Background: It has been conclusively established that intracranial aneurysms measuring a diameter below 7 mm pose a minimal risk of rupture. Conversely, those exhibiting irregular morphology or featuring the presence ...Background: It has been conclusively established that intracranial aneurysms measuring a diameter below 7 mm pose a minimal risk of rupture. Conversely, those exhibiting irregular morphology or featuring the presence of a sac necessitate a more stringent and rigorous management approach. Objective: The primary aim of this study is to delve into the morphological features of ruptured aneurysms situated in distinct regions of the brain. Furthermore, we endeavor to assess the degree of safety and efficacy associated with stent-assisted embolization as a treatment modality for these ruptured aneurysms. Methods: This retrospective study encompassed a cohort of 467 patients who presented with intracranial ruptured aneurysms and were diagnosed through a combination of computed tomography (CT) and digital subtraction angiography (DSA) at Nanfang Hospital of Southern Medical University, spanning from January 2009 to December 2019. The following clinical parameters were meticulously recorded: aneurysm height, width, neck measurements, immediate Raymond grade assessments, and any perioperative complications experienced. Results: Within the study population, the average dimensions of ruptured aneurysms were found to be 4.26 ± 2.10 mm (width), 4.86 ± 2.38 mm (height), and 4.04 ± 1.87 mm (neck). Categorically, the most prevalent types of aneurysms were 170 cases of anterior communicating artery aneurysms (accounting for 36.4%), followed by 161 cases of posterior communicating artery aneurysms (34.5%), 56 cases of middle cerebral artery aneurysms (12.0%), 13 cases of anterior cerebral artery aneurysms (2.8%), 45 cases of paraclinoid aneurysms (9.6%), 6 cases of superior pituitary artery aneurysms (1.3%), 7 cases of anterior choroidal artery aneurysms (1.5%), and 9 cases of vertebrobasilar artery aneurysms (2.0%). Notably, 18 patients (3.9%) presented with ruptured aneurysms coexisting with ascus. Regarding treatment approaches, 228 cases (48.8%) underwent stent-assisted embolization, 234 cases (50.1%) received coils embolization, and 5 cases (1.1%) were treated with the dual-catheter technique. Immediately post-treatment, 422 patients (90.4%) attained a Raymond Class I status, with a procedure-related complication rate of 0.9%. Importantly, no statistically significant differences were observed in the incidence of perioperative complications across the three distinct treatment groups (P = 0.505). Conclusion: The outcomes of this study affirm the safety and efficacy of stent-assisted embolization as a treatment modality for ruptured aneurysms.展开更多
Background Goose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant ener...Background Goose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant energy intake. As a result, goose offers an excellent model for studying obesity, metabolic disorders, and liver diseases in mammals. Although the impact of the three-dimensional arrangement of chromatin within the cell nucleus on gene expression and transcriptional regulation is widely acknowledged, the precise functions of chromatin architecture reorganization during fat deposition in goose liver tissues still need to be fully comprehended.Results In this study, geese exhibited more pronounced changes in the liver index and triglyceride(TG) content following the consumption of the high-fat diet(HFD) than mice without significant signs of inflammation. Additionally, we performed comprehensive analyses on 10 goose liver tissues(5 HFD, 5 normal), including generating highresolution maps of chromatin architecture, conducting whole-genome gene expression profiling, and identifying H3K27ac peaks in the livers of geese and mice subjected to the HFD. Our results unveiled a multiscale restructuring of chromatin architecture, encompassing Compartment A/B, topologically associated domains, and interactions between promoters and enhancers. The dynamism of the three-dimensional genome architecture, prompted by the HFD, assumed a pivotal role in the transcriptional regulation of crucial genes. Furthermore, we identified genes that regulate chromatin conformation changes, contributing to the metabolic adaptation process of lipid deposition and hepatic fat changes in geese in response to excessive energy intake. Moreover, we conducted a cross-species analysis comparing geese and mice exposed to the HFD, revealing unique characteristics specific to the goose liver compared to a mouse. These chromatin conformation changes help elucidate the observed characteristics of fat deposition and hepatic fat regulation in geese under conditions of excessive energy intake.Conclusions We examined the dynamic modifications in three-dimensional chromatin architecture and gene expression induced by an HFD in goose liver tissues. We conducted a cross-species analysis comparing that of mice. Our results contribute significant insights into the chromatin architecture of goose liver tissues, offering a novel perspective for investigating mammal liver diseases.展开更多
Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on ...Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes.Results Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages(d 90 of gestation, G90;d 0 after lactation, L0;d 20 after lactation, L20;2 d post natural involution, PI2;7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation(G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation(L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution(PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells to maintain the lactation potential of mammary glands for the next lactation cycle.Conclusion The molecular mechanisms of dedifferentiation, proliferation and redifferentiation of adipocytes and epithelial cells were revealed from late pregnancy to natural involution. This cell transcriptomic profile constitutes an essential reference for future studies in the development and remodeling of the mammary gland at different stages.展开更多
Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment o...Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.展开更多
Objective:To compare the antiplatelet effect and major adverse cerebrovascular events of Pipeline for intracranial aneurysms using glycoproteinⅡb/Ⅲa antagonists(GPI)eptifibatide and tirofiban.Methods:Retrospective a...Objective:To compare the antiplatelet effect and major adverse cerebrovascular events of Pipeline for intracranial aneurysms using glycoproteinⅡb/Ⅲa antagonists(GPI)eptifibatide and tirofiban.Methods:Retrospective analysis of relevant data of patients using GPIs combined with oral antiplatelet therapy in Nanfang Hospital of Southern Medical University from December 2017 to December 2019.The study was approved by the ethics Committee of Nanfang Hospital of Southern Medical University.According to the random use of GPIs drugs,they were assigned to the eptifibatide group and tirofiban group.Basic data,platelet inhibition rates at baseline,24 h and 72 h after administration,short-term major adverse cerebrovascular events,and bleeding complications were compared between the two groups.Results:A total of 47 patients were included in this study,including 24 patients in eptifibatide group and 23 patients in tirofiban group.There was no significant difference in average age(53.75 vs.53.91 years)and body mass index(BMI)(24.39 vs.22.73 kg/m2)between eptifibatide group and tirofiban group.There was no significant difference in coagulation factor function(R),fibrinogen function(K),fibrinolysis function(EPL),comprehensive coagulation index(Cl),arachidonic acid pathway inhibition rate(AA%)and adenosine diphosphate inhibition rate(ADP%).However,the baseline level of residual platelet function MA(ADP)in eptifibatide group was significantly higher than that in tirofiban group(50.79 vs.35.29 mm,P=0.0026).There was a statistical difference in the platelet aggregation function MA(65.38 vs.62.54 mm,p=0.0442),the rate of spontaneous hemorrhagic stroke(4.3%vs.0%)and the rate of asymptomatic minor bleeding(26.08%vs.4.1%)in the two groups(P<0.05).Conclusion:Both eptifibatide and tirofiban can effectively inhibit platelets,but the effect of etifeptide is better than that of tirofiban in preventing intracranial microhemorrhage and asymptomatic cerebral infarction.展开更多
Composite ceramic phosphor(CCP)is a candidate light-conversion material to obtain the high-quality laser lighting source.Phosphors based on the transmissive configuration model could not simultaneously meet the requir...Composite ceramic phosphor(CCP)is a candidate light-conversion material to obtain the high-quality laser lighting source.Phosphors based on the transmissive configuration model could not simultaneously meet the requirements of angular color uniformity and high thermal stability.In this study,a novel composite structure ceramic was designed,including Al_(2)O_(3)-YAG:Ce/YAG layered ceramic with a size of 1 mm×1 mm for lighting,and Al_(2)O_(3) ceramic(φ=16.0 mm)was used as the wrapping material due to its outstanding thermal stability.The prepared ceramics exhibited excellent thermal performance and no yellow ring phenomenon.Through this design,we achieved the match of the intensity distribution of the blue and yellow lights,resulting in a high angular color uniformity of 0.9 with a view angle of±80°.All ceramics showed no luminous saturation phenomenon,even the laser power density was increased up to 47.51 W/mm^(2).A high-brightness white-light source with a luminous flux of 618 lm,a luminous efficiency of 126 lm/W,a CCT of 6615 K,and a CRI of 69.9 was obtained in the transmissive configuration.In particular,the surface temperature of the ceramic was as low as 74.1℃ under a high laser radiation(47.51 W/mm^(2)).These results indicate that Al_(2)O_(3)/Al_(2)O_(3)-YAG:Ce/YAG composite structure ceramic is a promising luminescent material in the high-power laser lighting applications.展开更多
An optical spectrometer is a basic spectral instrument that probes microscopic physical and chemical properties of macroscopic objects but generally suffers from difficulty in broadband time-resolved measurement.In th...An optical spectrometer is a basic spectral instrument that probes microscopic physical and chemical properties of macroscopic objects but generally suffers from difficulty in broadband time-resolved measurement.In this work,we report the creation of ultrabroadband white-light laser with a 3-dB bandwidth covering 385 to 1,080 nm,pulse energy of 1.07 mJ,and pulse duration of several hundred femtoseconds by passing 3-mJ pulse energy,50-fs pulse duration Ti:Sapphire pulse laser through a cascaded fused silica plate and chirped periodically poled lithium niobate crystal.We utilize this unprecedented superflat,ultrabroadband,and intense femtosecond laser light source to build a single-shot(i.e.,single-pulse)subpicosecond pulse laser ultraviolet-visible-near-infrared spectrometer and successfully measure various atomic and molecular absorption spectra.The single-shot ultrafast spectrometer may open up a frontier to monitor simultaneously the ultrafast dynamics of multiple physical and chemical processes in various microscopic systems.展开更多
Dysfunction of CD8^(+)T cells in the tumor microenvironment(TME)contributes to tumor immune escape and immunotherapy tolerance.The effects of hormones such as leptin,steroid hormones,and glucocorticoids on T cell func...Dysfunction of CD8^(+)T cells in the tumor microenvironment(TME)contributes to tumor immune escape and immunotherapy tolerance.The effects of hormones such as leptin,steroid hormones,and glucocorticoids on T cell function have been reported previously.However,the mechanism underlying thyroid-stimulating hormone(TSH)/thyroid-stimulating hormone receptor(TSHR)signaling in CD8^(+)T cell exhaustion and tumor immune evasion remain poorly understood.This study was aimed at investigating the effects of TSH/TSHR signaling on the function of CD8^(+)T cells and immune evasion in colorectal cancer(CRC).Methods:TSHR expression levels in CD8^(+)T cells were assessed with immunofluorescence and flow cytometry.Functional investigations involved manipulation of TSHR expression in cellular and mouse models to study its role in CD8^(+)T cells.Mechanistic insights were mainly gained through RNAsequencing,Western blotting,chromatin immunoprecipitation and luciferase activity assay.Immunofluorescence,flow cytometry and Western blotting were used to investigate the source of TSH and TSHR in CRC tissues.Results:TSHR was highly expressed in cancer cells and CD8^(+)T cells in CRC tissues.TSH/TSHR signaling was identified as the intrinsic pathway promoting CD8^(+)T cell exhaustion.Conditional deletion of TSHR in CD8^(+)tumorinfiltrating lymphocytes(TILs)improved effector differentiation and suppressed the expression of immune checkpoint receptors such as programmed cell death 1(PD-1)and hepatitis A virus cellular receptor 2(HAVCR2 or TIM3)through the protein kinase A(PKA)/cAMP-response element binding protein(CREB)signaling pathway.CRC cells secreted TSHR via exosomes to increase the TSHR level in CD8^(+)T cells,resulting in immunosuppression in the TME.Myeloid-derived suppressor cells(MDSCs)was the main source of TSH within the TME.Low expression of TSHR in CRC was a predictor of immunotherapy response.Conclusions:The present findings highlighted the role of endogenous TSH/TSHR signaling in CD8^(+)T cell exhaustion and immune evasion in CRC.TSHR may be suitable as a predictive and therapeutic biomarker in CRC immunotherapy.展开更多
Background:A growing body of evidence has revealed that the mammalian genome is organized into hierarchical layers that are closely correlated with and may even be causally linked with variations in gene expression.Re...Background:A growing body of evidence has revealed that the mammalian genome is organized into hierarchical layers that are closely correlated with and may even be causally linked with variations in gene expression.Recent studies have characterized chromatin organization in various porcine tissues and cell types and compared them among species and during the early development of pigs.However,how chromatin organization differs among pig breeds is poorly understood.Results:In this study,we investigated the 3D genome organization and performed transcriptome characterization of two adipose depots(upper layer of backfat[ULB]and greater omentum[GOM])in wild boars and Bama pigs;the latter is a typical indigenous pig in China.We found that over 95%of the A/B compartments and topologically associating domains(TADs)are stable between wild boars and Bama pigs.In contrast,more than 70%of promoterenhancer interactions(PEIs)are dynamic and widespread,involving over a thousand genes.Alterations in chromatin structure are associated with changes in the expression of genes that are involved in widespread biological functions such as basic cellular functions,endocrine function,energy metabolism and the immune response.Approximately 95%and 97%of the genes associated with reorganized A/B compartments and PEIs in the two pig breeds differed between GOM and ULB,respectively.Conclusions:We reported 3D genome organization in adipose depots from different pig breeds.In a comparison of Bama pigs and wild boar,large-scale compartments and TADs were mostly conserved,while fine-scale PEIs were extensively reorganized.The chromatin architecture in these two pig breeds was reorganized in an adipose depotspecific manner.These results contribute to determining the regulatory mechanism of phenotypic differences between Bama pigs and wild boar.展开更多
Obesity related non-alcoholic fatty liver disease(NAFLD),which can progress to steatohepatitis and insulin resistance,has become a major chronic liver disease worldwide.1 As an adaptor of clathrin-mediated endocytosis...Obesity related non-alcoholic fatty liver disease(NAFLD),which can progress to steatohepatitis and insulin resistance,has become a major chronic liver disease worldwide.1 As an adaptor of clathrin-mediated endocytosis,Epsin1 plays a role in many diseases,including tumors,atherosclerosis and diabetic wound healing.展开更多
Pigs were domesticated independently in the Near East and China,indicating that a single reference genome from one individual is unable to represent the full spectrum of divergent sequences in pigs worldwide.Therefore...Pigs were domesticated independently in the Near East and China,indicating that a single reference genome from one individual is unable to represent the full spectrum of divergent sequences in pigs worldwide.Therefore,12 de novo pig assemblies from Eurasia were compared in this study to identify the missing sequences from the reference genome.As a result,72.5 Mb of nonredundant sequences(~3% of the genome)were found to be absent from the reference genome(Sscrofa11.1)and were defined as pan-sequences.Of the pan-sequences,9.0 Mb were dominant in Chinese pigs,in contrast with their low frequency in European pigs.One sequence dominant in Chinese pigs contained the complete genic region of the tazarotene-induced gene 3(TIG3)gene which is involved in fatty acid metabolism.Using flanking sequences and Hi-C based methods,27.7% of the sequences could be anchored to the reference genome.The supplementation of these sequences could contribute to the accurate interpretation of the 3D chromatin structure.A web-based pan-genome database was further provided to serve as a primary resource for exploration of genetic diversity and promote pig breeding and biomedical research.展开更多
Gut microbiota play important roles in host health and diseases.Several factors,in particular antibiotics,affect the gut microbiota of pigs.Cross-fostering has been applied as a regular practice to equalize litter siz...Gut microbiota play important roles in host health and diseases.Several factors,in particular antibiotics,affect the gut microbiota of pigs.Cross-fostering has been applied as a regular practice to equalize litter size,reduce pre-weaning mortality and increase body weight.However,the effect of cross-fostering on cecal microbiota is unclear.In this study,we fostered three Jinhua pigs to a Yorkshire sow.The fostered Jinhua piglets grew significantly faster than their biological siblings.To explore whether the cecal microbiota of piglets will alter during fostering,we characterized the cecal microbiota of allpiglets by examining the V3 hypervariable region of 16S rDNA.We observed altered cecal microbiota in these piglets using the Illumina HiSeq 2000 platform,and this was accompanied with an increase in growth rate after fostering.The relative abundance of Bacteroidetes in the fostered Jinhua piglets was decreased compared with their biological siblings,although still higher in comparison with their new littermates.Beta-diversity analysis also showed that the cecal microbiota of the adopted Jinhua piglets differed from their biological siblings with a shift toward their step-siblings.Our data show that cecal microbiota of piglets were altered after cross-fostering while the growth rate increased.展开更多
Livestock have undergone domestication and consequently strong selective pressure on genes or genomic regions that control desirable traits. To identify selection signatures in the genome of Chinese Rongchang pigs, we...Livestock have undergone domestication and consequently strong selective pressure on genes or genomic regions that control desirable traits. To identify selection signatures in the genome of Chinese Rongchang pigs, we generated a total of about 170 Gb of DNA sequence data with about 6.4-fold coverage for each of six female individuals. By combining these data with the publically available genome data of 10 Asian wild boars,we identified 449 protein-coding genes with selection signatures in Rongchang pigs, which are mainly involved in growth and hormone binding, nervous system development, and drug metabolism. The accelerated evolution of these genes may contribute to the dramatic phenotypic differences between Rongchang pigs and Chinese wild boars. This study illustrated how domestication and subsequent artificial selection have shaped patterns of genetic variation in Rongchang pigs and provides valuable genetic resources that can enhance the use of pigs in agricultural production and biomedical studies.展开更多
Intense ultrabroadband laser source of high pulse energy has attracted more and more attention in physics,chemistry,biology,material science,and other disciplines.We report design and realization of a chirped periodic...Intense ultrabroadband laser source of high pulse energy has attracted more and more attention in physics,chemistry,biology,material science,and other disciplines.We report design and realization of a chirped periodically poled lithium niobate nonlinear crystal that supports ultrabroadband second-harmonic generation covering 350-850 nm by implementing simultaneously up to 12 orders of quasiphase matching against ultrabroadband pump laser covering 700-1700 nm with an average high conversion efficiency of about 25.8%.We obtain a flat supercontinuum spectrum with a 10 dB bandwidth covering more than one octave(about 375-1200 nm)and 20 dB bandwidth covering more than two octaves(about 350-1500 nm)in the ultraviolet-visible-infrared regime and having intense energy as 0.17 mJ per pulse through synergic action of second-order and third-order nonlinearity under pump of 0.48 mJ per pulse Ti:sapphire femtosecond laser.This scheme would provide a promising method for the construction of supercontinuum laser source with extremely broad bandwidth,large pulse energy,and high peak power for a variety of basic science and high technology applications.展开更多
Genomic structural variations （SVs）, particularly insertions, deletions and inversions, can contribute to the heterogeneity of millions of nucleotides within a genome, and are likely to make an important contributio...Genomic structural variations （SVs）, particularly insertions, deletions and inversions, can contribute to the heterogeneity of millions of nucleotides within a genome, and are likely to make an important contribution to biological diversity and phenotypic variation （Alkan et al., 2011; Bickhart and Liu, 2014）. With the rapid development of the next-generation sequencing technologies and the new assembly methodolo- gies, the multiple de novo assemblies of genomes within a species allow researchers to explore more detailed SV maps （Li et al., 2011）. Compared with the traditional read depth algorithm using the whole-genome resequencing approach and array-based technologies （Baker, 2012; Wang et al., 2012;展开更多
文摘Background: It has been conclusively established that intracranial aneurysms measuring a diameter below 7 mm pose a minimal risk of rupture. Conversely, those exhibiting irregular morphology or featuring the presence of a sac necessitate a more stringent and rigorous management approach. Objective: The primary aim of this study is to delve into the morphological features of ruptured aneurysms situated in distinct regions of the brain. Furthermore, we endeavor to assess the degree of safety and efficacy associated with stent-assisted embolization as a treatment modality for these ruptured aneurysms. Methods: This retrospective study encompassed a cohort of 467 patients who presented with intracranial ruptured aneurysms and were diagnosed through a combination of computed tomography (CT) and digital subtraction angiography (DSA) at Nanfang Hospital of Southern Medical University, spanning from January 2009 to December 2019. The following clinical parameters were meticulously recorded: aneurysm height, width, neck measurements, immediate Raymond grade assessments, and any perioperative complications experienced. Results: Within the study population, the average dimensions of ruptured aneurysms were found to be 4.26 ± 2.10 mm (width), 4.86 ± 2.38 mm (height), and 4.04 ± 1.87 mm (neck). Categorically, the most prevalent types of aneurysms were 170 cases of anterior communicating artery aneurysms (accounting for 36.4%), followed by 161 cases of posterior communicating artery aneurysms (34.5%), 56 cases of middle cerebral artery aneurysms (12.0%), 13 cases of anterior cerebral artery aneurysms (2.8%), 45 cases of paraclinoid aneurysms (9.6%), 6 cases of superior pituitary artery aneurysms (1.3%), 7 cases of anterior choroidal artery aneurysms (1.5%), and 9 cases of vertebrobasilar artery aneurysms (2.0%). Notably, 18 patients (3.9%) presented with ruptured aneurysms coexisting with ascus. Regarding treatment approaches, 228 cases (48.8%) underwent stent-assisted embolization, 234 cases (50.1%) received coils embolization, and 5 cases (1.1%) were treated with the dual-catheter technique. Immediately post-treatment, 422 patients (90.4%) attained a Raymond Class I status, with a procedure-related complication rate of 0.9%. Importantly, no statistically significant differences were observed in the incidence of perioperative complications across the three distinct treatment groups (P = 0.505). Conclusion: The outcomes of this study affirm the safety and efficacy of stent-assisted embolization as a treatment modality for ruptured aneurysms.
基金supported by the National Key R&D Program of China (2022YFF1000100 to Long Jin and 2023YFD1300012 to Long Jin)the Sichuan Science and Technology Program (2022JDJQ0054 to Long Jin and 2021YFYZ0009 to Mingzhou Li)the National Natural Science Foundation of China (32225046 to Mingzhou Li)。
文摘Background Goose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant energy intake. As a result, goose offers an excellent model for studying obesity, metabolic disorders, and liver diseases in mammals. Although the impact of the three-dimensional arrangement of chromatin within the cell nucleus on gene expression and transcriptional regulation is widely acknowledged, the precise functions of chromatin architecture reorganization during fat deposition in goose liver tissues still need to be fully comprehended.Results In this study, geese exhibited more pronounced changes in the liver index and triglyceride(TG) content following the consumption of the high-fat diet(HFD) than mice without significant signs of inflammation. Additionally, we performed comprehensive analyses on 10 goose liver tissues(5 HFD, 5 normal), including generating highresolution maps of chromatin architecture, conducting whole-genome gene expression profiling, and identifying H3K27ac peaks in the livers of geese and mice subjected to the HFD. Our results unveiled a multiscale restructuring of chromatin architecture, encompassing Compartment A/B, topologically associated domains, and interactions between promoters and enhancers. The dynamism of the three-dimensional genome architecture, prompted by the HFD, assumed a pivotal role in the transcriptional regulation of crucial genes. Furthermore, we identified genes that regulate chromatin conformation changes, contributing to the metabolic adaptation process of lipid deposition and hepatic fat changes in geese in response to excessive energy intake. Moreover, we conducted a cross-species analysis comparing geese and mice exposed to the HFD, revealing unique characteristics specific to the goose liver compared to a mouse. These chromatin conformation changes help elucidate the observed characteristics of fat deposition and hepatic fat regulation in geese under conditions of excessive energy intake.Conclusions We examined the dynamic modifications in three-dimensional chromatin architecture and gene expression induced by an HFD in goose liver tissues. We conducted a cross-species analysis comparing that of mice. Our results contribute significant insights into the chromatin architecture of goose liver tissues, offering a novel perspective for investigating mammal liver diseases.
基金supported by the National Key R&D Program of China (2020YFA0509500,2021YFD1301101 and 2021YFA0805903)the Sichuan Science and Technology Program+3 种基金(2023YFN0088 and 2021YFYZ0030)the National Center of Technology Innovation for Pigs (SCCXTD-2023-08)the National Natural Science Foundation of China (32272837 and 32225046)Tianfu Agricultural Master Project。
文摘Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes.Results Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages(d 90 of gestation, G90;d 0 after lactation, L0;d 20 after lactation, L20;2 d post natural involution, PI2;7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation(G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation(L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution(PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells to maintain the lactation potential of mammary glands for the next lactation cycle.Conclusion The molecular mechanisms of dedifferentiation, proliferation and redifferentiation of adipocytes and epithelial cells were revealed from late pregnancy to natural involution. This cell transcriptomic profile constitutes an essential reference for future studies in the development and remodeling of the mammary gland at different stages.
基金funded by the National Natural Science Foundation of China(Grant No.81472753 and 81672634)。
文摘Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.
文摘Objective:To compare the antiplatelet effect and major adverse cerebrovascular events of Pipeline for intracranial aneurysms using glycoproteinⅡb/Ⅲa antagonists(GPI)eptifibatide and tirofiban.Methods:Retrospective analysis of relevant data of patients using GPIs combined with oral antiplatelet therapy in Nanfang Hospital of Southern Medical University from December 2017 to December 2019.The study was approved by the ethics Committee of Nanfang Hospital of Southern Medical University.According to the random use of GPIs drugs,they were assigned to the eptifibatide group and tirofiban group.Basic data,platelet inhibition rates at baseline,24 h and 72 h after administration,short-term major adverse cerebrovascular events,and bleeding complications were compared between the two groups.Results:A total of 47 patients were included in this study,including 24 patients in eptifibatide group and 23 patients in tirofiban group.There was no significant difference in average age(53.75 vs.53.91 years)and body mass index(BMI)(24.39 vs.22.73 kg/m2)between eptifibatide group and tirofiban group.There was no significant difference in coagulation factor function(R),fibrinogen function(K),fibrinolysis function(EPL),comprehensive coagulation index(Cl),arachidonic acid pathway inhibition rate(AA%)and adenosine diphosphate inhibition rate(ADP%).However,the baseline level of residual platelet function MA(ADP)in eptifibatide group was significantly higher than that in tirofiban group(50.79 vs.35.29 mm,P=0.0026).There was a statistical difference in the platelet aggregation function MA(65.38 vs.62.54 mm,p=0.0442),the rate of spontaneous hemorrhagic stroke(4.3%vs.0%)and the rate of asymptomatic minor bleeding(26.08%vs.4.1%)in the two groups(P<0.05).Conclusion:Both eptifibatide and tirofiban can effectively inhibit platelets,but the effect of etifeptide is better than that of tirofiban in preventing intracranial microhemorrhage and asymptomatic cerebral infarction.
基金the National Key R&D Program of China(2021YFB3501700,2023YFB3506600)National Natural Science Foundation of China(52202135,61975070,and 52302141)+5 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),International S&T Cooperation Program of Jiangsu Province(BZ2023007)Key Research and Development Project of Jiangsu Province(BE2023050,BE2021040)Natural Science foundation of Jiangsu Province(BK20221226)Graduate Research and Innovation Projects of Jiangsu Province(KYCX22_2845)Special Project for Technology Innovation of Xuzhou City(KC23380,KC21379,KC22461,and KC22497)Open Project of State Key Laboratory of Crystal Materials(KF2205).
文摘Composite ceramic phosphor(CCP)is a candidate light-conversion material to obtain the high-quality laser lighting source.Phosphors based on the transmissive configuration model could not simultaneously meet the requirements of angular color uniformity and high thermal stability.In this study,a novel composite structure ceramic was designed,including Al_(2)O_(3)-YAG:Ce/YAG layered ceramic with a size of 1 mm×1 mm for lighting,and Al_(2)O_(3) ceramic(φ=16.0 mm)was used as the wrapping material due to its outstanding thermal stability.The prepared ceramics exhibited excellent thermal performance and no yellow ring phenomenon.Through this design,we achieved the match of the intensity distribution of the blue and yellow lights,resulting in a high angular color uniformity of 0.9 with a view angle of±80°.All ceramics showed no luminous saturation phenomenon,even the laser power density was increased up to 47.51 W/mm^(2).A high-brightness white-light source with a luminous flux of 618 lm,a luminous efficiency of 126 lm/W,a CCT of 6615 K,and a CRI of 69.9 was obtained in the transmissive configuration.In particular,the surface temperature of the ceramic was as low as 74.1℃ under a high laser radiation(47.51 W/mm^(2)).These results indicate that Al_(2)O_(3)/Al_(2)O_(3)-YAG:Ce/YAG composite structure ceramic is a promising luminescent material in the high-power laser lighting applications.
基金support from the National Natural Science Foundation of China(11974119)Science and Technology Project of Guangdong(2020B010190001)+1 种基金Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06C594)National Key R&D Program of China(2018YFA 0306200).
文摘An optical spectrometer is a basic spectral instrument that probes microscopic physical and chemical properties of macroscopic objects but generally suffers from difficulty in broadband time-resolved measurement.In this work,we report the creation of ultrabroadband white-light laser with a 3-dB bandwidth covering 385 to 1,080 nm,pulse energy of 1.07 mJ,and pulse duration of several hundred femtoseconds by passing 3-mJ pulse energy,50-fs pulse duration Ti:Sapphire pulse laser through a cascaded fused silica plate and chirped periodically poled lithium niobate crystal.We utilize this unprecedented superflat,ultrabroadband,and intense femtosecond laser light source to build a single-shot(i.e.,single-pulse)subpicosecond pulse laser ultraviolet-visible-near-infrared spectrometer and successfully measure various atomic and molecular absorption spectra.The single-shot ultrafast spectrometer may open up a frontier to monitor simultaneously the ultrafast dynamics of multiple physical and chemical processes in various microscopic systems.
基金supported by the National Key R&D Program of China(Grant No.2021YFF1201004)the National Natural Science Foundation of China(Grant No.82273358,No.81802306,No.81903002,No.81672821,No.82071742,No.32270926)Natural Science Foundation of Guangdong Province of China(Grant No.2019A1515012196,No.2022A1515012059).
文摘Dysfunction of CD8^(+)T cells in the tumor microenvironment(TME)contributes to tumor immune escape and immunotherapy tolerance.The effects of hormones such as leptin,steroid hormones,and glucocorticoids on T cell function have been reported previously.However,the mechanism underlying thyroid-stimulating hormone(TSH)/thyroid-stimulating hormone receptor(TSHR)signaling in CD8^(+)T cell exhaustion and tumor immune evasion remain poorly understood.This study was aimed at investigating the effects of TSH/TSHR signaling on the function of CD8^(+)T cells and immune evasion in colorectal cancer(CRC).Methods:TSHR expression levels in CD8^(+)T cells were assessed with immunofluorescence and flow cytometry.Functional investigations involved manipulation of TSHR expression in cellular and mouse models to study its role in CD8^(+)T cells.Mechanistic insights were mainly gained through RNAsequencing,Western blotting,chromatin immunoprecipitation and luciferase activity assay.Immunofluorescence,flow cytometry and Western blotting were used to investigate the source of TSH and TSHR in CRC tissues.Results:TSHR was highly expressed in cancer cells and CD8^(+)T cells in CRC tissues.TSH/TSHR signaling was identified as the intrinsic pathway promoting CD8^(+)T cell exhaustion.Conditional deletion of TSHR in CD8^(+)tumorinfiltrating lymphocytes(TILs)improved effector differentiation and suppressed the expression of immune checkpoint receptors such as programmed cell death 1(PD-1)and hepatitis A virus cellular receptor 2(HAVCR2 or TIM3)through the protein kinase A(PKA)/cAMP-response element binding protein(CREB)signaling pathway.CRC cells secreted TSHR via exosomes to increase the TSHR level in CD8^(+)T cells,resulting in immunosuppression in the TME.Myeloid-derived suppressor cells(MDSCs)was the main source of TSH within the TME.Low expression of TSHR in CRC was a predictor of immunotherapy response.Conclusions:The present findings highlighted the role of endogenous TSH/TSHR signaling in CD8^(+)T cell exhaustion and immune evasion in CRC.TSHR may be suitable as a predictive and therapeutic biomarker in CRC immunotherapy.
基金supported by grants from the National Key R&D Program of China(2020YFA0509500)the National Natural Science Foundation of China(U19A2036,31772576,31530073 and 31802044)+1 种基金the Sichuan Science and Technology Program(2021YFYZ0009 and 2021YFYZ0030)the International Cooperation Project of Science and Technology Department of Sichuan Province(2021YFH0033).
文摘Background:A growing body of evidence has revealed that the mammalian genome is organized into hierarchical layers that are closely correlated with and may even be causally linked with variations in gene expression.Recent studies have characterized chromatin organization in various porcine tissues and cell types and compared them among species and during the early development of pigs.However,how chromatin organization differs among pig breeds is poorly understood.Results:In this study,we investigated the 3D genome organization and performed transcriptome characterization of two adipose depots(upper layer of backfat[ULB]and greater omentum[GOM])in wild boars and Bama pigs;the latter is a typical indigenous pig in China.We found that over 95%of the A/B compartments and topologically associating domains(TADs)are stable between wild boars and Bama pigs.In contrast,more than 70%of promoterenhancer interactions(PEIs)are dynamic and widespread,involving over a thousand genes.Alterations in chromatin structure are associated with changes in the expression of genes that are involved in widespread biological functions such as basic cellular functions,endocrine function,energy metabolism and the immune response.Approximately 95%and 97%of the genes associated with reorganized A/B compartments and PEIs in the two pig breeds differed between GOM and ULB,respectively.Conclusions:We reported 3D genome organization in adipose depots from different pig breeds.In a comparison of Bama pigs and wild boar,large-scale compartments and TADs were mostly conserved,while fine-scale PEIs were extensively reorganized.The chromatin architecture in these two pig breeds was reorganized in an adipose depotspecific manner.These results contribute to determining the regulatory mechanism of phenotypic differences between Bama pigs and wild boar.
基金This study was supported by the National Natural Science Foundation of China(No.31900834)the China's Overseas Expertise Introduction Project for Discipline Innovation("111 Project")(No.D17015).
文摘Obesity related non-alcoholic fatty liver disease(NAFLD),which can progress to steatohepatitis and insulin resistance,has become a major chronic liver disease worldwide.1 As an adaptor of clathrin-mediated endocytosis,Epsin1 plays a role in many diseases,including tumors,atherosclerosis and diabetic wound healing.
基金supported by the National Natural Science Foundation of China(31822052 and 31572381)the Science&Technology Support Program of Sichuan(2016NYZ0042 and 2017NZDZX0002)。
文摘Pigs were domesticated independently in the Near East and China,indicating that a single reference genome from one individual is unable to represent the full spectrum of divergent sequences in pigs worldwide.Therefore,12 de novo pig assemblies from Eurasia were compared in this study to identify the missing sequences from the reference genome.As a result,72.5 Mb of nonredundant sequences(~3% of the genome)were found to be absent from the reference genome(Sscrofa11.1)and were defined as pan-sequences.Of the pan-sequences,9.0 Mb were dominant in Chinese pigs,in contrast with their low frequency in European pigs.One sequence dominant in Chinese pigs contained the complete genic region of the tazarotene-induced gene 3(TIG3)gene which is involved in fatty acid metabolism.Using flanking sequences and Hi-C based methods,27.7% of the sequences could be anchored to the reference genome.The supplementation of these sequences could contribute to the accurate interpretation of the 3D chromatin structure.A web-based pan-genome database was further provided to serve as a primary resource for exploration of genetic diversity and promote pig breeding and biomedical research.
基金supported by the National Special Foundation for Transgenic Species of China(2014ZX0800950B,2011ZX08006-003)the Specialized Research Fund of Ministry of Agriculture of China(NYCYTX-009)+3 种基金the Fundof Fok Ying-Tung Education Foundation(141117)the Fund for Distinguished Young Scientists of Sichuan Province(2013JQ0013)the Program for Changjiang Scholars and Innovative Research Teamin University(IRT13083)to Mingzhou Li and Xuewei Lithe‘‘100-Talent Program’’in Sichuan Science Foundation for Youths of Sichuan Province to Ying Li
文摘Gut microbiota play important roles in host health and diseases.Several factors,in particular antibiotics,affect the gut microbiota of pigs.Cross-fostering has been applied as a regular practice to equalize litter size,reduce pre-weaning mortality and increase body weight.However,the effect of cross-fostering on cecal microbiota is unclear.In this study,we fostered three Jinhua pigs to a Yorkshire sow.The fostered Jinhua piglets grew significantly faster than their biological siblings.To explore whether the cecal microbiota of piglets will alter during fostering,we characterized the cecal microbiota of allpiglets by examining the V3 hypervariable region of 16S rDNA.We observed altered cecal microbiota in these piglets using the Illumina HiSeq 2000 platform,and this was accompanied with an increase in growth rate after fostering.The relative abundance of Bacteroidetes in the fostered Jinhua piglets was decreased compared with their biological siblings,although still higher in comparison with their new littermates.Beta-diversity analysis also showed that the cecal microbiota of the adopted Jinhua piglets differed from their biological siblings with a shift toward their step-siblings.Our data show that cecal microbiota of piglets were altered after cross-fostering while the growth rate increased.
基金supported by the National High Technology Research and Development Program of China (2013AA102502)Chongqing Agricultural Development Foundation (12404,14440 and 15428)+3 种基金the National Natural Science Foundation of China (31372284,31401073,31472081,31522055,31601919 and 31601930)the Program for Innovative Research Team of Sichuan Province (2015TD0012)the National Program for Support of Top-notch Young Professionals,the Young Scholars of the Yangtze River
文摘Livestock have undergone domestication and consequently strong selective pressure on genes or genomic regions that control desirable traits. To identify selection signatures in the genome of Chinese Rongchang pigs, we generated a total of about 170 Gb of DNA sequence data with about 6.4-fold coverage for each of six female individuals. By combining these data with the publically available genome data of 10 Asian wild boars,we identified 449 protein-coding genes with selection signatures in Rongchang pigs, which are mainly involved in growth and hormone binding, nervous system development, and drug metabolism. The accelerated evolution of these genes may contribute to the dramatic phenotypic differences between Rongchang pigs and Chinese wild boars. This study illustrated how domestication and subsequent artificial selection have shaped patterns of genetic variation in Rongchang pigs and provides valuable genetic resources that can enhance the use of pigs in agricultural production and biomedical studies.
基金The authors are grateful for the financial support from the National Natural Science Foundation of China(11974119)Science and Technology Project of Guangdong(2020B010190001)+1 种基金Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06C594)National Key R&D Program of China(2018YFA 0306200).
文摘Intense ultrabroadband laser source of high pulse energy has attracted more and more attention in physics,chemistry,biology,material science,and other disciplines.We report design and realization of a chirped periodically poled lithium niobate nonlinear crystal that supports ultrabroadband second-harmonic generation covering 350-850 nm by implementing simultaneously up to 12 orders of quasiphase matching against ultrabroadband pump laser covering 700-1700 nm with an average high conversion efficiency of about 25.8%.We obtain a flat supercontinuum spectrum with a 10 dB bandwidth covering more than one octave(about 375-1200 nm)and 20 dB bandwidth covering more than two octaves(about 350-1500 nm)in the ultraviolet-visible-infrared regime and having intense energy as 0.17 mJ per pulse through synergic action of second-order and third-order nonlinearity under pump of 0.48 mJ per pulse Ti:sapphire femtosecond laser.This scheme would provide a promising method for the construction of supercontinuum laser source with extremely broad bandwidth,large pulse energy,and high peak power for a variety of basic science and high technology applications.
基金supported by the National High Technology Research and Development Program of China(863 Program)(No.2013AA102502)the National Natural Science Foundation of China(Nos.31372284 and 31402046)+1 种基金the Fund of Fok Ying-Tung Education Foundation(No.141117)the Fund for Distinguished Young Scientists of Sichuan Province(No. 2013JQ0013)
文摘Genomic structural variations （SVs）, particularly insertions, deletions and inversions, can contribute to the heterogeneity of millions of nucleotides within a genome, and are likely to make an important contribution to biological diversity and phenotypic variation （Alkan et al., 2011; Bickhart and Liu, 2014）. With the rapid development of the next-generation sequencing technologies and the new assembly methodolo- gies, the multiple de novo assemblies of genomes within a species allow researchers to explore more detailed SV maps （Li et al., 2011）. Compared with the traditional read depth algorithm using the whole-genome resequencing approach and array-based technologies （Baker, 2012; Wang et al., 2012;
