Objective:To investigate the clinical efficacy of Modified Gegen Qinlian Decoction combined with probiotics(Clostridium butyricum live capsules)in treating radiation enteritis(RE)in tumor patients,as well as its regul...Objective:To investigate the clinical efficacy of Modified Gegen Qinlian Decoction combined with probiotics(Clostridium butyricum live capsules)in treating radiation enteritis(RE)in tumor patients,as well as its regulatory effect on the structure of intestinal flora,providing clinical evidence for the integrated traditional Chinese and Western medicine treatment of radiation enteritis.Methods:A total of 40 patients with radiation enteritis admitted to the Oncology Department of Linfen Central Hospital from September 2023 to December 2024 were selected and divided into an observation group and a control group according to the random number table method,with 20 cases in each group.The control group was treated with Clostridium butyricum live capsules,while the observation group was treated with Modified Gegen Qinlian Decoction in addition to the treatment given to the control group.Both groups received a 4-week treatment course.Intestinal function indicators and changes in intestinal flora structure were compared between the two groups before and after treatment,and clinical efficacy was evaluated.Results:After 4 weeks of treatment,the total effective rate in the observation group versus the control group was(95.00%vs 65.00%),with a statistically significant difference(P<0.05).The fecal formation rate in the observation group(85.00%vs 60.00%)was significantly higher than that in the control group,and the defecation frequency(2.15±0.42 vs 3.85±0.65)times/day was significantly lower than that in the control group,with statistically significant differences(P<0.05).After treatment,the quantities of Bifidobacterium(6.85±0.72 L vs 5.23±0.61 L)gCFU/g and Lactobacillus(6.52±0.68 L vs 4.98±0.57 L)gCFU/g in the observation group were significantly higher than those in the control group,while the quantities of Escherichia coli(4.12±0.53 L vs 5.67±0.65 L)gCFU/g and Staphylococcus(3.85±0.48 L vs 5.23±0.59 L)gCFU/g were significantly lower than those in the control group,with statistically significant differences(P<0.05).Conclusion:Clinical studies have confirmed that the synergistic treatment of radiation enteritis with Modified Gegen Qinlian Decoction and probiotics can significantly improve patients’clinical symptoms and restore the balance of intestinal flora,providing an effective regimen for clinical treatment.展开更多
This study systematically investigates the influences of annealing treatment on the energy state,microstructure and macroscopic mechanical behaviors of metallic glasses(MGs).By reducing the energy state,the annealing ...This study systematically investigates the influences of annealing treatment on the energy state,microstructure and macroscopic mechanical behaviors of metallic glasses(MGs).By reducing the energy state,the annealing process significantly enhances the structural ordering degree and uniformity of MGs,thereby improving their overall mechanical reliability.Specifically,annealing promotes the formation of localized icosahedral short-range order,a structural signature that contributes to improved nanohardness and tensile strength.Furthermore,the release and redistribution of internal stress during annealing further optimize the internal stress state,significantly enhancing the fracture resistance and achieving reliable mechanical performance.This study not only elucidates the regulatory mechanisms of annealing on the microstructure of MGs but also provides theoretical support and experimental evidence for exploring MG materials with high strength and high fracture reliability.展开更多
Machining performance of thin-walled components made by aeronautical difficult-toprocess materials is a significant issue in the aviation manufacturing industry.Although wire electric discharge machining-low speed(WED...Machining performance of thin-walled components made by aeronautical difficult-toprocess materials is a significant issue in the aviation manufacturing industry.Although wire electric discharge machining-low speed(WEDM-LS)is one of typical non-contact machining processes without macro cutting force,which does well in removing hardness and brittleness materials via pulsed discharge at high temperature,but few researchers have studied the thermal distortion behavior leading to a considerable geometric error in the WEDM-LS of thin-walled components.In this paper,a transverse magnetic field assisted method is applied for affecting the uniformity of discharge point distribution so as to reduce the distortion in WEDM-LS processing thin-wall component.First,the generation mechanism of this new distortion behavior and the impact mechanism of transverse magnetic field(TMF)on distortion are demonstrated by theoretical analysis.In order to further figure out the distortion behavior in the TMF-WEDM process,a new thermophysical model considering the discharge point distribution is established to simulate temperature field,residual stress field and distortion profiles.Then a large number of Taguchi experiments are carried out to investigate the influences of process parameters including pulse discharge energy(pulse on time,pulse off time,and current)and magnetic field strength on distortion in WEDM-LS.To comparatively analyze simulated and experimental results,the accuracy of established thermophysical model is verified within a relative error of 18.38%in distortion.Moreover,it can be revealed that transverse magnetic field contribute to significantly improve the longitudinal distribution uniformity with maximum increase of 12.32%at magnetic field strength:0.15 T,leading to significant reductions of 32.77%in distortion and 22.68%in recast layer.Eventually,we also presented the variation of residual stress and recast layer along thickness direction under different distortion behavior,which are in good agreement with that of distortion behavior.展开更多
The definitions of the third-order elastic,piezoelectric,and dielectric constants and the properties of the associated tensors are discussed.Based on the energy conservation and coordinate transformation,the relations...The definitions of the third-order elastic,piezoelectric,and dielectric constants and the properties of the associated tensors are discussed.Based on the energy conservation and coordinate transformation,the relations among the third-order constants are obtained.Furthermore,the relations among the third-order elastic,piezoelectric,and dielectric constants of the seven crystal systems and isotropic materials are listed in detail.These third-order constants relations play an important role in solving nonlinear problems of elastic and piezoelectric materials.It is further found that all third-order piezoelectric constants are 0 for 15 kinds of point groups,while all third-order dielectric constants are 0 for 16 kinds of point groups as well as isotropic material.The reason is that some of the point groups are centrally symmetric,and the other point groups are high symmetry.These results provide the foundation to measure these constants,to choose material,and to research nonlinear problems.Moreover,these results are helpful not only for the study of nonlinear elastic and piezoelectric problems,but also for the research on flexoelectric effects and size effects.展开更多
Shut-in after fracturing has become an important supporting technology for volume fracturing in unconventional oil and gas wells, which is helpful for gas and water imbibition replacement to increase single well produ...Shut-in after fracturing has become an important supporting technology for volume fracturing in unconventional oil and gas wells, which is helpful for gas and water imbibition replacement to increase single well production. In this paper, the hydraulic pressure, capillary pressure and osmotic pressure, the three main forces that affect well production, are calculated and compared in the Sulige tight sandstone gas field and Fuling shale gas field. The results show that the total forces affecting well production in the Sulige gas field are similar to those in the Fuling shale gas field, and it has the potential to exhibit shut-in after fracturing. For the characteristics of “low pressure” and “water blocking risk” in Sulige gas field, it is suggested that:(1)injecting N_(2) or CO_(2) during hydraulic fracturing and reasonably controlling the shut-in time after fracturing, such as shut-in for approximately 30 h, can ensure effective natural fluid flowback while replenishing energy to the formation and reduce the damage caused by water blocking and (2)the waterproof lock slickwater is used in the test wells, and the result shows that slickwater can reduce the reservoir damage and increase well production when compared with guanidine gum fracturing fluid. This research can provide some basis and reference for the field test of shut-in after fracturing in the Sulige tight sandstone gas field.展开更多
The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy.Here,we report two perylene diimide-based metallac...The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy.Here,we report two perylene diimide-based metallacages that can form stable host–vip complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers(hypocrellin A).Such host–vip complexation not only prevents the aggregation of photosensitizers in aqueous environments,but also offers fluorescence resonance energy transfer(FRET)from the metallacage to the photosensitizers to further improve the singlet oxygen generation(Φ_(Δ)=0.66).The complexes are further assembled with amphiphilic polymers,forming nanoparticles with improved stability for anticancer study.Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation,showing great potential for cancer photodynamic therapy.This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host–vip complexation-based FRET,which will open a new avenue for host–vip chemistry-based supramolecular theranostics.展开更多
Although having been increasingly studied, there is still controversy as to when the addition of nanoparticles could improve the drag reduction performance of polymer drag reducer and particularly what is the underlyi...Although having been increasingly studied, there is still controversy as to when the addition of nanoparticles could improve the drag reduction performance of polymer drag reducer and particularly what is the underlying mechanism from the fluid dynamics viewpoint. The drag reduction effects of adding SiO_(2) nanoparticles to various polymer polyacrylamide(PAM) solutions were examined in this work.The optimal combination of SiO_(2) nanoparticles with cationic polyacrylamide was confirmed.Interestingly,the addition of SiO_(2) nanoparticles to cationic polyacrylamide solution was shown to be quite efficient for reducing drag, but only at higher flow rates with Reynolds numbers more than 6000, below which the nanoparticle addition is even negative. The addition of SiO_(2) nanoparticles to the PAM solution is supposed to play a dual role. The first is an increase in flow resistance caused by the Brownian motion of nanoparticles, while the second is a decrease in flow resistance caused by acting as nodes to protect the polymer chain from shear-induced breaking under high shear action. At optimal nanoparticle concentration and under higher Reynolds numbers, the later effect is dominant, which could improve the drag reduction performance of polymer drag reducers. Our work should serve as a guide for the application of natural gas fracturing, where the flow rate is frequently very high.展开更多
Three-dimensional(3D)printing technology,as a novel technical method,can convert conventional computed tomography(CT)or magnetic resonance imaging(MRI)scans to computer-aided design files and develop a 2D spatial stru...Three-dimensional(3D)printing technology,as a novel technical method,can convert conventional computed tomography(CT)or magnetic resonance imaging(MRI)scans to computer-aided design files and develop a 2D spatial structure into a 3D imaging structure.In recent years,the technology has been widely used in numerous areas,including head and neck surgery,orthopedics,and bio-medicinal research.This article uses examples of 3D printed tumor models to develop Response Evaluation Criteria In Solid Tumors(RECIST)standards to evaluate the changes in tumors.RECIST standard is currently recognized as the standard for assessment of chemotherapy.Under the RECIST standard,changes occurring in tumors before and after the surgery,are evaluated.The assessment depends upon a CT evaluation of the changes in the lesions with the largest diameters.In addition,the disease progression and stability of remission is also assessed.Three-dimensional printing technology is more intuitive in the evaluation of changes to human tumors following chemotherapy and targeted therapy.However,a few reports are available.展开更多
To evaluate the efficacy and safety of KN026,a novel bispecific HER2(ECD2 and ECD4)antibody,plus KN046,a PD-L1,and CTLA4 bispecific antibody,in patients with advanced HER2-positive solid tumors.We conducted two sequen...To evaluate the efficacy and safety of KN026,a novel bispecific HER2(ECD2 and ECD4)antibody,plus KN046,a PD-L1,and CTLA4 bispecific antibody,in patients with advanced HER2-positive solid tumors.We conducted two sequentially designed phase Ib and Il studies with similar target populations and evaluation schedules.The primary endpoints included safety,maximum tolerated dose(MTD),the recommended phase Il dose(RP2D)for the phase Ib study,and the objective response rate(ORR)and duration of response(DoR)for the phase llstudy.Hereby,we solely report the results from 113 nonbreast cancer patients.In phase Ib,MTD was not reached.Dose 3 was confirmed to be acceptable for the phase lIl study.An objective response has been exclusively observed in HER2-positive patients.Any grade treatment-related adverse events(TRAEs)were reported in 108(95.6%)patients.The most common TRAEs were infusion reactions(38.9%),anemia(37.2%),elevated AST(31.0%),and diarrhea(30.1%).Among the 108 patients evaluated for efficacy,the overall ORR was 55.6%(95%Cl,45.7%,65.1%).In the HER2-positive GC subgroup,38 patients received this regimen as the 1st-line treatment and 30 patients achieved an objective response,with an ORR of 78.9%(95%Cl,62.7%,90.4%).Among 27 pretreated patients,the ORR was 44.4%(95%Cl,25.5%,64.7%).In the other HER2-positive solid tumor subgroup(n=34),the ORR was 52.9%(95%CI 35.1%,70.2%).Thus,KN026 plus KN04 exhibits promising efficacy and acceptable safety profiles in HER2-positive nonbreast cancer,as does the 1st-line treatment for GC.展开更多
Wastewater heat pump technology,as a renewable energy source,demonstrates significant potential for the recovery and utilization of thermal energy from urban wastewater.This review systematically summarizes the curren...Wastewater heat pump technology,as a renewable energy source,demonstrates significant potential for the recovery and utilization of thermal energy from urban wastewater.This review systematically summarizes the current research status,technical advantages,challenges,and future development trends of wastewater heat pump technology.First,the impact of wastewater characteristics on system performance was analyzed,focusing on suspended solids(SS),corrosive components,and non-Newtonian fluid behavior that constrain flow and heat transfer mechanisms.The causes of key issues,such as scale deposition and heat transfer efficiency decay,are revealed,along with existing solutions,such as electromagnetic scale removal and ultrasonic anti-scale methods.Additionally,the review discusses innovative developments in equipment by different researchers,including automatic screening and filtration devices,modular indirect heat exchangers,and corrosion-resistant nonmetallic materials,which have effectively enhanced system reliability and economics.Finally,an economic and environmental benefit analysis indicated that while wastewater source heat pump systems have higher initial investment costs,their long-term operational costs and carbon emissions are significantly lower than those of traditional fossil fuel-based systems.This review integrates the research outcomes of wastewater heat pump technology over the past decade,aiming to provide references for global technological development and advocate for interdisciplinary collaboration and policy support to facilitate the transition from laboratory research to large-scale practical applications.展开更多
Seasonal variations in gut microbiota of small mammals and how they are influenced by environmental variables are relatively poorly understood.We sampled 162 wild plateau pikas(Ochotona curzoniae)in 4 seasons over 2 a...Seasonal variations in gut microbiota of small mammals and how they are influenced by environmental variables are relatively poorly understood.We sampled 162 wild plateau pikas(Ochotona curzoniae)in 4 seasons over 2 and a half years and recorded the air temperature,precipitation,and nutrient content in edible vegetation at the sampling site.After conducting 16S rRNA and shotgun metagenomic sequencing,we found that the highest alpha diversity,the relative abundance of Firmicutes,and the simplest co-occurrence network occurred in winter,whereas the highest relative abundance of Proteobacteria and the most complex network structure were observed in spring.The highest relative abundance of Verrucomicrobiota and Spirochaetota was seen in summer and autumn,respectively.Air temperature,precipitation,and the contents of crude protein,crude fiber,and polysaccharide in vegetation had significant effects on the seasonal changes in gut microbiota.Diet contributed more to microbial variation than climatic factors.Metagenomic analysis revealed that the amino acid metabolism pathway and axillary activity enzymes were most abundant in summer,while abundance of carbohydrate-binding modules and carbohydrate esterases was highest in spring.These microbial variations were related to the changes in dietary nutrition,indicating that gut microbiota of plateau pika contribute to the efficient use of food resources.This study provides new evidence of how external environmental factors affect the intestinal environment of small mammals.展开更多
During metal additive manufacturing,the porosity of the as-built part deteriorates the mechanical property and even hinders the further application of metal additive manufacturing.Particularly,the mechanisms of keyhol...During metal additive manufacturing,the porosity of the as-built part deteriorates the mechanical property and even hinders the further application of metal additive manufacturing.Particularly,the mechanisms of keyhole pores associated with the keyhole fluctuation are not fully understood.To reveal the mechanisms of the keyhole pores formation,we adopt a multiphysics thermal-fluid flow model incorporating heat transfer,liquid flow,metal evaporation,Marangoni effect,and Darcy’s law to simulate the keyhole pore formation process,and the results are validated with the in situ X-ray images.The simulation results present the instant bubble formation due to the keyhole instability and motion of the instant bubble pinning on the solidification front.Furthermore,comparing the keyhole pore formation under different laser scanning speeds shows that the keyhole pore is sensitive to the manufacturing parameters.Additionally,the simulation under a low ambient pressure shows the feasibility of improving the keyhole stability to reduce and even avoid the formation of keyhole pores.展开更多
A microsatellite-enriched library of plateau pika （Ochotona curzoniae） was constructed according to the strong affinity between biotin and streptavidin. Firstly, genomic DNA was fragmented by ultrasonication, which ...A microsatellite-enriched library of plateau pika （Ochotona curzoniae） was constructed according to the strong affinity between biotin and streptavidin. Firstly, genomic DNA was fragmented by ultrasonication, which is a major improvement over traditional methods. Linker-ligated DNA fragments were hybridized with biotinylated microsatellite probes, and then were subjected to streptavidin-coated magnetic beads. PCR amplification was performed to obtain double-stranded DNA fragments containing microsatellites. Ligation and transformation were carried out by using the pGEM-T Vector System I and Escherichia coli DH10B competent cells. Sequencing results showed that 80.2% of clones contained microsatellite repeat motif. Several modifications make this protocol time-efficient and technically easier than the traditional ones; particularly, composition and relative abundance of microsatellite repeats in plateau pika genome were truly represented through the optimized PCR conditions. This method has also been successfully applied to construct microsatellite-enriched genomic libraries of Chinese hamster （Cricetulus griseus） and small abalone [Haliotis diversicolor （Reeve）] with high rates of positive clones, demonstrating its feasibility and stability.展开更多
Over the last decade,oncolytic virus(OV)therapy has shown its promising potential in tumor treatment.The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help pred...Over the last decade,oncolytic virus(OV)therapy has shown its promising potential in tumor treatment.The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help predict patients’responses.As particular self-amplifying biotherapeutics,the anti-tumor effects of OVs are highly dependent on the host factors for viral infection and replication.By using weighted gene co-expression network analysis(WGCNA),we found matrix remodeling associated 8(MXRA8)is positively correlated with the oncolysis induced by oncolytic virus M1(OVM).展开更多
Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficienc...Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient evidence.This multicenter,randomized,phase 3 trial(ClinicalTrials.gov NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this study.Overall median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT group.Grade 3-4 adverse events(AEs)within two years posttransplantation in the two groups were similar.Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period posttransplantation.Haplo-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.展开更多
Botulinum neurotoxins serotype A(BoNT/A)is the deadliest toxins known to humans and the"Category A"agent for bioterrorism.Over the past 20 years,significant efforts have been put forth to develop effective i...Botulinum neurotoxins serotype A(BoNT/A)is the deadliest toxins known to humans and the"Category A"agent for bioterrorism.Over the past 20 years,significant efforts have been put forth to develop effective inhibitors of BoNT/A.Unfortunately,few identified inhibitors possess noteworthy efficacy against BoNT/A in vivo.Here,we performed a high-throughput virtual screening based on the structure-based docking simulations and found a novel potent scaffold 2-thionicotinate that inhibits the BoNT/A light chain(LC).We then synthesized and optimized a novel series of 2-thionicotinate derivatives and comprehensively evaluated their activity against BoNT/A in vitro and in vivo.An optimized compound ZM299 effectively exhibits anti-BoNT/A activity in primary neurons and displayed remarkably therapeutic efficacy against BoNT/A in vivo,which could raise the survival rate of intoxicated mice to 100%(12/12)after lethal doses of BoNT/A exposures.These findings demonstrate that 2-thionicotinates is a promising scaffold for producing more effective anti-BoNT/A analogs,and compound ZM299 is worthy of further preclinical evaluation as a drug candidate for the treatment of botulism.展开更多
基金Four“batches”innovation project of invigorating medicine through science and technology of Shanxi province(Project No.:2023XM059)。
文摘Objective:To investigate the clinical efficacy of Modified Gegen Qinlian Decoction combined with probiotics(Clostridium butyricum live capsules)in treating radiation enteritis(RE)in tumor patients,as well as its regulatory effect on the structure of intestinal flora,providing clinical evidence for the integrated traditional Chinese and Western medicine treatment of radiation enteritis.Methods:A total of 40 patients with radiation enteritis admitted to the Oncology Department of Linfen Central Hospital from September 2023 to December 2024 were selected and divided into an observation group and a control group according to the random number table method,with 20 cases in each group.The control group was treated with Clostridium butyricum live capsules,while the observation group was treated with Modified Gegen Qinlian Decoction in addition to the treatment given to the control group.Both groups received a 4-week treatment course.Intestinal function indicators and changes in intestinal flora structure were compared between the two groups before and after treatment,and clinical efficacy was evaluated.Results:After 4 weeks of treatment,the total effective rate in the observation group versus the control group was(95.00%vs 65.00%),with a statistically significant difference(P<0.05).The fecal formation rate in the observation group(85.00%vs 60.00%)was significantly higher than that in the control group,and the defecation frequency(2.15±0.42 vs 3.85±0.65)times/day was significantly lower than that in the control group,with statistically significant differences(P<0.05).After treatment,the quantities of Bifidobacterium(6.85±0.72 L vs 5.23±0.61 L)gCFU/g and Lactobacillus(6.52±0.68 L vs 4.98±0.57 L)gCFU/g in the observation group were significantly higher than those in the control group,while the quantities of Escherichia coli(4.12±0.53 L vs 5.67±0.65 L)gCFU/g and Staphylococcus(3.85±0.48 L vs 5.23±0.59 L)gCFU/g were significantly lower than those in the control group,with statistically significant differences(P<0.05).Conclusion:Clinical studies have confirmed that the synergistic treatment of radiation enteritis with Modified Gegen Qinlian Decoction and probiotics can significantly improve patients’clinical symptoms and restore the balance of intestinal flora,providing an effective regimen for clinical treatment.
基金financially supported by the National Natural Science Foundation of China(Nos.52071118,52371025,and 52171154)supported by the China Scholarship Council(CSC,No.202206120120)for visiting Ph.D.student program at Seoul National University.
文摘This study systematically investigates the influences of annealing treatment on the energy state,microstructure and macroscopic mechanical behaviors of metallic glasses(MGs).By reducing the energy state,the annealing process significantly enhances the structural ordering degree and uniformity of MGs,thereby improving their overall mechanical reliability.Specifically,annealing promotes the formation of localized icosahedral short-range order,a structural signature that contributes to improved nanohardness and tensile strength.Furthermore,the release and redistribution of internal stress during annealing further optimize the internal stress state,significantly enhancing the fracture resistance and achieving reliable mechanical performance.This study not only elucidates the regulatory mechanisms of annealing on the microstructure of MGs but also provides theoretical support and experimental evidence for exploring MG materials with high strength and high fracture reliability.
基金supported by National Natural Science Foundation of China(NSFC)(Nos.51705171 and 51975228)Natural Science Foundation of Guangdong(No.2020A151501638)the Program of China Scholarship Council(No.201806160076)。
文摘Machining performance of thin-walled components made by aeronautical difficult-toprocess materials is a significant issue in the aviation manufacturing industry.Although wire electric discharge machining-low speed(WEDM-LS)is one of typical non-contact machining processes without macro cutting force,which does well in removing hardness and brittleness materials via pulsed discharge at high temperature,but few researchers have studied the thermal distortion behavior leading to a considerable geometric error in the WEDM-LS of thin-walled components.In this paper,a transverse magnetic field assisted method is applied for affecting the uniformity of discharge point distribution so as to reduce the distortion in WEDM-LS processing thin-wall component.First,the generation mechanism of this new distortion behavior and the impact mechanism of transverse magnetic field(TMF)on distortion are demonstrated by theoretical analysis.In order to further figure out the distortion behavior in the TMF-WEDM process,a new thermophysical model considering the discharge point distribution is established to simulate temperature field,residual stress field and distortion profiles.Then a large number of Taguchi experiments are carried out to investigate the influences of process parameters including pulse discharge energy(pulse on time,pulse off time,and current)and magnetic field strength on distortion in WEDM-LS.To comparatively analyze simulated and experimental results,the accuracy of established thermophysical model is verified within a relative error of 18.38%in distortion.Moreover,it can be revealed that transverse magnetic field contribute to significantly improve the longitudinal distribution uniformity with maximum increase of 12.32%at magnetic field strength:0.15 T,leading to significant reductions of 32.77%in distortion and 22.68%in recast layer.Eventually,we also presented the variation of residual stress and recast layer along thickness direction under different distortion behavior,which are in good agreement with that of distortion behavior.
基金Project supported by the National Natural Science Foundation of China(Nos.11872186 and11272126)the Fundamental Research Funds for the Central Universities(No.HUST:2016JCTD114)
文摘The definitions of the third-order elastic,piezoelectric,and dielectric constants and the properties of the associated tensors are discussed.Based on the energy conservation and coordinate transformation,the relations among the third-order constants are obtained.Furthermore,the relations among the third-order elastic,piezoelectric,and dielectric constants of the seven crystal systems and isotropic materials are listed in detail.These third-order constants relations play an important role in solving nonlinear problems of elastic and piezoelectric materials.It is further found that all third-order piezoelectric constants are 0 for 15 kinds of point groups,while all third-order dielectric constants are 0 for 16 kinds of point groups as well as isotropic material.The reason is that some of the point groups are centrally symmetric,and the other point groups are high symmetry.These results provide the foundation to measure these constants,to choose material,and to research nonlinear problems.Moreover,these results are helpful not only for the study of nonlinear elastic and piezoelectric problems,but also for the research on flexoelectric effects and size effects.
基金China National Science and Technology Major Projects (2016ZX05050) “Large-scale low-permeability core formation oil and gas reservoir development demonstration project in Ordos Basin”.
文摘Shut-in after fracturing has become an important supporting technology for volume fracturing in unconventional oil and gas wells, which is helpful for gas and water imbibition replacement to increase single well production. In this paper, the hydraulic pressure, capillary pressure and osmotic pressure, the three main forces that affect well production, are calculated and compared in the Sulige tight sandstone gas field and Fuling shale gas field. The results show that the total forces affecting well production in the Sulige gas field are similar to those in the Fuling shale gas field, and it has the potential to exhibit shut-in after fracturing. For the characteristics of “low pressure” and “water blocking risk” in Sulige gas field, it is suggested that:(1)injecting N_(2) or CO_(2) during hydraulic fracturing and reasonably controlling the shut-in time after fracturing, such as shut-in for approximately 30 h, can ensure effective natural fluid flowback while replenishing energy to the formation and reduce the damage caused by water blocking and (2)the waterproof lock slickwater is used in the test wells, and the result shows that slickwater can reduce the reservoir damage and increase well production when compared with guanidine gum fracturing fluid. This research can provide some basis and reference for the field test of shut-in after fracturing in the Sulige tight sandstone gas field.
基金supported by the National Natural Science Foundation of China(22171219 and 22222112)Innovation Talent Promotion Plan of Shaanxi Province for Science and Technology Innovation Team(2023-CX-TD-51)+2 种基金Key Laboratory Fund for Plasma Physics(6142A04210108)the Interdisciplinary Training Program for Doctoral Candidate of Xi’an Jiaotong University(IDT2105)National Natural Science Foundation NSAF Joint Fund(U2230112).
文摘The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy.Here,we report two perylene diimide-based metallacages that can form stable host–vip complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers(hypocrellin A).Such host–vip complexation not only prevents the aggregation of photosensitizers in aqueous environments,but also offers fluorescence resonance energy transfer(FRET)from the metallacage to the photosensitizers to further improve the singlet oxygen generation(Φ_(Δ)=0.66).The complexes are further assembled with amphiphilic polymers,forming nanoparticles with improved stability for anticancer study.Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation,showing great potential for cancer photodynamic therapy.This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host–vip complexation-based FRET,which will open a new avenue for host–vip chemistry-based supramolecular theranostics.
基金the financial supports of the National Natural Science Foundation of China (51961130386)the National Science Fund for Distinguished Young Scholars (52025061)supported by the China Fundamental Research Funds for the Central Universities。
文摘Although having been increasingly studied, there is still controversy as to when the addition of nanoparticles could improve the drag reduction performance of polymer drag reducer and particularly what is the underlying mechanism from the fluid dynamics viewpoint. The drag reduction effects of adding SiO_(2) nanoparticles to various polymer polyacrylamide(PAM) solutions were examined in this work.The optimal combination of SiO_(2) nanoparticles with cationic polyacrylamide was confirmed.Interestingly,the addition of SiO_(2) nanoparticles to cationic polyacrylamide solution was shown to be quite efficient for reducing drag, but only at higher flow rates with Reynolds numbers more than 6000, below which the nanoparticle addition is even negative. The addition of SiO_(2) nanoparticles to the PAM solution is supposed to play a dual role. The first is an increase in flow resistance caused by the Brownian motion of nanoparticles, while the second is a decrease in flow resistance caused by acting as nodes to protect the polymer chain from shear-induced breaking under high shear action. At optimal nanoparticle concentration and under higher Reynolds numbers, the later effect is dominant, which could improve the drag reduction performance of polymer drag reducers. Our work should serve as a guide for the application of natural gas fracturing, where the flow rate is frequently very high.
基金Supported by a grant from the National Natural Science Foundation of China(No.81702622)。
文摘Three-dimensional(3D)printing technology,as a novel technical method,can convert conventional computed tomography(CT)or magnetic resonance imaging(MRI)scans to computer-aided design files and develop a 2D spatial structure into a 3D imaging structure.In recent years,the technology has been widely used in numerous areas,including head and neck surgery,orthopedics,and bio-medicinal research.This article uses examples of 3D printed tumor models to develop Response Evaluation Criteria In Solid Tumors(RECIST)standards to evaluate the changes in tumors.RECIST standard is currently recognized as the standard for assessment of chemotherapy.Under the RECIST standard,changes occurring in tumors before and after the surgery,are evaluated.The assessment depends upon a CT evaluation of the changes in the lesions with the largest diameters.In addition,the disease progression and stability of remission is also assessed.Three-dimensional printing technology is more intuitive in the evaluation of changes to human tumors following chemotherapy and targeted therapy.However,a few reports are available.
基金supported by the National Natural Science Foundation of China(91959205 to L.S.)the Natural Science Foundation of Beijing Municipality(Z200015 to X.T.Z).
文摘To evaluate the efficacy and safety of KN026,a novel bispecific HER2(ECD2 and ECD4)antibody,plus KN046,a PD-L1,and CTLA4 bispecific antibody,in patients with advanced HER2-positive solid tumors.We conducted two sequentially designed phase Ib and Il studies with similar target populations and evaluation schedules.The primary endpoints included safety,maximum tolerated dose(MTD),the recommended phase Il dose(RP2D)for the phase Ib study,and the objective response rate(ORR)and duration of response(DoR)for the phase llstudy.Hereby,we solely report the results from 113 nonbreast cancer patients.In phase Ib,MTD was not reached.Dose 3 was confirmed to be acceptable for the phase lIl study.An objective response has been exclusively observed in HER2-positive patients.Any grade treatment-related adverse events(TRAEs)were reported in 108(95.6%)patients.The most common TRAEs were infusion reactions(38.9%),anemia(37.2%),elevated AST(31.0%),and diarrhea(30.1%).Among the 108 patients evaluated for efficacy,the overall ORR was 55.6%(95%Cl,45.7%,65.1%).In the HER2-positive GC subgroup,38 patients received this regimen as the 1st-line treatment and 30 patients achieved an objective response,with an ORR of 78.9%(95%Cl,62.7%,90.4%).Among 27 pretreated patients,the ORR was 44.4%(95%Cl,25.5%,64.7%).In the other HER2-positive solid tumor subgroup(n=34),the ORR was 52.9%(95%CI 35.1%,70.2%).Thus,KN026 plus KN04 exhibits promising efficacy and acceptable safety profiles in HER2-positive nonbreast cancer,as does the 1st-line treatment for GC.
基金sponsored by the Open Foundation of Liaoning Provincial Engineering Research Center of Building Carbon Neutrality(Grant No.LJ232410153048)the financial support from the Natural Science Foundation of Liaoning Province of China(Grant No.2024-BSLH-251).
文摘Wastewater heat pump technology,as a renewable energy source,demonstrates significant potential for the recovery and utilization of thermal energy from urban wastewater.This review systematically summarizes the current research status,technical advantages,challenges,and future development trends of wastewater heat pump technology.First,the impact of wastewater characteristics on system performance was analyzed,focusing on suspended solids(SS),corrosive components,and non-Newtonian fluid behavior that constrain flow and heat transfer mechanisms.The causes of key issues,such as scale deposition and heat transfer efficiency decay,are revealed,along with existing solutions,such as electromagnetic scale removal and ultrasonic anti-scale methods.Additionally,the review discusses innovative developments in equipment by different researchers,including automatic screening and filtration devices,modular indirect heat exchangers,and corrosion-resistant nonmetallic materials,which have effectively enhanced system reliability and economics.Finally,an economic and environmental benefit analysis indicated that while wastewater source heat pump systems have higher initial investment costs,their long-term operational costs and carbon emissions are significantly lower than those of traditional fossil fuel-based systems.This review integrates the research outcomes of wastewater heat pump technology over the past decade,aiming to provide references for global technological development and advocate for interdisciplinary collaboration and policy support to facilitate the transition from laboratory research to large-scale practical applications.
基金supported by the Grant from CAS No.152111KYSB20160089Qinghai innovation platform construction project by Chinese Academy of Sciences(2021-ZJ-Y01)+2 种基金the project of western light for interdisciplinary teamScience and Technology Department of Qinghai Province Major Project“Sanjiangyaun National Park Animal Genome Program”the Natural Science Foundation of Qinghai Province(2019-ZJ-7024).
文摘Seasonal variations in gut microbiota of small mammals and how they are influenced by environmental variables are relatively poorly understood.We sampled 162 wild plateau pikas(Ochotona curzoniae)in 4 seasons over 2 and a half years and recorded the air temperature,precipitation,and nutrient content in edible vegetation at the sampling site.After conducting 16S rRNA and shotgun metagenomic sequencing,we found that the highest alpha diversity,the relative abundance of Firmicutes,and the simplest co-occurrence network occurred in winter,whereas the highest relative abundance of Proteobacteria and the most complex network structure were observed in spring.The highest relative abundance of Verrucomicrobiota and Spirochaetota was seen in summer and autumn,respectively.Air temperature,precipitation,and the contents of crude protein,crude fiber,and polysaccharide in vegetation had significant effects on the seasonal changes in gut microbiota.Diet contributed more to microbial variation than climatic factors.Metagenomic analysis revealed that the amino acid metabolism pathway and axillary activity enzymes were most abundant in summer,while abundance of carbohydrate-binding modules and carbohydrate esterases was highest in spring.These microbial variations were related to the changes in dietary nutrition,indicating that gut microbiota of plateau pika contribute to the efficient use of food resources.This study provides new evidence of how external environmental factors affect the intestinal environment of small mammals.
基金This research is supported by A^(*)STAR under its AME IRG Grant(Project No.A20E5c0091).
文摘During metal additive manufacturing,the porosity of the as-built part deteriorates the mechanical property and even hinders the further application of metal additive manufacturing.Particularly,the mechanisms of keyhole pores associated with the keyhole fluctuation are not fully understood.To reveal the mechanisms of the keyhole pores formation,we adopt a multiphysics thermal-fluid flow model incorporating heat transfer,liquid flow,metal evaporation,Marangoni effect,and Darcy’s law to simulate the keyhole pore formation process,and the results are validated with the in situ X-ray images.The simulation results present the instant bubble formation due to the keyhole instability and motion of the instant bubble pinning on the solidification front.Furthermore,comparing the keyhole pore formation under different laser scanning speeds shows that the keyhole pore is sensitive to the manufacturing parameters.Additionally,the simulation under a low ambient pressure shows the feasibility of improving the keyhole stability to reduce and even avoid the formation of keyhole pores.
文摘A microsatellite-enriched library of plateau pika （Ochotona curzoniae） was constructed according to the strong affinity between biotin and streptavidin. Firstly, genomic DNA was fragmented by ultrasonication, which is a major improvement over traditional methods. Linker-ligated DNA fragments were hybridized with biotinylated microsatellite probes, and then were subjected to streptavidin-coated magnetic beads. PCR amplification was performed to obtain double-stranded DNA fragments containing microsatellites. Ligation and transformation were carried out by using the pGEM-T Vector System I and Escherichia coli DH10B competent cells. Sequencing results showed that 80.2% of clones contained microsatellite repeat motif. Several modifications make this protocol time-efficient and technically easier than the traditional ones; particularly, composition and relative abundance of microsatellite repeats in plateau pika genome were truly represented through the optimized PCR conditions. This method has also been successfully applied to construct microsatellite-enriched genomic libraries of Chinese hamster （Cricetulus griseus） and small abalone [Haliotis diversicolor （Reeve）] with high rates of positive clones, demonstrating its feasibility and stability.
基金We acknowledge Dr.Zhe Liu of the Guangdong Provincial Center for Disease Control and Prevention for his assistance with cryo-EM.Miss.Liumei Wu and Miss.Jing Tang assisted with transfection assay and RNA-scope assay.This work was supported by the National Natural Science Foundation of China(No.81973342,82073883,81772675,81903652,and 81802536)the National Key R&D Program of China(2021YFA0909800)the Science and Technology Program of Guangzhou(No.201707020003).
文摘Over the last decade,oncolytic virus(OV)therapy has shown its promising potential in tumor treatment.The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help predict patients’responses.As particular self-amplifying biotherapeutics,the anti-tumor effects of OVs are highly dependent on the host factors for viral infection and replication.By using weighted gene co-expression network analysis(WGCNA),we found matrix remodeling associated 8(MXRA8)is positively correlated with the oncolysis induced by oncolytic virus M1(OVM).
基金supported by grants from the National Key Research and Development Program(2022YFC2502700)National Natural Science Foundation of China(82020108003,82370213,82370215,82300242,82070187,82000180)+5 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Jiangsu Provincial Medical Innovation Center(CXZX202201)Excellent Youth Science Fund of Jiangsu Province(BK20211553)Suzhou Science Project(SKY2021104,SKY2021039)Suzhou Science and Technology Project(SLT201911)Translational Research Grant of NCRCH(2021ZKMB01).
文摘Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient evidence.This multicenter,randomized,phase 3 trial(ClinicalTrials.gov NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this study.Overall median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT group.Grade 3-4 adverse events(AEs)within two years posttransplantation in the two groups were similar.Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period posttransplantation.Haplo-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.
基金the National Natural Science Foundation of China(Nos.82173743 and U20A20136).
文摘Botulinum neurotoxins serotype A(BoNT/A)is the deadliest toxins known to humans and the"Category A"agent for bioterrorism.Over the past 20 years,significant efforts have been put forth to develop effective inhibitors of BoNT/A.Unfortunately,few identified inhibitors possess noteworthy efficacy against BoNT/A in vivo.Here,we performed a high-throughput virtual screening based on the structure-based docking simulations and found a novel potent scaffold 2-thionicotinate that inhibits the BoNT/A light chain(LC).We then synthesized and optimized a novel series of 2-thionicotinate derivatives and comprehensively evaluated their activity against BoNT/A in vitro and in vivo.An optimized compound ZM299 effectively exhibits anti-BoNT/A activity in primary neurons and displayed remarkably therapeutic efficacy against BoNT/A in vivo,which could raise the survival rate of intoxicated mice to 100%(12/12)after lethal doses of BoNT/A exposures.These findings demonstrate that 2-thionicotinates is a promising scaffold for producing more effective anti-BoNT/A analogs,and compound ZM299 is worthy of further preclinical evaluation as a drug candidate for the treatment of botulism.
