Firefighting protective clothing is a crucial protective equipment for firefighters to minimize skin burn and ensure safety firefighting operation and rescue mission.A recent increasing concern is to develop self-powe...Firefighting protective clothing is a crucial protective equipment for firefighters to minimize skin burn and ensure safety firefighting operation and rescue mission.A recent increasing concern is to develop self-powered fire warning materials that can be incorporated into the firefighting clothing to achieve active fire protection for firefighters before the protective clothing catches fire on fireground.However,it is still a challenge to facilely design and manufacture thermoelectric(TE)textile(TET)-based fire warning electronics with dynamic surface conformability and breathability.Here,we develop an alternate coaxial wet-spinning strategy to continuously produce alternating p/n-type TE aerogel fibers involving n-type Ti_(3)C_(2)T_(x)MXene and p-type MXene/SWCNT-COOH as core materials,and tough aramid nanofiber as protective shell,which simultaneously ensure the flexibility and high-efficiency TE power generation.With such alternating p/n-type TE fibers,TET-based self-powered fire warning sensors with high mechanical stability and wearability are successfully fabricated through stitching the alternating p-n segment TE fibers into aramid fabric.The results indicate that TET-based fire warning electronics containing 50 p-n pairs produce the open-circuit voltage of 7.5 mV with a power density of 119.79 nW cm-2 at a temperature difference of 300℃.The output voltage signal is then calculated as corresponding surface temperature of firefighting clothing based on a linear relationship between TE voltage and temperature.The fire alarm response time and flame-retardant properties are further displayed.Such self-powered fire warning electronics are true textiles that offer breathability and compatibility with body movement,demonstrating their potential application in firefighting clothing.展开更多
Many titanium alloy subcomponents are subjected to fatigue loading in aerospace engineering,resulting in fatigue failure.The fatigue behavior of Ti_(2)AlNb alloy subcomponents was investigated based on the Seeger fati...Many titanium alloy subcomponents are subjected to fatigue loading in aerospace engineering,resulting in fatigue failure.The fatigue behavior of Ti_(2)AlNb alloy subcomponents was investigated based on the Seeger fatigue life theory and the improved Lemaitre damage evolution theory.Firstly,the finite element models of the standard openhole specimen and Y-section subcomponents have been established by ABAQUS.The damage model parameters were determined by fatigue tests,and the reliability of fatigue life simulation results of the Ti_(2)AlNb alloy standard open-hole specimen was verified.Meanwhile,the fatigue life of Ti_(2)AlNb alloy Y-section subcomponents was predicted.Under the same initial conditions,the average error of fatigue life predicted by two different models was 20.6%.Finally,the effects of loading amplitude,temperature,and Y-interface angle on fatigue properties of Ti_(2)AlNb Y-section subcomponents were investigated.These results provide a new idea for evaluating the fatigue life of various Ti_(2)AlNb alloy subcomponents.展开更多
High concentrated and heterogeneous distribution of gas hydrates have been identified in the gas hydrate production test region in the Shenhu area,South China Sea.The gas hydrate-bearing sediments with high saturation...High concentrated and heterogeneous distribution of gas hydrates have been identified in the gas hydrate production test region in the Shenhu area,South China Sea.The gas hydrate-bearing sediments with high saturation locate at two ridges of submarine canyon with different thickness and saturations just above the bottom simulating reflection.The crossplots of gamma ray,acoustic impedance(P-impedance)and porosity at four sites show that the sediments can be divided into the upper and lower layers at different depths,indicating different geotechnical reservoir properties.Therefore,the depositional environments and physical properties at two ridges are analyzed and compared to show the different characteristics of hydrate reservoir.High porosity,high P-wave velocity,and coarse grain size indicate better reservoir quality and higher energy depositional environment for gas hydrate at Sites W18 and W19 than those at Sites W11 and W17.Our interpretation is that the base of canyon deposits at Sites W18 and W19 characterized by upward-coarsening units may be turbidity sand layers,thus significantly improving the reservoir quality with increasing gas hydrate saturation.The shelf and slope sliding deposits compose of the fine-grained sediments at Sites W11 and W17.The gas hydrate production test sites were conducted at the ridge of W11 and W17,mainly because of the thicker and larger area of gas hydrate-bearing reservoirs than those at Sites W18 and W19.All the results provide useful insights for assessing reservoir quality in the Shenhu area.展开更多
According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac effica...According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry(HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids,monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine,and aconine in SD rats were used to validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diesterditerpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids.Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoesterditerpenoid alkaloids and amine-diterpenoid alkaloids.展开更多
Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its com...Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell activators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside IV,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory components of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.展开更多
Therapeutic drug monitoring(TDM)has played an important role in clinical medicine for precise dosing.Currently,chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs...Therapeutic drug monitoring(TDM)has played an important role in clinical medicine for precise dosing.Currently,chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs of clinical drug therapy.However,some problems still exist in practical applications,such as complicated operation and the influence of endogenous substances.Surface plasmon resonance(SPR)has been applied to detect the concentrations of small molecules,including pesticide residues in crops and antibiotics in milk,which indicates its potential for in vivo drug detection.In this study,a new SPR-based biosensor for detecting chloramphenicol(CAP)in blood samples was developed and validated using methodological verification,including precision,accuracy,matrix effect,and extraction recovery rate,and compared with the classic ultra-performance liquid chromatographyultraviolet(UPLC-UV)method.The detection range of SPR was 0.1-50 ng/mL and the limit of detection was 0.099±0.023 ng/mL,which was lower than that of UPLC-UV.The intra-day and inter-day accuracies of SPR were 98%-114% and 110%-122%,which met the analysis requirement.The results show that the SPR biosensor is identical to UPLC-UV in the detection of CAP in rat blood samples;moreover,the SPR biosensor has better sensitivity.Therefore,the present study shows that SPR technology can be used for the detection of small molecules in the blood samples and has the potential to become a method for therapeutic drug monitoring.展开更多
Introduction Primary liver cancer is a significant health issue in China,where it ranks fourth in morbidity and second in mortality among all malignant tumors.[1-4]The 5-year overall survival rate of Chinese patients ...Introduction Primary liver cancer is a significant health issue in China,where it ranks fourth in morbidity and second in mortality among all malignant tumors.[1-4]The 5-year overall survival rate of Chinese patients with liver cancer from 2012 to 2015 was only 12.2%for males and 13.1%for females.[5]Hepatocellular carcinoma(HCC)accounts for 75-85%of primary liver cancers.[6]Furthermore,most liver cancers are unresectable at diagnosis.To combat this,conversion therapy is used,which involves systematic treatments like anti-angiogenic drugs or molecular targeted therapy combined with immunotherapies,as well as locoregional treatments such as transcatheter arterial chemoembolization(TACE),hepatic artery infusion chemotherapy(HAIC),ablation therapy,and radiation therapy.The goal is to eliminate unresectable status and increase the chances of surgery.The reported 5-year survival rate after salvage surgery following tumor downstaging varied from 24.9-57%.展开更多
Background and Originality Content,Inclusion single crystals(IsCs)are characterized by the encapsulation of guest molecules within the crystal lattice of a host framework,resulting in,well-defined channels or cavities...Background and Originality Content,Inclusion single crystals(IsCs)are characterized by the encapsulation of guest molecules within the crystal lattice of a host framework,resulting in,well-defined channels or cavities throughout the material. Host molecules can be broadly di.Videdinto wo main categories.i)The more widespreadgroup is unimolecular inclusion compounds where one host molecule interacts with one guest species.Familiar examples of this cate-gory include calixarenes,cyclodextrins,crown ethers,bai cavitands.cucurbituils,uoaciyclophanes,and various carcerands,ii) the other is multimoiecular inclusion caompounds where two or more host molecules are involved in forming cavities,channels,or layers in the crystal structure to accommodate guest molecules.Host molecules of,this kind include urea,choleic acis,Dianin's compound,etc.,and crystline porous materials such as metal-organic poliyhedrali and porous organic[18]cagesll are well-known examples.展开更多
Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected pa...Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.展开更多
Cell membrane affinity chromatography has been widely applied in membrane protein(MP)-targeted drug screening and interaction analysis.However,in current methods,the MP sources are derived from cell lines or recombina...Cell membrane affinity chromatography has been widely applied in membrane protein(MP)-targeted drug screening and interaction analysis.However,in current methods,the MP sources are derived from cell lines or recombinant protein expression,which are time-consuming for cell culture or purification,and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase.In this study,a novel in situ synthesis membrane protein affinity chromatography(iSMAC)method was developed utilizing cell-free protein expression(CFE)and covalent immobilized affinity chromatography,which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase.The advantages of iSMAC are:1)There is no need to culture cells or prepare recombinant proteins;2)Specific and purified MPs with stable and controllable content can be obtained within 2 h;3)MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase;4)The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites.iSMAC was successfully applied to screen PDGFRβinhibitors from Salvia miltiorrhiza and Schisandra chinensis.Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h.Two new PDGFRβinhibitors,salvianolic acid B and gomisin D,were screened out with KD values of 13.44 and 7.39μmol/L,respectively.In vitro experiments confirmed that the two compounds decreasedα-SMA and collagen Ⅰ mRNA levels raised by TGF-βin HSC-T6 cells through regulating the phosphorylation of p38,AKT and ERK.In vivo,Sal B could also attenuate CCl_(4)-induced liver fibrosis by downregulating PDGFRβdownstream related protein levels.The iSMAC method can be applied to other general MPs,and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.展开更多
Brown adipose tissue(BAT)is an energy-expending organ that produces heat.Expansion or activation of BAT prevents obesity and diabetes.Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1(UC...Brown adipose tissue(BAT)is an energy-expending organ that produces heat.Expansion or activation of BAT prevents obesity and diabetes.Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1(UCP1)activation triggered via a b-adrenergic pathway.Here,we report that the cold-sensing transient receptor potential melastatin 8(TRPM8)is functionally present in mouse BAT.Challenging brown adipocytes with menthol,a TRPM8 agonist,up-regulates UCP1 expression and requires protein kinase A activation.Upon mimicking long-term cold exposure with chronic dietary menthol application,menthol significantly increased the core temperatures and locomotor activity in wild-type mice;these effects were absent in both TRPM82/2 and UCP12/2 mice.Dietary obesity and glucose abnormalities were also prevented by menthol treatment.Our results reveal a previously unrecognized role for TRPM8,suggesting that stimulation of this channel mediates BAT thermogenesis,which could constitute a promising way to treat obesity.展开更多
PbS-based thermoelectric materials have attracted extensive attention in recent years for the advantages of earth abundancy and low cost,which is considered to be a substitute for traditional PbTe material.However,the...PbS-based thermoelectric materials have attracted extensive attention in recent years for the advantages of earth abundancy and low cost,which is considered to be a substitute for traditional PbTe material.However,their high thermal conductivity restricts its development.Hence,in order to improve their thermoelectric performance from reducing the thermal conductivity,a kind of dendritic PbS with controlled crystal grain and morphology are obtained by solution synthesis.By adjusting the amount of surfactant(CTAB),the specific formation process of dendrites is regulated.After sintering,the dendritic PbS nanoparticles are easy to form porous structure due to the overlapping and staggered arrangement of dendritic branches.For comparison,we also prepare a kind of regular octahedral PbS and a dense packing arrangement is formed because of the integrity of the octahedral structure.DFT-based Boltzmann transport equation is used to prove the crucial role of porous structure in scattering phonon.Finally,a maximum zT=1.0 at 773 K in n-type PbS is obtained,which still keep a high-speed growth and is expected to get higher zT value in a higher temperature region.Our work may shed light to other thermoelectric materials from the formation of porous structure to reduce the thermal conductivity.展开更多
As an important part of demand side,residential users have the characteristics of imperfect rationality and strong randomness,which are rarely considered in the existing study.Moreover,to effectively improve the energ...As an important part of demand side,residential users have the characteristics of imperfect rationality and strong randomness,which are rarely considered in the existing study.Moreover,to effectively improve the energy efficiency,integrated demand response(IDR)is proposed as an effective measure to reduce the local energy supply pressure.This paper focuses on a scenario for IDR programs,in which the intelligent building aggregator(IBA)wants to encourage residential users to participate in IDR according to a proper contract price policy.To analyze how the participation degree tendency evolves over time,an evolutionary game approach is proposed considering residential users’bounded-rationality.A symmetric evolutionary game model and an asymmetric evolutionary game model are established,and the stability of equilibrium points in the above models is proven.Simulation results show that different contract price policies will obviously influence residential users’strategy,and affect the stable equilibrium points of the evolutionary game.The simulation results provide an effective reference for IBA to set proper and effective price incentives.展开更多
Dralll is a type liP restriction endonucleases (REases) that recognizes and creates a double strand break within the gapped palindromic sequence CACTNNN^GTG of double-stranded DNA indicates nicking on the bottom st...Dralll is a type liP restriction endonucleases (REases) that recognizes and creates a double strand break within the gapped palindromic sequence CACTNNN^GTG of double-stranded DNA indicates nicking on the bottom strand; indicates nicking on the top strand). However, wild type Dralll shows significant star activity. In this study, it was found that the prominent star site is CATSGTT;GTG, consisting of a star 5' half (CAT) and a canonical 3' half (GTG). Dralll nicks the 3' canonical half site at a faster rate than the 5' star half site, in contrast to the similar rate with the canonical full site. The crystal structure of the Dralll protein was solved. It indicated, as supported by mutagenesis, that Dralll possesses a ~13a- metal HNH active site. The structure revealed extensive intra-molecular interactions between the N-terminal domain and the C-terminal domain containing the HNH active site. Disruptions of these interactions through site- directed mutagenesis drastically increased cleavage fidelity. The understanding of fidelity mechanisms will enable generation of high fidelity REases.展开更多
The application of machine learning(ML)-based methods to the study of thermoelectric(TE)materials is promising.Although conventional ML algorithms can achieve high prediction performance,their lack of interpretability...The application of machine learning(ML)-based methods to the study of thermoelectric(TE)materials is promising.Although conventional ML algorithms can achieve high prediction performance,their lack of interpretability severely obstructs researchers from extracting material-oriented insights from ML models.In this work,high ML-based prediction performance was achieved with respect to TE power factors(PFs),and the results were well understood by the SHapley Additive exPlanations(SHAP),a method to identify the correlations between targets and descriptors.We designed a robust PF prediction model for diamond-like compounds via a stacking technique,and the model achieved a coefficient of determination value above 0.95 on the test set.From the SHAP analysis,the PFs were negatively correlated with electronegativity and positively correlated with the descriptor“volume per atom”based on the previously reported dataset.TE domain knowledge was adopted to understand these correlations.This work shows that ML models can achieve high accuracy while exhibiting good interpretability,making them useful for materials scientists.展开更多
P-glycoprotein(P-gp)highly expressed in cancer cells can lead to multidrug resistance(MDR)and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment.I...P-glycoprotein(P-gp)highly expressed in cancer cells can lead to multidrug resistance(MDR)and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment.In this study,we established a label-free and detergent-free system combining surface plasmon resonance(SPR)biosensor with styrene maleic acid(SMA)polymer membrane proteins(MPs)stabilization technology to screen potential P-gp inhibitors.First,P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes(SMALPs).Following that,SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system,and the affinity between P-gp and small molecule ligand was determined.The methodological investigation proved that the screening system had good specificity and stability.Nine P-gp ligands were screened out from 50 natural products,and their affinity constants with P-gp were also determined.The in vitro cell verification experiments demonstrated that tetrandrine,fangchinoline,praeruptorin B,neobaicalein,and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin(Adr).Moreover,tetrandrine,praeruptorin B,and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp.This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system.SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp.The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.展开更多
基金This work was financially supported by the Opening Project of National Local Joint Laboratory for Advanced Textile Processing and Clean Production(FX2022006)Guiding Project of Natural Science Foundation of Hubei province(2022CFC072)+2 种基金Guiding Project of Scientific Research Plan of Education Department of Hubei Province(B2022081)Shenghong Key Scientific Research Project of Emergency Support and Public Safety Fiber Materials and Products(2022-rw0101)Science and Technology Guidance Program of China National Textile and Apparel Council(2022002).
文摘Firefighting protective clothing is a crucial protective equipment for firefighters to minimize skin burn and ensure safety firefighting operation and rescue mission.A recent increasing concern is to develop self-powered fire warning materials that can be incorporated into the firefighting clothing to achieve active fire protection for firefighters before the protective clothing catches fire on fireground.However,it is still a challenge to facilely design and manufacture thermoelectric(TE)textile(TET)-based fire warning electronics with dynamic surface conformability and breathability.Here,we develop an alternate coaxial wet-spinning strategy to continuously produce alternating p/n-type TE aerogel fibers involving n-type Ti_(3)C_(2)T_(x)MXene and p-type MXene/SWCNT-COOH as core materials,and tough aramid nanofiber as protective shell,which simultaneously ensure the flexibility and high-efficiency TE power generation.With such alternating p/n-type TE fibers,TET-based self-powered fire warning sensors with high mechanical stability and wearability are successfully fabricated through stitching the alternating p-n segment TE fibers into aramid fabric.The results indicate that TET-based fire warning electronics containing 50 p-n pairs produce the open-circuit voltage of 7.5 mV with a power density of 119.79 nW cm-2 at a temperature difference of 300℃.The output voltage signal is then calculated as corresponding surface temperature of firefighting clothing based on a linear relationship between TE voltage and temperature.The fire alarm response time and flame-retardant properties are further displayed.Such self-powered fire warning electronics are true textiles that offer breathability and compatibility with body movement,demonstrating their potential application in firefighting clothing.
基金the financial support provided by the National Science and TechnologyMajor Project(No.J2019-VI-0003-0116)the Six Talent Peaks Project in Jiangsu Province(Grant No.2019-KTHY-059).
文摘Many titanium alloy subcomponents are subjected to fatigue loading in aerospace engineering,resulting in fatigue failure.The fatigue behavior of Ti_(2)AlNb alloy subcomponents was investigated based on the Seeger fatigue life theory and the improved Lemaitre damage evolution theory.Firstly,the finite element models of the standard openhole specimen and Y-section subcomponents have been established by ABAQUS.The damage model parameters were determined by fatigue tests,and the reliability of fatigue life simulation results of the Ti_(2)AlNb alloy standard open-hole specimen was verified.Meanwhile,the fatigue life of Ti_(2)AlNb alloy Y-section subcomponents was predicted.Under the same initial conditions,the average error of fatigue life predicted by two different models was 20.6%.Finally,the effects of loading amplitude,temperature,and Y-interface angle on fatigue properties of Ti_(2)AlNb Y-section subcomponents were investigated.These results provide a new idea for evaluating the fatigue life of various Ti_(2)AlNb alloy subcomponents.
基金Supported by the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(No.GML2019ZD0104)the National Natural Science Foundation of China(Nos.U19B2005,42076072)+1 种基金the Pilot National Laboratory for Marine Science and Technology(Qingdao)Initial Foundation(No.JCZX202019)the Research Start-up Funds of Zhufeng Scholars Program。
文摘High concentrated and heterogeneous distribution of gas hydrates have been identified in the gas hydrate production test region in the Shenhu area,South China Sea.The gas hydrate-bearing sediments with high saturation locate at two ridges of submarine canyon with different thickness and saturations just above the bottom simulating reflection.The crossplots of gamma ray,acoustic impedance(P-impedance)and porosity at four sites show that the sediments can be divided into the upper and lower layers at different depths,indicating different geotechnical reservoir properties.Therefore,the depositional environments and physical properties at two ridges are analyzed and compared to show the different characteristics of hydrate reservoir.High porosity,high P-wave velocity,and coarse grain size indicate better reservoir quality and higher energy depositional environment for gas hydrate at Sites W18 and W19 than those at Sites W11 and W17.Our interpretation is that the base of canyon deposits at Sites W18 and W19 characterized by upward-coarsening units may be turbidity sand layers,thus significantly improving the reservoir quality with increasing gas hydrate saturation.The shelf and slope sliding deposits compose of the fine-grained sediments at Sites W11 and W17.The gas hydrate production test sites were conducted at the ridge of W11 and W17,mainly because of the thicker and larger area of gas hydrate-bearing reservoirs than those at Sites W18 and W19.All the results provide useful insights for assessing reservoir quality in the Shenhu area.
基金financially supported by the National Natural Science Foundation of China (81573396)Military Innovation Funding (16CXZ012)
文摘According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry(HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids,monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine,and aconine in SD rats were used to validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diesterditerpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids.Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoesterditerpenoid alkaloids and amine-diterpenoid alkaloids.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82073814,81973291,82122066,and 82003909)the Rising-Star Program of Shanghai Science and Technology Committee(Grant No.:19QA1411500).
文摘Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell activators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside IV,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory components of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.
基金sponsored by the National Natural Science Foundation of China(Grant No.:82174092)Science and Technology Commission of Shanghai Municipality(Grant No.:21ZR1483000)Shanghai Pujiang Program(Grant No.:21PJD083).
文摘Therapeutic drug monitoring(TDM)has played an important role in clinical medicine for precise dosing.Currently,chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs of clinical drug therapy.However,some problems still exist in practical applications,such as complicated operation and the influence of endogenous substances.Surface plasmon resonance(SPR)has been applied to detect the concentrations of small molecules,including pesticide residues in crops and antibiotics in milk,which indicates its potential for in vivo drug detection.In this study,a new SPR-based biosensor for detecting chloramphenicol(CAP)in blood samples was developed and validated using methodological verification,including precision,accuracy,matrix effect,and extraction recovery rate,and compared with the classic ultra-performance liquid chromatographyultraviolet(UPLC-UV)method.The detection range of SPR was 0.1-50 ng/mL and the limit of detection was 0.099±0.023 ng/mL,which was lower than that of UPLC-UV.The intra-day and inter-day accuracies of SPR were 98%-114% and 110%-122%,which met the analysis requirement.The results show that the SPR biosensor is identical to UPLC-UV in the detection of CAP in rat blood samples;moreover,the SPR biosensor has better sensitivity.Therefore,the present study shows that SPR technology can be used for the detection of small molecules in the blood samples and has the potential to become a method for therapeutic drug monitoring.
基金supported by the National Key Research and Development Program of China(2021YFB3502200,2018YFB0703600,and 2019YFA0704901)the National Natural Science Foundation of China(52172216,92163212,and 12174242)+4 种基金the Key Research Project of Zhejiang Laboratory(2021PE0AC02)the support from Guangdong Innovation Research Team Project(2017ZT07C062)Guangdong Provincial Key-Lab program(2019B030301001)Shenzhen Municipal Key-Lab program(ZDSYS20190902092905285)supported by the Center for Computational Science and Engineering at Southern University of Science and Technology。
文摘Introduction Primary liver cancer is a significant health issue in China,where it ranks fourth in morbidity and second in mortality among all malignant tumors.[1-4]The 5-year overall survival rate of Chinese patients with liver cancer from 2012 to 2015 was only 12.2%for males and 13.1%for females.[5]Hepatocellular carcinoma(HCC)accounts for 75-85%of primary liver cancers.[6]Furthermore,most liver cancers are unresectable at diagnosis.To combat this,conversion therapy is used,which involves systematic treatments like anti-angiogenic drugs or molecular targeted therapy combined with immunotherapies,as well as locoregional treatments such as transcatheter arterial chemoembolization(TACE),hepatic artery infusion chemotherapy(HAIC),ablation therapy,and radiation therapy.The goal is to eliminate unresectable status and increase the chances of surgery.The reported 5-year survival rate after salvage surgery following tumor downstaging varied from 24.9-57%.
基金support from the National Natural Science Foundation of China(52061135103 and 52203287).
文摘Background and Originality Content,Inclusion single crystals(IsCs)are characterized by the encapsulation of guest molecules within the crystal lattice of a host framework,resulting in,well-defined channels or cavities throughout the material. Host molecules can be broadly di.Videdinto wo main categories.i)The more widespreadgroup is unimolecular inclusion compounds where one host molecule interacts with one guest species.Familiar examples of this cate-gory include calixarenes,cyclodextrins,crown ethers,bai cavitands.cucurbituils,uoaciyclophanes,and various carcerands,ii) the other is multimoiecular inclusion caompounds where two or more host molecules are involved in forming cavities,channels,or layers in the crystal structure to accommodate guest molecules.Host molecules of,this kind include urea,choleic acis,Dianin's compound,etc.,and crystline porous materials such as metal-organic poliyhedrali and porous organic[18]cagesll are well-known examples.
文摘Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.
基金supported by the National Natural Science Foundation of China (Grant Nos. 82073814, 81973275, 82003909, 81973291, 82122066, 81803815)Rising-Star Program of Shanghai Science and Technology Committee (19QA1411500)
文摘Cell membrane affinity chromatography has been widely applied in membrane protein(MP)-targeted drug screening and interaction analysis.However,in current methods,the MP sources are derived from cell lines or recombinant protein expression,which are time-consuming for cell culture or purification,and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase.In this study,a novel in situ synthesis membrane protein affinity chromatography(iSMAC)method was developed utilizing cell-free protein expression(CFE)and covalent immobilized affinity chromatography,which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase.The advantages of iSMAC are:1)There is no need to culture cells or prepare recombinant proteins;2)Specific and purified MPs with stable and controllable content can be obtained within 2 h;3)MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase;4)The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites.iSMAC was successfully applied to screen PDGFRβinhibitors from Salvia miltiorrhiza and Schisandra chinensis.Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h.Two new PDGFRβinhibitors,salvianolic acid B and gomisin D,were screened out with KD values of 13.44 and 7.39μmol/L,respectively.In vitro experiments confirmed that the two compounds decreasedα-SMA and collagen Ⅰ mRNA levels raised by TGF-βin HSC-T6 cells through regulating the phosphorylation of p38,AKT and ERK.In vivo,Sal B could also attenuate CCl_(4)-induced liver fibrosis by downregulating PDGFRβdownstream related protein levels.The iSMAC method can be applied to other general MPs,and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.
基金supported by grants from the National Basic Research Program of China (2012CB517805 and 2012CB517806)the National Natural Science Foundation of China (30890042)supported by the Program for Changjiang Scholars from the Ministry of Education in China.
文摘Brown adipose tissue(BAT)is an energy-expending organ that produces heat.Expansion or activation of BAT prevents obesity and diabetes.Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1(UCP1)activation triggered via a b-adrenergic pathway.Here,we report that the cold-sensing transient receptor potential melastatin 8(TRPM8)is functionally present in mouse BAT.Challenging brown adipocytes with menthol,a TRPM8 agonist,up-regulates UCP1 expression and requires protein kinase A activation.Upon mimicking long-term cold exposure with chronic dietary menthol application,menthol significantly increased the core temperatures and locomotor activity in wild-type mice;these effects were absent in both TRPM82/2 and UCP12/2 mice.Dietary obesity and glucose abnormalities were also prevented by menthol treatment.Our results reveal a previously unrecognized role for TRPM8,suggesting that stimulation of this channel mediates BAT thermogenesis,which could constitute a promising way to treat obesity.
基金B.X.thanks financial supports from the National Natural Science Foundation of China(No.21801133),Jiangsu Specially Appointed Professorship,Innovation and Entrepreneurship Talents in Jiangsu Province and State Key Laboratory of Coordination Chemistry,School of Chemistry and Chemical Engineering,Nanjing University.J.T.and T.F.acknowledge the support from the University of Utah.
文摘PbS-based thermoelectric materials have attracted extensive attention in recent years for the advantages of earth abundancy and low cost,which is considered to be a substitute for traditional PbTe material.However,their high thermal conductivity restricts its development.Hence,in order to improve their thermoelectric performance from reducing the thermal conductivity,a kind of dendritic PbS with controlled crystal grain and morphology are obtained by solution synthesis.By adjusting the amount of surfactant(CTAB),the specific formation process of dendrites is regulated.After sintering,the dendritic PbS nanoparticles are easy to form porous structure due to the overlapping and staggered arrangement of dendritic branches.For comparison,we also prepare a kind of regular octahedral PbS and a dense packing arrangement is formed because of the integrity of the octahedral structure.DFT-based Boltzmann transport equation is used to prove the crucial role of porous structure in scattering phonon.Finally,a maximum zT=1.0 at 773 K in n-type PbS is obtained,which still keep a high-speed growth and is expected to get higher zT value in a higher temperature region.Our work may shed light to other thermoelectric materials from the formation of porous structure to reduce the thermal conductivity.
基金supported by Science and Technology Project of State Grid Corporation of China(No.5230HQ19000J)。
文摘As an important part of demand side,residential users have the characteristics of imperfect rationality and strong randomness,which are rarely considered in the existing study.Moreover,to effectively improve the energy efficiency,integrated demand response(IDR)is proposed as an effective measure to reduce the local energy supply pressure.This paper focuses on a scenario for IDR programs,in which the intelligent building aggregator(IBA)wants to encourage residential users to participate in IDR according to a proper contract price policy.To analyze how the participation degree tendency evolves over time,an evolutionary game approach is proposed considering residential users’bounded-rationality.A symmetric evolutionary game model and an asymmetric evolutionary game model are established,and the stability of equilibrium points in the above models is proven.Simulation results show that different contract price policies will obviously influence residential users’strategy,and affect the stable equilibrium points of the evolutionary game.The simulation results provide an effective reference for IBA to set proper and effective price incentives.
文摘Dralll is a type liP restriction endonucleases (REases) that recognizes and creates a double strand break within the gapped palindromic sequence CACTNNN^GTG of double-stranded DNA indicates nicking on the bottom strand; indicates nicking on the top strand). However, wild type Dralll shows significant star activity. In this study, it was found that the prominent star site is CATSGTT;GTG, consisting of a star 5' half (CAT) and a canonical 3' half (GTG). Dralll nicks the 3' canonical half site at a faster rate than the 5' star half site, in contrast to the similar rate with the canonical full site. The crystal structure of the Dralll protein was solved. It indicated, as supported by mutagenesis, that Dralll possesses a ~13a- metal HNH active site. The structure revealed extensive intra-molecular interactions between the N-terminal domain and the C-terminal domain containing the HNH active site. Disruptions of these interactions through site- directed mutagenesis drastically increased cleavage fidelity. The understanding of fidelity mechanisms will enable generation of high fidelity REases.
基金The work of this paper was supported by the National Key R&D Programs of China(No.2017YFB0701501 and 2018YFB0703600).
文摘The application of machine learning(ML)-based methods to the study of thermoelectric(TE)materials is promising.Although conventional ML algorithms can achieve high prediction performance,their lack of interpretability severely obstructs researchers from extracting material-oriented insights from ML models.In this work,high ML-based prediction performance was achieved with respect to TE power factors(PFs),and the results were well understood by the SHapley Additive exPlanations(SHAP),a method to identify the correlations between targets and descriptors.We designed a robust PF prediction model for diamond-like compounds via a stacking technique,and the model achieved a coefficient of determination value above 0.95 on the test set.From the SHAP analysis,the PFs were negatively correlated with electronegativity and positively correlated with the descriptor“volume per atom”based on the previously reported dataset.TE domain knowledge was adopted to understand these correlations.This work shows that ML models can achieve high accuracy while exhibiting good interpretability,making them useful for materials scientists.
基金supported by the National Natural Science Foundation of China(No.82173777,81872829,81673386,82174092)the Science and Technology Commission of Shanghai Municipality(21ZR1483000)。
文摘P-glycoprotein(P-gp)highly expressed in cancer cells can lead to multidrug resistance(MDR)and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment.In this study,we established a label-free and detergent-free system combining surface plasmon resonance(SPR)biosensor with styrene maleic acid(SMA)polymer membrane proteins(MPs)stabilization technology to screen potential P-gp inhibitors.First,P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes(SMALPs).Following that,SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system,and the affinity between P-gp and small molecule ligand was determined.The methodological investigation proved that the screening system had good specificity and stability.Nine P-gp ligands were screened out from 50 natural products,and their affinity constants with P-gp were also determined.The in vitro cell verification experiments demonstrated that tetrandrine,fangchinoline,praeruptorin B,neobaicalein,and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin(Adr).Moreover,tetrandrine,praeruptorin B,and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp.This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system.SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp.The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.
基金the National Natural Science Foundation of China(22090043 and 21622101)Guangxi Natural Science Foundation(2019GXNSFGA245006)for financial support+2 种基金the National Natural Science Foundation of China(21527803 and 21621061)the Ministry of Science and Technology of China(2016YFA0301004)for financial supportthe funding from China Postdoctoral Science Foundation(8206300392)。