AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment...AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.展开更多
BACKGROUND The role of primary-level medical pharmacists in medical institutions in China is limited;therefore,it is necessary to explore the role of pharmacists in the process of drug treatment.CASE SUMMARY A Chinese...BACKGROUND The role of primary-level medical pharmacists in medical institutions in China is limited;therefore,it is necessary to explore the role of pharmacists in the process of drug treatment.CASE SUMMARY A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer.The rationale for drug treatment was evaluated,and adjustments were made to the antacid and anti-infective regimen,as well as the dose and frequency of administration.Body temperature,routine blood examination,and adverse drug reactions were strictly monitored.During treatment,the pharmacist recommended anti-infective therapy with ampicillin-sulbactam,which effectively controlled the infection.Additionally,the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment,combined with Chinese patent medicine such as Kangfuxin Liquid.This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection.CONCLUSION A pharmacist participated in the treatment process,provided individualized medication adjustment,and achieved good clinical results.展开更多
BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main m...BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.展开更多
Severe polysulfide shuttling and sluggish sulfur redox kinetics significantly decrease sulfur utilization and cycling stability in lithium-sulfur batteries(LSBs).Herein,we develop a hollow CoO/CoP-Box core-shell heter...Severe polysulfide shuttling and sluggish sulfur redox kinetics significantly decrease sulfur utilization and cycling stability in lithium-sulfur batteries(LSBs).Herein,we develop a hollow CoO/CoP-Box core-shell heterostructure as a model and multifunctional catalyst modified on separators to induce interfacial charge modulation and expose more active sites for promoting the adsorption and catalytic conversion ability of sulfur species.Theoretical and experimental findings verify that the in-situ formed core-shell hetero-interface induces the formation of P-Co-O binding and charge redistribution to activate surface O active sites for binding lithium polysulfides(LiPSs)via strong Li-O bonding,thus strongly adsorbing with Li PSs.Meanwhile,the strong Li-O bonding weakens the competing Li-S bonding in LiPSs or Li2S adsorbed on CoO/CoP-Box surface,plus the hollow heterostructure provides abundant active sites and fast electron/Li+transfer,so reducing Li2S nucleation/dissolution activation energy.As expected,LSBs with CoO/CoP-Box modified separator and traditional sulfur/carbon black cathode display a large initial capacity of 1240 mA h g^(-1)and a long cycling stability with 300 cycles(~60.1%capacity retention)at 0.5C.Impressively,the thick sulfur cathode(sulfur loading:5.2 mg cm^(-2))displays a high initial areal capacity of 6.9 mA h cm^(-2).This work verifies a deep mechanism understanding and an effective strategy to induce interfacial charge modulation and enhance active sites for designing efficient dual-directional Li-S catalysts via engineering hollow core-shell hetero-structure.展开更多
Holiday Tourism Circle of Beijing (HTCB) is one of the nine key regions of Chinese tourism industry in the period of the 11th Five-Year Project. According to Tourist Marginal Utility Theory, Time-Distance Method is us...Holiday Tourism Circle of Beijing (HTCB) is one of the nine key regions of Chinese tourism industry in the period of the 11th Five-Year Project. According to Tourist Marginal Utility Theory, Time-Distance Method is used to define HTCB in this paper. Chengde City, famous for its cultural tourism, is regard as one of the regions in Holiday Tourism Circle of Beijing. And this geographical advantage, in the context of the boom of tourism in China, is featured by the changes of tourist product structure and development model. In this paper, the influence upon Chengde tourism spatial structure has been discussed from tourist market, location and transportation. Chengde tourism spatial structure has been rebuilt with particular references to the factors of tourism destination district, tourist area, nodes, routes, and origin markets. In this paper, Chengde will develop tourism industry with the central heritage area as the center and northern forest and pasture area and southern mountain and lake area as the two wings.展开更多
Structural damage is significantly influenced by the various parameters of a close-in explosion.To establish a close-in blast loading model for cylindrical charges according to these parameters,a series of field exper...Structural damage is significantly influenced by the various parameters of a close-in explosion.To establish a close-in blast loading model for cylindrical charges according to these parameters,a series of field experiments and a systematic numerical analysis were conducted.A high-fidelity finite element model developed using AUTODYN was first validated using blast data collected from field tests conducted in this and previous studies.A quantitative analysis was then performed to determine the influence of the charge shape,aspect ratio(length to diameter),orientation,and detonation configuration on the characteristics and distributions of the blast loading(incident peak overpressure and impulse)according to scaled distance.The results revealed that the secondary peak overpressure generated by a cylindrical charge was mainly distributed along the axial direction and was smaller than the overpressure generated by an equivalent spherical charge.The effects of charge shape on the blast loading at 45°and 67.5°in the axial plane could be neglected at scaled distances greater than 2 m/kg^(1/3);the effect of aspect ratios greater than 2 on the peak overpressure in the 90°(radial)direction could be neglected at all scaled distances;and double-end detonation increased the radial blast loading by up to 60%compared to singleend detonation.Finally,an empirical cylindrical charge blast loading model was developed considering the influences of charge aspect ratio,orientation,and detonation configuration.The results obtained in this study can serve as a reference for the design of blast tests using cylindrical charges and aid engineers in the design of blast-resistant structures.展开更多
When an explosion occurs close to or partially within the face of a concrete structure, fragments are rapidly launched from the opposite face of the structure owing to concrete spalling, posing a significant risk to n...When an explosion occurs close to or partially within the face of a concrete structure, fragments are rapidly launched from the opposite face of the structure owing to concrete spalling, posing a significant risk to nearby personnel and equipment. To study the lead fragment velocity of ultra-high-performance concrete(UHPC), partially embedded explosion experiments were performed on UHPC slabs of limited thickness using a cylindrical trinitrotoluene charge. The launch angles and velocities of the resulting fragments were the determined using images collected by high-speed camera to document the concrete spalling and fragment launching process. The results showed that UHPC slabs without fiber reinforcement had a fragment velocity distribution of 0-118.3 m/s, which are largely identical to that for a normal-strength concrete(NSC) slab. In addition, the fragment velocity was negatively correlated to the angle between the velocity vector and vertical direction. An empirical Eq. for the lead spall velocity of UHPC and NSC slabs was then proposed based on a large volume of existing experimental data.展开更多
BACKGROUND The transforming growth factor β(TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type Ⅱ receptor(TGFβR2), followed by the recruitment of TGFβR1 fin...BACKGROUND The transforming growth factor β(TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type Ⅱ receptor(TGFβR2), followed by the recruitment of TGFβR1 finally triggering downstream signaling pathway.AIM To find drugs targeting TGFβR2 that inhibit TGFβR1/TGFβR2 complex formation, theoretically inhibit TGFβ signaling pathway, and thereby ameliorate liver fibrosis.METHODS Food and Drug Administration-approved drugs were screened for binding affinity with TGFβR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8(CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect.RESULTS We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine(DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFβ induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFβR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFβR2 disrupted the binding of TGFβR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson’s trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver.CONCLUSION DHE alleviates liver fibrosis by binding to TGFβR2 thereby suppressing TGFβ signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.展开更多
At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional...At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional(3D)printing technology has made a great breakthrough in the clinical application of orthopedic implants.This study explored the combination of 3D printing and tissue engineering to precisely reconstruct the auricle.First,a polylactic acid(PLA)polymer scaffold with a precisely customized patient appearance was fabricated,and then auricle cartilage fragments were loaded into the 3D-printed porous PLA scaffold to promote auricle reconstruction.In vitro,gelatin methacrylamide(GelMA)hydrogels loaded with different sizes of rabbit ear cartilage fragments were studied to assess the regenerative activity of various autologous cartilage fragments.In vivo,rat ear cartilage fragments were placed in an accurately designed porous PLA polymer ear scaffold to promote auricle reconstruction.The results indicated that the chondrocytes in the cartilage fragments could maintain the morphological phenotype in vitro.After three months of implantation observation,it was conducive to promoting the subsequent regeneration of cartilage in vivo.The autologous cartilage fragments combined with 3D printing technology show promising potential in auricle reconstruction.展开更多
Radio-frequency(RF)breakdown analysis and location are critical for successful development of high-gradient traveling-wave(TW)accelerators,especially those expected to generate high-intensity,high-power beams.Compared...Radio-frequency(RF)breakdown analysis and location are critical for successful development of high-gradient traveling-wave(TW)accelerators,especially those expected to generate high-intensity,high-power beams.Compared with commonly used schemes involving dedicated devices or complicated techniques,a convenient approach for breakdown locating based on transmission line(TL)theory offers advantages in the typical constant-gradient TW-accelerating structure.To deliver such an approach,an equivalent TL model has been constructed to equate the TW-accelerating structure based on the fun-damental theory of the TL transient response in the time domain.An equivalence relationship between the TW-accelerating structure and the TL model has been established via analytical derivations associated with grid charts and verified by TL circuit simulations.Furthermore,to validate the proposed fault-locating method in practical applications,an elaborate analysis via such a method has been conducted for the recoverable RF-breakdown phenomena observed at an existing prototype of a TW-accelerating-structure-based beam injector constructed at the Huazhong University of Science and Technology.In addition,further considerations and discussion for extending the applications of the proposed method have been given.This breakdown-locating approach involving the transient response in the framework of TL theory can be a conceivable supple-ment to existing methods,facilitating solution to construction problems at an affordable cost.展开更多
Hubble tension between the local measurement and global observation has been a key problem in cosmology.In this paper,we consider the quintessence scalar field,phantom field and quintom field as the dark energy to rec...Hubble tension between the local measurement and global observation has been a key problem in cosmology.In this paper,we consider the quintessence scalar field,phantom field and quintom field as the dark energy to reconcile this problem.Different from most previous work,we start from the dimensionless equation of state(w)of dark energy,not a parameterization of potential.The combined analysis shows that observational data sets favor Hubble constant H0=71.3-0.917+0.854 km s^(-1)Mpc^(-1),which can reconcile Hubble tension within 1.20σ.We also perform a Bayes factor analysis using the MCEvidence code,and confirm that the phantom scalar field is still the most effective.To investigate the reason of Hubble tension,we analyze the density parameter.The comparison shows that the scalar fields provide a slightly largerΩbh2 and smallerΩch2 than the standardΛCDM model.We finally analyze a possible reason of Hubble tension from the kinematic acceleration?.We find an interesting physical phenomenon.The acceleration a in these scalar fields are similar as theΛCDM model at about redshift z>0.5.However,they increase and deviate from each other at low redshift,especially in the near future.Only the?in phantom scalar field will decrease in the future.展开更多
基金Supported by the Key Research&Development Program of Shaanxi Province(No.2022SF-311,No.2024SFYBXM-328,No.2024SF-YBXM-325)the Natural Science Basic Research Program of Shaanxi Province,China(No.2021JQ-385).
文摘AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.
文摘BACKGROUND The role of primary-level medical pharmacists in medical institutions in China is limited;therefore,it is necessary to explore the role of pharmacists in the process of drug treatment.CASE SUMMARY A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer.The rationale for drug treatment was evaluated,and adjustments were made to the antacid and anti-infective regimen,as well as the dose and frequency of administration.Body temperature,routine blood examination,and adverse drug reactions were strictly monitored.During treatment,the pharmacist recommended anti-infective therapy with ampicillin-sulbactam,which effectively controlled the infection.Additionally,the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment,combined with Chinese patent medicine such as Kangfuxin Liquid.This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection.CONCLUSION A pharmacist participated in the treatment process,provided individualized medication adjustment,and achieved good clinical results.
基金Supported by National Natural Science Foundation of China,No.82270845。
文摘BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.
基金supported by the National Natural Science Foundation of China(51972066)the Natural Science Foundation of Guangdong Province of China(2021A1515011718)the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017。
文摘Severe polysulfide shuttling and sluggish sulfur redox kinetics significantly decrease sulfur utilization and cycling stability in lithium-sulfur batteries(LSBs).Herein,we develop a hollow CoO/CoP-Box core-shell heterostructure as a model and multifunctional catalyst modified on separators to induce interfacial charge modulation and expose more active sites for promoting the adsorption and catalytic conversion ability of sulfur species.Theoretical and experimental findings verify that the in-situ formed core-shell hetero-interface induces the formation of P-Co-O binding and charge redistribution to activate surface O active sites for binding lithium polysulfides(LiPSs)via strong Li-O bonding,thus strongly adsorbing with Li PSs.Meanwhile,the strong Li-O bonding weakens the competing Li-S bonding in LiPSs or Li2S adsorbed on CoO/CoP-Box surface,plus the hollow heterostructure provides abundant active sites and fast electron/Li+transfer,so reducing Li2S nucleation/dissolution activation energy.As expected,LSBs with CoO/CoP-Box modified separator and traditional sulfur/carbon black cathode display a large initial capacity of 1240 mA h g^(-1)and a long cycling stability with 300 cycles(~60.1%capacity retention)at 0.5C.Impressively,the thick sulfur cathode(sulfur loading:5.2 mg cm^(-2))displays a high initial areal capacity of 6.9 mA h cm^(-2).This work verifies a deep mechanism understanding and an effective strategy to induce interfacial charge modulation and enhance active sites for designing efficient dual-directional Li-S catalysts via engineering hollow core-shell hetero-structure.
文摘Holiday Tourism Circle of Beijing (HTCB) is one of the nine key regions of Chinese tourism industry in the period of the 11th Five-Year Project. According to Tourist Marginal Utility Theory, Time-Distance Method is used to define HTCB in this paper. Chengde City, famous for its cultural tourism, is regard as one of the regions in Holiday Tourism Circle of Beijing. And this geographical advantage, in the context of the boom of tourism in China, is featured by the changes of tourist product structure and development model. In this paper, the influence upon Chengde tourism spatial structure has been discussed from tourist market, location and transportation. Chengde tourism spatial structure has been rebuilt with particular references to the factors of tourism destination district, tourist area, nodes, routes, and origin markets. In this paper, Chengde will develop tourism industry with the central heritage area as the center and northern forest and pasture area and southern mountain and lake area as the two wings.
基金supported by the National Natural Science Foundation of China[No.51978166]。
文摘Structural damage is significantly influenced by the various parameters of a close-in explosion.To establish a close-in blast loading model for cylindrical charges according to these parameters,a series of field experiments and a systematic numerical analysis were conducted.A high-fidelity finite element model developed using AUTODYN was first validated using blast data collected from field tests conducted in this and previous studies.A quantitative analysis was then performed to determine the influence of the charge shape,aspect ratio(length to diameter),orientation,and detonation configuration on the characteristics and distributions of the blast loading(incident peak overpressure and impulse)according to scaled distance.The results revealed that the secondary peak overpressure generated by a cylindrical charge was mainly distributed along the axial direction and was smaller than the overpressure generated by an equivalent spherical charge.The effects of charge shape on the blast loading at 45°and 67.5°in the axial plane could be neglected at scaled distances greater than 2 m/kg^(1/3);the effect of aspect ratios greater than 2 on the peak overpressure in the 90°(radial)direction could be neglected at all scaled distances;and double-end detonation increased the radial blast loading by up to 60%compared to singleend detonation.Finally,an empirical cylindrical charge blast loading model was developed considering the influences of charge aspect ratio,orientation,and detonation configuration.The results obtained in this study can serve as a reference for the design of blast tests using cylindrical charges and aid engineers in the design of blast-resistant structures.
基金supported by the National Natural Science Foundation of China[No.51978166]。
文摘When an explosion occurs close to or partially within the face of a concrete structure, fragments are rapidly launched from the opposite face of the structure owing to concrete spalling, posing a significant risk to nearby personnel and equipment. To study the lead fragment velocity of ultra-high-performance concrete(UHPC), partially embedded explosion experiments were performed on UHPC slabs of limited thickness using a cylindrical trinitrotoluene charge. The launch angles and velocities of the resulting fragments were the determined using images collected by high-speed camera to document the concrete spalling and fragment launching process. The results showed that UHPC slabs without fiber reinforcement had a fragment velocity distribution of 0-118.3 m/s, which are largely identical to that for a normal-strength concrete(NSC) slab. In addition, the fragment velocity was negatively correlated to the angle between the velocity vector and vertical direction. An empirical Eq. for the lead spall velocity of UHPC and NSC slabs was then proposed based on a large volume of existing experimental data.
基金Supported by the Special Research Project for Capital Health Development,No.2022-2-2174the Beijing Municipal Science and Technology Commission,No.Z191100007619037.
文摘BACKGROUND The transforming growth factor β(TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type Ⅱ receptor(TGFβR2), followed by the recruitment of TGFβR1 finally triggering downstream signaling pathway.AIM To find drugs targeting TGFβR2 that inhibit TGFβR1/TGFβR2 complex formation, theoretically inhibit TGFβ signaling pathway, and thereby ameliorate liver fibrosis.METHODS Food and Drug Administration-approved drugs were screened for binding affinity with TGFβR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8(CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect.RESULTS We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine(DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFβ induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFβR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFβR2 disrupted the binding of TGFβR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson’s trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver.CONCLUSION DHE alleviates liver fibrosis by binding to TGFβR2 thereby suppressing TGFβ signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.
基金supported by the National Natural Science Foundation of China(No.81171731)the Project of Chengdu Science and Technology Bureau(Nos.2021-YF05-01619-SN and 2021-RC05-00022-CG)+2 种基金the Science and Technology Project of Tibet Autonomous Region(Nos.XZ202202YD0013C and XZ201901-GB-08)the Sichuan Science and Technology Program(No.2022YFG0066)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Nos.ZYJC21026,ZYGD21001 and ZYJC21077).
文摘At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional(3D)printing technology has made a great breakthrough in the clinical application of orthopedic implants.This study explored the combination of 3D printing and tissue engineering to precisely reconstruct the auricle.First,a polylactic acid(PLA)polymer scaffold with a precisely customized patient appearance was fabricated,and then auricle cartilage fragments were loaded into the 3D-printed porous PLA scaffold to promote auricle reconstruction.In vitro,gelatin methacrylamide(GelMA)hydrogels loaded with different sizes of rabbit ear cartilage fragments were studied to assess the regenerative activity of various autologous cartilage fragments.In vivo,rat ear cartilage fragments were placed in an accurately designed porous PLA polymer ear scaffold to promote auricle reconstruction.The results indicated that the chondrocytes in the cartilage fragments could maintain the morphological phenotype in vitro.After three months of implantation observation,it was conducive to promoting the subsequent regeneration of cartilage in vivo.The autologous cartilage fragments combined with 3D printing technology show promising potential in auricle reconstruction.
基金supported by the National Natural Science Foundation of China(No.11905074).
文摘Radio-frequency(RF)breakdown analysis and location are critical for successful development of high-gradient traveling-wave(TW)accelerators,especially those expected to generate high-intensity,high-power beams.Compared with commonly used schemes involving dedicated devices or complicated techniques,a convenient approach for breakdown locating based on transmission line(TL)theory offers advantages in the typical constant-gradient TW-accelerating structure.To deliver such an approach,an equivalent TL model has been constructed to equate the TW-accelerating structure based on the fun-damental theory of the TL transient response in the time domain.An equivalence relationship between the TW-accelerating structure and the TL model has been established via analytical derivations associated with grid charts and verified by TL circuit simulations.Furthermore,to validate the proposed fault-locating method in practical applications,an elaborate analysis via such a method has been conducted for the recoverable RF-breakdown phenomena observed at an existing prototype of a TW-accelerating-structure-based beam injector constructed at the Huazhong University of Science and Technology.In addition,further considerations and discussion for extending the applications of the proposed method have been given.This breakdown-locating approach involving the transient response in the framework of TL theory can be a conceivable supple-ment to existing methods,facilitating solution to construction problems at an affordable cost.
基金Ming-Jian Zhang is supported by the Natural Science Foundation of Shandong Province(Grant No.ZR2021MA075)Li Chen is supported by the Natural Science Foundation of Shandong Province(Grant No.ZR2019MA033)。
文摘Hubble tension between the local measurement and global observation has been a key problem in cosmology.In this paper,we consider the quintessence scalar field,phantom field and quintom field as the dark energy to reconcile this problem.Different from most previous work,we start from the dimensionless equation of state(w)of dark energy,not a parameterization of potential.The combined analysis shows that observational data sets favor Hubble constant H0=71.3-0.917+0.854 km s^(-1)Mpc^(-1),which can reconcile Hubble tension within 1.20σ.We also perform a Bayes factor analysis using the MCEvidence code,and confirm that the phantom scalar field is still the most effective.To investigate the reason of Hubble tension,we analyze the density parameter.The comparison shows that the scalar fields provide a slightly largerΩbh2 and smallerΩch2 than the standardΛCDM model.We finally analyze a possible reason of Hubble tension from the kinematic acceleration?.We find an interesting physical phenomenon.The acceleration a in these scalar fields are similar as theΛCDM model at about redshift z>0.5.However,they increase and deviate from each other at low redshift,especially in the near future.Only the?in phantom scalar field will decrease in the future.
