Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related t...Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.展开更多
Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal ...Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.展开更多
Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
The Solar Upper Transition Region Imager(SUTRI)onboard the Space Advanced Technology demonstration satellite(SATech-01),which was launched to a Sun-synchronous orbit at a height of~500 km in 2022 July,aims to test the...The Solar Upper Transition Region Imager(SUTRI)onboard the Space Advanced Technology demonstration satellite(SATech-01),which was launched to a Sun-synchronous orbit at a height of~500 km in 2022 July,aims to test the on-orbit performance of our newly developed Sc/Si multi-layer reflecting mirror and the 2k×2k EUV CMOS imaging camera and to take full-disk solar images at the Ne VII 46.5 nm spectral line with a filter width of~3 nm.SUTRI employs a Ritchey-Chrétien optical system with an aperture of 18 cm.The on-orbit observations show that SUTRI images have a field of view of~416×416 and a moderate spatial resolution of~8″without an image stabilization system.The normal cadence of SUTRI images is 30 s and the solar observation time is about16 hr each day because the earth eclipse time accounts for about 1/3 of SATech-01's orbit period.Approximately15 GB data is acquired each day and made available online after processing.SUTRI images are valuable as the Ne VII 46.5 nm line is formed at a temperature regime of~0.5 MK in the solar atmosphere,which has rarely been sampled by existing solar imagers.SUTRI observations will establish connections between structures in the lower solar atmosphere and corona,and advance our understanding of various types of solar activity such as flares,filament eruptions,coronal jets and coronal mass ejections.展开更多
Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this stu...Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this study,we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer(PTC).In parallel,we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule(BTN)patients.Distinct microbial signatures were identified in PTC,BTN,and their adjacent nontumor tissues.Intra-thyroid tissue bacteria were verified by means of bacteria staining,fluorescence in situ hybridization,and immunoelectron microscopy.We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN,which included enrichment in PTC of the pathobionts Rhodococcus,Neisseria,Streptococcus,Halomonas,and Devosia,and depletion of the beneficial bacteria Amycolatopsis.These differentially abundant bacteria could differentiate PTC tumor tissues(PTC-T)from BTN tissues(BTN-T)with an area under the curve(AUC)of 81.66%.Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T.Immunefunction-corresponding bacteria(i.e.,Erwinia,Bacillus,and Acinetobacter)were found to be enriched in PTC with Hashimoto’s thyroiditis.Moreover,our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes,including BRAF,KRAS,IRAK4,CTNNB1,PIK3CA,MAP3K7,and EGFR.In conclusion,our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.展开更多
Precisely tuning the spacing of the active centers on the atomic scale is of great significance to improve the catalytic activity and deepen the understanding of the catalytic mechanism,but still remains a challenge.H...Precisely tuning the spacing of the active centers on the atomic scale is of great significance to improve the catalytic activity and deepen the understanding of the catalytic mechanism,but still remains a challenge.Here,we develop a strategy to dilute catalytically active metal interatomic spacing(d_(M-M))with light atoms and discover the unusual adsorption patterns.For example,by elevating the content of boron as interstitial atoms,the atomic spacing of osmium(d_(Os-Os))gradually increases from 2.73 to 2.96?.More importantly,we find that,with the increase in dOs-Os,the hydrogen adsorption-distance relationship is reversed via downshifting d-band states,which breaks the traditional cognition,thereby optimizing the H adsorption and H_2O dissociation on the electrode surface during the catalytic process;this finally leads to a nearly linear increase in hydrogen evolution reaction activity.Namely,the maximum dOs-Os of 2.96?presents the optimal HER activity(8 mV@10 mA cm^(-2))in alkaline media as well as suppressed O adsorption and thus promoted stability.It is believed that this novel atomic-level distance modulation strategy of catalytic sites and the reversed hydrogen adsorption-distance relationship can shew new insights for optimal design of highly efficient catalysts.展开更多
Sweetpotato(Ipomoea batatas(L.)Lam.)is a widely grown food crop especially in developing countries.Increasing storage-root yield and dry-matter content has been the main breeding objective of the crop,and DNA marker-a...Sweetpotato(Ipomoea batatas(L.)Lam.)is a widely grown food crop especially in developing countries.Increasing storage-root yield and dry-matter content has been the main breeding objective of the crop,and DNA marker-assisted breeding is needed for this purpose.In this study,using a mapping population of 500 F1 individuals from a cross between Xushu 18(female)and Xu 781(male),we constructed a highdensity genetic linkage map of sweetpotato using 601 simple-sequence repeat(SSR)primer pairs.The Xushu 18 map contained 90 linkage groups with 5547 SSR markers and spanned 18,263.5 cM,and the Xu 781 map contained 90 linkage groups with 4599 SSR markers and spanned 18,043.7 cM,representing the highest genome coverage yet reported for sweetpotato.We identified 33 QTL for storage-root yield and 16 QTL for dry-matter content,explaining respectively 6.5%–47.5%and 3.2%–18.9%of variation.These results provide a foundation for fine-mapping and cloning of QTL and for marker-assisted breeding in sweetpotato.展开更多
The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial...The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.展开更多
The transition region is the key region between the lower solar atmosphere and the corona, which has been limitedly understood by human beings. Therefore, the Solar Upper Transition Region Imager(SUTRI) was proposed b...The transition region is the key region between the lower solar atmosphere and the corona, which has been limitedly understood by human beings. Therefore, the Solar Upper Transition Region Imager(SUTRI) was proposed by Chinese scientists and launched in 2022 July. Right now, the first imaging observation of the upper transition region around 46.5 nm has been carried out by SUTRI. To ensure the spectral and temporal resolution of the SUTRI telescope, we have developed a narrowband Sc/Si multilayer. Based on the extreme ultraviolet(EUV)reflectivity measurements, the multilayer structure has been modified for ensuring the peak position of reflectivity was at 46.5 nm. Finally, the narrowband Sc/Si multilayer was successfully deposited on the hyperboloid primary mirror and secondary mirrors. The deviation of multilayer thickness uniformity was below than 1%, and the average EUV reflectivity at 46.1 nm was 27.8% with a near-normal incident angle of 5°. The calculated bandwidth of the reflectivity curve after primary and secondary mirrors was 2.82 nm, which could ensure the requirements of spectral resolution and reflectivity of SUTRI telescope to achieve its scientific goals.展开更多
This paper describes a fabrication process for the hyperboloidal concave mirror of a 46.5 nm telescope. The180 mm aperture hyperboloidal concave mirror and 70 mm aperture compensator are machined directly from chemica...This paper describes a fabrication process for the hyperboloidal concave mirror of a 46.5 nm telescope. The180 mm aperture hyperboloidal concave mirror and 70 mm aperture compensator are machined directly from chemical mechanical polishing of a spherical surface to a high-accuracy aspherical surface by ion beam figuring.The aspherical measurement method is the Dall null test. To minimize system errors in the measurement process,the rotational measurement method with six rotations is used in the null test. The results of the analysis for the ME(first solve the machined surface profile, then solve the system errors) and EM(first solve the system errors, then solve the machined surface profile) methods of calculation in the measurement are given. The ME method is a more accurate rotational test method, and the six rotations are appropriate for rotational measurements. After the figuring process, the hyperboloidal concave mirror surface profile reached 8.27 nm rms and the compensator surface profile is approximately 4 nm rms. The roughness of the hyperboloidal concave mirror is smooth to0.160 nm rms.展开更多
Objective:Gestational diabetes mellitus(GDM)is the most common metabolic disorder during pregnancy.LncRNA HLA complex group 27(HCG27)plays a crucial role in various metabolic diseases.However,the relationship between ...Objective:Gestational diabetes mellitus(GDM)is the most common metabolic disorder during pregnancy.LncRNA HLA complex group 27(HCG27)plays a crucial role in various metabolic diseases.However,the relationship between lncRNA HCG27 and GDM is not clear.This study aimed to verify a competing endogenous RNA(ceRNA)interaction regulation axis of miR-378a-3p/mitogen-activated protein kinase 1(MAPK1)regulated by HCG27 in GDM.Methods:LncRNA HCG27 and miR-378a-3p were detected by RT-qPCR.The expression of MAPK1 in umbilical vein endothelial cells(HUVECs)was detected by RT-qPCR and that in the placenta by Western blotting.To explore the relationship among lncRNA HCG27,miR-378a-3p,MAPK1 and the glucose uptake ability of HUVECs,vector HCG27,si-HCG27,miR-378a-3p mimic and inhibitor were transfected to achieve overexpression and inhibition of HCG27 or miR-378a-3p.The interaction between miR-378a-3p and lncRNA HCG27 or MAPK1 was confirmed by the dual-luciferase reporter assay.Besides,glucose consumption by HUVECs was detected by the glucose assay kit.Results:HCG27 expression was significantly decreased in both the placenta and primary umbilical vein endothelial cells,while the expression of miR-378a-3p was significantly increased in GDM tissues,and the expression of MAPK1 was decreased in GDM tissues.This ceRNA interaction regulation axiswas proved to affect the glucose uptake function of HUVECs.The transfection of si-HCG27 could significantly reduce the expression of the MAPK1 protein.If the MAPK1 overexpression plasmid was transfected simultaneously with si-HCG27 transfection,the reduced glucose uptake in HUVECs resulting from the decrease in lncRNA HCG27 was reversed.MiR-378a-3p mimic can significantly reduce the mRNA expression of MAPK1 in HUVECs,whereas miR-378a-3p inhibitor can significantly increase the mRNA expression of MAPK1.The inhibition of miR-378a-3p could restore the decreased glucose uptake of HUVECs treated with si-HCG27.Besides,overexpression of lncRNA HCG27 could restore the glucose uptake ability of the palmitic acid-induced insulin resistance model of HUVECs to normal.Conclusion:LncRNA HCG27 promotes glucose uptake of HUVECs by miR-378a-3p/MAPK1 pathway,which may provide potential therapeutic targets for GDM.Besides,the fetal umbilical cord blood and umbilical vein endothelial cells collected from pregnant women with GDM after delivery could be used to detect the presence of adverse molecular markers of metabolic memory,so as to provide guidance for predicting the risk of cardiovascular diseases and health screening of offspring.展开更多
Multi-stream carrier aggregation is a key technology to expand bandwidth and improve the throughput of the fifth-generation wireless communication systems.However,due to the diversified propagation properties of diffe...Multi-stream carrier aggregation is a key technology to expand bandwidth and improve the throughput of the fifth-generation wireless communication systems.However,due to the diversified propagation properties of different frequency bands,the traffic migration task is much more challenging,especially in hybrid sub-6 GHz and millimeter wave bands scenario.Existing schemes either neglected to consider the transmission rate difference between multistream carrier,or only consider simple low mobility scenario.In this paper,we propose a low-complexity traffic splitting algorithm based on fuzzy proportional integral derivative control mechanism.The proposed algorithm only relies on the local radio link control buffer information of sub-6 GHz and mmWave bands,while frequent feedback from user equipment(UE)side is minimized.As shown in the numerical examples,the proposed traffic splitting mechanism can achieve more than 90%link resource utilization ratio for different UE transmission requirements with different mobilities,which corresponds to 10%improvement if compared with conventional baselines.展开更多
Cancer is one of the leading causes of death worldwide.The early diagnosis of cancer remains one of the greatest cancer research challenges.Epigenetic alterations,such as altered DNA methylation,that occur during the ...Cancer is one of the leading causes of death worldwide.The early diagnosis of cancer remains one of the greatest cancer research challenges.Epigenetic alterations,such as altered DNA methylation,that occur during the early stages of carcinogenesis have been proposed as candidate cancer biomarkers.In recent years detection of small amounts of methylated DNA in samples,including blood and stool,has demonstrated the feasibility of DNA methylation as a molecular cancer biomarker.The translational promise of aberrant DNA methylation includes screening and detecting cancer,evaluating prognosis,assessing treatment efficacy,and detecting minimal residual disease(Figure 1).展开更多
The Solar Upper Transition Region Imager(SUTRI)focuses on the solar transition region to achieve dynamic imaging observation of the upper transition region.In this paper,we report the optical system design,mechanical ...The Solar Upper Transition Region Imager(SUTRI)focuses on the solar transition region to achieve dynamic imaging observation of the upper transition region.In this paper,we report the optical system design,mechanical design,ultrasmooth mirror manufacture and measurement,EUV multilayer film coating,prelaunch installation and calibration for the SUTRI payload at IPOE,Tongji University.Finally,the SUTRI carried by the SATech-01 satellite was successfully set to launch.All functions of this telescope were normal,and the observation results obtained in orbit were consistent with the design.展开更多
To the Editor:Choledochocele,also known as type III choledochal cysts in the classification by Todani et al.[1],is a congenital abnormality of the biliary system.It is characterized by a cystic dilation of intramural ...To the Editor:Choledochocele,also known as type III choledochal cysts in the classification by Todani et al.[1],is a congenital abnormality of the biliary system.It is characterized by a cystic dilation of intramural segment of the distal common bile duct(CBD)protruding into the descending duodenum.Choledochocele makes up about 0.5%−4%of choledochal cysts[1,2].Compared with other subtypes,the incidence of choledochocele is extremely low and it frequently presents in adults at a relatively older age,with an average age of 51 years[3].The diagnosis and treatment are challenging.Here,we present a case of a young female patient with this rare disease entity,who recovered after effective endoscopic retrograde cholangiopancreatography(ERCP)management.展开更多
Kashin-Beck disease(KBD)is an endemic osteoarthropathy.Its distribution region covers a long and narrow belt on the Pacific side and belongs to continental climate with short summer,long frost period,and large tempera...Kashin-Beck disease(KBD)is an endemic osteoarthropathy.Its distribution region covers a long and narrow belt on the Pacific side and belongs to continental climate with short summer,long frost period,and large temperature differences between day and night.In particular,KBD patients are typically scattered in the rural areas with seasonal features such as cold winters and rainy autumns.Etiological studies have demonstrated that the carrier of pathogenic factors is the grains produced in endemic areas.Risk factors for KBD include fungal contamination of grains due to poor storage conditions associated with cold weather.The epidemiological characteristics of KBD include agricultural area,early age of onset,gender equality,family aggregation,regional differences,and annual fluctuations.A series of preventive measures have been successfully taken in the past decades.National surveillance data indicate that the annual incidence of KBD is gradually declining.展开更多
Studying the relationship between rhizosphere microorganisms and root exudates is of great significance for the interaction between rhizosphere microorganisms and plants, and the prevention and control of soil-borne d...Studying the relationship between rhizosphere microorganisms and root exudates is of great significance for the interaction between rhizosphere microorganisms and plants, and the prevention and control of soil-borne diseases. This article analyzed the effects of different microorganisms on tobacco root exudates and rhizosphere microorganisms. It was found that the bacterial wilt pathogen can greatly increase acids and amines, while the probiotic <i>B. amyloliquefaciens</i> ZM9 can eliminate some acids and amines. The results of the study show that the root exudates of pathogenic bacteria may contain a variety of allelochemicals that cause soil-borne diseases.展开更多
基金supported by the National Natural Science Foundation of China,No.81971097(to JY)。
文摘Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.
基金supported by Fujian Provincial Natural Science(2020J01122587)National Natural Science Foundation of China(82103355,82102255,and 82222901)+1 种基金RGC Theme-based Research Scheme(T12-703/19-R)Research grants Council-General Research Fund(14117422 and 14117123)。
文摘Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
基金supported by the National Natural Science Foundation of China(NSFC)under Grants 11825301,12003016,12073077the National Key R&D Program of China No.2021YFA0718600+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences with the Grant No.XDA15018400the Youth Innovation Promotion Association of CAS(2023061)。
文摘The Solar Upper Transition Region Imager(SUTRI)onboard the Space Advanced Technology demonstration satellite(SATech-01),which was launched to a Sun-synchronous orbit at a height of~500 km in 2022 July,aims to test the on-orbit performance of our newly developed Sc/Si multi-layer reflecting mirror and the 2k×2k EUV CMOS imaging camera and to take full-disk solar images at the Ne VII 46.5 nm spectral line with a filter width of~3 nm.SUTRI employs a Ritchey-Chrétien optical system with an aperture of 18 cm.The on-orbit observations show that SUTRI images have a field of view of~416×416 and a moderate spatial resolution of~8″without an image stabilization system.The normal cadence of SUTRI images is 30 s and the solar observation time is about16 hr each day because the earth eclipse time accounts for about 1/3 of SATech-01's orbit period.Approximately15 GB data is acquired each day and made available online after processing.SUTRI images are valuable as the Ne VII 46.5 nm line is formed at a temperature regime of~0.5 MK in the solar atmosphere,which has rarely been sampled by existing solar imagers.SUTRI observations will establish connections between structures in the lower solar atmosphere and corona,and advance our understanding of various types of solar activity such as flares,filament eruptions,coronal jets and coronal mass ejections.
基金supported by the National Natural Science Foundation of China(81772850 and 82273300)。
文摘Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this study,we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer(PTC).In parallel,we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule(BTN)patients.Distinct microbial signatures were identified in PTC,BTN,and their adjacent nontumor tissues.Intra-thyroid tissue bacteria were verified by means of bacteria staining,fluorescence in situ hybridization,and immunoelectron microscopy.We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN,which included enrichment in PTC of the pathobionts Rhodococcus,Neisseria,Streptococcus,Halomonas,and Devosia,and depletion of the beneficial bacteria Amycolatopsis.These differentially abundant bacteria could differentiate PTC tumor tissues(PTC-T)from BTN tissues(BTN-T)with an area under the curve(AUC)of 81.66%.Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T.Immunefunction-corresponding bacteria(i.e.,Erwinia,Bacillus,and Acinetobacter)were found to be enriched in PTC with Hashimoto’s thyroiditis.Moreover,our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes,including BRAF,KRAS,IRAK4,CTNNB1,PIK3CA,MAP3K7,and EGFR.In conclusion,our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.
基金financially sponsored by the National Natural Science Foundation of China(Grant Nos.22075223,22179104)the State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(Wuhan University of Technology)(2022-ZD-4)。
文摘Precisely tuning the spacing of the active centers on the atomic scale is of great significance to improve the catalytic activity and deepen the understanding of the catalytic mechanism,but still remains a challenge.Here,we develop a strategy to dilute catalytically active metal interatomic spacing(d_(M-M))with light atoms and discover the unusual adsorption patterns.For example,by elevating the content of boron as interstitial atoms,the atomic spacing of osmium(d_(Os-Os))gradually increases from 2.73 to 2.96?.More importantly,we find that,with the increase in dOs-Os,the hydrogen adsorption-distance relationship is reversed via downshifting d-band states,which breaks the traditional cognition,thereby optimizing the H adsorption and H_2O dissociation on the electrode surface during the catalytic process;this finally leads to a nearly linear increase in hydrogen evolution reaction activity.Namely,the maximum dOs-Os of 2.96?presents the optimal HER activity(8 mV@10 mA cm^(-2))in alkaline media as well as suppressed O adsorption and thus promoted stability.It is believed that this novel atomic-level distance modulation strategy of catalytic sites and the reversed hydrogen adsorption-distance relationship can shew new insights for optimal design of highly efficient catalysts.
基金supported by the National Key Research and Development Program of China(2019YFD1001300,2019YFD1001301)the Earmarked Fund for CARS-10-Sweetpotato(CARS-10)+1 种基金the Beijing Food Crops Innovation Consortium Program(BAIC02-2022)Hebei Key R&D Program(20326320D,22322911D)。
文摘Sweetpotato(Ipomoea batatas(L.)Lam.)is a widely grown food crop especially in developing countries.Increasing storage-root yield and dry-matter content has been the main breeding objective of the crop,and DNA marker-assisted breeding is needed for this purpose.In this study,using a mapping population of 500 F1 individuals from a cross between Xushu 18(female)and Xu 781(male),we constructed a highdensity genetic linkage map of sweetpotato using 601 simple-sequence repeat(SSR)primer pairs.The Xushu 18 map contained 90 linkage groups with 5547 SSR markers and spanned 18,263.5 cM,and the Xu 781 map contained 90 linkage groups with 4599 SSR markers and spanned 18,043.7 cM,representing the highest genome coverage yet reported for sweetpotato.We identified 33 QTL for storage-root yield and 16 QTL for dry-matter content,explaining respectively 6.5%–47.5%and 3.2%–18.9%of variation.These results provide a foundation for fine-mapping and cloning of QTL and for marker-assisted breeding in sweetpotato.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82071287,81870916)the National Natural Science Foundation of China(Grant No.:81971097)+3 种基金the Basic Public Interests Research Plan of Zhejiang Province,China(Grant No.:GF18H090006)the National Natural Science Foundation of China(Grant No.:81701214)the National Natural Science Foundation of China(Grant No.:82001299)the Natural Science Foundation of Zhejiang Province,China(Grant No.:TGD23C040017).
文摘The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.
基金funded by the National Natural Science Foundation of China (NSFC) under Nos. 12003016, 12204353and 62105244。
文摘The transition region is the key region between the lower solar atmosphere and the corona, which has been limitedly understood by human beings. Therefore, the Solar Upper Transition Region Imager(SUTRI) was proposed by Chinese scientists and launched in 2022 July. Right now, the first imaging observation of the upper transition region around 46.5 nm has been carried out by SUTRI. To ensure the spectral and temporal resolution of the SUTRI telescope, we have developed a narrowband Sc/Si multilayer. Based on the extreme ultraviolet(EUV)reflectivity measurements, the multilayer structure has been modified for ensuring the peak position of reflectivity was at 46.5 nm. Finally, the narrowband Sc/Si multilayer was successfully deposited on the hyperboloid primary mirror and secondary mirrors. The deviation of multilayer thickness uniformity was below than 1%, and the average EUV reflectivity at 46.1 nm was 27.8% with a near-normal incident angle of 5°. The calculated bandwidth of the reflectivity curve after primary and secondary mirrors was 2.82 nm, which could ensure the requirements of spectral resolution and reflectivity of SUTRI telescope to achieve its scientific goals.
基金funded by the National Key R&D Program of China (2022YFF0709101)the National Natural Science Foundation of China (NSFC) under Nos. 62105244 and 61621001。
文摘This paper describes a fabrication process for the hyperboloidal concave mirror of a 46.5 nm telescope. The180 mm aperture hyperboloidal concave mirror and 70 mm aperture compensator are machined directly from chemical mechanical polishing of a spherical surface to a high-accuracy aspherical surface by ion beam figuring.The aspherical measurement method is the Dall null test. To minimize system errors in the measurement process,the rotational measurement method with six rotations is used in the null test. The results of the analysis for the ME(first solve the machined surface profile, then solve the system errors) and EM(first solve the system errors, then solve the machined surface profile) methods of calculation in the measurement are given. The ME method is a more accurate rotational test method, and the six rotations are appropriate for rotational measurements. After the figuring process, the hyperboloidal concave mirror surface profile reached 8.27 nm rms and the compensator surface profile is approximately 4 nm rms. The roughness of the hyperboloidal concave mirror is smooth to0.160 nm rms.
基金supported by the National Key Research and Development Program of China(No.2021YFC2701502)the Health Commission of Scientific Research Project of Hubei Province(No.WJ2021M129).
文摘Objective:Gestational diabetes mellitus(GDM)is the most common metabolic disorder during pregnancy.LncRNA HLA complex group 27(HCG27)plays a crucial role in various metabolic diseases.However,the relationship between lncRNA HCG27 and GDM is not clear.This study aimed to verify a competing endogenous RNA(ceRNA)interaction regulation axis of miR-378a-3p/mitogen-activated protein kinase 1(MAPK1)regulated by HCG27 in GDM.Methods:LncRNA HCG27 and miR-378a-3p were detected by RT-qPCR.The expression of MAPK1 in umbilical vein endothelial cells(HUVECs)was detected by RT-qPCR and that in the placenta by Western blotting.To explore the relationship among lncRNA HCG27,miR-378a-3p,MAPK1 and the glucose uptake ability of HUVECs,vector HCG27,si-HCG27,miR-378a-3p mimic and inhibitor were transfected to achieve overexpression and inhibition of HCG27 or miR-378a-3p.The interaction between miR-378a-3p and lncRNA HCG27 or MAPK1 was confirmed by the dual-luciferase reporter assay.Besides,glucose consumption by HUVECs was detected by the glucose assay kit.Results:HCG27 expression was significantly decreased in both the placenta and primary umbilical vein endothelial cells,while the expression of miR-378a-3p was significantly increased in GDM tissues,and the expression of MAPK1 was decreased in GDM tissues.This ceRNA interaction regulation axiswas proved to affect the glucose uptake function of HUVECs.The transfection of si-HCG27 could significantly reduce the expression of the MAPK1 protein.If the MAPK1 overexpression plasmid was transfected simultaneously with si-HCG27 transfection,the reduced glucose uptake in HUVECs resulting from the decrease in lncRNA HCG27 was reversed.MiR-378a-3p mimic can significantly reduce the mRNA expression of MAPK1 in HUVECs,whereas miR-378a-3p inhibitor can significantly increase the mRNA expression of MAPK1.The inhibition of miR-378a-3p could restore the decreased glucose uptake of HUVECs treated with si-HCG27.Besides,overexpression of lncRNA HCG27 could restore the glucose uptake ability of the palmitic acid-induced insulin resistance model of HUVECs to normal.Conclusion:LncRNA HCG27 promotes glucose uptake of HUVECs by miR-378a-3p/MAPK1 pathway,which may provide potential therapeutic targets for GDM.Besides,the fetal umbilical cord blood and umbilical vein endothelial cells collected from pregnant women with GDM after delivery could be used to detect the presence of adverse molecular markers of metabolic memory,so as to provide guidance for predicting the risk of cardiovascular diseases and health screening of offspring.
基金supported by the National Natural Science Foundation of China (NSFC) under Grants 62071284, 61871262, 61901251 and 61904101the National Key Research and Development Program of China under Grants 2019YFE0196600+2 种基金the Innovation Program of Shanghai Municipal Science and Technology Commission under Grant 20JC1416400Pudong New Area Science & Technology Development Fundresearch funds from Shanghai Institute for Advanced Communication and Data Science (SICS)
文摘Multi-stream carrier aggregation is a key technology to expand bandwidth and improve the throughput of the fifth-generation wireless communication systems.However,due to the diversified propagation properties of different frequency bands,the traffic migration task is much more challenging,especially in hybrid sub-6 GHz and millimeter wave bands scenario.Existing schemes either neglected to consider the transmission rate difference between multistream carrier,or only consider simple low mobility scenario.In this paper,we propose a low-complexity traffic splitting algorithm based on fuzzy proportional integral derivative control mechanism.The proposed algorithm only relies on the local radio link control buffer information of sub-6 GHz and mmWave bands,while frequent feedback from user equipment(UE)side is minimized.As shown in the numerical examples,the proposed traffic splitting mechanism can achieve more than 90%link resource utilization ratio for different UE transmission requirements with different mobilities,which corresponds to 10%improvement if compared with conventional baselines.
基金supported by the National Natural Science Foundation of China(Grant Nos.82202837,81730016,and 81972761)the National Key R&D Program of China(Grant Nos.2016YFC1303200,2022YFC2505100,and 2017YFC0908300)。
文摘Cancer is one of the leading causes of death worldwide.The early diagnosis of cancer remains one of the greatest cancer research challenges.Epigenetic alterations,such as altered DNA methylation,that occur during the early stages of carcinogenesis have been proposed as candidate cancer biomarkers.In recent years detection of small amounts of methylated DNA in samples,including blood and stool,has demonstrated the feasibility of DNA methylation as a molecular cancer biomarker.The translational promise of aberrant DNA methylation includes screening and detecting cancer,evaluating prognosis,assessing treatment efficacy,and detecting minimal residual disease(Figure 1).
基金the National Key R&D Program of China(2022YFF0709101)the National Natural Science Foundation of China(NSFC)under grant Nos.61621001,62105244,12003016 and 12204353.
文摘The Solar Upper Transition Region Imager(SUTRI)focuses on the solar transition region to achieve dynamic imaging observation of the upper transition region.In this paper,we report the optical system design,mechanical design,ultrasmooth mirror manufacture and measurement,EUV multilayer film coating,prelaunch installation and calibration for the SUTRI payload at IPOE,Tongji University.Finally,the SUTRI carried by the SATech-01 satellite was successfully set to launch.All functions of this telescope were normal,and the observation results obtained in orbit were consistent with the design.
基金the Natural Science Foundation of Zhejiang Province(LQ21H160025).
文摘To the Editor:Choledochocele,also known as type III choledochal cysts in the classification by Todani et al.[1],is a congenital abnormality of the biliary system.It is characterized by a cystic dilation of intramural segment of the distal common bile duct(CBD)protruding into the descending duodenum.Choledochocele makes up about 0.5%−4%of choledochal cysts[1,2].Compared with other subtypes,the incidence of choledochocele is extremely low and it frequently presents in adults at a relatively older age,with an average age of 51 years[3].The diagnosis and treatment are challenging.Here,we present a case of a young female patient with this rare disease entity,who recovered after effective endoscopic retrograde cholangiopancreatography(ERCP)management.
文摘Kashin-Beck disease(KBD)is an endemic osteoarthropathy.Its distribution region covers a long and narrow belt on the Pacific side and belongs to continental climate with short summer,long frost period,and large temperature differences between day and night.In particular,KBD patients are typically scattered in the rural areas with seasonal features such as cold winters and rainy autumns.Etiological studies have demonstrated that the carrier of pathogenic factors is the grains produced in endemic areas.Risk factors for KBD include fungal contamination of grains due to poor storage conditions associated with cold weather.The epidemiological characteristics of KBD include agricultural area,early age of onset,gender equality,family aggregation,regional differences,and annual fluctuations.A series of preventive measures have been successfully taken in the past decades.National surveillance data indicate that the annual incidence of KBD is gradually declining.
基金The authors are grateful for the financial supports from the project of Ministry of Industry and Information Technology of China(No.2019-00899-1-1)the Natural Science Foundation of Shaanxi Province,China(No.2021JM-060)Fundamental Research Funds for the Central Universities,China(No.3102019QD0409).
文摘Studying the relationship between rhizosphere microorganisms and root exudates is of great significance for the interaction between rhizosphere microorganisms and plants, and the prevention and control of soil-borne diseases. This article analyzed the effects of different microorganisms on tobacco root exudates and rhizosphere microorganisms. It was found that the bacterial wilt pathogen can greatly increase acids and amines, while the probiotic <i>B. amyloliquefaciens</i> ZM9 can eliminate some acids and amines. The results of the study show that the root exudates of pathogenic bacteria may contain a variety of allelochemicals that cause soil-borne diseases.
