification,while the southern part shows obvious lateral variations in the V_(S)structure,both of which may have been affected by the Qilian orogenic event,the collision and assembly of the South China and the North China block,and the lateral extrusion of the Tibetan Plateau.展开更多
Heine is an iron-containing tetrapyrrole that plays a critical role in regulating a variety of biological processes including oxy- gen and electron transport, gas sensing, signal transduction, biological clock, and mi...Heine is an iron-containing tetrapyrrole that plays a critical role in regulating a variety of biological processes including oxy- gen and electron transport, gas sensing, signal transduction, biological clock, and microRNA processing. Most metazoan cells synthesize heine via a conserved pathway comprised of eight enzyme-cataiyzed reactions. Heme can also be acquired from food or extracellular environment. Cellular heine homeostasis is maintained through the coordinated regulation of synthesis, transport, and degradation. This review presents the current knowledge of the synthesis and transport of heine in metazoans and highlights recent advances in the regulation of these pathways.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19).To halt the pandemic,multiple SARS-CoV-2 vaccines have been developed and several have been allow...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19).To halt the pandemic,multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout worldwide.With novel SARS-CoV-2 variants emerging and circulating widely,whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious discussion.Moreover,some studies revealed the long-term changes of immune responses post SARS-CoV-2 infection or vaccination and the factors that might impact the vaccine-induced immunity.Thus,in this review,we have summarized the influence of mutational hotspots on the vaccine efficacy and characteristics of variants of interest and concern.We have also discussed the reasons that might result in discrepancies in the efficacy of different vaccines estimated in different trials.Furthermore,we provided an overview of the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines,such as special disease conditions,sex,and pre-existing immunity,with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under the prevalence of diverse SARS-CoV-2 variants.展开更多
The key difference between the coronavirus disease 2019(COVID-19)and previous coronaviruses such as SARS and MERS is that some infected people do not display obvious symptoms but are contagious during the incubation p...The key difference between the coronavirus disease 2019(COVID-19)and previous coronaviruses such as SARS and MERS is that some infected people do not display obvious symptoms but are contagious during the incubation period for 14 days(1)or longer.Recently,there are many discussions about whether all persons should wear masks when they go out during the COVID-19 pandemic.The main reasons for the opposition are that the effectiveness of masks in preventing infection is not clear,ordinary people rarely wear masks correctly,everyone wearing masks may cause social panic,there are not enough masks,etc.(2–3).展开更多
DNA double-strand breaks（DSBs）,which arise following exposure to a number of endogenous and exogenous agents,can be repaired by either the homologous recombination（HR）or non-homologous end-joining（NHEJ） pathways...DNA double-strand breaks（DSBs）,which arise following exposure to a number of endogenous and exogenous agents,can be repaired by either the homologous recombination（HR）or non-homologous end-joining（NHEJ） pathways in eukaryotic cells.A vital step in HR repair is DNA end resection,which generates a long 30single-stranded DNA（ss DNA） tail that can invade the homologous DNA strand.The generation of 30 ss DNA is not only essential for HR repair,but also promotes activation of the ataxia telangiectasia and Rad3-related protein（ATR）.Multiple factors,including the MRN/X complex,C-terminal-binding protein interacting protein（Ct IP）/Sae2,exonuclease 1（EXO1）,Bloom syndrome protein（BLM）/Sgs1,DNA2 nuclease/helicase,and several chromatin remodelers,cooperate to complete the process of end resection.Here we review the basic machinery involved in DNA end resection in eukaryotic cells.展开更多
Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint(SAC)signaling.As an upstream factor of SAC,the precise and dynamic kinetochore...Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint(SAC)signaling.As an upstream factor of SAC,the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC signaling.However,the underlying molecular mechanism remains elusive.Here,we demonstrated that the multisite interactions between Mps1 and Ndc80 complex(Ndc80C)govern Mps1 kinetochore targeting.Importantly,we identified direct interaction between Mps1 tetratricopeptide repeat domain and Ndc80C.We further identified that Mps1 C-terminal fragment,which contains the protein kinase domain and C-tail,enhances Mps1 kinetochore localization.Mechanistically,Mps1 C-terminal fragment mediates its dimerization.Perturbation of C-tail attenuates the kinetochore targeting and activity of Mps1,leading to aberrant mitosis due to compromised SAC function.Taken together,our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling.展开更多
Purpose To explore the potential of X-ray imaging for early-stage lung cancer screening and to help finding an optimal lung cancer screening method.Methods Experimentally and simulatively comparing performances of dif...Purpose To explore the potential of X-ray imaging for early-stage lung cancer screening and to help finding an optimal lung cancer screening method.Methods Experimentally and simulatively comparing performances of different X-ray techniques(absorption-contrast imaging and phase-contrast imaging)for model lung cancer samples.Results Absorption imaging shows performance equal to or better than that of low-radiation dose.Conclusion Absorption imaging is still the most promising imaging method for early lung cancer detection.展开更多
To the Editor:Cardiac arrest(CA)is one of the leading causes of adult death globally.According to the latest American Heart Association reports,[1]the incidences of Emergency Medical Service-assessed adult out-of-hosp...To the Editor:Cardiac arrest(CA)is one of the leading causes of adult death globally.According to the latest American Heart Association reports,[1]the incidences of Emergency Medical Service-assessed adult out-of-hospital cardiac arrest(OHCA)and in-hospital cardiac arrest(IHCA)were 140.7/100,000 and 10.2/1000,respectively.展开更多
Adipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression,yet the underlying mechanisms and functional mediators remain elusive.We isolat...Adipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression,yet the underlying mechanisms and functional mediators remain elusive.We isolated primary preadipocytes from mammary fat pads of human breast cancer patients and generated mature adipocytes and cancer-associated adipocytes(CAAs)in vitro.The CAAs exhibited significantly different gene expression profiles as assessed by transcriptome sequencing.One of the highly expressed genes in CAAs is granulocyte colony-stimulating factor(G-CSF).Treatment with recombinant human G-CSF protein or stable expression of human G-CSF in triple-negative breast cancer(TNBC)cell lines enhanced epithelial–mesenchymal transition,migration,and invasion of cancer cells,by activating Stat3.Accordantly,targeting G-CSF/Stat3 signaling with G-CSF-neutralizing antibody,a chemical inhibitor,or siRNAs for Stat3 could all abrogate CAA-or G-CSF-induced migration and invasion of breast cancer cells.The pro-invasive genes MMP2 and MMP9 were identified as target genes of G-CSF in TNBC cells.Furthermore,in human breast cancer tissues,elevated G-CSF expression in adipocytes is well correlated with activated Stat3 signal in cancer cells.Together,our results suggest a novel strategy to intervene with invasive breast cancers by targeting CAA-derived G-CSF.展开更多
基金Supported by the Science and Technology Program of Guangdong Province(No.2022A1515010030)the National Natural Science Foundation of China(No.32102817)+3 种基金the Department of Education of Guangdong Province(Nos.2020ZDZX1045,2021KCXTD026)the earmarked fund for CARS-49,Students Innovation and Entrepreneurship Training Program(No.CXXL2022015)the Technology Program of Guangdong Zhanjiang(No.2022A01010)the Hengli Biosciences Excellence Project of Guangdong Ocean University(No.B23335-4)。
文摘Microplastics(MPs),particularly polyvinyl chloride microplastics(PVC MPs)have become a notable environmental pollutant that affect various marine organisms such as Pinctada fucata martensii.As filter feeders,these bivalves consume significant volumes of water containing MPs,leading to contact with and ingestion of MPs.Moreover,given the ecological and economic importance of P.f.martensii in artificial pearl production,investigating the effects of PVC MPs exposure is crucial.This study aimed to investigate the effects of PVC MPs exposure on nucleus retention,pearl formation,oxidative stress by examining superoxide dismutase(SOD)activity,catalase(CAT)activity,lipid peroxidation(LPO),and total antioxidant capacity(TAOC)of P.f.martensii,while also exploring transcriptomic changes at different concentrations and exposure time points,including a recovery period.The pearl oysters were exposed to PVC MPs at concentrations of 1-,2.5-,and 5-mg PVC MPs/L for 10 d followed by 6 d of recovery.After 1-,4-,10-d of exposure,and additional 6 d of recovery,samples were taken and analyzed.Findings revealed that only prolonged exposure(10 d)to PVC MPs affected SOD activity,while CAT activity,LPO,and TAOC remained unaffected throughout the experiment.Notably,SOD activity was restored during the 6-d recovery phase.Transcriptome analysis highlighted significant gene alterations linked to various pathways,affecting cellular processes,environmental information processing,genetic information processing,metabolism,and organismal systems,with an increase in pathway-related genes during recovery,implying a potential role of PVC MPs as gene inhibitors.This study provided insights into the effects of PVC MPs on P.f.martensii,shedding light on pearl retention,oxidative systems,and molecular pathways influenced by PVC MPs.Additionally,it contributed novel information on potential MPs exposure biomarkers,particularly relevant to marine organisms like P.f.martensii.
基金Supported by the Strategic Priority Research Program of Chinese Academy of Sciences(Nos.XDA13020103,XDA19060301)the National Science&Technology Fundamental Resources Investigation Program of China(No.2018FY100106)the National Key Research and Development Program “Marine Environment Security Project”(Nos.2017YFC0506302,2018YFC1406503)
文摘Deep-sea organisms survive in an extremely harsh environment.There must be some genetic adaptation mechanisms for them.We systematically characterized and compared the complete mitochondrial genome(mitogenome)of a deep-sea crab(Chaceon granulates)with those of shallow crabs.The mitogenome of the crab was 16126 bp in length,and encoded 37 genes as most of a metazoan mitogenome,including 13 protein-coding genes(PCGs),22 transfer RNA(tRNA)genes,and 2 ribosomal RNA(rRNA)genes.The gene arrangement and orientation was conserved in the crabs.However,a unique mitogenome element regulator,the origin of light-strand replication(O L),was firstly predicted in the present crab mitogenome.In addition,further positive selection analysis showed that two residues(33 S in ND3 and 502 I in ND5)in C.granulates mitogenome were positively selected,indicated the selective evolution of the deep-sea crab.Therefore,the mitogenome of deep-sea C.granulates showed a unique OL element and positive selection.These special features would influence the mitochondrial energy metabolism,and be involved in the adaptation of deepsea environment,such as oxygen deficits and low temperatures.
文摘The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels.This is a crosssectional study conducted at Androscience,Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo,Brazil,with 508 male patients,aged 18-60 years,from 2007 to 2017.Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria.Patients were divided into normozoospermic group(NZG,n=124)and a group with seminal abnormalities(SAG,n=136).Evaluation included complete physical examination,past medical history,habits and lifestyle factors,two complete seminal analysis with sperm functional tests,serum levels of 25-hydroxy-vitamin D_(3)(25(OH)VD_(3)),total and free testosterone,luteinizing hormone(LH),follicle-stimulating hormone(FSH),sex hormone-binding globulin(SHBG),total cholesterol,homeostatic model assessment of insulin resistance(HOMA-IR)index,and karyotype.The mean concentration of 25(OH)VD_(3)was significantly lower in the SAG(P<0.001)and positively correlated with all baseline seminal parameters and total testosterone levels.In addition,serum vitamin D_(3)concentration was found to be positively correlated with sperm concentration(β=2.103;P<0.001),total number of spermatozoa with progressive motility(β=2.069;P=0.003),total number of motile spermatozoa(β=2.571;P=0.015),and strict morphology(β=0.056;P=0.006),regardless of other variables.This is the first comparative study to address the issue of serum vitamin D_(3)content between normozoospermic patients and those with sperm abnormalities.It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality,male reproductive potential,and testosterone levels.
文摘Viral infections have haunted humankind since times immemorial.Overpopulation,globalization,and extensive deforestation have created an ideal environment for a viral spread with unknown and multiple shedding routes.Many viruses can infect the male reproductive tract,with potential adverse consequences to male reproductive health,including infertility and cancer.Moreover,some genital tract viral infections can be sexually transmitted,potentially impacting the resulting offspring's health.We have summarized the evidence concerning the presence and adverse effects of the relevant viruses on the reproductive tract(mumps virus,human immunodeficiency virus,herpes virus,human papillomavirus,hepatitis B and C viruses,Ebola virus,Zika virus,influenza virus,and coronaviruses),their routes of infection,target organs and cells,prevalence and pattern of virus shedding in semen,as well as diagnosis/testing and treatment strategies.The pathophysiological understanding in the male genital tract is essential to assess its clinical impact on male reproductive health and guide future research.
基金supported by the National Key R&D Program of China(No.2016YFA0300102)the National Natural Science Foundation of China(No.11675179,No.11434009,and No.11374010)+2 种基金the Fundamental Research Funds for the Central Universities(No.WK2340000065)partially carried out at the University of Science and Technology of China(USTC)center for Micro and Nanoscale Research and Fabricationthe support from the magnetic circular dichroism endstation at Hefei Light Source
文摘Transition-metal oxides have attracted much attention due to its abundant crystalline phases and intriguing physical properties. However, some of these compounds are difficult to be fabricated directly in film form due to the ease of valence variation of transition-metal elements.In this work, we reveal the reversible structural transition between SrVO3 and Sr2V2O7 films via thermal treatment in oxygen atmosphere or in vacuum. Based on this, Sr2V2O7 epitaxial films are successfully synthesized and studied. Property characterizations show that the semitransparent and metallic SrVO3 could reversibly switch into transparent and insulating Sr2V2O7, implying potential applications in controllable electronic and optical devices.
基金Supported by the National Key Research and Development Program of China under Grant No 2016YFA0300102the National Natural Science Foundation of China under Grant Nos 11675179,11434009 and 11374010the Fundamental Research Funds for the Central Universities under Grant No WK2340000065
文摘MICAtronics, based on the functional oxide/mica heterostructures, has recently attracted much attention due to its potential applications in transparent, flexible electronics and devices. However, the weak van der Waals interaction decreases the tolerable lattice mismatch and thus limits the species of function oxides that are able to be epitaxially grown on mica. We successfully fabricate relatively high-quality epitaxial anatase TiO2 thin films on mica substrates. Structural analyses reveal that the carefully chosen growth temperature(650℃) and suitable crystalline phase(anatase phase) of TiO2 are the key issues for this van der Waals epitaxy. Moreover, as a buffer layer, the TiO2 layer successfully suppresses the decomposition of BiFeO3 and the difficulty of epitaxial growth of BiFeO3 is decreased. Therefore, relatively high-quality anatase TiO2 is proved to be an effective buffer layer for fabricating more functional oxides on mica.
基金supported by the National Natural Science Foundation of China(No.U1632273,No.21673214,No.U1732272,and No.U1832165)
文摘Direct Z-scheme CdO-CdS 1-dimensional nanorod arrays were constructed through a facile and simple hydrothermal process. The structure, morphology, photoelectrochemical properties and H2 evolution activity of this catalyst were investigated systematically. The morphology of the obtained nanorod is a regular hexagonal prism with 100-200 nm in diameter. The calcination temperature and time were optimized carefully to achieve the highest photoelectrochemical performance. The as-fabricated hybrid system achieved a photocurrent density up to 6.5 mA/cm2 and H2 evolution rate of 240 μmol·cm-2·h-1 at 0 V vs. Ag/AgCl, which is about 2-fold higher than that of the bare CdS nanorod arrays. The PEC performance exceeds those previously reported similar systems. A direct Z-scheme photocatalytic mechanism was proposed based on the structure and photoelectrochemical performance characterization results, which can well explain the high separation efficiency of photoinduced carriers and the excellent redox ability.
基金the National Natural Science Foundation of China(U1632273,21673214,U1732272,U1832165).
文摘This study investigated the positive effect of surface modification with ozone on the photocatalytic performance of anatase TiO_(2)with dominated(001)facets for toluene degradation.The performance of photocatalyst was tested on a home-made volatile organic compounds degradation system.The ozone modification,toluene adsorption and degradation mechanism were established by a combination of various characterization methods,in situ diffuse reflectance infrared fourier transform spectroscopy,and density functional theory calculation.The surface modification with ozone can significantly enhance the photocatalytic degradation performance for toluene.The abundant unsaturated coordinated 5 c-Ti sites on(001)facets act as the adsorption sites for ozone.The formed Ti–O bonds reacted with H_(2)O to generate a large amount of isolated Ti5 c-OH which act as the adsorption sites for toluene,and thus significantly increase the adsorption capacity for toluene.The outstanding photocatalytic performance of ozone-modified TiO2 is due to its high adsorption ability for toluene and the abundant surface hydroxyl groups,which produce very reactive OH·radicals under irradiation.Furthermore,the O_(2)generated via ozone dissociation could combine with the photogenerated electrons to form superoxide radicals which are also conductive to the toluene degradation.
基金supported by the Science and Technology Program of Guangdong Province (No.2022A1515010030)the National Natural Science Foundation of China (No.32102817)+3 种基金the Program for Sientific Research Start-up Funds of Guangdong Ocean University (No.060302022304)the Department of Education of Guangdong Province (Nos.2020ZDZX1045 and 2021KCXTD026)the Earmarked Fund for CARS-49the Guangdong Provincial Special Fund for Modern Agriculture Industry Technology Innovation Teams (No.2023KJ146)。
文摘The yellow-colored line of pearl oyster Pinctada fucata martensii displays a yellow prismatic layer and a white nacreous layer that can be used as an ideal model for research on shell color formation.Micro-Raman spectroscopy and transcriptome analyses were performed to explore the potential molecular mechanism underlying the phenotype differentiation.The micro-Raman spectroscopy results indicate that the prismatic layer exhibits distinct characteristic peaks of carotenoids,while these peaks are not prominent in the nacreous layer.In the transcriptome comparison of the central zone of mantle and mantle edge tissue,which function in nacreous and prismatic layer formation,respectively,935 significantly differentially expressed genes(DEGs)were identified,with 385 genes upregulated and 227 genes downregulated(|log_(2)(Fold change)|>1 and false discovery rate<0.05)in the mantle edge tissue.Among these genes,some were associated with melanoma/melanogenesis,such as tyrosinase,zinc metalloprotease,glutathione S-transferase,and ATP-binding cassette sub-family;some were associated with the carotenoid-related pathway,including scavenger receptors,cytochrome P450 and lipoprotein receptor.Genes associated with porphyrin metabolism,including porphobilinogen deaminase,and copper/zinc superoxide dismutase,and genes associated with shell matrix protein,including amorphous calcium carbonate binding protein,shematrin,PIF,and collagen,also exhibited significantly different expressions.It is speculated that the different colours between prismatic layer and nacreous layer in the yellow-colored line of P.f.martensii might be resulted from melanin,carotenoids and porphyrin metabolism,while genes related to shell structure and biomineralization might also affect coloration.Our results provide new insights to understand the mechanism of shell color formation in mollusca.
基金supported by the National Natural Science Foundation of China(No.31271432)the National Basic Research Program of China(Nos.2012CB966600 and 2014CB943100)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20130101110116)
文摘Autophagy is a central lysosomal degradation pathway required for maintaining cellular homeostasis and its dysfunction is associated with numerous human diseases. To identify players in autophagy, we tested ~ 1200 chemically induced mutations on the X chromosome in Drosophila fat body clones and discovered that shibire （shi） plays an essential role in starvation-induced autophagy, shi encodes a dynamin protein required for fission of clathrin-coated vesicles from the plasma membrane during endocytosis. We showed that Shi is dispensable for autophagy initiation and autophagosome--lysosome fusion, but required for lysosomal/autolysosomal acidification. We also showed that other endocytic core machinery components like clathrin and AP2 play similar but not identical roles in regulating autophagy and lysosomal function as dynamin. Previous studies suggested that dynamin directly regulates autophagosome formation and autophagic lysosome reformation （ALR） through its excision activity, Here, we provide evidence that dynamin also regulates autophagy indirectly by regulating lysosomal function.
基金supported by the Chinese National Natural Science Funds(82041009,31925013,31671457,91753139,and 31871405)Zhejiang University Joint Pingduoduo“Virus Infectious Disease Prevention and Control funds”,a special program from the Ministry of Science and Technology of China(2016YFA0502500)+2 种基金Jiangsu Provincial Distinguished Young Scholars award(BK20180043)the Zhejiang Natural Science Fund(LD19C070001),the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003)A project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcitabine,and oxaliplatin)regimen in advanced NKTL.Nine patients underwent six 21-day cycles of anti-PD-1 antibody(day 1),pegaspargase 2000 U/m2(day 1),gemcitabine 1 g/m2(days 1 and 8)and oxaliplatin 130 mg/m2(day 1),followed by anti-PD-1 antibody maintenance every 3 weeks.Programmed death-ligand 1(PD-L1)expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing(NGS)analysis.Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography(18FDG-PET)and computed tomography or magnetic resonance imaging.Eight patients exhibited significant responses,comprising of seven complete remissions and one partial remission(overall response rate:88.9%).After a median follow-up of 10.6 months,6/9 patients(66.7%)remained in complete remission.The most common grade 3/4 adverse events were anemia(33.3%),neutropenia(33.3%),and thrombocytopenia(33.3%);all of which were manageable and resolved.Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression(5/6,83.3%).NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy.Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D,TET2,and BCORL1 might indicate a poor response to immunochemotherapy.In conclusion,the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL.PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.
基金supported by the National Natural Science Foundation of China(Grant Nos.41688103 and 42004041)
文摘As the two largest cratonic basins in China,the Ordos Basin and the Sichuan Basin are of key importance for understanding the evolutionary history of the Chinese continent.In this study,the shear-wave velocity(V_(S))structures of the shallow crust(depth up to 10 km)beneath the two basins are imaged based on the frequency-dependence of direct P-wave amplitudes in receiver functions.The teleseismic data used in the study came from 160 broadband seismic stations,including permanent and temporary stations.The results show that the V_(S)and the thickness of the sediments in the Ordos Basin and the Sichuan Basin are respectively lower and thicker in the west than in the east.In the Ordos Basin,the shallow crustal V_(S)increases gradually from 2.10 km s^(−1)in the northwest to 2.65 km s^(−1)in the southeast and the thickest sediments are 7–8 km in the northwest and 5 km in the east.In the Sichuan Basin,the shallow crustal V_(S)increases from 2.4 km s^(−1)in the west to 2.7 km s^(−1)in the east and the thickness of the sediments decreases from>7 km in the west to 6 km in the east.The east-west difference of the shallow crustal structures of the two basins may have been controlled by the Cenozoic India-Eurasia collision.The western parts of the basins near the collision have a higher deposition rate,while in the parts inside the basins far from the collision,the V_(S)slowly increases with depth,indicating that these areas have experienced a more uniform deposition process.In addition,both basins are characterized by velocity structures that are higher along the edges and lower inside of the basins.The edges of the basins suffered strong denudation due to the uplifting and deformation influenced by tectonic evolution.The downward gradient of the shear-wave velocity beneath the Ordos Basin is twice that of the Sichuan Basin,which may be caused by the different deposition and denudation rates of the two basins resulting from differences in structural evolution and thermal events.In addition,the northern Ordos Basin exhibits a strong structural horizontal stratification,while the southern part shows obvious lateral variations in the V_(S)structure,both of which may have been affected by the Qilian orogenic event,the collision and assembly of the South China and the North China block,and the lateral extrusion of the Tibetan Plateau.
基金supported by the National Natural Science Foundation of China(31371435)the National Key Basic Research Program of China(2015CB150300)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Thousand Youth Talents Program of China
文摘Heine is an iron-containing tetrapyrrole that plays a critical role in regulating a variety of biological processes including oxy- gen and electron transport, gas sensing, signal transduction, biological clock, and microRNA processing. Most metazoan cells synthesize heine via a conserved pathway comprised of eight enzyme-cataiyzed reactions. Heme can also be acquired from food or extracellular environment. Cellular heine homeostasis is maintained through the coordinated regulation of synthesis, transport, and degradation. This review presents the current knowledge of the synthesis and transport of heine in metazoans and highlights recent advances in the regulation of these pathways.
基金This work was supported by the National Natural Science Foundation of China(82041009,31871405,31925013,U20A20393,32125016 and 32100699)a special program from the Ministry of Science and Technology of China(2016YFA0502500)+5 种基金the China National Postdoctoral Program for Innovative Talents(BX2021208)the China Postdoctoral Science Foundation(2021M692350)the Zhejiang Natural Science Fund(LD19C070001)the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003)a project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,Zhejiang Provincial Natural Science Foundation under Grant(LBY21H060001)the Medical and the Medical and Health Research Project of Zhejiang Province(2020RC115).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19).To halt the pandemic,multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout worldwide.With novel SARS-CoV-2 variants emerging and circulating widely,whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious discussion.Moreover,some studies revealed the long-term changes of immune responses post SARS-CoV-2 infection or vaccination and the factors that might impact the vaccine-induced immunity.Thus,in this review,we have summarized the influence of mutational hotspots on the vaccine efficacy and characteristics of variants of interest and concern.We have also discussed the reasons that might result in discrepancies in the efficacy of different vaccines estimated in different trials.Furthermore,we provided an overview of the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines,such as special disease conditions,sex,and pre-existing immunity,with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under the prevalence of diverse SARS-CoV-2 variants.
基金supported by the“innovation practice training plan for college students of the Chinese Academy of Sciences”,and the NSFC under contract U1732108.
文摘The key difference between the coronavirus disease 2019(COVID-19)and previous coronaviruses such as SARS and MERS is that some infected people do not display obvious symptoms but are contagious during the incubation period for 14 days(1)or longer.Recently,there are many discussions about whether all persons should wear masks when they go out during the COVID-19 pandemic.The main reasons for the opposition are that the effectiveness of masks in preventing infection is not clear,ordinary people rarely wear masks correctly,everyone wearing masks may cause social panic,there are not enough masks,etc.(2–3).
基金supported in part by the grants from the National Natural Science Foundation of China (Grant Nos.31071243 and 31171347)the Fundamental Research Funds for the Central Universities of Chinathe Research Fund for the Doctoral Program of Higher Education of China (Grant No.20110101120152)
文摘DNA double-strand breaks（DSBs）,which arise following exposure to a number of endogenous and exogenous agents,can be repaired by either the homologous recombination（HR）or non-homologous end-joining（NHEJ） pathways in eukaryotic cells.A vital step in HR repair is DNA end resection,which generates a long 30single-stranded DNA（ss DNA） tail that can invade the homologous DNA strand.The generation of 30 ss DNA is not only essential for HR repair,but also promotes activation of the ataxia telangiectasia and Rad3-related protein（ATR）.Multiple factors,including the MRN/X complex,C-terminal-binding protein interacting protein（Ct IP）/Sae2,exonuclease 1（EXO1）,Bloom syndrome protein（BLM）/Sgs1,DNA2 nuclease/helicase,and several chromatin remodelers,cooperate to complete the process of end resection.Here we review the basic machinery involved in DNA end resection in eukaryotic cells.
基金supported by the National Key R&D Program of China(2017YFA 0102900 and 2017 YFA 0503600)the National Natural Science Fondation of China(31671407 and 31871359 to Z.D.+4 种基金31621002,31430054,91854203,and 31320103904 to X.Y.31301099 and 21672201 to X.G.31471275 to D.W.),Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19040000)Chinese Academy of Sciences Center for Excellence in Molecular Cell Science(2015 HSC-UE010)MOE Innovative Team(IRT_17R102).
文摘Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint(SAC)signaling.As an upstream factor of SAC,the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC signaling.However,the underlying molecular mechanism remains elusive.Here,we demonstrated that the multisite interactions between Mps1 and Ndc80 complex(Ndc80C)govern Mps1 kinetochore targeting.Importantly,we identified direct interaction between Mps1 tetratricopeptide repeat domain and Ndc80C.We further identified that Mps1 C-terminal fragment,which contains the protein kinase domain and C-tail,enhances Mps1 kinetochore localization.Mechanistically,Mps1 C-terminal fragment mediates its dimerization.Perturbation of C-tail attenuates the kinetochore targeting and activity of Mps1,leading to aberrant mitosis due to compromised SAC function.Taken together,our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling.
基金We sincerely appreciated the kind assistance of the staff of the 4W1A beamline of the Beijing Synchrotron Radiation Facility and the BL13W1 beamline of the Shanghai Synchrotron Radi-ation Facility.Our researches are funded by NSFC 11305200NSFC U1732108NSFC 11675208 and NSFC 11627901。
文摘Purpose To explore the potential of X-ray imaging for early-stage lung cancer screening and to help finding an optimal lung cancer screening method.Methods Experimentally and simulatively comparing performances of different X-ray techniques(absorption-contrast imaging and phase-contrast imaging)for model lung cancer samples.Results Absorption imaging shows performance equal to or better than that of low-radiation dose.Conclusion Absorption imaging is still the most promising imaging method for early lung cancer detection.
文摘To the Editor:Cardiac arrest(CA)is one of the leading causes of adult death globally.According to the latest American Heart Association reports,[1]the incidences of Emergency Medical Service-assessed adult out-of-hospital cardiac arrest(OHCA)and in-hospital cardiac arrest(IHCA)were 140.7/100,000 and 10.2/1000,respectively.
基金This work was supported by grants from the National Natural Science Foundation of China(NSFC31871378 and 31671460 to X.Y.and 81760509 to X.X.)the Natural Science Foundation of Jiangxi Provinee of China(20171ACB21004 to X.Y.and 20181BAB205043 to X.X.).
文摘Adipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression,yet the underlying mechanisms and functional mediators remain elusive.We isolated primary preadipocytes from mammary fat pads of human breast cancer patients and generated mature adipocytes and cancer-associated adipocytes(CAAs)in vitro.The CAAs exhibited significantly different gene expression profiles as assessed by transcriptome sequencing.One of the highly expressed genes in CAAs is granulocyte colony-stimulating factor(G-CSF).Treatment with recombinant human G-CSF protein or stable expression of human G-CSF in triple-negative breast cancer(TNBC)cell lines enhanced epithelial–mesenchymal transition,migration,and invasion of cancer cells,by activating Stat3.Accordantly,targeting G-CSF/Stat3 signaling with G-CSF-neutralizing antibody,a chemical inhibitor,or siRNAs for Stat3 could all abrogate CAA-or G-CSF-induced migration and invasion of breast cancer cells.The pro-invasive genes MMP2 and MMP9 were identified as target genes of G-CSF in TNBC cells.Furthermore,in human breast cancer tissues,elevated G-CSF expression in adipocytes is well correlated with activated Stat3 signal in cancer cells.Together,our results suggest a novel strategy to intervene with invasive breast cancers by targeting CAA-derived G-CSF.
