BACKGROUND With the continuous progress of colorectal cancer treatment technology,the survival rate of patients has improved significantly,but the problem of postoperative neurocognitive dysfunction has gradually attr...BACKGROUND With the continuous progress of colorectal cancer treatment technology,the survival rate of patients has improved significantly,but the problem of postoperative neurocognitive dysfunction has gradually attracted attention.AIM To analyze the risk factors for delayed postoperative neurocognitive recovery(DNR)after laparoscopic colorectal cancer surgery and constructed a risk prediction model to provide an evidence-based reference for the prevention and treatment of DNR after laparoscopic colorectal cancer surgery.METHODS The clinical data of 227 patients with colorectal cancer who underwent laparoscopic surgery and regional cerebral saturation oxygenation(rScO2)monitoring at our hospital from March 2020 to July 2022 were retrospectively analyzed.Common factors and potential factors affecting postoperative DNR were used as analysis variables,and univariate analysis and multifactor analysis were carried out step by step to determine the predictors of the model and construct a risk prediction model.The predictive performance of the model was assessed by the receiver operating characteristic(ROC)curve,the calibration curve was used to assess the fit of the model to the data,and a nomogram was drawn.In addition,30 patients who met the inclusion and exclusion criteria from January 2023 to July 2023 were selected for external verification of the prediction model.RESULTS The incidence of postoperative DNR in the modeling group was 15.4%(35/227).Multivariate analysis revealed that age,years of education,diabetes status,and the lowest rScO2 value were the independent influencing factors of postoperative DNR(all P<0.05).Accordingly,a DNR risk prediction model was constructed after laparoscopic colorectal cancer surgery.The area under the ROC curve of the model was 0.757(95%CI:0.676-0.839,P<0.001),and the Hosmer-Lemeshow test of the calibration curve suggested that the model was well fitted(P=0.516).The C-index for external validation of the row was 0.617.CONCLUSION The DNR risk prediction model associated with rScO2 monitoring can be used for individualized assessment of patients undergoing laparoscopic colorectal cancer surgery and provides a clinical basis for the prevention of DNR after surgery.展开更多
A new X-ray imaging and biomedical application beamline(BL13HB)has been implemented at the Shanghai Radiation Synchrotron Facility(SSRF)as an upgrade to the old X-ray imaging and biomedical application beamline(BL13W1...A new X-ray imaging and biomedical application beamline(BL13HB)has been implemented at the Shanghai Radiation Synchrotron Facility(SSRF)as an upgrade to the old X-ray imaging and biomedical application beamline(BL13W1).This is part of the Phase II construction project of the SSRF.The BL13HB is dedicated to 2D and 3D static and dynamic X-ray imaging,with a field of view of up to 48.5 mm×5.2 mm and spatial resolution as high as 0.8μm.A super-bending magnet is used as the X-ray source in BL13HB,which has a maximum magnetic field of 2.293 T.The energy range of monochromatic X-ray photons from a double-multiplayer monochromator was 8–40 keV,and the white beam mode was provided on the beamline for dynamic X-ray imaging and dynamic X-ray micro-CT.While maintaining the previous experimental setup of BL13W1,new equipment was added to the beamline experimental station.The beamline is equipped with different sets of X-ray imaging detectors for several experimental methods such as micro-CT,dynamic micro-CT,and pair distribution function.The experimental station of BL13HB is designed specifically for various in situ dynamic experiments,and BL13HB has been open to users since June 2021.展开更多
The MYB transcription factor is one of the largest gene families in plants,playing an important role in regulating plant growth,development,response to stress,senescence,and especially the anthocyanin biosynthesis.In ...The MYB transcription factor is one of the largest gene families in plants,playing an important role in regulating plant growth,development,response to stress,senescence,and especially the anthocyanin biosynthesis.In this study,A total of 217 MYB genes,including 901R-MYBs,124 R2R3-MYBs,and 3 R1R2R3-MYBs have been identified from the potato genome.The 1R-MYB and R2R3-MYB family members could be divided into 20 and 35 subgroups respectively.Analysis of gene structure and protein motifs revealed that members within the same subgroup presented similar exon/intron and motif organization,further supporting the results of phylogenetic analysis.Potato is an ideal plant to reveal the tissue-specific anthocyanins biosynthesis regulated by MYB,as the anthocyanins could be accumulated in different tissues,showing colorful phenotypes.Five pairs of colored and colorless tissues,stigma,petal,stem,leaf,and tuber flesh,were applied to the transcriptomic analysis.A total of 70 MYB genes were found to be differentially expressed between colored and colorless tissues,and these differentially expressed genes were suspected to regulate the biosynthesis of anthocyanin of different tissues.Co-expression analysis identified numerous potential interactive regulators of anthocyanins biosynthesis,involving 39 MYBs,24 bHLHs,2 WD-repeats,and 29 biosynthesis genes.Genome-wide association study(GWAS)of tuber flesh color revealed amajor signal at the end of Chromosome 10,which was co-localized with reported I gene(StMYB88),controlling tuber peel color.Analyses of DEGs(Differentially Expression Genes)revealed that both StMYB88 and StMYB89 were closely related to regulating anthocyanin biosynthesis of tuber flesh.This work offers a comprehensive overview of the MYB family in potato and will lay a foundation for the functional validation of these genes in the tissue-specific regulation of anthocyanin biosynthesis.展开更多
This paper introduces some latest developments regarding the X-ray imaging methodology and applications of the X-ray imaging and biomedical application beamline(BL13W1)at Shanghai Synchrotron Radiation Facility in the...This paper introduces some latest developments regarding the X-ray imaging methodology and applications of the X-ray imaging and biomedical application beamline(BL13W1)at Shanghai Synchrotron Radiation Facility in the past 5 years.The photon energy range of the beamline is 8–72.5 keV.Several sets of X-ray imaging detectors with different pixel sizes(0.19–24 lm)are used to realize X-ray microcomputed tomography(X-ray micro-CT)and X-ray in-line phase-contrast imaging.To satisfy the requirements of user experiments,new X-ray imaging methods and image processing techniques are developed.In vivo dynamic micro-CT experiments with living insects are performed in 0.5 s(sampling rate of 2 Hz,2 tomograms/s)with a monochromatic beam from a wiggler source and in 40 ms(sampling rate of 25 Hz,25 tomograms/s)with a white beam from a bending magnet source.A new X-ray imaging method known as move contrast X-ray imaging is proposed,with which blood flow and moving tissues in raw images can be distinguished according to their moving frequencies in the time domain.Furthermore,X-ray speckle-tracking imaging with twice exposures to eliminate the edge enhancement effect is developed.A high-precision quantification method is realized to measure complex three-dimensional blood vessels obtained via X-ray micro-CT.X-ray imaging methods such as three-dimensional X-ray diffraction microscopy,small-angle X-ray scattering CT,and X-ray fluorescence CT are developed,in which the X-ray micro-CT imaging method is combined with other contrast mechanisms such as diffraction,scattering,and fluorescence contrasts respectively.Moreover,an X-ray nano-CT experiment is performed with a 100 nm spatial resolution.Typical user experimental results from the fields of material science,biomedicine,paleontology,physics,chemistry,and environmental science obtained on the beamline are provided.展开更多
Background: There is no data regarding prognostic impact of interleukin(IL)-26 on outcomes of patients with hepatocellular carcinoma(HCC). The present study aimed to evaluate the prognostic impact of IL-26 on HCC pati...Background: There is no data regarding prognostic impact of interleukin(IL)-26 on outcomes of patients with hepatocellular carcinoma(HCC). The present study aimed to evaluate the prognostic impact of IL-26 on HCC patients undergoing liver resection. Methods: From 2003 to 2008, 122 patients with HCC who received surgical curative resection were enrolled. Patients were stratified into IL-26-upper and-lower groups according to the median expression level from immunohistochemical staining of resected specimens. Prognostic impact of IL-26 was estimated using Kaplan–Meier curves. Univariate and multivariate analyses were performed to evaluate timedependent prognostic impact and independency of IL-26. Demographic and clinical factors that were associated with IL-26 were comprehensively identified. Results: Prognosis of the patients with high level of IL-26 revealed to be significantly unfavorable in both cumulative recurrence-free survival( P < 0.001) and overall survival( P = 0.002). Upper expression of IL-26(HR: 1.643;95% CI: 1.021 to 2.644;P = 0.041) and microvascular invasion(HR: 3.303;95% CI: 1.255 to 8.696;P = 0.016) were identified as significant independent prognostic factors for overall survival in the multivariable analysis. Conclusions: IL-26 is a novel prognostic factor for HCC after resection. Evaluation of IL-26 expression may be potentially valuable in clinical therapy when planning individualized follow-up schedule and evaluating candidates for prophylactic adjuvant treatment to prevent recurrence.展开更多
Cyano substitution is vital to the molecular design of polymer semiconductors toward highly efficient organic solar cells.However,how regioselectivity impacts relevant optoelectronic properties in cyano-substituted bi...Cyano substitution is vital to the molecular design of polymer semiconductors toward highly efficient organic solar cells.However,how regioselectivity impacts relevant optoelectronic properties in cyano-substituted bithiophene systems remain poorly understood.Three regioisomeric cyano-functionalized dialkoxybithiophenes BT_(HH),BT_(HT),and BT_(TT) with headto-head,head-to-tail,and tail-to-tail linkage,respectively,were synthesized and characterized in this work.The resulting polymer semiconductors(PBDTBTs)based on these building blocks were prepared accordingly.The regiochemistry and property relationships of PBDTBTs were investigated in detail.The BTHH moiety has a higher torsional barrier than the analogs BT_(HT) and BT_(TT),and the regiochemistry of dialkoxybithiophenes leads to fine modulation in the optoelectronic properties of these polymers,such as optical absorption,band gap,and energy levels of frontier molecular orbitals.Organic field-effect transistors based on PBDTBT_(HH) had higher hole mobility(4.4×10^(-3) cm^(2)/(V·s))than those(ca.10^(-4) cm^(2)/(V·s))of the other two polymer analogs.Significantly different short-circuit current densities and fill factors were obtained in polymer solar cells using PBDTBTs as the electron donors.Such difference was probed in greater detail by performing space-charge-limited current mobility,thin-film morphology,and transient photocurrent/photovoltage characterizations.The findings highlight that the BTHH unit is a promising building block for the construction of polymer donors for highperformance organic photovoltaic cells.展开更多
The phospholipid membrane plays a key role in myriad biological processes and phenomena, and the arrangement structure of membrane determines its function. However, the molecular arrangement structure of phospholipids...The phospholipid membrane plays a key role in myriad biological processes and phenomena, and the arrangement structure of membrane determines its function. However, the molecular arrangement structure of phospholipids in cell membranes is difficult to detect experimentally. On the basis of molecular dynamic simulations both in a non-destructive way and at native environment, we observed and confirmed that the phospholipids self-assemble to a hexagonal arrangement structure under physiological conditions. The underlying mechanism was revealed to be that there are hexagonal arrangement regions with a lower free energy around each lipid molecule. The findings potentially advance the understanding of biological functions of phospholipid bilayers.展开更多
Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabo...Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species(ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes,convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with c AMP and c GMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes(i.e., HPRT1), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase(XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase(XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.展开更多
Preservation of growth factor sensitivity and bioactivity(e.g.,bone morphogenetic protein-2(BMP-2))post-immobilization to tissue engineering scaffolds remains a great challenge.Here,we develop a stable and soft surfac...Preservation of growth factor sensitivity and bioactivity(e.g.,bone morphogenetic protein-2(BMP-2))post-immobilization to tissue engineering scaffolds remains a great challenge.Here,we develop a stable and soft surface modification strategy to address this issue.BMP-2(a model growth factor)is covalently immobilized onto homogeneous poly(glycidyl methacrylate)(PGMA)polymer brushes which are grafted onto substrate surfaces(Au,quartz glass,silica wafer,or common biomaterials)via surface-initiated atom transfer radical polymerization.This surface modification method multiplies the functionalized interfacial area;it is simple,fast,gentle,and has little effect on the loaded protein owing to the cilia motility.The immobilized BMP-2(i-BMP-2)on the surface of homogeneous PGMA polymer brushes exhibits excellent bioactivity(-87%bioactivity of free BMP-2 in vitro and 20%-50%higher than scaffolds with free BMP-2 in vivo),with conformation and secondary structure well-preserved after covalent immobilization and ethanol sterilization.Moreover,the osteogenic activity of i-BMP-2 on the nanoline pattern(PGMA-poly(N-isopropylacrylamide))shows-110%bioactivity of free BMP-2.This is superior compared to conventional protein covalent immobilization strategies in terms of both bioactivity preservation and therapeutic efficacy.PGMA polymer brushes can be used to modify surfaces of different tissue-engineered scaffolds,which facilitates in situ immobilization of growth factors,and accelerates repair of a wide range of tissue types.展开更多
Neutrophil extracellular traps (NETs) participate in the rapid inhibition and clearance of pathogens during infection;however, the molecular regulation of NET formation remains poorly understood. In the current study,...Neutrophil extracellular traps (NETs) participate in the rapid inhibition and clearance of pathogens during infection;however, the molecular regulation of NET formation remains poorly understood. In the current study, we found that inhibition of the wild-type p53-induced phosphatase 1 (Wip1) significantly suppressed the activity of Staphylococcus aureus (S. aureus) and accelerated abscess healing in S. aureus-induced abscess model mice by enhancing NET formation. A Wip1 inhibitor significantly enhanced NET formation in mouse and human neutrophils in vitro. High-resolution mass spectrometry and biochemical assays demonstrated that Coro1a is a substrate of Wip1. Further experiments also revealed that Wip1 preferentially and directly interacts with phosphorylated Coro1a than compared to unphosphorylated inactivated Coro1a. The phosphorylated Ser426 site of Coro1a and the 28–90 aa domain of Wip1 are essential for the direct interaction of Coro1a and Wip1 and for Wip1 dephosphorylation of p-Coro1a Ser426. Wip1 deletion or inhibition in neutrophils significantly upregulated the phosphorylation of Coro1a-Ser426, which activated phospholipase C and subsequently the calcium pathway, the latter of which promoted NET formation after infection or lipopolysaccharide stimulation. This study revealed Coro1a to be a novel substrate of Wip1 and showed that Wip1 is a negative regulator of NET formation during infection. These results support the potential application of Wip1 inhibitors to treat bacterial infections.展开更多
Despite the diverse etiologies of drug-induced liver injury(DILI),innate immunity activation is a common feature involved in DILI progression.However,the involvement of innate immunity regulation in inflammation resol...Despite the diverse etiologies of drug-induced liver injury(DILI),innate immunity activation is a common feature involved in DILI progression.However,the involvement of innate immunity regulation in inflammation resolution and liver regeneration in DILI remains obscure.Herein,we identified the chemokine CCL5 as a central mediator of innate immunity regulation in the pathogenesis of DILI.First,we showed that serum and hepatic CCL5 levels are elevated in both DILI patients and an APAP-induced liver injury(AILI)mouse model.Interestingly,both nonparenchymal cells and stressed hepatocytes are cell sources of CCL5 induction in response to liver injury.Functional experiments showed that CCL5 deficiency has no effect on the early phase of AILI but promotes liver repair in the late phase mainly by promoting inflammation resolution and liver regeneration,which are associated with an increased number of hepatic M2 macrophages.Mechanistically,CCL5 can directly activate M1 polarization and impede M2 polarization through the CCR1-and CCR5-mediated activation of the MAPK and NF-κB pathways.We then showed that CCL5 inhibition mediated by either a CCL5-neutralizing antibody or the antagonist Met-CCL5 can greatly alleviate liver injury and improve survival in an AILI mouse model.Our data demonstrate CCL5 induction during DILI,identify CCL5 as a novel innate immunity regulator in macrophage polarization,and suggest that CCL5 blockage is a promising therapeutic strategy for the treatment of DILI.展开更多
文摘BACKGROUND With the continuous progress of colorectal cancer treatment technology,the survival rate of patients has improved significantly,but the problem of postoperative neurocognitive dysfunction has gradually attracted attention.AIM To analyze the risk factors for delayed postoperative neurocognitive recovery(DNR)after laparoscopic colorectal cancer surgery and constructed a risk prediction model to provide an evidence-based reference for the prevention and treatment of DNR after laparoscopic colorectal cancer surgery.METHODS The clinical data of 227 patients with colorectal cancer who underwent laparoscopic surgery and regional cerebral saturation oxygenation(rScO2)monitoring at our hospital from March 2020 to July 2022 were retrospectively analyzed.Common factors and potential factors affecting postoperative DNR were used as analysis variables,and univariate analysis and multifactor analysis were carried out step by step to determine the predictors of the model and construct a risk prediction model.The predictive performance of the model was assessed by the receiver operating characteristic(ROC)curve,the calibration curve was used to assess the fit of the model to the data,and a nomogram was drawn.In addition,30 patients who met the inclusion and exclusion criteria from January 2023 to July 2023 were selected for external verification of the prediction model.RESULTS The incidence of postoperative DNR in the modeling group was 15.4%(35/227).Multivariate analysis revealed that age,years of education,diabetes status,and the lowest rScO2 value were the independent influencing factors of postoperative DNR(all P<0.05).Accordingly,a DNR risk prediction model was constructed after laparoscopic colorectal cancer surgery.The area under the ROC curve of the model was 0.757(95%CI:0.676-0.839,P<0.001),and the Hosmer-Lemeshow test of the calibration curve suggested that the model was well fitted(P=0.516).The C-index for external validation of the row was 0.617.CONCLUSION The DNR risk prediction model associated with rScO2 monitoring can be used for individualized assessment of patients undergoing laparoscopic colorectal cancer surgery and provides a clinical basis for the prevention of DNR after surgery.
基金supported by the National Major Scientific Instruments and Equipment Development Project of China(No.11627901)the National Key Research and Development Program of China(Nos.2021YFF0701202 and 2021YFA1600703)the National Natural Science Foundation of China(Nos.U1932205,12275343)。
文摘A new X-ray imaging and biomedical application beamline(BL13HB)has been implemented at the Shanghai Radiation Synchrotron Facility(SSRF)as an upgrade to the old X-ray imaging and biomedical application beamline(BL13W1).This is part of the Phase II construction project of the SSRF.The BL13HB is dedicated to 2D and 3D static and dynamic X-ray imaging,with a field of view of up to 48.5 mm×5.2 mm and spatial resolution as high as 0.8μm.A super-bending magnet is used as the X-ray source in BL13HB,which has a maximum magnetic field of 2.293 T.The energy range of monochromatic X-ray photons from a double-multiplayer monochromator was 8–40 keV,and the white beam mode was provided on the beamline for dynamic X-ray imaging and dynamic X-ray micro-CT.While maintaining the previous experimental setup of BL13W1,new equipment was added to the beamline experimental station.The beamline is equipped with different sets of X-ray imaging detectors for several experimental methods such as micro-CT,dynamic micro-CT,and pair distribution function.The experimental station of BL13HB is designed specifically for various in situ dynamic experiments,and BL13HB has been open to users since June 2021.
基金the National Natural Science Foundation of China(Grant No.31601756)the National Science Fund of Yunnan for Distinguished Young Scholars(Grant No.202001AV070003)。
文摘The MYB transcription factor is one of the largest gene families in plants,playing an important role in regulating plant growth,development,response to stress,senescence,and especially the anthocyanin biosynthesis.In this study,A total of 217 MYB genes,including 901R-MYBs,124 R2R3-MYBs,and 3 R1R2R3-MYBs have been identified from the potato genome.The 1R-MYB and R2R3-MYB family members could be divided into 20 and 35 subgroups respectively.Analysis of gene structure and protein motifs revealed that members within the same subgroup presented similar exon/intron and motif organization,further supporting the results of phylogenetic analysis.Potato is an ideal plant to reveal the tissue-specific anthocyanins biosynthesis regulated by MYB,as the anthocyanins could be accumulated in different tissues,showing colorful phenotypes.Five pairs of colored and colorless tissues,stigma,petal,stem,leaf,and tuber flesh,were applied to the transcriptomic analysis.A total of 70 MYB genes were found to be differentially expressed between colored and colorless tissues,and these differentially expressed genes were suspected to regulate the biosynthesis of anthocyanin of different tissues.Co-expression analysis identified numerous potential interactive regulators of anthocyanins biosynthesis,involving 39 MYBs,24 bHLHs,2 WD-repeats,and 29 biosynthesis genes.Genome-wide association study(GWAS)of tuber flesh color revealed amajor signal at the end of Chromosome 10,which was co-localized with reported I gene(StMYB88),controlling tuber peel color.Analyses of DEGs(Differentially Expression Genes)revealed that both StMYB88 and StMYB89 were closely related to regulating anthocyanin biosynthesis of tuber flesh.This work offers a comprehensive overview of the MYB family in potato and will lay a foundation for the functional validation of these genes in the tissue-specific regulation of anthocyanin biosynthesis.
基金This work was supported by the National Key Research and Development Program of China(Nos.2017YFA0403801,2016YFA0401302,2017YFA0206004,2018YFC1200204)the National Major Scientific Instruments and Equipment Development Project of China(No.11627901).
文摘This paper introduces some latest developments regarding the X-ray imaging methodology and applications of the X-ray imaging and biomedical application beamline(BL13W1)at Shanghai Synchrotron Radiation Facility in the past 5 years.The photon energy range of the beamline is 8–72.5 keV.Several sets of X-ray imaging detectors with different pixel sizes(0.19–24 lm)are used to realize X-ray microcomputed tomography(X-ray micro-CT)and X-ray in-line phase-contrast imaging.To satisfy the requirements of user experiments,new X-ray imaging methods and image processing techniques are developed.In vivo dynamic micro-CT experiments with living insects are performed in 0.5 s(sampling rate of 2 Hz,2 tomograms/s)with a monochromatic beam from a wiggler source and in 40 ms(sampling rate of 25 Hz,25 tomograms/s)with a white beam from a bending magnet source.A new X-ray imaging method known as move contrast X-ray imaging is proposed,with which blood flow and moving tissues in raw images can be distinguished according to their moving frequencies in the time domain.Furthermore,X-ray speckle-tracking imaging with twice exposures to eliminate the edge enhancement effect is developed.A high-precision quantification method is realized to measure complex three-dimensional blood vessels obtained via X-ray micro-CT.X-ray imaging methods such as three-dimensional X-ray diffraction microscopy,small-angle X-ray scattering CT,and X-ray fluorescence CT are developed,in which the X-ray micro-CT imaging method is combined with other contrast mechanisms such as diffraction,scattering,and fluorescence contrasts respectively.Moreover,an X-ray nano-CT experiment is performed with a 100 nm spatial resolution.Typical user experimental results from the fields of material science,biomedicine,paleontology,physics,chemistry,and environmental science obtained on the beamline are provided.
基金supported by grants from the National Natural Science Foundation of China(81670562,81670598 and 81472243)the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171911)the National Key R&D Pro-gram for Precision Medicine(2017YFC908101)
文摘Background: There is no data regarding prognostic impact of interleukin(IL)-26 on outcomes of patients with hepatocellular carcinoma(HCC). The present study aimed to evaluate the prognostic impact of IL-26 on HCC patients undergoing liver resection. Methods: From 2003 to 2008, 122 patients with HCC who received surgical curative resection were enrolled. Patients were stratified into IL-26-upper and-lower groups according to the median expression level from immunohistochemical staining of resected specimens. Prognostic impact of IL-26 was estimated using Kaplan–Meier curves. Univariate and multivariate analyses were performed to evaluate timedependent prognostic impact and independency of IL-26. Demographic and clinical factors that were associated with IL-26 were comprehensively identified. Results: Prognosis of the patients with high level of IL-26 revealed to be significantly unfavorable in both cumulative recurrence-free survival( P < 0.001) and overall survival( P = 0.002). Upper expression of IL-26(HR: 1.643;95% CI: 1.021 to 2.644;P = 0.041) and microvascular invasion(HR: 3.303;95% CI: 1.255 to 8.696;P = 0.016) were identified as significant independent prognostic factors for overall survival in the multivariable analysis. Conclusions: IL-26 is a novel prognostic factor for HCC after resection. Evaluation of IL-26 expression may be potentially valuable in clinical therapy when planning individualized follow-up schedule and evaluating candidates for prophylactic adjuvant treatment to prevent recurrence.
基金supported by the National Natural Science Foundation of China(Nos.52173172,52173171,and 21801124)the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province(2021B1515020027)+6 种基金Guangdong Basic and Applied Basic Research Foundation(2021A1515110892)China Postdoctoral Science Foundation(2021M700062)the Shenzhen Science and Technology Innovation Commission(JCYJ202103243104813035 and JCYJ20180504165709042)the Open Fund of the State Key Laboratory of Luminescent Materials and Devices(South China University of Technology)financial support from the Songshan Lake Materials Laboratory(2021SLABFK03)financial support from the NRF of Korea(2016M1A2A2940911,2017K2A9A2A12000315)supported by the Center for Computational Science and Engineering of Southern University of Science and Technology。
文摘Cyano substitution is vital to the molecular design of polymer semiconductors toward highly efficient organic solar cells.However,how regioselectivity impacts relevant optoelectronic properties in cyano-substituted bithiophene systems remain poorly understood.Three regioisomeric cyano-functionalized dialkoxybithiophenes BT_(HH),BT_(HT),and BT_(TT) with headto-head,head-to-tail,and tail-to-tail linkage,respectively,were synthesized and characterized in this work.The resulting polymer semiconductors(PBDTBTs)based on these building blocks were prepared accordingly.The regiochemistry and property relationships of PBDTBTs were investigated in detail.The BTHH moiety has a higher torsional barrier than the analogs BT_(HT) and BT_(TT),and the regiochemistry of dialkoxybithiophenes leads to fine modulation in the optoelectronic properties of these polymers,such as optical absorption,band gap,and energy levels of frontier molecular orbitals.Organic field-effect transistors based on PBDTBT_(HH) had higher hole mobility(4.4×10^(-3) cm^(2)/(V·s))than those(ca.10^(-4) cm^(2)/(V·s))of the other two polymer analogs.Significantly different short-circuit current densities and fill factors were obtained in polymer solar cells using PBDTBTs as the electron donors.Such difference was probed in greater detail by performing space-charge-limited current mobility,thin-film morphology,and transient photocurrent/photovoltage characterizations.The findings highlight that the BTHH unit is a promising building block for the construction of polymer donors for highperformance organic photovoltaic cells.
基金Project supported by the National Natural Science Foundation of China(Grant No.11904231)the National Key R&D Program of China(Grant Nos.2018YFE0205501 and 2018YFB1801500)Shanghai Sailing Program,China(Grant No.19YF1434100)。
文摘The phospholipid membrane plays a key role in myriad biological processes and phenomena, and the arrangement structure of membrane determines its function. However, the molecular arrangement structure of phospholipids in cell membranes is difficult to detect experimentally. On the basis of molecular dynamic simulations both in a non-destructive way and at native environment, we observed and confirmed that the phospholipids self-assemble to a hexagonal arrangement structure under physiological conditions. The underlying mechanism was revealed to be that there are hexagonal arrangement regions with a lower free energy around each lipid molecule. The findings potentially advance the understanding of biological functions of phospholipid bilayers.
基金supported by the National Natural Science Foundation of China(NSFC)(31900310 to R.T.)Key Project of the NSFC(32030011 and 31630071 to G.Y.)+2 种基金NSFC(31950410545 to I.S.)Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Jiangsu Specially-Appointed Professors Program(to I.S.)。
文摘Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species(ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes,convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with c AMP and c GMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes(i.e., HPRT1), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase(XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase(XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.
基金supported by the National Natural Science Foundation of China(22108306 and 22078362)Shandong Provincial Natural Science Foundation(ZR2021YQ15 and ZR2020QB174)+3 种基金PetroChina Innovation Foundation(2019D-5007-0401)Taishan Scholars Program of Shandong Province(tsqn201909065)the Fundamental Research Funds for the Central Universities(22CX07009A,19CX05001A)Postgraduate Innovation Fund of China University of Petroleum(East China)(YCX2020037).
基金financial support from RGC Senior Research Fellow Scheme(SRFS2122-5S04),Research Grants Council of Hong KongCollaborative Research Fund(C5044-21GF)from the Research Grants Council of Hong Kong and National Excellent Young Scientists Fund(Hong Kong and Macao,82122002),National Natural Science Foundation of China+1 种基金support from National Natural Science Foundation of China(No.32071337)Shanghai Pujiang Program(20PJ1402600).
文摘Preservation of growth factor sensitivity and bioactivity(e.g.,bone morphogenetic protein-2(BMP-2))post-immobilization to tissue engineering scaffolds remains a great challenge.Here,we develop a stable and soft surface modification strategy to address this issue.BMP-2(a model growth factor)is covalently immobilized onto homogeneous poly(glycidyl methacrylate)(PGMA)polymer brushes which are grafted onto substrate surfaces(Au,quartz glass,silica wafer,or common biomaterials)via surface-initiated atom transfer radical polymerization.This surface modification method multiplies the functionalized interfacial area;it is simple,fast,gentle,and has little effect on the loaded protein owing to the cilia motility.The immobilized BMP-2(i-BMP-2)on the surface of homogeneous PGMA polymer brushes exhibits excellent bioactivity(-87%bioactivity of free BMP-2 in vitro and 20%-50%higher than scaffolds with free BMP-2 in vivo),with conformation and secondary structure well-preserved after covalent immobilization and ethanol sterilization.Moreover,the osteogenic activity of i-BMP-2 on the nanoline pattern(PGMA-poly(N-isopropylacrylamide))shows-110%bioactivity of free BMP-2.This is superior compared to conventional protein covalent immobilization strategies in terms of both bioactivity preservation and therapeutic efficacy.PGMA polymer brushes can be used to modify surfaces of different tissue-engineered scaffolds,which facilitates in situ immobilization of growth factors,and accelerates repair of a wide range of tissue types.
基金supported by grants from the National Natural Science Foundation for General and Key Programs(31930041,YZ)the National Key Research and Development Program of China(2017YFA0105002,2017YFA0104401,2017YFA0104402,YZ)+1 种基金the Knowledge Innovation Program of the Chinese Academy of Sciences(XDA16030301,YZ)the Doctoral Research Foundation Project of Affiliated Hospital of Guizhou Medical University(gyfybsky-2022-1,WZ)。
文摘Neutrophil extracellular traps (NETs) participate in the rapid inhibition and clearance of pathogens during infection;however, the molecular regulation of NET formation remains poorly understood. In the current study, we found that inhibition of the wild-type p53-induced phosphatase 1 (Wip1) significantly suppressed the activity of Staphylococcus aureus (S. aureus) and accelerated abscess healing in S. aureus-induced abscess model mice by enhancing NET formation. A Wip1 inhibitor significantly enhanced NET formation in mouse and human neutrophils in vitro. High-resolution mass spectrometry and biochemical assays demonstrated that Coro1a is a substrate of Wip1. Further experiments also revealed that Wip1 preferentially and directly interacts with phosphorylated Coro1a than compared to unphosphorylated inactivated Coro1a. The phosphorylated Ser426 site of Coro1a and the 28–90 aa domain of Wip1 are essential for the direct interaction of Coro1a and Wip1 and for Wip1 dephosphorylation of p-Coro1a Ser426. Wip1 deletion or inhibition in neutrophils significantly upregulated the phosphorylation of Coro1a-Ser426, which activated phospholipase C and subsequently the calcium pathway, the latter of which promoted NET formation after infection or lipopolysaccharide stimulation. This study revealed Coro1a to be a novel substrate of Wip1 and showed that Wip1 is a negative regulator of NET formation during infection. These results support the potential application of Wip1 inhibitors to treat bacterial infections.
基金This work was supported by the National Key Research and Development Program of China(2017YFC0908100 to Q.X.)the National Key Sci-Tech Special Project of China(2018ZX10723204-006-004 to X.K.)+1 种基金the National Natural Science Foundation of China(81873582 and 81670562 to X.K.,81670598 to Q.X.,31870905 and 31671453 to H.W.)the Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20171911 to X.K.).
文摘Despite the diverse etiologies of drug-induced liver injury(DILI),innate immunity activation is a common feature involved in DILI progression.However,the involvement of innate immunity regulation in inflammation resolution and liver regeneration in DILI remains obscure.Herein,we identified the chemokine CCL5 as a central mediator of innate immunity regulation in the pathogenesis of DILI.First,we showed that serum and hepatic CCL5 levels are elevated in both DILI patients and an APAP-induced liver injury(AILI)mouse model.Interestingly,both nonparenchymal cells and stressed hepatocytes are cell sources of CCL5 induction in response to liver injury.Functional experiments showed that CCL5 deficiency has no effect on the early phase of AILI but promotes liver repair in the late phase mainly by promoting inflammation resolution and liver regeneration,which are associated with an increased number of hepatic M2 macrophages.Mechanistically,CCL5 can directly activate M1 polarization and impede M2 polarization through the CCR1-and CCR5-mediated activation of the MAPK and NF-κB pathways.We then showed that CCL5 inhibition mediated by either a CCL5-neutralizing antibody or the antagonist Met-CCL5 can greatly alleviate liver injury and improve survival in an AILI mouse model.Our data demonstrate CCL5 induction during DILI,identify CCL5 as a novel innate immunity regulator in macrophage polarization,and suggest that CCL5 blockage is a promising therapeutic strategy for the treatment of DILI.
