Grain filling influences grain size and quality in cereal crops. The molecular mechanisms that regulate grain endosperm development remain elusive. In this study, we characterized a filling-defective and grain width m...Grain filling influences grain size and quality in cereal crops. The molecular mechanisms that regulate grain endosperm development remain elusive. In this study, we characterized a filling-defective and grain width mutant, fgw1, whose mutation increased rice seed width mainly via cell division and expansion in grains. Sucrose contents were higher but starch contents lower in the fgw1 mutant during the grainfilling stage, resulting in inferior endosperm of opaque, white appearance with loosely packed starch granules. Map-based cloning revealed that FGW1 encoded a protein containing DUF630/DUF632domains, localized in the plasma membrane with preferential expression in the panicle. RNA interference in FGW1 resulted in increased grain width and weight, whereas overexpression of FGW1 led to slightly narrower kernels and better grain filling. In a yeast two-hybrid assay, FGW1 interacted directly with the 14–3–3 protein GF14f, bimolecular fluorescence complementation verified that the site of interaction was the membrane, and the mutated FGW1 protein failed to interact with GF14f. The expression of GF14f was down-regulated in fgw1, and the activities of AGPase, StSase, and SuSase in the endosperm of fgw1increased similarly to those of a reported GF14f-RNAi. Transcriptome analysis indicated that FGW1 also regulates cellular processes and carbohydrate metabolism. Thus, FGW1 regulated grain formation via the GF14f pathway.展开更多
Objective: To explore the related factors of surgical treatment of patients with corpus luteum rupture and establish a risk prediction model of surgical treatment of corpus luteum rupture. Methods: 222 patients with c...Objective: To explore the related factors of surgical treatment of patients with corpus luteum rupture and establish a risk prediction model of surgical treatment of corpus luteum rupture. Methods: 222 patients with corpus luteum rupture treated in Jingzhou First People’s Hospital from January 2015 to March 2022 were analyzed retrospectively, including 45 cases of surgery and 177 cases of conservative treatment. The training set and validation set were randomly assigned according to 7:3. We collected the basic information, laboratory and ultrasonic examination data of 222 patients. Logistic regression analysis was used to determine the independent risk factors and combined predictors of surgical treatment of corpus luteum rupture. The risk prediction model was established and the nomogram was drawn. The discrimination and calibration of the prediction model were verified and evaluated by receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow goodness of fit test;Decision curve analysis (DCA) was used to evaluate the clinical effectiveness of the prediction model. Results: Univariate logistic regression showed that whole abdominal pain (OR: 2.314, 95% CI: 1.090 - 4.912), abdominal muscle tension (OR: 2.379, 95% CI: 1.112 - 5.089), adnexal mass ≥ 4 cm (OR: 3.926, 95% CI: 1.771 - 8.266), hemoglobin Conclusion: The nomogram prediction model containing three predictive variables (hemoglobin, depth of pelvic effusion under ultrasound and cervical lifting pain) can be used to predict the risk of surgical treatment in patients with corpus luteum rupture.展开更多
Background: Arsenic metabolism is primarily undergoing in hepatocytes, but the underlying mechanisms are to be defined. It is essential to study the response of aquaporin AQP9, protein kinase p38, and JNK with the sti...Background: Arsenic metabolism is primarily undergoing in hepatocytes, but the underlying mechanisms are to be defined. It is essential to study the response of aquaporin AQP9, protein kinase p38, and JNK with the stimulation of arsenic in mouse models of hepatocellular carcinoma. Methods: Mouse model of hepatocellular carcinoma (HCC) was induced with H22 cells injected subcutaneously on the lateral side of each right axilla in C57BL/6 mice. Then, western blotting and co-immunoprecipitation were used to detect the protein expression and phosphorylation of molecules AQP9, p38 and JNK in mouse models of hepatocellular carcinoma, respectively. The hepatocellular distribution of AQP9 was examined by the immunofluorescent method. Results: In both wild mice and a mouse model of liver tumor, there was no significant difference in the expressions of AQP9, protein kinase p38, and JNK after arsenic treatment, but the phosphorylation expression levels of the three were significantly increased to varying degrees, and the tumor model Compared with the wild-type group, the expression increased. Laser confocal experiments showed that in HepG2 cells, phosphorylated AQP9 was mainly distributed on the cell membrane under the stimulation of arsenic. Conclusion: Arsenic stimulation can increase the phosphorylation of AQP9, p38, and JNK in both wild-type C57 mice and liver tumor mice models. Arsenic stimulation facilitates phosphorylated-AQP9 predominantly distributed on the cell membrane of hepatoma cells HepG2.展开更多
<strong>Background:</strong> Although semen analysis is a basic method to evaluate male fertility, there was a certain deviation between the semen examination and the actual situation in clinical applicati...<strong>Background:</strong> Although semen analysis is a basic method to evaluate male fertility, there was a certain deviation between the semen examination and the actual situation in clinical application. <strong>Objective:</strong> To evaluate the application value of semen examination items in the diagnosis of male infertility. <strong>Method:</strong> Males recruited from the Third Affiliated Hospital of Sun Yat-sen University from June 2017 to December 2018 were divided into three groups: normal fertility group, physical examination group (premarital physical examination), and male infertility group. Each group received the following examination such as semen analysis (including semen volume, sperm concentration, progressive motility, total motility, round cell concentration), acrosin activity, and sperm morphology. All the semen analysis items mentioned above were operated according to the <em>WHO laboratory manual for the examination and procession of human semen</em> (<em>Fifth edition</em>) and related documents. <strong>Results:</strong> The normal fertility group and physical examination group showed significantly higher levels in sperm concentration, progressive motility, total motility, and sperm morphology than those in the male infertility group (<em>P</em> < 0.05);both the normal fertility group and the physical examination group have a higher qualified rate in sperm concentration, progressive motility, total motility and sperm morphology than the male infertility group, all <em>P</em> < 0.001. The percentage of patients having all qualified items in each group was 28.13%, 6.67%, and 6.51% separately. <strong>Conclusion:</strong> The diagnosis efficiency was higher in sperm concentration, progressive motility, total motility, and sperm morphology than in other semen examination items. A more objective and efficient method of semen examination should be explored to facilitate the diagnoses of male infertility in the future.展开更多
<strong>Purpose:</strong> To identify prognostic factors in patients with coronavirus disease 2019 (COVID-19)-associated severe acute respiratory distress syndrome (ARDS). <strong>Methods:</strong...<strong>Purpose:</strong> To identify prognostic factors in patients with coronavirus disease 2019 (COVID-19)-associated severe acute respiratory distress syndrome (ARDS). <strong>Methods:</strong> In this study, we included 45 patients with COVID-19-associated ARDS hospitalized at The First Affiliated Hospital of Yangtze University in Jingzhou, Hubei, China, between January 22, 2020, and March 6, 2020. Clinical data and outcomes were reviewed and analyzed according to the Berlin definition. <strong>Findings:</strong> Men were more likely to develop severe ARDS than women (11 [91.7%] vs. 1 [8.3%]). Factors associated with severe ARDS included sex (male) (hazard ratio [HR], 13.75;95% confidence interval [CI], 1.45 - 130.24), neutrophil count (HR, 55.00;95% CI, 5.02 - 602.15), lymphocyte count (HR, 40.00;95% CI, 4.83 - 331.00), prothrombin time (HR, 12.14;95% CI, 1.19 - 123.62), D-dimer (HR, 11.00;95% CI, 1.16 - 103.94), total bilirubin levels (HR, 5.00;95% CI, 0.93 - 26.79), albumin (HR, 17.5;95% CI, 2.67 - 114.85), blood urea nitrogen levels (HR, 28.60;95% CI, 2.89 - 283.06), lactate dehydrogenase levels (HR, 6.00;95% CI, 1.17 - 30.73), and C-reactive protein levels (HR, 15.87;95% CI, 2.40 - 111.11). <strong>Conclusion:</strong> Laboratory indicators, such as neutrophil count and lymphocyte count, could play an important role in the diagnosis of severe ARDS and guide clinical decision-making for patients with ARDS.展开更多
In Haigh Westergaard stress space linear combination of twin shear stress and Tresca yield functions is called the mean yield （MY） criterion. The mathematical relationship of the criterion and its plastic work rate ...In Haigh Westergaard stress space linear combination of twin shear stress and Tresca yield functions is called the mean yield （MY） criterion. The mathematical relationship of the criterion and its plastic work rate done per unit volume were derived. A generalized worked example of slab forging was analyzed by the criterion and its corresponding plastic work rate done per unit volume. Then, the precision of the solution was compared with those by Mises and Twin shear stress yield criterions, respectively. It turned out that the calculated results by MY criterion were in good agreement with those by Mises criterion.展开更多
The instability of saline soil foundation affects the safety of artificial construction,and may cause ground collapse,building destruction and road damage.It is fundamental to reduce the potential engineering geologic...The instability of saline soil foundation affects the safety of artificial construction,and may cause ground collapse,building destruction and road damage.It is fundamental to reduce the potential engineering geological disasters by exploring the dynamic evolution of saline soil.Most of the previous researches of saline soil were conducted by simulated experiments and traditional geodetic surveying methods.Restricted to the limited sampling points,the spatiotemporal evolution characteristics of saline soil were difficult to find out in a large scale.This paper exploited SBAS-InSAR method to extract the deformation of the Qarhan Salt Lake(in Qinghai,China)section along Qinghai-Tibet railway,based on 119 image data acquired by Sentinel-1A from 2015 to 2020.The results showed that the deformation trends varied frequently in this saline mud flat.Between the adjacent areas with different deformation trends along Qinghai-Tibet railway,discontinuities caused by uplift and subsidence were very obvious.Besides,among the areas with brine exploitation or artificial construction,the maximum subsidence rate reached50 mm/yr,and the maximum cumulative subsidence exceeded 320 mm in the latest 5 years.In the saline mud flat closed to the rivers and lakes,the deformation trend was continuous uplift.Nevertheless,there were obvious seasonal deformation characteristics in those areas far away from the water body.Further analysis found out a sharply subsidence caused by the salt collapsibility appeared in rainy seasons.While an uplift trend induced by the salt swelling or frost heave was remarkable in dry seasons.Subsequently,the relationships were analyzed between the time series deformation and external environmental fac-tors.Furthermore,the deformation mechanism of saline soilin the Qarhan Salt Lake region was inter-preted then.In general,this study provides complete spatiotemporal evolution information of saline soil,and demonstrates the deformation characteristics of saline soil in the Qarhan Salt Lake region suc-cessfully.Related results would contribute to the safety monitoring for large-scale infrastructure con-struction in the saline soil areas.展开更多
The purpose of the study was to investigate the impact of rat cytomegalovirus （RCMV） infection on the development of the nervous system in rat embryos, and to evaluate the involvement of Wnt signaling pathway key mo...The purpose of the study was to investigate the impact of rat cytomegalovirus （RCMV） infection on the development of the nervous system in rat embryos, and to evaluate the involvement of Wnt signaling pathway key molecules and the downstream gene neurogenin 1 （Ngnl） in RCMV infected neural stem cells （NSCs）. Infection and control groups were established, each containing 20 pregnant Wistar rats. Rats in the infection group were inoculated with RCMV by intraperitoneal injection on the first day of pregnancy. Rat E20 embryos were taken to evaluate the teratogenic rate. NSCs were isolated from El3 embryos, and maintained in vitro. We found： 1） Poor fetal development was found in the infection group with low survival and high malformation rates. 2） The proliferation and differentiation of NSCs were affected. In the infection group, NSCs proliferated more slowly and had a lower neurosphere formation rate than the control. The differentiation ratio from NSCs to neurons and glial cells was significantly different from that of the control, showed by immunofluorescenee staining. 3） Ngnl mRNA expression and the nuclear p-catenin protein level were significantly lower than the control on day 2 when NSCs differentiated. 4） The Morris water maze test was performed on 4-week pups, and the infected rats were found worse in learning and memory ability. In a summary, RCMV infection caused abnormalities in the rat embryonic nervous system, significantly inhibited NSC proliferation and differentiation, and inhibited the expression of key molecules in the Wnt/β-catenin signaling pathway so as to affect NSCs differentiation. This may be an important mechanism by which RCMV causes embryonic nervous system abnormalities.展开更多
Ground subsidence is one of the key factors damaging transportation facilities, e.g., road networks consisting of highways and railways. In this paper, we propose to apply the persistent scatterer synthetic aperture r...Ground subsidence is one of the key factors damaging transportation facilities, e.g., road networks consisting of highways and railways. In this paper, we propose to apply the persistent scatterer synthetic aperture radar interferometry （PS-InSAR） approach that uses high- resolution TerraSAR-X （TSX） imagery to extract the regional scale subsidence rates （i.e., average annual sub- sidence in mm/year） along road networks. The primary procedures involve interferometric pair selection, interfer- ogram generation, persistent scatterer （PS） detection, PS networking, phase parameterization, and subsidence rate estimation. The Xiqing District in southwest Tianjin （China） is selected as the study area. This district contains one railway line and several highway lines. A total of 15 TSX images covering this area between April 2009 and June 2010 are utilized to obtain the subsidence rates by using the PS-InSAR （PSI） approach. The subsidence rates derived from PSI range from -68.7 to -1.3 mm/year. These findings show a significantly uneven subsidence pattern along the road network. Comparison between the PSI-derived subsidence rates and the leveling data obtained along the highways shows that the mean and standard deviation （SD） of the discrepancies between the two types of subsidence rates are 0.1 and 4-3.2 mm/year, respectively. The results indicate that the high-resolution TSX PSI is capable of providing comprehensive and detailed subsidence information regarding road networks with millimeter-level accuracy. Further inspections under geo- logical conditions and land-use categories in the study area indicate that the observed subsidence is highly related to aquifer compression due to groundwater pumping. Therefore, measures should be taken to mitigate groundwater extraction for the study area.展开更多
<span style="font-family:Verdana;">To explore the differences of male semen parameters in different seasons of the year, so as to explore the potential climatic factors affecting spermatogenesis and ma...<span style="font-family:Verdana;">To explore the differences of male semen parameters in different seasons of the year, so as to explore the potential climatic factors affecting spermatogenesis and male reproductive ability</span><span style="font-family:Verdana;">,</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> we retrospectively analyzed 21,715 semen analysis data from January 2018 to February 2021, grouped by year and season, and finally the relationships among semen parameters and semen and meteorological parameters were compared. Environmental exposures prior to 3 months were analyzed and correlation analysis was performed.</span><span style="font-family:Verdana;">The semen concentration decreased year by year (p < 0.01). However, the Progressive motility (PR) and total PR number had been increased (p < 0.01). There were statistical differences in sperm parameters which include semen volume, sperm concentration, total sperm number, progressive motility (PR), total PR number and total motility in different seasons, winter and spring were better than summer and autumn (p < 0.01). Total sperm number and sperm concentration were positively correlated with PR (R = 0.420, R = 0.440, p < 0.01). There was no correlation between daylight duration and semen parameters. Sperm parameters were positively or negatively correlated with environmental temperature, air pressure or humidity which had an overall effect on semen quality. It is suggested that seasonal factors should be considered when evaluating male reproductive ability. Besides referring to conventional semen parameters, other factors such as season and climate should also be considered.</span></span>展开更多
Lotus(Nelumbo)is one of the top ten flowers in China,which has high ornamental,edible and medicinal value.Lotus has a been cultivated for thousands of years.Through discovery and cultivation,more than 4,000 cultivars ...Lotus(Nelumbo)is one of the top ten flowers in China,which has high ornamental,edible and medicinal value.Lotus has a been cultivated for thousands of years.Through discovery and cultivation,more than 4,000 cultivars have been recorded.However,the information related to lotus breeding is quite scattered,and the related genetic rules and trait formation mechanisms are still poorly understood,which has caused a greater impact on lotus genetic breeding.This article systematically introduces lotus germplasm resources,including wild species and cultivated species,summarizes lotus breeding methods and breeding directions,and focuses on the latest progress in the isolation and functional identification of structural and regulatory genes related to important horticultural traits.Prospects for the protection and utilization of lotus resources,breeding and industrialization are reported.展开更多
Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in patients.As a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been repor...Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in patients.As a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological processes.However,it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation.Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation.Results:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of hepatocytes.Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine.In addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes.Targeting Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.展开更多
Stimulator of interferon genes(STING)has recentlybeen found to play a crucial role in cardiac sterile inflammation and dysfunction.The role of stimulator of interferon genes(STING)in cardiac sterile inflammation and d...Stimulator of interferon genes(STING)has recentlybeen found to play a crucial role in cardiac sterile inflammation and dysfunction.The role of stimulator of interferon genes(STING)in cardiac sterile inflammation and dysfunction has been recently discovered.This study aims to examine the involvement of STING in pathological cardiac remodeling and the mechanisms that govern the activation of the STING pathway.To investigate this,transverse aortic constriction(TAC)was performed on STING knockout mice to induce pressure over-load-induced cardiac remodeling.Subsequently,cardiac function,remodeling,and inflammation levels were evaluated.The STING pathway was found to be activated in the pressure overload-stressed heart and angiotensin II(Ang Il)-stimulated cardiac fibroblasts.Loss of STING expression led to a significant reduction in inflammatory responses,mitochondrial fragmenta-tion,and oxidative stress in the heart,resulting in attenuated cardiac remodeling and dysfunc-tion.Furthermore,the exacerbation of pressure overload-induced sTING-mediated inflammation and pathological cardiac remodeling was observed when mitophagy was sup-pressed through the silencing of Parkin,an E3 ubiquitin ligase.Taken together,these findings indicate that STING represents a newly identified and significant molecule implicated in the process of pathological cardiac remodeling and that mitophagy is an upstream mechanism that regulates STING activation.Targeting STING may therefore provide a novel therapeutic strategy for pathological cardiac remodeling and heart failure.展开更多
Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disea...Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disease.We conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls.Interestingly,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR.No significant SNPs were observed between SSNSWR and SDNS/FRNS.Meanwhile,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA.Thus,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/FRNS.The study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.展开更多
To the Editor:A 62-year-old woman presented to the dermatology department with a 5-month history of multiple painless cutaneous abscesses and ulcers[Figure 1A],occurring 1 month after a transvaginal hysterectomy due t...To the Editor:A 62-year-old woman presented to the dermatology department with a 5-month history of multiple painless cutaneous abscesses and ulcers[Figure 1A],occurring 1 month after a transvaginal hysterectomy due to uterine prolapse.Her general condition was good before and after the surgery,with no abnormal physical signs apart from metroptosis.She reported no fever,night sweat,cough,or abdominal pain,but 10 kg weight-loss.She has no history of diabetes,autoimmune diseases,or chronic infectious diseases.There was no similar illness in her family.展开更多
Bismuth-based electrocatalysts are promising candidates for electrochemical CO_(2)reduction to formate attributing to the accelerated formation of*OCHO intermediate,while the high-energy consumption remains a major ch...Bismuth-based electrocatalysts are promising candidates for electrochemical CO_(2)reduction to formate attributing to the accelerated formation of*OCHO intermediate,while the high-energy consumption remains a major challenge for practicability.Herein,we present the ultrathin Bi_(2)O_(2)CO_(3)nanosheets with abundant oxygen vacancy(Vo-BOC-NS)reconstructed from S,N-co-doped bismuth oxides that can act as durable electrocatalyst for CO_(2)-to-formate conversion with faradic efficiency(FEformate)of>95%,partial current density of 286 mA cm^(-2) with energy efficiency of 73.8%at-0.62 V(vs.RHE)and low overpotential of 200 mV in a flow electrolyzer.The theoretical calculations decipher that the oxygen vacancy can optimize*OCOH adsorption/desorption for the accelerated conversion kinetics.The pair-electrosynthesis tactic of formate co-production can enable a superior FE_(formate) of>90%at wide cell voltage of 2–3.3 V and total yield rate of 3742μmol cm^(-2)h^(-1)at 3.3 V,suggesting great potential for future industrialization.展开更多
Since cancer stem cells(CSCs)were first identified in leukemia in 1994,they have been considered promising therapeutic targets for cancer therapy.These cells have self-renewal capacity and differentiation potential an...Since cancer stem cells(CSCs)were first identified in leukemia in 1994,they have been considered promising therapeutic targets for cancer therapy.These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies,such as recurrence,metastasis,heterogeneity,multidrug resistance,and radiation resistance.The biological activities of CSCs are regulated by several pluripotent transcription factors,such as OCT4,Sox2,Nanog,KLF4,and MYC.In addition,many intracellular signaling pathways,such as Wnt,NF-κB(nuclear factor-κB),Notch,Hedgehog,JAK-STAT(Janus kinase/signal transducers and activators of transcription),PI3K/AKT/mTOR(phosphoinositide 3-kinase/AKT/mammalian target of rapamycin),TGF(transforming growth factor)/SMAD,and PPAR(peroxisome proliferator-activated receptor),as well as extracellular factors,such as vascular niches,hypoxia,tumor-associated macrophages,cancer-associated fibroblasts,cancer-associated mesenchymal stem cells,extracellular matrix,and exosomes,have been shown to be very important regulators of CSCs.Molecules,vaccines,antibodies,and CAR-T(chimeric antigen receptor T cell)cells have been developed to specifically target CSCs,and some of these factors are already undergoing clinical trials.This review summarizes the characterization and identification of CSCs,depicts major factors and pathways that regulate CSC development,and discusses potential targeted therapy for CSCs.展开更多
Foxtail millet(Setaria italica),which was domesticatedfromthewild speciesgreenfoxtail(Setaria viridis),isa richsource of phytonutrientsfor humans.To evaluate how breeding changed themetabolome offoxtail millet grains,...Foxtail millet(Setaria italica),which was domesticatedfromthewild speciesgreenfoxtail(Setaria viridis),isa richsource of phytonutrientsfor humans.To evaluate how breeding changed themetabolome offoxtail millet grains,we generated and analyzed the datasets encompassing the genomes,transcriptomes,metabolomes,and anti-inflammatory indices from 398 foxtail millet accessions.We identified hundreds of common variants that influence numerous secondary metabolites.We observed tremendous differences in natural variations of the metabolites and their underlying genetic architectures between distinct sub-groups of foxtail millet.Furthermore,we found that the selection of the gene alleles associated with yellow grains led to altered profiles of metabolites such as carotenoids and endogenous phytohormones.Using CRiSPR-mediated genome editing wevalidated the function of PHYTOENE SYNTHASE1(PSY1)gene in affecting milletgrain colorand quality.Interestingly,our in vitro cell inflammation assays showed that 83 metabolites in millet grains have anti-inflammatory effects.Taken together,ourmulti-omics study illustrates how the breeding history of foxtail millet has shaped its metabolite profile.The datasets we generated in this study also provide important resources for further understanding how millet grain quality is affected by different metabolites,laying the foundations for future millet genetic research and metabolome-assisted improvement.展开更多
基金sponsored by the National Key Research and Development Program of China(2022YFD1201600, 2016YFD0100501)Natural Science Foundation of Chongqing of China (cstc2020jcyj-msxm0539)+1 种基金the National Natural Science Foundation of China (32171964)Chongqing Natural Science Foundation Innovation Group (cstc2021jcyjcxttX0004)。
文摘Grain filling influences grain size and quality in cereal crops. The molecular mechanisms that regulate grain endosperm development remain elusive. In this study, we characterized a filling-defective and grain width mutant, fgw1, whose mutation increased rice seed width mainly via cell division and expansion in grains. Sucrose contents were higher but starch contents lower in the fgw1 mutant during the grainfilling stage, resulting in inferior endosperm of opaque, white appearance with loosely packed starch granules. Map-based cloning revealed that FGW1 encoded a protein containing DUF630/DUF632domains, localized in the plasma membrane with preferential expression in the panicle. RNA interference in FGW1 resulted in increased grain width and weight, whereas overexpression of FGW1 led to slightly narrower kernels and better grain filling. In a yeast two-hybrid assay, FGW1 interacted directly with the 14–3–3 protein GF14f, bimolecular fluorescence complementation verified that the site of interaction was the membrane, and the mutated FGW1 protein failed to interact with GF14f. The expression of GF14f was down-regulated in fgw1, and the activities of AGPase, StSase, and SuSase in the endosperm of fgw1increased similarly to those of a reported GF14f-RNAi. Transcriptome analysis indicated that FGW1 also regulates cellular processes and carbohydrate metabolism. Thus, FGW1 regulated grain formation via the GF14f pathway.
文摘Objective: To explore the related factors of surgical treatment of patients with corpus luteum rupture and establish a risk prediction model of surgical treatment of corpus luteum rupture. Methods: 222 patients with corpus luteum rupture treated in Jingzhou First People’s Hospital from January 2015 to March 2022 were analyzed retrospectively, including 45 cases of surgery and 177 cases of conservative treatment. The training set and validation set were randomly assigned according to 7:3. We collected the basic information, laboratory and ultrasonic examination data of 222 patients. Logistic regression analysis was used to determine the independent risk factors and combined predictors of surgical treatment of corpus luteum rupture. The risk prediction model was established and the nomogram was drawn. The discrimination and calibration of the prediction model were verified and evaluated by receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow goodness of fit test;Decision curve analysis (DCA) was used to evaluate the clinical effectiveness of the prediction model. Results: Univariate logistic regression showed that whole abdominal pain (OR: 2.314, 95% CI: 1.090 - 4.912), abdominal muscle tension (OR: 2.379, 95% CI: 1.112 - 5.089), adnexal mass ≥ 4 cm (OR: 3.926, 95% CI: 1.771 - 8.266), hemoglobin Conclusion: The nomogram prediction model containing three predictive variables (hemoglobin, depth of pelvic effusion under ultrasound and cervical lifting pain) can be used to predict the risk of surgical treatment in patients with corpus luteum rupture.
文摘Background: Arsenic metabolism is primarily undergoing in hepatocytes, but the underlying mechanisms are to be defined. It is essential to study the response of aquaporin AQP9, protein kinase p38, and JNK with the stimulation of arsenic in mouse models of hepatocellular carcinoma. Methods: Mouse model of hepatocellular carcinoma (HCC) was induced with H22 cells injected subcutaneously on the lateral side of each right axilla in C57BL/6 mice. Then, western blotting and co-immunoprecipitation were used to detect the protein expression and phosphorylation of molecules AQP9, p38 and JNK in mouse models of hepatocellular carcinoma, respectively. The hepatocellular distribution of AQP9 was examined by the immunofluorescent method. Results: In both wild mice and a mouse model of liver tumor, there was no significant difference in the expressions of AQP9, protein kinase p38, and JNK after arsenic treatment, but the phosphorylation expression levels of the three were significantly increased to varying degrees, and the tumor model Compared with the wild-type group, the expression increased. Laser confocal experiments showed that in HepG2 cells, phosphorylated AQP9 was mainly distributed on the cell membrane under the stimulation of arsenic. Conclusion: Arsenic stimulation can increase the phosphorylation of AQP9, p38, and JNK in both wild-type C57 mice and liver tumor mice models. Arsenic stimulation facilitates phosphorylated-AQP9 predominantly distributed on the cell membrane of hepatoma cells HepG2.
文摘<strong>Background:</strong> Although semen analysis is a basic method to evaluate male fertility, there was a certain deviation between the semen examination and the actual situation in clinical application. <strong>Objective:</strong> To evaluate the application value of semen examination items in the diagnosis of male infertility. <strong>Method:</strong> Males recruited from the Third Affiliated Hospital of Sun Yat-sen University from June 2017 to December 2018 were divided into three groups: normal fertility group, physical examination group (premarital physical examination), and male infertility group. Each group received the following examination such as semen analysis (including semen volume, sperm concentration, progressive motility, total motility, round cell concentration), acrosin activity, and sperm morphology. All the semen analysis items mentioned above were operated according to the <em>WHO laboratory manual for the examination and procession of human semen</em> (<em>Fifth edition</em>) and related documents. <strong>Results:</strong> The normal fertility group and physical examination group showed significantly higher levels in sperm concentration, progressive motility, total motility, and sperm morphology than those in the male infertility group (<em>P</em> < 0.05);both the normal fertility group and the physical examination group have a higher qualified rate in sperm concentration, progressive motility, total motility and sperm morphology than the male infertility group, all <em>P</em> < 0.001. The percentage of patients having all qualified items in each group was 28.13%, 6.67%, and 6.51% separately. <strong>Conclusion:</strong> The diagnosis efficiency was higher in sperm concentration, progressive motility, total motility, and sperm morphology than in other semen examination items. A more objective and efficient method of semen examination should be explored to facilitate the diagnoses of male infertility in the future.
文摘<strong>Purpose:</strong> To identify prognostic factors in patients with coronavirus disease 2019 (COVID-19)-associated severe acute respiratory distress syndrome (ARDS). <strong>Methods:</strong> In this study, we included 45 patients with COVID-19-associated ARDS hospitalized at The First Affiliated Hospital of Yangtze University in Jingzhou, Hubei, China, between January 22, 2020, and March 6, 2020. Clinical data and outcomes were reviewed and analyzed according to the Berlin definition. <strong>Findings:</strong> Men were more likely to develop severe ARDS than women (11 [91.7%] vs. 1 [8.3%]). Factors associated with severe ARDS included sex (male) (hazard ratio [HR], 13.75;95% confidence interval [CI], 1.45 - 130.24), neutrophil count (HR, 55.00;95% CI, 5.02 - 602.15), lymphocyte count (HR, 40.00;95% CI, 4.83 - 331.00), prothrombin time (HR, 12.14;95% CI, 1.19 - 123.62), D-dimer (HR, 11.00;95% CI, 1.16 - 103.94), total bilirubin levels (HR, 5.00;95% CI, 0.93 - 26.79), albumin (HR, 17.5;95% CI, 2.67 - 114.85), blood urea nitrogen levels (HR, 28.60;95% CI, 2.89 - 283.06), lactate dehydrogenase levels (HR, 6.00;95% CI, 1.17 - 30.73), and C-reactive protein levels (HR, 15.87;95% CI, 2.40 - 111.11). <strong>Conclusion:</strong> Laboratory indicators, such as neutrophil count and lymphocyte count, could play an important role in the diagnosis of severe ARDS and guide clinical decision-making for patients with ARDS.
基金This research was supported by the National Natural Sci—ence Foundation of China(Grant No.50474015)
文摘In Haigh Westergaard stress space linear combination of twin shear stress and Tresca yield functions is called the mean yield （MY） criterion. The mathematical relationship of the criterion and its plastic work rate done per unit volume were derived. A generalized worked example of slab forging was analyzed by the criterion and its corresponding plastic work rate done per unit volume. Then, the precision of the solution was compared with those by Mises and Twin shear stress yield criterions, respectively. It turned out that the calculated results by MY criterion were in good agreement with those by Mises criterion.
基金This research was jointly funded by the National Key R&D Program of China(Grant No.2017YFB0502700)the National Natural Science Foundation of China(Grant No.41771402,41804009,42071410)+1 种基金the Scientific R&D Plan of China Railway Corporation(No.JXKT-1801-2-2-7,P2018G004)the Sichuan Science and Technology Support Project(No.2018JY0664,20YYJC4292,2020YJ0322)。
文摘The instability of saline soil foundation affects the safety of artificial construction,and may cause ground collapse,building destruction and road damage.It is fundamental to reduce the potential engineering geological disasters by exploring the dynamic evolution of saline soil.Most of the previous researches of saline soil were conducted by simulated experiments and traditional geodetic surveying methods.Restricted to the limited sampling points,the spatiotemporal evolution characteristics of saline soil were difficult to find out in a large scale.This paper exploited SBAS-InSAR method to extract the deformation of the Qarhan Salt Lake(in Qinghai,China)section along Qinghai-Tibet railway,based on 119 image data acquired by Sentinel-1A from 2015 to 2020.The results showed that the deformation trends varied frequently in this saline mud flat.Between the adjacent areas with different deformation trends along Qinghai-Tibet railway,discontinuities caused by uplift and subsidence were very obvious.Besides,among the areas with brine exploitation or artificial construction,the maximum subsidence rate reached50 mm/yr,and the maximum cumulative subsidence exceeded 320 mm in the latest 5 years.In the saline mud flat closed to the rivers and lakes,the deformation trend was continuous uplift.Nevertheless,there were obvious seasonal deformation characteristics in those areas far away from the water body.Further analysis found out a sharply subsidence caused by the salt collapsibility appeared in rainy seasons.While an uplift trend induced by the salt swelling or frost heave was remarkable in dry seasons.Subsequently,the relationships were analyzed between the time series deformation and external environmental fac-tors.Furthermore,the deformation mechanism of saline soilin the Qarhan Salt Lake region was inter-preted then.In general,this study provides complete spatiotemporal evolution information of saline soil,and demonstrates the deformation characteristics of saline soil in the Qarhan Salt Lake region suc-cessfully.Related results would contribute to the safety monitoring for large-scale infrastructure con-struction in the saline soil areas.
基金Shandong Province High-level Talent of Health 1020 Project Fund(No.2008-1)Science and Technology Creative Research of Weifang Medical University(No.K11TS1010)+1 种基金A Project of Shandong Province Higher Educational Science and Technology Program(No.J12LK04)National Natural Science Foundation of China(30900775)
文摘The purpose of the study was to investigate the impact of rat cytomegalovirus （RCMV） infection on the development of the nervous system in rat embryos, and to evaluate the involvement of Wnt signaling pathway key molecules and the downstream gene neurogenin 1 （Ngnl） in RCMV infected neural stem cells （NSCs）. Infection and control groups were established, each containing 20 pregnant Wistar rats. Rats in the infection group were inoculated with RCMV by intraperitoneal injection on the first day of pregnancy. Rat E20 embryos were taken to evaluate the teratogenic rate. NSCs were isolated from El3 embryos, and maintained in vitro. We found： 1） Poor fetal development was found in the infection group with low survival and high malformation rates. 2） The proliferation and differentiation of NSCs were affected. In the infection group, NSCs proliferated more slowly and had a lower neurosphere formation rate than the control. The differentiation ratio from NSCs to neurons and glial cells was significantly different from that of the control, showed by immunofluorescenee staining. 3） Ngnl mRNA expression and the nuclear p-catenin protein level were significantly lower than the control on day 2 when NSCs differentiated. 4） The Morris water maze test was performed on 4-week pups, and the infected rats were found worse in learning and memory ability. In a summary, RCMV infection caused abnormalities in the rat embryonic nervous system, significantly inhibited NSC proliferation and differentiation, and inhibited the expression of key molecules in the Wnt/β-catenin signaling pathway so as to affect NSCs differentiation. This may be an important mechanism by which RCMV causes embryonic nervous system abnormalities.
基金supported by the National Basic Research Program of China(973 Program)under Grant 2012CB719901the National Natural Science Foundation of China under Grant 41074005the 2013 Doctoral Innovation Funds of Southwest Jiaotong University
文摘Ground subsidence is one of the key factors damaging transportation facilities, e.g., road networks consisting of highways and railways. In this paper, we propose to apply the persistent scatterer synthetic aperture radar interferometry （PS-InSAR） approach that uses high- resolution TerraSAR-X （TSX） imagery to extract the regional scale subsidence rates （i.e., average annual sub- sidence in mm/year） along road networks. The primary procedures involve interferometric pair selection, interfer- ogram generation, persistent scatterer （PS） detection, PS networking, phase parameterization, and subsidence rate estimation. The Xiqing District in southwest Tianjin （China） is selected as the study area. This district contains one railway line and several highway lines. A total of 15 TSX images covering this area between April 2009 and June 2010 are utilized to obtain the subsidence rates by using the PS-InSAR （PSI） approach. The subsidence rates derived from PSI range from -68.7 to -1.3 mm/year. These findings show a significantly uneven subsidence pattern along the road network. Comparison between the PSI-derived subsidence rates and the leveling data obtained along the highways shows that the mean and standard deviation （SD） of the discrepancies between the two types of subsidence rates are 0.1 and 4-3.2 mm/year, respectively. The results indicate that the high-resolution TSX PSI is capable of providing comprehensive and detailed subsidence information regarding road networks with millimeter-level accuracy. Further inspections under geo- logical conditions and land-use categories in the study area indicate that the observed subsidence is highly related to aquifer compression due to groundwater pumping. Therefore, measures should be taken to mitigate groundwater extraction for the study area.
文摘<span style="font-family:Verdana;">To explore the differences of male semen parameters in different seasons of the year, so as to explore the potential climatic factors affecting spermatogenesis and male reproductive ability</span><span style="font-family:Verdana;">,</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> we retrospectively analyzed 21,715 semen analysis data from January 2018 to February 2021, grouped by year and season, and finally the relationships among semen parameters and semen and meteorological parameters were compared. Environmental exposures prior to 3 months were analyzed and correlation analysis was performed.</span><span style="font-family:Verdana;">The semen concentration decreased year by year (p < 0.01). However, the Progressive motility (PR) and total PR number had been increased (p < 0.01). There were statistical differences in sperm parameters which include semen volume, sperm concentration, total sperm number, progressive motility (PR), total PR number and total motility in different seasons, winter and spring were better than summer and autumn (p < 0.01). Total sperm number and sperm concentration were positively correlated with PR (R = 0.420, R = 0.440, p < 0.01). There was no correlation between daylight duration and semen parameters. Sperm parameters were positively or negatively correlated with environmental temperature, air pressure or humidity which had an overall effect on semen quality. It is suggested that seasonal factors should be considered when evaluating male reproductive ability. Besides referring to conventional semen parameters, other factors such as season and climate should also be considered.</span></span>
基金supported by the National Natural Science Foundation of China(Grants No's 31971710 and 32071829)Fundamental Research Funds of the Central Government(Special Project of Lotus Germplasm Resources)(KYZZ2021003).
文摘Lotus(Nelumbo)is one of the top ten flowers in China,which has high ornamental,edible and medicinal value.Lotus has a been cultivated for thousands of years.Through discovery and cultivation,more than 4,000 cultivars have been recorded.However,the information related to lotus breeding is quite scattered,and the related genetic rules and trait formation mechanisms are still poorly understood,which has caused a greater impact on lotus genetic breeding.This article systematically introduces lotus germplasm resources,including wild species and cultivated species,summarizes lotus breeding methods and breeding directions,and focuses on the latest progress in the isolation and functional identification of structural and regulatory genes related to important horticultural traits.Prospects for the protection and utilization of lotus resources,breeding and industrialization are reported.
基金supported by grants from the National Natural Science Foundation of China(Nos.82100691,82070673,and 81870447)the Guangdong Natural Science Foundation(No.2021A1515010726)+1 种基金the China Postdoctoral Science Foundation(No.2021M693631)the Medical Scientific Research Foundation of Guangdong Province of China(No.A2021160).
文摘Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in patients.As a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological processes.However,it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation.Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation.Results:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of hepatocytes.Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine.In addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes.Targeting Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.
基金supported by grants from the Natural Science Foundation of China (No.82070238)the China Postdoctoral Science Foundation (No.2022M720601)+3 种基金the Natural Science Foundation of Chongqing,China (No.CSTB2022NSCQMSx0913)the Program for Youth Innovation in Future Medicine,Chongqing Medical University (No.W0168)the Science Fund of the First Affiliated Hospital of Chongqing Medical University (No.PYJJ2021-05)the Postdoctoral Incubation Project of The First Affiliated Hospital of Chongqing Medical University (No.CYYY-BSHPYXM-202204)。
文摘Stimulator of interferon genes(STING)has recentlybeen found to play a crucial role in cardiac sterile inflammation and dysfunction.The role of stimulator of interferon genes(STING)in cardiac sterile inflammation and dysfunction has been recently discovered.This study aims to examine the involvement of STING in pathological cardiac remodeling and the mechanisms that govern the activation of the STING pathway.To investigate this,transverse aortic constriction(TAC)was performed on STING knockout mice to induce pressure over-load-induced cardiac remodeling.Subsequently,cardiac function,remodeling,and inflammation levels were evaluated.The STING pathway was found to be activated in the pressure overload-stressed heart and angiotensin II(Ang Il)-stimulated cardiac fibroblasts.Loss of STING expression led to a significant reduction in inflammatory responses,mitochondrial fragmenta-tion,and oxidative stress in the heart,resulting in attenuated cardiac remodeling and dysfunc-tion.Furthermore,the exacerbation of pressure overload-induced sTING-mediated inflammation and pathological cardiac remodeling was observed when mitophagy was sup-pressed through the silencing of Parkin,an E3 ubiquitin ligase.Taken together,these findings indicate that STING represents a newly identified and significant molecule implicated in the process of pathological cardiac remodeling and that mitophagy is an upstream mechanism that regulates STING activation.Targeting STING may therefore provide a novel therapeutic strategy for pathological cardiac remodeling and heart failure.
基金funded by the China National Natural Science Foundation(No.81970618,82170720,82200788)China National Clinical Research Centre Foundation(No.NCRC-2019-GP-02)+2 种基金Science and Technology Research Project of Chongqing Education Commission of China(No.KJZDM201900401)Chongqing Science and Health Joint Medical Research Project(China)(No.2023GGXM001)National Key R&D Program of China(No.2022YFC2705101).
文摘Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disease.We conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls.Interestingly,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR.No significant SNPs were observed between SSNSWR and SDNS/FRNS.Meanwhile,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA.Thus,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/FRNS.The study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.
文摘To the Editor:A 62-year-old woman presented to the dermatology department with a 5-month history of multiple painless cutaneous abscesses and ulcers[Figure 1A],occurring 1 month after a transvaginal hysterectomy due to uterine prolapse.Her general condition was good before and after the surgery,with no abnormal physical signs apart from metroptosis.She reported no fever,night sweat,cough,or abdominal pain,but 10 kg weight-loss.She has no history of diabetes,autoimmune diseases,or chronic infectious diseases.There was no similar illness in her family.
基金Genqiang Zhang acknowledges the financial support from the National Natural Science Foundation of China(Grant No.52072359)the Recruitment Program of Global Experts and the Fundamental Research Funds for the Central Universities(WK2060000016).
文摘Bismuth-based electrocatalysts are promising candidates for electrochemical CO_(2)reduction to formate attributing to the accelerated formation of*OCHO intermediate,while the high-energy consumption remains a major challenge for practicability.Herein,we present the ultrathin Bi_(2)O_(2)CO_(3)nanosheets with abundant oxygen vacancy(Vo-BOC-NS)reconstructed from S,N-co-doped bismuth oxides that can act as durable electrocatalyst for CO_(2)-to-formate conversion with faradic efficiency(FEformate)of>95%,partial current density of 286 mA cm^(-2) with energy efficiency of 73.8%at-0.62 V(vs.RHE)and low overpotential of 200 mV in a flow electrolyzer.The theoretical calculations decipher that the oxygen vacancy can optimize*OCOH adsorption/desorption for the accelerated conversion kinetics.The pair-electrosynthesis tactic of formate co-production can enable a superior FE_(formate) of>90%at wide cell voltage of 2–3.3 V and total yield rate of 3742μmol cm^(-2)h^(-1)at 3.3 V,suggesting great potential for future industrialization.
基金supported by the National Key Research and Development Program of China(nos.2016YFC1302204,2017YFC1308600)the National Science Foundation of China(nos.81672502,81872071,81902664)the Natural Science Foundation of Chongqing(no.cstc2019jcyj-zdxmX0033).
文摘Since cancer stem cells(CSCs)were first identified in leukemia in 1994,they have been considered promising therapeutic targets for cancer therapy.These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies,such as recurrence,metastasis,heterogeneity,multidrug resistance,and radiation resistance.The biological activities of CSCs are regulated by several pluripotent transcription factors,such as OCT4,Sox2,Nanog,KLF4,and MYC.In addition,many intracellular signaling pathways,such as Wnt,NF-κB(nuclear factor-κB),Notch,Hedgehog,JAK-STAT(Janus kinase/signal transducers and activators of transcription),PI3K/AKT/mTOR(phosphoinositide 3-kinase/AKT/mammalian target of rapamycin),TGF(transforming growth factor)/SMAD,and PPAR(peroxisome proliferator-activated receptor),as well as extracellular factors,such as vascular niches,hypoxia,tumor-associated macrophages,cancer-associated fibroblasts,cancer-associated mesenchymal stem cells,extracellular matrix,and exosomes,have been shown to be very important regulators of CSCs.Molecules,vaccines,antibodies,and CAR-T(chimeric antigen receptor T cell)cells have been developed to specifically target CSCs,and some of these factors are already undergoing clinical trials.This review summarizes the characterization and identification of CSCs,depicts major factors and pathways that regulate CSC development,and discusses potential targeted therapy for CSCs.
基金This workwas supportedby the National KeyR&DProgramof China(2019YFD1000700 and 2019YFD1000702)the JointFunds of theNational Natural Science Foundation of China(U21A20216)+4 种基金the Key R&D Program of Shanxi Province(201903D11006)theMajor Special Science and Technology Projects in Shanxi Province(202101140601027)the National Natural Science Foundation of China(32001608 and 31771810)the Scientific and Technological Innovation Programs of Shanxi Agricultural University(2017YJ27)Lundbeck Foundation(R346-2020-1546)grants.S.P.also acknowledges the financial aid of an ARC Discovery grant(DP19001941),Villum Investigator(25915),DNRF Chair(DNRF155),Novo Nordisk Laureate(NNF190C0056076),NovoNordisk Emerging Investigator(NNF20OC0060564).
文摘Foxtail millet(Setaria italica),which was domesticatedfromthewild speciesgreenfoxtail(Setaria viridis),isa richsource of phytonutrientsfor humans.To evaluate how breeding changed themetabolome offoxtail millet grains,we generated and analyzed the datasets encompassing the genomes,transcriptomes,metabolomes,and anti-inflammatory indices from 398 foxtail millet accessions.We identified hundreds of common variants that influence numerous secondary metabolites.We observed tremendous differences in natural variations of the metabolites and their underlying genetic architectures between distinct sub-groups of foxtail millet.Furthermore,we found that the selection of the gene alleles associated with yellow grains led to altered profiles of metabolites such as carotenoids and endogenous phytohormones.Using CRiSPR-mediated genome editing wevalidated the function of PHYTOENE SYNTHASE1(PSY1)gene in affecting milletgrain colorand quality.Interestingly,our in vitro cell inflammation assays showed that 83 metabolites in millet grains have anti-inflammatory effects.Taken together,ourmulti-omics study illustrates how the breeding history of foxtail millet has shaped its metabolite profile.The datasets we generated in this study also provide important resources for further understanding how millet grain quality is affected by different metabolites,laying the foundations for future millet genetic research and metabolome-assisted improvement.
