Precise modulation of the structure and composition of electrocatalysts is critical for promoting the kinetically sluggish process of oxygen reduction reaction(ORR)and oxygen evolution reaction(OER).Covalent organic f...Precise modulation of the structure and composition of electrocatalysts is critical for promoting the kinetically sluggish process of oxygen reduction reaction(ORR)and oxygen evolution reaction(OER).Covalent organic frameworks(COF)offer a novel way to create highly efficient electrocatalysts due to their tunable composition,structure and surface area.Herein,we report a high-efficiency bifunctional electrocatalyst comprising Co nanoparticles embedded within N-doped carbons(Co@NCs)for Zn-air batteries(ZABs).The Co@NC is yielded via the coordination of a triazine COF with Co-containing precursors and subsequent calcination under inert atmosphere.The as-prepared Co@NC exhibits remarkable ORR/OER performance and great potential in rechargeable ZABs.The liquid ZAB constructed with Co@NC provides both high specific capacity and power density.Remarkably,the ZAB exhibits a voltage gap of 0.8 V during discharge and charge cycles and high stability for 220 h compared to the Pt/C-assembled battery.This strategy for regulating electrocatalytic activities of COF-derived carbon materials could be expanded for creating various carbon catalysts.展开更多
Bi- and Cu-substituted Ca3Co4O9 samples were prepared by conventional solid-state reaction method and the effect of element substitution on the microstructures and thermoelectric properties was investigated. Partial s...Bi- and Cu-substituted Ca3Co4O9 samples were prepared by conventional solid-state reaction method and the effect of element substitution on the microstructures and thermoelectric properties was investigated. Partial substitution of Cu for Co leads to an increase in electrical conductivity and a decrease in Seebeck coeffcient due to the rise of hole concentration. The microstructure of Cu-substituted sample is almost unchanged compared with undoped Ca3Co4O9. On the other hand, partial substitution of Bi for Ca gives rise to a significant increase in the grain size, and c-axis-oriented structure can be formed in Ca2.7Bi0.3Co4O9, resulting in an obvious increase in electrical conductivity. Cu and Bi co-substitution further increases the grain growth and the electrical conductivity of Ca2.7Bi0.3Co3.7Cu0.3O9. Thus, Cu and Bi co-substitution samples possess the optimal thermoelectric performance at high temperature and the highest value of power factor can reach 3.1×10-4 Wm-1·K-2 at 1000 K.展开更多
Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1(EC_(50)=1.0 nmol/L),but the poor metabolic stability in human liver microsomes(t_(1/2)=1...Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1(EC_(50)=1.0 nmol/L),but the poor metabolic stability in human liver microsomes(t_(1/2)=14.6 min)and insufficient selectivity(SI=2059)with high cytotoxicity(CC_(50)=2.08μmol/L)remained major issues associated with JK-4b.The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b,leading to the discovery of a novel series of fluorine-substituted NH_(2)-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain(EC_(50)=1.8–349 nmol/L).The best compound 5t in this collection(EC_(50)=1.8 nmol/L,CC_(50)=117μmol/L)was 32-fold in selectivity(SI=66,443)compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains,such as L100I,K103N,E138K,and Y181C.The metabolic stability of 5t was also significantly improved(t_(1/2)=74.52 min),approximately 5-fold higher than JK-4b in human liver microsomes(t_(1/2)=14.6 min).Also,5t possessed good stability in both human and monkey plasma.No significant in vitro inhibition effect toward CYP enzyme and hERG was observed.The single-dose acute toxicity test did not induce mice death or obvious pathological damage.These findings pave the way for further development of 5t as a drug candidate.展开更多
Long noncoding RNAs(lncRNAs)play a critical role in the regulation of atherosclerosis.Here,we investigated the role of the lncRNA growth arrest-specific 5(lncR-GAS5)in atherogenesis.We found that the enforced expressi...Long noncoding RNAs(lncRNAs)play a critical role in the regulation of atherosclerosis.Here,we investigated the role of the lncRNA growth arrest-specific 5(lncR-GAS5)in atherogenesis.We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis,which presented as increased plaque size and reduced collagen content.Moreover,impaired autophagy was observed,as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells.By contrast,lncR-GAS5 knockdown promoted autophagy.Moreover,serine/arginine-rich splicing factor 10(SRSF10)knockdown increased the LC3II/LC3I ratio and decreased the P62 level,thus enhancing the formation of autophagic vacuoles,autolysosomes,and autophagosomes.Mechanistically,lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium,which was reversed by the knockdown of SRSF10.Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene,SRSF10.Notably,miR-193-5p overexpression decreased plaque size and increased collagen content.Altogether,these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy.In conclusion,lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway.Thus,miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.展开更多
Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria,which include:1)recruitment and polarization of the macrophages from M1(pro-inflammatory)to M2(anti-infl...Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria,which include:1)recruitment and polarization of the macrophages from M1(pro-inflammatory)to M2(anti-inflammatory)phenotype,2)enhance vascularization,and 3)activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing.So far,no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation,angiogenesis,and osteogenesis.Therefore,in this study,we designed bone cement comprised of strontium and copper-incorporated borosilicate glass(Sr/Cu-BSG)in the liquid phase of chitosan to modulate bone healing.In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1)while down-regulating pro-inflammatory genes(IL-1βand IL-6)in macrophages at 3 days.Sr and Cu ions also increased the expressions of angiogenic genes(VEGF and bFGF)in HUVECs at 5 days and osteogenic genes(Runx-2,OCN,and OPN)in hBMSCs at 7,14,and 21 days.5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory,angiogenic,and osteogenic properties among the bone cement groups with different Sr and Cu ratios.Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results,where the degradation rate of Sr/Cu-BSG matched the bone healing rate.Similar to in vitro,the 5Sr3Cu-BSG group also showed the highest bone formation in vivo.Excellent physical and chemical properties,along with its bone repairing ability,make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.展开更多
The regeneration of alveolar bone is still clinical challenge,particularly accompanied with diabetes,causing metabolic disorder with a protracted low-grade inflammatory phenotype.As a result,the anticipated loading of...The regeneration of alveolar bone is still clinical challenge,particularly accompanied with diabetes,causing metabolic disorder with a protracted low-grade inflammatory phenotype.As a result,the anticipated loading of biomaterials is highly suspicious in spontaneous modulation of cells function,which is mostly disturbed by constant inflammation.In this study,we developed glucose and hydrogen peroxide dual-responsive borosilicate glass(BSG)scaffolds loaded with epigallocatechin gallate(EGCG)to synergistically modulate the abnormal inflammation of diabetic alveolar bone defects.It was found that the release of EGCG by BSG could directly regulate the shift of macrophages from M1 to the M2 phenotype by promoting autophagy and lessening the inhibition of autophagic flux.Moreover,EGCG can also indirectly regulate the polarization phenotype of macrophages by reducing the activation of NF-κb in stem cells and restoring its immunoregulatory capacity.Therefore,the addition of EGCG to BSG scaffold in diabetes allows for a more striking modulation of the macrophage phenotype in a timely manner.The altered macrophage phenotype reduces local inflammation and thus increases the ability to repair diabetic alveolar bone,showing promise for the treatment of alveolar defect in diabetic patients.展开更多
A visible-light-induced C-5 selective C-H borylation of imidazo[1,2-a]pyridines with NHC-BH3 via Minisci-type radical borylation re-action has been developed for the first time.The present sustainable protocol provide...A visible-light-induced C-5 selective C-H borylation of imidazo[1,2-a]pyridines with NHC-BH3 via Minisci-type radical borylation re-action has been developed for the first time.The present sustainable protocol provides a new family of regioselectively C5-borylated imidazopyridines that would otherwise be difficult to prepare.It is a supplement to site-selective borylation of azines(nitrogen-con-taining aromatic heterocycles)and the assembly of sp2 carbon-boron bond.展开更多
During the years 2006–2009,lakes in the Qinghai-Tibetan Plateau(QTP)were investigated using satellite remote sensing strategies.We report the results of this investigation as well as follow-up research and expanded w...During the years 2006–2009,lakes in the Qinghai-Tibetan Plateau(QTP)were investigated using satellite remote sensing strategies.We report the results of this investigation as well as follow-up research and expanded work.For the investigation,we mainly focused on lakes whose areas are more than 1 km2.The remote sensing data that we used included 408 scenes of CBERS CCD images and 5 scenes of Landsat ETM?images in Qinghai Province and Tibet Autonomous Region.All these data were acquired around years 2005–2006.Besides remote sensing images,we also collected 1,259 topographic maps.Numbers and areas of lakes were analyzed statistically,which were then compared with those coming from the first lake investigation(implemented between the1960s and 1980s).According to our investigation,up to and around year 2005–2006,the total number of lakes in the QTP was 1,055(222 in Qinghai and 833 in Tibet),accounting for more than 30%of that of China.Thirty newborn lakes with area[1 km2were found,and 5 dead lakes with initial area[1 km2were also found.Among those 13 big lakes([500 km2),Yamzhog Yumco had seriously shrunk,and it has continued to shrink in recent years;Qinghai Lake had shrunk during the period,but some new researches indicated that it has been expanding since the year 2004;Siling Co,Nam Co,and Chibuzhang Co had expanded in the period.We divided the newborn lakes into six categories according to their forming reasons,including river expansion,wetland conversion,etc.The changes of natural conditions led to the death of four lakes,and human exploitation was the main reason for the death of Dalianhai Lake in Qinghai.We picked out three regions which were sensitive to the change of climate and ecological environment:Nagqu Region,Kekexili Region,and the source area of the Yellow River(SAYR).Lakes in both Nagqu and Kekexili have been expanded;meanwhile,most lakes in the SAYR have obviously been shrunk.These regional patterns of lake changes were highly related to variations of temperature,glacier,precipitation,and evaporation.Our investigation and analysis will provide references for researches related to lake changes in the QTP and the response to climate fluctuations.展开更多
Blueschist accompanied by pelitic schist expose along the Xinlin-Xiguitu fault in the Toudaoqiao area, northeastern China. In this paper, the blueschist is systematically studied on the petrography and mineral chemist...Blueschist accompanied by pelitic schist expose along the Xinlin-Xiguitu fault in the Toudaoqiao area, northeastern China. In this paper, the blueschist is systematically studied on the petrography and mineral chemistry. The amphiboles in the blueschist are zoned from winchite core to magnesioriebeckite/glaucophane rim to winchite outermost rim. The peak metamorphic conditions are defined by the mineral assemblage of magnesioriebeckite/glaucophane, epidote, high-Si phengite(Si<7.1), chlorite, albite, hematite and quartz, indicating an epidote-blueschist facies metamorphism. The P-T conditions are estimated as T=350–400 ℃ and P=10-12 kbar. The occurrence of the blueschist along the Xinlin-Xiguitu fault strongly suggests the fault is the suture between the Ergun and the Xing'an blocks situated in the eastern portions of the Central Asia Orogenic Belt(CAOB).展开更多
The Central Qilian Block is a Precambrian block in the Qilian Orogen,which has long drawn international attention for the study of orogeny and continental dynamics.The Huangyuan Group in the Datong area is one of the ...The Central Qilian Block is a Precambrian block in the Qilian Orogen,which has long drawn international attention for the study of orogeny and continental dynamics.The Huangyuan Group in the Datong area is one of the Precambrian metamorphic basement units in the Central Qilian Block and reflects metamorphism in the Barrovian garnet zone and sillimanite zone from south to north.Based on detailed fieldwork,this study presents a systematic study of petrography,mineral chemistry and phase equilibria of schists and gneisses from the two metamorphic zones.The garnet metamorphic zone is composed of micaschist,garnet-bearing micaschist and felsic leptynite,with interlayered plagioclase amphibolite.The sillimanite metamorphic zone consists of garnet-bearing biotite micaschist,sillimanite-bearing biotite-plagioclase gneiss and felsic leptynite.Garnet from the garnet metamorphic zone shows growth zoning with increasing almandine and pyrope and decreasing spessartine from core to rim.Garnet from the sillimanite metamorphic zone is almost homogeneous.Towards the outer rim,the contents of almandine and pyrope slightly decrease and grossular slightly increase.Biotite in both metamorphic zones is ferro-biotite.Plagioclase is oligoclase in garnet metamorphic zone and andesine in sillimanite metamorphic zone.Phase equilibrium modeling of a sample from garnet metamorphic zone resulted in a clockwise P-T path with a prograde stage(4.5–5.0 kbar,520–530℃),a peak P stage(9.8–10.2 kbar,560–570℃),a stage of thermal relaxation(8.0–8.5 kbar,580–590℃)and finally a retrograde stage(6.8–7.0 kbar,560–580℃).Thermodynamic modeling of a sample from the sillimanite metamorphic zone indicates a prograde stage(5.5–6.0 kbar,540–550℃)and a peak stage(7.8–8.5 kbar,660–690℃).The results indicate that the Huangyuan Group experienced medium-pressure amphibolite-facies metamorphism,which resulted from continental-continental collision between the Qaidam Block and the Central Qilian Block.展开更多
Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed th...Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.展开更多
Performances of superconducting nanowire single-photon detectors(SNSPDs) based on low TCmaterials strongly depend on the operating temperatures. We have fabricated infrared-sensitive niobium SNSPDs based on doped niob...Performances of superconducting nanowire single-photon detectors(SNSPDs) based on low TCmaterials strongly depend on the operating temperatures. We have fabricated infrared-sensitive niobium SNSPDs based on doped niobium(Nb*) films and measured them in He-3cryocooler. The critical current approaches to the de-pairing current at 0.3 K. Therefore, with the decrease in temperatures, we have observed a monotonous increase of count rate at the wavelength of 1,521 nm and exponential decrease of dark count rate at all bias currents. The possible origin of dark counts for doped Nb devices is also discussed.展开更多
The Qilian Orogen marks the junction of the North China, South China and Tarim cratons. The mechanism of continental growth during the formation of the orogen remains unclear. Based on detailed fieldwork, we present a...The Qilian Orogen marks the junction of the North China, South China and Tarim cratons. The mechanism of continental growth during the formation of the orogen remains unclear. Based on detailed fieldwork, we present a systematic study of petrography, mineral chemistry and phase equilibria of garnet amphibolites from the Hualong Group, which represents the Precambrian basement in the southern accretionary belt of the Qilian Orogen. The garnet amphibolites mainly consist of amphibole, plagioclase, garnet and quartz, with minor pyroxene, biotite and ilmenite. A peak stage of upper amphibolite facies to low-temperature granulite facies metamorphism and retrograde metamorphism in the amphibolite facies affected the samples. Garnet has a homogeneous composition of Alm66–71 Grs14–17 Prp9–12 Sps3–5, amphibole is ferro-hornblende, biotite belongs to the ferro-biotite species and pyroxene is dominated by orthopyroxene with few clinopyroxene. Pseudosection modeling of the garnet amphibolite samples indicates clockwise P-T paths. The samples witness peak metamorphism at conditions of ~4.9–6.3 kbar and ~755–820 ℃ in the upper amphibolite facies to lowtemperature granulite facies, and retrograde cooling and decompression at conditions of ~2.5–3.1 kbar and ~525–545 ℃. It is inferred that peak metamorphism with high temperature and low pressure occurred at ca. 450 Ma during northward subduction of the South Qilian oceanic crust beneath the central Qilian Block. When continental collision occurred between the central Qilian and the Qaidam blocks, the Hualong Block was accreted onto the South Qilian accretionary complex and experienced amphibolite facies retrograde metamorphism at ca. 440 Ma.展开更多
Drug delivery systems(DDS) are used to deliver therapeutic drugs to improve selectivity and reduce side effects. With the development of nanotechnology, many nanocarriers have been developed and applied to drug delive...Drug delivery systems(DDS) are used to deliver therapeutic drugs to improve selectivity and reduce side effects. With the development of nanotechnology, many nanocarriers have been developed and applied to drug delivery, including mesoporous silica. Mesoporous silica nanoparticles(MSNs) have attracted a lot of attention for simple synthesis, biocompatibility, high surface area and pore volume. Based on the pore system and surface modification, gated mesoporous silica nanoparticles can be designed to realize on-command drug release, which provides a new approach for selective delivery of antitumor drugs.Herein, this review mainly focuses on the “gate keepers” of mesoporous silica for drug controlled release in nearly few years(2017–2020). We summarize the mechanism of drug controlled release in gated MSNs and different gated materials: inorganic gated materials, organic gated materials, self-gated drug molecules, and biological membranes. The facing challenges and future prospects of gated MSNs are discussed rationally in the end.展开更多
The Global Navigation Satellite System Reflectometry(GNSS-R) has been proven to be a powerful technique for retrieving geophysical parameters of ocean and land. Airborne GNSS-R is an important experimental platform, b...The Global Navigation Satellite System Reflectometry(GNSS-R) has been proven to be a powerful technique for retrieving geophysical parameters of ocean and land. Airborne GNSS-R is an important experimental platform, because it is not only needed as validation for spaceborne application, but also possesses the advantages to be capable of remote sensing of small and medium scale targets, such as rivers and lakes. This paper presents an overview of China's airborne GNSS-R campaign conducted on May 30, 2014, in Henan. The campaign has two objectives, i.e.:(1) to examine the capability of a GNSS-R payload developed by National Space Science Center,Chinese Academy of Sciences(NSSC, CAS) for airborneobservations and(2) to study the algorithms for soil moisture and river remote sensing, including altimetry and flow velocity measurement. A previous paper has presented results of soil moisture retrieval as part I, and in this paper,initial results of the Yellow River remote sensing are presented as part II. This paper presents the river altimetry results and explores a new potential application of GNSS-R technology, which is used to detect the flow velocity of the river. The river surface height results observed by code delay altimetry method were consistent with the height results of GPS dual-frequency differential positioning altimetry. The GNSS-R altimetry results showed that decimeter level heights were achieved in 1-min sliding average. Comparing with in situ measurements, the GNSSR flow velocity result was reasonable; the error was about0.027 m/s, which indicated the validity and feasibility of using GNSS-R technique to detect river flow velocity.展开更多
基金supported by the Natural Science Foundation of Shandong Province(ZR2019PB013)the Training Program of Innovation and Entrepreneurship for Undergraduates of Liaocheng University(CXCY2022277)。
文摘Precise modulation of the structure and composition of electrocatalysts is critical for promoting the kinetically sluggish process of oxygen reduction reaction(ORR)and oxygen evolution reaction(OER).Covalent organic frameworks(COF)offer a novel way to create highly efficient electrocatalysts due to their tunable composition,structure and surface area.Herein,we report a high-efficiency bifunctional electrocatalyst comprising Co nanoparticles embedded within N-doped carbons(Co@NCs)for Zn-air batteries(ZABs).The Co@NC is yielded via the coordination of a triazine COF with Co-containing precursors and subsequent calcination under inert atmosphere.The as-prepared Co@NC exhibits remarkable ORR/OER performance and great potential in rechargeable ZABs.The liquid ZAB constructed with Co@NC provides both high specific capacity and power density.Remarkably,the ZAB exhibits a voltage gap of 0.8 V during discharge and charge cycles and high stability for 220 h compared to the Pt/C-assembled battery.This strategy for regulating electrocatalytic activities of COF-derived carbon materials could be expanded for creating various carbon catalysts.
基金supported by the Foundation for University Key Teacher of Henan Province, China (2008136)Doctoral Fund of Henan Institute of Engineering(D2007011), China
文摘Bi- and Cu-substituted Ca3Co4O9 samples were prepared by conventional solid-state reaction method and the effect of element substitution on the microstructures and thermoelectric properties was investigated. Partial substitution of Cu for Co leads to an increase in electrical conductivity and a decrease in Seebeck coeffcient due to the rise of hole concentration. The microstructure of Cu-substituted sample is almost unchanged compared with undoped Ca3Co4O9. On the other hand, partial substitution of Bi for Ca gives rise to a significant increase in the grain size, and c-axis-oriented structure can be formed in Ca2.7Bi0.3Co4O9, resulting in an obvious increase in electrical conductivity. Cu and Bi co-substitution further increases the grain growth and the electrical conductivity of Ca2.7Bi0.3Co3.7Cu0.3O9. Thus, Cu and Bi co-substitution samples possess the optimal thermoelectric performance at high temperature and the highest value of power factor can reach 3.1×10-4 Wm-1·K-2 at 1000 K.
基金supported by National Natural Science Foundation of China(Nos.21871055 and 22077018)'National Key R&D Program of China(2017YFA0506000).
文摘Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1(EC_(50)=1.0 nmol/L),but the poor metabolic stability in human liver microsomes(t_(1/2)=14.6 min)and insufficient selectivity(SI=2059)with high cytotoxicity(CC_(50)=2.08μmol/L)remained major issues associated with JK-4b.The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b,leading to the discovery of a novel series of fluorine-substituted NH_(2)-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain(EC_(50)=1.8–349 nmol/L).The best compound 5t in this collection(EC_(50)=1.8 nmol/L,CC_(50)=117μmol/L)was 32-fold in selectivity(SI=66,443)compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains,such as L100I,K103N,E138K,and Y181C.The metabolic stability of 5t was also significantly improved(t_(1/2)=74.52 min),approximately 5-fold higher than JK-4b in human liver microsomes(t_(1/2)=14.6 min).Also,5t possessed good stability in both human and monkey plasma.No significant in vitro inhibition effect toward CYP enzyme and hERG was observed.The single-dose acute toxicity test did not induce mice death or obvious pathological damage.These findings pave the way for further development of 5t as a drug candidate.
基金supported,in part,by the National Natural Science Foundation of China(Nos.81773735,81973313,and 81503069)the National Key R&D Program of China(No.2017YFC1702003)+1 种基金the Natural Science Foundation of Heilongjiang Province(No.ZD2022H002)the Fundamental Research Funds for the Provincial Universities-Academician Mr.Yu Weihan Foundation for Distinguished Young Scholars(No.JFYWH202001).
文摘Long noncoding RNAs(lncRNAs)play a critical role in the regulation of atherosclerosis.Here,we investigated the role of the lncRNA growth arrest-specific 5(lncR-GAS5)in atherogenesis.We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis,which presented as increased plaque size and reduced collagen content.Moreover,impaired autophagy was observed,as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells.By contrast,lncR-GAS5 knockdown promoted autophagy.Moreover,serine/arginine-rich splicing factor 10(SRSF10)knockdown increased the LC3II/LC3I ratio and decreased the P62 level,thus enhancing the formation of autophagic vacuoles,autolysosomes,and autophagosomes.Mechanistically,lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium,which was reversed by the knockdown of SRSF10.Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene,SRSF10.Notably,miR-193-5p overexpression decreased plaque size and increased collagen content.Altogether,these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy.In conclusion,lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway.Thus,miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
基金This work was supported by the National Key R&D Program of China(Grant No.2021YFC2400500 and 2018YFC1106300)the National Natural Science Foundation of China(Grant No.52072398,31870956,32161160327,U2001221,31771041,81860385)+2 种基金the Frontier Science Key Research Programs of CAS(Grant No.QYZDB-SSW-JSC030)the Shenzhen Significant Strategy Layout Project(Grant No.JCYJ20200109114620793)Natural Science Foundation of Guangxi Province(Grant No.2020GXNSFBA297154 and 2022GXNSFAA035472).
文摘Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria,which include:1)recruitment and polarization of the macrophages from M1(pro-inflammatory)to M2(anti-inflammatory)phenotype,2)enhance vascularization,and 3)activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing.So far,no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation,angiogenesis,and osteogenesis.Therefore,in this study,we designed bone cement comprised of strontium and copper-incorporated borosilicate glass(Sr/Cu-BSG)in the liquid phase of chitosan to modulate bone healing.In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1)while down-regulating pro-inflammatory genes(IL-1βand IL-6)in macrophages at 3 days.Sr and Cu ions also increased the expressions of angiogenic genes(VEGF and bFGF)in HUVECs at 5 days and osteogenic genes(Runx-2,OCN,and OPN)in hBMSCs at 7,14,and 21 days.5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory,angiogenic,and osteogenic properties among the bone cement groups with different Sr and Cu ratios.Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results,where the degradation rate of Sr/Cu-BSG matched the bone healing rate.Similar to in vitro,the 5Sr3Cu-BSG group also showed the highest bone formation in vivo.Excellent physical and chemical properties,along with its bone repairing ability,make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.
基金supported by the National Key R&D Program of China(2021YFC2400500)National Natural Science Foundation of China(Nos.U2001221 and 32161160327)+1 种基金Shenzhen Science and Technology Program(JCYJ20200109114620793 and JSGGKQTD20210831174330015)Guangdong Basic and Applied Basic Research Foundation(2022B 1515120048 and 2023A1515011727).
文摘The regeneration of alveolar bone is still clinical challenge,particularly accompanied with diabetes,causing metabolic disorder with a protracted low-grade inflammatory phenotype.As a result,the anticipated loading of biomaterials is highly suspicious in spontaneous modulation of cells function,which is mostly disturbed by constant inflammation.In this study,we developed glucose and hydrogen peroxide dual-responsive borosilicate glass(BSG)scaffolds loaded with epigallocatechin gallate(EGCG)to synergistically modulate the abnormal inflammation of diabetic alveolar bone defects.It was found that the release of EGCG by BSG could directly regulate the shift of macrophages from M1 to the M2 phenotype by promoting autophagy and lessening the inhibition of autophagic flux.Moreover,EGCG can also indirectly regulate the polarization phenotype of macrophages by reducing the activation of NF-κb in stem cells and restoring its immunoregulatory capacity.Therefore,the addition of EGCG to BSG scaffold in diabetes allows for a more striking modulation of the macrophage phenotype in a timely manner.The altered macrophage phenotype reduces local inflammation and thus increases the ability to repair diabetic alveolar bone,showing promise for the treatment of alveolar defect in diabetic patients.
基金This work was supported by the Innovation and Strong School Project of Guangdong Pharmaceutical University(2021ZDzX2028)the Scientific and Technological Innovation Leading Talent Project of Zhongshan City(LJ2021009)a Start-up Grant from Guangdong Pharmaceutical University(Grant Nos.51361303,51361304).
文摘A visible-light-induced C-5 selective C-H borylation of imidazo[1,2-a]pyridines with NHC-BH3 via Minisci-type radical borylation re-action has been developed for the first time.The present sustainable protocol provides a new family of regioselectively C5-borylated imidazopyridines that would otherwise be difficult to prepare.It is a supplement to site-selective borylation of azines(nitrogen-con-taining aromatic heterocycles)and the assembly of sp2 carbon-boron bond.
基金supported by the National Key Basic Research Program on Global Change of China(2011CB952001)the National Key Basic Research Special Foundation of China(2006FY1106000)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)and the Open Fund Program of the State Key Laboratory of RemoteSensing Science,China(OFSLRSS201112)
文摘During the years 2006–2009,lakes in the Qinghai-Tibetan Plateau(QTP)were investigated using satellite remote sensing strategies.We report the results of this investigation as well as follow-up research and expanded work.For the investigation,we mainly focused on lakes whose areas are more than 1 km2.The remote sensing data that we used included 408 scenes of CBERS CCD images and 5 scenes of Landsat ETM?images in Qinghai Province and Tibet Autonomous Region.All these data were acquired around years 2005–2006.Besides remote sensing images,we also collected 1,259 topographic maps.Numbers and areas of lakes were analyzed statistically,which were then compared with those coming from the first lake investigation(implemented between the1960s and 1980s).According to our investigation,up to and around year 2005–2006,the total number of lakes in the QTP was 1,055(222 in Qinghai and 833 in Tibet),accounting for more than 30%of that of China.Thirty newborn lakes with area[1 km2were found,and 5 dead lakes with initial area[1 km2were also found.Among those 13 big lakes([500 km2),Yamzhog Yumco had seriously shrunk,and it has continued to shrink in recent years;Qinghai Lake had shrunk during the period,but some new researches indicated that it has been expanding since the year 2004;Siling Co,Nam Co,and Chibuzhang Co had expanded in the period.We divided the newborn lakes into six categories according to their forming reasons,including river expansion,wetland conversion,etc.The changes of natural conditions led to the death of four lakes,and human exploitation was the main reason for the death of Dalianhai Lake in Qinghai.We picked out three regions which were sensitive to the change of climate and ecological environment:Nagqu Region,Kekexili Region,and the source area of the Yellow River(SAYR).Lakes in both Nagqu and Kekexili have been expanded;meanwhile,most lakes in the SAYR have obviously been shrunk.These regional patterns of lake changes were highly related to variations of temperature,glacier,precipitation,and evaporation.Our investigation and analysis will provide references for researches related to lake changes in the QTP and the response to climate fluctuations.
基金supported by 973 program (No.2013CB429802) to Y.J.Liuthe National Natural Science Foundation of China (Grant 41302175) to W.M.LiJilin University and JSPS Grant-in-Aid for Scientific Research (Nos.17340149, 24340124) to A.Takasu, Shimane University, Japan
文摘Blueschist accompanied by pelitic schist expose along the Xinlin-Xiguitu fault in the Toudaoqiao area, northeastern China. In this paper, the blueschist is systematically studied on the petrography and mineral chemistry. The amphiboles in the blueschist are zoned from winchite core to magnesioriebeckite/glaucophane rim to winchite outermost rim. The peak metamorphic conditions are defined by the mineral assemblage of magnesioriebeckite/glaucophane, epidote, high-Si phengite(Si<7.1), chlorite, albite, hematite and quartz, indicating an epidote-blueschist facies metamorphism. The P-T conditions are estimated as T=350–400 ℃ and P=10-12 kbar. The occurrence of the blueschist along the Xinlin-Xiguitu fault strongly suggests the fault is the suture between the Ergun and the Xing'an blocks situated in the eastern portions of the Central Asia Orogenic Belt(CAOB).
基金funded by the National Natural Science Foundation of China (No. 41520104003)the National Key R & D Program of China (No. 2016YFC0600403)+1 种基金the China Geological Survey (No. DD20160201)the Fundamental Research Funds for the Central Universities,China University of Geosciences (Wuhan) (Nos. CUGL170404,CUG160232)
文摘The Central Qilian Block is a Precambrian block in the Qilian Orogen,which has long drawn international attention for the study of orogeny and continental dynamics.The Huangyuan Group in the Datong area is one of the Precambrian metamorphic basement units in the Central Qilian Block and reflects metamorphism in the Barrovian garnet zone and sillimanite zone from south to north.Based on detailed fieldwork,this study presents a systematic study of petrography,mineral chemistry and phase equilibria of schists and gneisses from the two metamorphic zones.The garnet metamorphic zone is composed of micaschist,garnet-bearing micaschist and felsic leptynite,with interlayered plagioclase amphibolite.The sillimanite metamorphic zone consists of garnet-bearing biotite micaschist,sillimanite-bearing biotite-plagioclase gneiss and felsic leptynite.Garnet from the garnet metamorphic zone shows growth zoning with increasing almandine and pyrope and decreasing spessartine from core to rim.Garnet from the sillimanite metamorphic zone is almost homogeneous.Towards the outer rim,the contents of almandine and pyrope slightly decrease and grossular slightly increase.Biotite in both metamorphic zones is ferro-biotite.Plagioclase is oligoclase in garnet metamorphic zone and andesine in sillimanite metamorphic zone.Phase equilibrium modeling of a sample from garnet metamorphic zone resulted in a clockwise P-T path with a prograde stage(4.5–5.0 kbar,520–530℃),a peak P stage(9.8–10.2 kbar,560–570℃),a stage of thermal relaxation(8.0–8.5 kbar,580–590℃)and finally a retrograde stage(6.8–7.0 kbar,560–580℃).Thermodynamic modeling of a sample from the sillimanite metamorphic zone indicates a prograde stage(5.5–6.0 kbar,540–550℃)and a peak stage(7.8–8.5 kbar,660–690℃).The results indicate that the Huangyuan Group experienced medium-pressure amphibolite-facies metamorphism,which resulted from continental-continental collision between the Qaidam Block and the Central Qilian Block.
基金supported by the National Natural Science Foundation of China(81321004,81621064,Jiandong Jiang81322050,Zonggen Peng)+2 种基金National Mega-Project for “R&D for Innovative drugs”,Ministry of Science and Technology,China(2012ZX09301-002-001,Jiandong Jiang,2018ZX09711001-003-010,Zonggen Peng)Ministry of Education,China(NCET-12-0072,Zonggen Peng)CAMS Innovation Fund for Medical Sciences,China(CIFMS)(2017-I2M-3-012,Zonggen Peng)
文摘Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.
基金financially supported by theNational Basic Research Program of China(2011CBA00107,2011CBA00202)the National Natural Science Foundation of China(11227904 and 61101012)
文摘Performances of superconducting nanowire single-photon detectors(SNSPDs) based on low TCmaterials strongly depend on the operating temperatures. We have fabricated infrared-sensitive niobium SNSPDs based on doped niobium(Nb*) films and measured them in He-3cryocooler. The critical current approaches to the de-pairing current at 0.3 K. Therefore, with the decrease in temperatures, we have observed a monotonous increase of count rate at the wavelength of 1,521 nm and exponential decrease of dark count rate at all bias currents. The possible origin of dark counts for doped Nb devices is also discussed.
基金funded by the National Natural Science Foundation of China (No. 41520104003)the National Key R & D Program of China (No. 2016YFC0600403)+1 种基金the China Geological Survey (No. DD20160201)the Fundamental Research Funds for the Central Universities, China University of Geosciences (Wuhan) (Nos. CUGL170404, CUG160232)
文摘The Qilian Orogen marks the junction of the North China, South China and Tarim cratons. The mechanism of continental growth during the formation of the orogen remains unclear. Based on detailed fieldwork, we present a systematic study of petrography, mineral chemistry and phase equilibria of garnet amphibolites from the Hualong Group, which represents the Precambrian basement in the southern accretionary belt of the Qilian Orogen. The garnet amphibolites mainly consist of amphibole, plagioclase, garnet and quartz, with minor pyroxene, biotite and ilmenite. A peak stage of upper amphibolite facies to low-temperature granulite facies metamorphism and retrograde metamorphism in the amphibolite facies affected the samples. Garnet has a homogeneous composition of Alm66–71 Grs14–17 Prp9–12 Sps3–5, amphibole is ferro-hornblende, biotite belongs to the ferro-biotite species and pyroxene is dominated by orthopyroxene with few clinopyroxene. Pseudosection modeling of the garnet amphibolite samples indicates clockwise P-T paths. The samples witness peak metamorphism at conditions of ~4.9–6.3 kbar and ~755–820 ℃ in the upper amphibolite facies to lowtemperature granulite facies, and retrograde cooling and decompression at conditions of ~2.5–3.1 kbar and ~525–545 ℃. It is inferred that peak metamorphism with high temperature and low pressure occurred at ca. 450 Ma during northward subduction of the South Qilian oceanic crust beneath the central Qilian Block. When continental collision occurred between the central Qilian and the Qaidam blocks, the Hualong Block was accreted onto the South Qilian accretionary complex and experienced amphibolite facies retrograde metamorphism at ca. 440 Ma.
基金the financial support from the National Natural Science Foundation of China (No. 32071342)Guangdong Special Support Program (No. 2019TQ05Y209)+5 种基金Natural Science Foundation of Guangdong Province (No. 2021A1515010431)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (No. SZGSP001)Shenzhen Key Laboratory of Kindey Diseases(No. ZDSYS201504301616234)the Key Project of Basic Research of Shenzhen (No. JCYJ20200109113603854)the International Cooperation Research Project of Shenzhen (No. GJHZ20180418190557102)the Special Funds of Key Disciplines Construction from Guangdong and Zhongshan Cooperating。
文摘Drug delivery systems(DDS) are used to deliver therapeutic drugs to improve selectivity and reduce side effects. With the development of nanotechnology, many nanocarriers have been developed and applied to drug delivery, including mesoporous silica. Mesoporous silica nanoparticles(MSNs) have attracted a lot of attention for simple synthesis, biocompatibility, high surface area and pore volume. Based on the pore system and surface modification, gated mesoporous silica nanoparticles can be designed to realize on-command drug release, which provides a new approach for selective delivery of antitumor drugs.Herein, this review mainly focuses on the “gate keepers” of mesoporous silica for drug controlled release in nearly few years(2017–2020). We summarize the mechanism of drug controlled release in gated MSNs and different gated materials: inorganic gated materials, organic gated materials, self-gated drug molecules, and biological membranes. The facing challenges and future prospects of gated MSNs are discussed rationally in the end.
基金supported by the National Youth Natural Science Foundations of China(41405040 and 41405039)the Scientific Research and Equipment Development Project of Chinese Academy of Sciences(YZ201129)the 12th Five-Year Plan of Civil Aerospace Technology Advanced Research Projects(Y1K0030044)
文摘The Global Navigation Satellite System Reflectometry(GNSS-R) has been proven to be a powerful technique for retrieving geophysical parameters of ocean and land. Airborne GNSS-R is an important experimental platform, because it is not only needed as validation for spaceborne application, but also possesses the advantages to be capable of remote sensing of small and medium scale targets, such as rivers and lakes. This paper presents an overview of China's airborne GNSS-R campaign conducted on May 30, 2014, in Henan. The campaign has two objectives, i.e.:(1) to examine the capability of a GNSS-R payload developed by National Space Science Center,Chinese Academy of Sciences(NSSC, CAS) for airborneobservations and(2) to study the algorithms for soil moisture and river remote sensing, including altimetry and flow velocity measurement. A previous paper has presented results of soil moisture retrieval as part I, and in this paper,initial results of the Yellow River remote sensing are presented as part II. This paper presents the river altimetry results and explores a new potential application of GNSS-R technology, which is used to detect the flow velocity of the river. The river surface height results observed by code delay altimetry method were consistent with the height results of GPS dual-frequency differential positioning altimetry. The GNSS-R altimetry results showed that decimeter level heights were achieved in 1-min sliding average. Comparing with in situ measurements, the GNSSR flow velocity result was reasonable; the error was about0.027 m/s, which indicated the validity and feasibility of using GNSS-R technique to detect river flow velocity.
