Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxymatrine,a...Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxymatrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mechanism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological prediction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-kB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in acceleratingMKdifferentiation and thrombopoiesis via the STING/NF-kB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.展开更多
Rice yield in the black soil region of Northeast China has been declining due to severe soil fertility degradation caused by both biotic and abiotic factors.Artificial humic substance(A-HS)has attracted much attention...Rice yield in the black soil region of Northeast China has been declining due to severe soil fertility degradation caused by both biotic and abiotic factors.Artificial humic substance(A-HS)has attracted much attention due to its high cost-effectiveness and great potential to improve soil fertility.However,the specific effects of A-HS on nutrient contents in rice nursery soils remain unclear.This study systematically investigated the effects of rational application of A-HS on soil nutrient turnover and yield and analyzed the changes in soil nutrients and microbial communities at Qianfeng Farm,Northeast China.The results indicated that the application of A-HS significantly increased soil dissolved organic matter and nutrient contents in the native and seedling soils.In addition,the root growth and yield of the seedlings at maturity were effectively promoted.More interestingly,the application of A-HS significantly altered plant growth-promoting rhizobacteria,such as Noviherbaspirillum,Klebsiella,and Pedobacter,improving natural barrier formation and soil nutrient conversion.It could be concluded that A-HS significantly enhanced crop nutrient uptake and accumulation by altering soil bacterial communities.In general,the application of A-HS could be profitable and sustainable in rice production.The current study from multiple aspects provides valuable insights into the benefits of A-HS in promoting crop growth and development,which could have important implications for agriculture and food security.展开更多
With the rapid development of flexible equipment,high-energy/-power requirements have been proposed for energy storage devices.Nevertheless,the poor conductivities of metallic oxides and their low levels of transmissi...With the rapid development of flexible equipment,high-energy/-power requirements have been proposed for energy storage devices.Nevertheless,the poor conductivities of metallic oxides and their low levels of transmission of electrons/ions hinder their widespread application.Here,a sandwich-structured Co_(3)O_(4)-Fe_(3)O_(4)(CFO) composite with binder-free was synthesized on a carbon cloth substrate via co-precipitation and partial ion exchange.The appropriate substitution of Co_(3)O_(4)with Fe_(3)O_(4)is favorable in promoting the rapid transfer of electrolyte ions and alleviating changes in volume during the electrochemical studies.When the duration of the substitution reaction is 20 min,the obtained electrode delivers a maximum specific capacitance of 1196.2 Fg^(-1)at a current density of 1 A g^(-1)and a superior capacity retention of~71%when the current density varies from 1to 30 Ag^(-1).Furthermore,the fabricated CFO//activated carbon flexible all-solid-state supercapacitor exhibits arespective maximum energy and power density of 68.7Wh kg^(-1)and 16,000 W kg^(-1)and excellent flexibility.It also displays a specific capacity retention of 81.3%under four continuous bending states at a current density of 6A g^(-1)over 10,000 cycles.These remarkable electrochemical char ac teristics suggest that the sandwich-structured CFO composite displays considerable potential for application in flexible high-energy/-power supercapacitors.展开更多
As a distributed machine learning method,federated learning(FL)has the advantage of naturally protecting data privacy.It keeps data locally and trains local models through local data to protect the privacy of local da...As a distributed machine learning method,federated learning(FL)has the advantage of naturally protecting data privacy.It keeps data locally and trains local models through local data to protect the privacy of local data.The federated learning method effectively solves the problem of artificial Smart data islands and privacy protection issues.However,existing research shows that attackersmay still steal user information by analyzing the parameters in the federated learning training process and the aggregation parameters on the server side.To solve this problem,differential privacy(DP)techniques are widely used for privacy protection in federated learning.However,adding Gaussian noise perturbations to the data degrades the model learning performance.To address these issues,this paper proposes a differential privacy federated learning scheme based on adaptive Gaussian noise(DPFL-AGN).To protect the data privacy and security of the federated learning training process,adaptive Gaussian noise is specifically added in the training process to hide the real parameters uploaded by the client.In addition,this paper proposes an adaptive noise reduction method.With the convergence of the model,the Gaussian noise in the later stage of the federated learning training process is reduced adaptively.This paper conducts a series of simulation experiments on realMNIST and CIFAR-10 datasets,and the results show that the DPFL-AGN algorithmperforms better compared to the other algorithms.展开更多
Lithium/potassium ion capacitors(LICs/PICs) have been proposed to bridge the performance gap between high-energy batteries and high-power capacitors.However,their development is hindered by the choice,electrochemical ...Lithium/potassium ion capacitors(LICs/PICs) have been proposed to bridge the performance gap between high-energy batteries and high-power capacitors.However,their development is hindered by the choice,electrochemical performance,and preparation technique of the battery-type anode materials.Herein,a nitrogen and phosphorus dual-doped multilayer graphene(NPG) material is designed and synthesized through an arc discharge process,using low-cost graphite and solid nitrogen and phosphorus sources.When employed as the anode material,NPG exhibits high capacity,remarkable rate capability,and stable cycling performance in both lithium and potassium ion batteries.This excellent electrochemical performance is ascribed to the synergistic effect of nitrogen and phosphorus doping,which enhances the electrochemical conductivity,provides a higher number of ion storage sites,and leads to increased interlayer spacing.Full carbon-based NPG‖LiPF6‖active carbon(AC) LICs and NPG‖KPF6‖AC PICs are assembled and show excellent electrochemical performance,with competitive energy and power densities.This work provides a route for the large-scale production of dual-doped graphene as a universal anode material for high-performance alkali ion batteries and capacitors.展开更多
It is highly desirable to design and synthesize two-dimensional nanostructured electrode materials with high electrical conductivity,large electrolyte-accessible surface area and more exposed active sites for energy s...It is highly desirable to design and synthesize two-dimensional nanostructured electrode materials with high electrical conductivity,large electrolyte-accessible surface area and more exposed active sites for energy storage applications.Herein,MXene/Co Al-LDH heterostructure has been prepared through electrostatic ordered hetero-assembly of monolayer MXene and edge-rich Co Al-LDH nanosheets in a faceto-face manner on molecular-scale for supercapacitor applications.Benefiting from the unique structure,strong interfacial interaction and synergistic effects between MXene and Co Al-LDH nanosheets,the electrical conductivity and exposed electrolyte-accessible active sites are significantly enhanced.The asprepared MXene/Co Al-LDH-80%(ML-80)film exhibits high volumetric capacity of 2472 C cm-3 in 3 M KOH electrolyte with high rate capability of 70.6%at 20 A g-1.Notably,to the best of our knowledge,the high volumetric capacity is the highest among other previously reported values for supercapacitors in aqueous electrolytes.Furthermore,our asymmetric supercapacitor device fabricated with ML-80 and MXene/graphene composite as cathode and anode,respectively,exhibits impressive volumetric energy density of 85.4 Wh L-1 with impressive cycling stability of 94.4%retention ratio after 30,000 continuous charge/discharge cycles.展开更多
Nowadays,iron ions as a ubiquitous heavy metal pollutant are gradually concerned and the convenient and quick removal of excessive iron ions in groundwater has become a major challenge for the safety of drinking water...Nowadays,iron ions as a ubiquitous heavy metal pollutant are gradually concerned and the convenient and quick removal of excessive iron ions in groundwater has become a major challenge for the safety of drinking water.In this study,boron-doped biochar(B-BC)was successfully prepared at various preparation conditions with the addition of boric acid.The as-prepared material has a more developed pore structure and a larger specific surface area(up to 897.97 m2/g).A series of characterization results shows that boric acid effectively activates biochar,and boron atoms are successfully doped on biochar.Compared with the ratio of raw materials,the pyrolysis temperature has a greater influence on the amount of boron doping.Based on Langmuir model,the maximum adsorption capacity of 800 B-BC1:2 at25℃,40℃,55℃ are 50.02 mg/g,95.09 mg/g,132.78 mg/g,respectively.Pseudo-second-order kinetic model can better describe the adsorption process,the adsorption process is mainly chemical adsorption.Chemical complexation,ions exchange,and co-precipitation may be the main mechanisms for Fe2+removal.展开更多
Urea oxidation is a significant reaction for utilizing urea-rich wastewater or human urine as sustainable power sources which can ease the water eutrophication while generate electricity. A direct urea-hydrogen peroxi...Urea oxidation is a significant reaction for utilizing urea-rich wastewater or human urine as sustainable power sources which can ease the water eutrophication while generate electricity. A direct urea-hydrogen peroxide fuel cell is a new kind of fuel cell employing urea as fuel and hydrogen peroxide as oxidant which possesses a larger cell voltage. Herein, this work tries to promote the kinetics process of urea oxidation by preparing low-cost and high-efficient NiCo2S4 nanowires modified carbon sponge electrode. The carbon sponge used in this work with a similar three-dimensional multi-channel structure to Ni foam, is prepared by carbonizing recycled polyurethane sponge which is also a process of recycling waste. The performance of the prepared catalyst in an alkaline solution is investigated in a three-electrode system.With the introduction of Co element to the catalyst, a reduced initial urea oxidation potential and a high performance are obtained. Furthermore, a direct urea-hydrogen peroxide fuel cell is assembled using the NiCo2S4 nanowires modified carbon sponge anode. Results indicate that the prepared catalyst provides a chance to solve the current problems that hinder the development of urea electrooxidation(high initial urea oxidation potential, low performance, and high electrode costs).展开更多
A hot primary-air pipe system is the bridge connecting an air-preheater with a coal mill in power generation stations.The effective geometrical configuration of the pipe network greatly affects the air flow distributi...A hot primary-air pipe system is the bridge connecting an air-preheater with a coal mill in power generation stations.The effective geometrical configuration of the pipe network greatly affects the air flow distribution and consequently influences the safe and economic operation of milling systems in power stations.In order to improve the properties of the air flow,in the present work the SIMPLEC method is used to simulate numerically the flow field for the original layout of the system.As a result,the internal mechanisms influencing the uneven pressure drop in each branch are explored and three optimization schemes are proposed accordingly.The numerical results indicate that,for the original layout,the local pressure drop of the tee section accounts for approximately 74%of the total drop of the system,with other pressure drops depending on the specific branch considered.It is shown that after optimization,a roughly balanced flow resistance and flow rate can be obtained.Compared with the original layout,the pressure drop relating to different branches is significantly reduced.展开更多
MXene-based electrode materials exhibit favorable supercapacitor performance in sulfuric acid due to praised pseudocapacitance charge storage mechanism.However,self-stacking of conventional MXene electrodes severely r...MXene-based electrode materials exhibit favorable supercapacitor performance in sulfuric acid due to praised pseudocapacitance charge storage mechanism.However,self-stacking of conventional MXene electrodes severely restricts their electrochemical performance,especially at high loading.Herein,a flexible cross-linked porous Ti3C2Tx-MXene-reduced graphene oxide(Ti3C2Tx-RGO)film is skillfully designed and synthesized by microscopic explosion of graphene oxide(GO)at sudden high te mperature.The generated chamber structure between layers could hold a few of electrolyte,leading to a close-fitting reaction at interlayer and avoiding complex ions transmission paths.The Ti3C2Tx-RGO film displayed a preferable rate performance than that of pure Ti3C2Tx film and a high capacitance of 505 F/g at 2 mV/s.Furthermore,the uniform intralayer structure and unique energy storage process lead to thicknessindependenct electrochemical performances.This work provides a simple and feasible improvement approach for the design of MXene-based electrodes,which can be spread other electrochemical systems limited by ions transport,such as metal ions batteries and catalysis.展开更多
Sodium ion batteries and capacitors have demonstrated their potential applications for next-generation low-cost energy storage devices.These devices’s rate ability is determined by the fast sodium ion storage behavio...Sodium ion batteries and capacitors have demonstrated their potential applications for next-generation low-cost energy storage devices.These devices’s rate ability is determined by the fast sodium ion storage behavior in electrode materials.Herein,a defective TiO2@reduced graphene oxide(M-TiO2@rGO)self-supporting foam electrode is constructed via a facile MXene decomposition and graphene oxide self-assembling process.The employment of the MXene parent phase exhibits distinctive advantages,enabling defect engineering,nanoengineering,and fluorine-doped metal oxides.As a result,the M-TiO2@rGO electrode shows a pseudocapacitance-dominated hybrid sodium storage mechanism.The pseudocapacitance-dominated process leads to high capacity,remarkable rate ability,and superior cycling performance.Significantly,an M-TiO2@rGO//Na3 V2(PO4)3 sodium full cell and an M-TiO2@rGO//HPAC sodium ion capacitor are fabricated to demonstrate the promising application of M-TiO2@rGO.The sodium ion battery presents a capacity of 177.1 mAh g-1 at 500 mA g-1 and capacity retention of 74%after 200 cycles.The sodium ion capacitor delivers a maximum energy density of 101.2 Wh kg-1 and a maximum power density of 10,103.7 W kg-1.At 1.0 A g-1,it displays an energy retention of 84.7%after 10,000 cycles.展开更多
Aqueous rechargeable zinc ion batteries are very attractive in large-scale storage applications,because they have high safety,low cost and good durability.Nonetheless,their advancements are hindered by a dearth of pos...Aqueous rechargeable zinc ion batteries are very attractive in large-scale storage applications,because they have high safety,low cost and good durability.Nonetheless,their advancements are hindered by a dearth of positive host materials(cathode)due to sluggish diffusion of Zn2+in the solid inorganic frameworks.Here,we report a novel organic electrode material of poly 3,4,9,10-perylentetracarboxylic dianhydride(PPTCDA)/graphene aerogel(GA).The 3D interconnected porous architecture synthesized through a simple solvothermal reaction,where the PPTCDA is homogenously embedded in the GA nanosheets.The self-assembly of PPTCDA/GA coin-type cell will not only significantly improve the durability and extend lifetime of the devices,but also reduce the electronic waste and economic cost.The self-assembled structure does not require the auxiliary electrode and conductive agent to prepare the electrode material,which is a simple method for preparing the coin-type cell and a foundation for the next large-scale production.The PPTCDA/GA delivers a high capacity of≥200 m Ah g^–1 with the voltage of 0.0~1.5 V.After 300 cycles,the capacity retention rate still close to 100%.The discussion on the mechanism of Zn2+intercalation/deintercalation in the PPTCDA/GA electrode is explored by Fourier transform infrared spectrometer(FT-IR),X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS)characterizations.The morphology and structure of PPTCDA/GA are examined by scanning electron microscopy(SEM)and transmission electron microscopy(TEM).展开更多
Lithium-sulfur batteries attract lots of attention due to their high specific capacity,low cost,and environmental friendliness.However,the low sulfur utilization and short cycle life extremely hinder their application...Lithium-sulfur batteries attract lots of attention due to their high specific capacity,low cost,and environmental friendliness.However,the low sulfur utilization and short cycle life extremely hinder their application.Herein,we design and fabricate a three-dimensional electrode by a simple filtration method to achieve a high-sulfur loading.Biomass porous carbon is employed as a current collector,which not only enhances the electronic transport but also effectively limits the volume expansion of the active material.Meanwhile,an optimized carboxymethyl cellulose binder is chosen.The chemical bonding restricts the shuttle effect,leading to improved electrochemical performance.Under the ultrahigh sulfur load of 28mg/cm2,the high capacity of 18mAh/cm2 is still maintained,and stable cycling performance is obtained.This study demonstrates a viable strategy to develop promising lithium-sulfur batteries with a three-dimensional electrode,which promotes sulfur loading and electrochemical performance.展开更多
To overcome the disadvantages of inhomogeneous microstructures and poor mechanical properties of additively manufactured Ti-6Al-4V alloys,a novel technique of hybrid deposition and synchronous micro-rolling is propose...To overcome the disadvantages of inhomogeneous microstructures and poor mechanical properties of additively manufactured Ti-6Al-4V alloys,a novel technique of hybrid deposition and synchronous micro-rolling is proposed.The micro-rolling leads to equiaxed prior β grains,thin discontinuous intergranular α,and equiaxed primary α,in contrast to the coarse columnar prior β grains without the application of micro-rolling.The recrystallization by micro-rolling results in discontinuous intergranular α via the mechanism of strain and interface-induced grain boundary migration.The evolution of α globularization,driven by a solute concentration gradient,starts from the sub-boundary until the formation of equiaxed primary α.Simultaneous strengthening and toughening are achieved,which means an increase in yield strength,ultimate tensile strength,fracture elongation,and work hardening rate.The formation of α recrystallization leads to more fine grain boundaries to strengthen the yield strength,and the improvement of ductility is due to the better-coordinated deformation ability of discontinuous intergranular α and equiaxed primary α.As a result,the fracture mode in micro-rolling changes from intergranular type to transgranular type.展开更多
ZnCo_2O_4 nanocluster particles(NCPs) were prepared through a designed hydrothermal method, with the assistance of a surfactant, sodium dodecyl benzene sulfonate. The crystalline structure and surface morphology of Zn...ZnCo_2O_4 nanocluster particles(NCPs) were prepared through a designed hydrothermal method, with the assistance of a surfactant, sodium dodecyl benzene sulfonate. The crystalline structure and surface morphology of ZnCo_2O_4 were investigated by XRD, XPS, SEM, TEM, and BET analyses. The results of SEM and TEM suggest a clear nanocluster particle structure of cubic ZnCo_2O_4(*100 nm in diameter), which consists of aggregated primary nanoparticles(*10 nm in diameter), is achieved. The electrochemical behavior of synthesized ZnCo_2O_4 NCPs was investigated by galvanostatic discharge/charge measurements and cyclic voltammetry. The ZnCo_2O_4 NCPs exhibit a high reversible capacity of 700 mAh g^(-1) over 100 cycles under a current density of 100 mA g^(-1) with an excellent coulombic efficiency of 98.9% and a considerable cycling stability. This work demonstrates a facile technique designed to synthesize ZnCo_2O_4 NCPs which show great potential as anode materials for lithium ion batteries.展开更多
A novel plastic/multi-walled carbon nanotube（MWNTs）-nickel（Ni）-platinum（Pt） electrode（PMNP） is prepared by chemical-reducing Pt onto the surface of Ni film covered plastic/MWNTs（PM） substrate. The MWNTs are ...A novel plastic/multi-walled carbon nanotube（MWNTs）-nickel（Ni）-platinum（Pt） electrode（PMNP） is prepared by chemical-reducing Pt onto the surface of Ni film covered plastic/MWNTs（PM） substrate. The MWNTs are adhered by a piece of commercial double faced adhesive tape on the surface of plastic paper and the Ni film is prepared by a simple electrodeposition method. The morphology and phase structure of the PMNP electrode are characterized by scanning electron microscopy,transmission electron microscope and X-ray diffractometer. The catalytic activity of the PMNP electrode for Na BH4 electrooxidation is investigated by means of cyclic voltammetry and chronoamperometry. The catalyst combines tightly with the plastic paper and exhibits a good stability. MWNTs serve as both conductive material and hydrogen storage material and the Ni film and Pt are employed as electrochemical catalysts. The PMNP electrode exhibits a high electrocatalytic performance and the oxidation current density reaches to 10.76 A/（mg·cm） in 0.1 mol/dm3 Na BH4at0 V,which is much higher than those in the previous reports. The using of waste plastic reduces the discarding of white pollution and consumption of metal resources.展开更多
Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators(e.g...Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators(e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges,including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result,the design of new epigenetic modulators(e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging(Hy T) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review,we aim to provide an in-depth illustration of new degrading strategies(2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.展开更多
Cervical cancer,the most common gynecological malignancy,significantly and adversely af-fects women’s physical health and well-being.Traditional surgical interventions and chemotherapy,while potentially effective,oft...Cervical cancer,the most common gynecological malignancy,significantly and adversely af-fects women’s physical health and well-being.Traditional surgical interventions and chemotherapy,while potentially effective,often entail serious side effects that have led to an urgent need for novel therapeutic methods.Photothermal therapy(PTT)has emerged as a promising approach due to its ability to minimize damage to healthy tissue.Connecting a biothiol detection group to PTT-sensitive molecules can improve tumor targeting and further minimize potential side effects.In this study,we developed a near-infrared fluorescence(NIRF)/photoacoustic(PA)dual-mode probe,S-NBD,which demonstrated robust PTT per-formance.This innovative probe is capable of activating NIRF/PA signals to enable the detection of bio-thiols with high emission wavelength(838 nm)and large Stokes shift(178 nm),allowing for in vivo monitoring of cancer cells.Additionally,the probe achieved an outstanding photothermal conversion ef-ficiency of 67.1%.The application of laser irradiation(660 nm,1.0 W/cm^(2),5 min)was able to achieve complete tumor ablation without recurrence.In summary,this seminal study presents a pioneering NIRF/PA dual-mode dicyanoisophorone-based probe for biothiol imaging,incorporating features from PTT for the first time.This pioneering approach achieves the dual objectives of improving tumor diagnosis and treatment.展开更多
Fe(hydr)oxides have a substantial impact on the structure and stability of soil organic carbon(SOC)pools and also drive organic carbon turnover processes via reduction–oxidation reactions.Currently,many studies have ...Fe(hydr)oxides have a substantial impact on the structure and stability of soil organic carbon(SOC)pools and also drive organic carbon turnover processes via reduction–oxidation reactions.Currently,many studies have paid much attention to organic matter–Fe mineral–microbial interactions on SOC turnover,while there is few research on how exogenous carbon addition abiotically regulates the intrinsic mechanisms of Fe-mediated organic carbon conversion.The study investigated the coupling process of artificial humic acid(A-HA)and Fe(hydr)oxide,the mechanism of inner-sphere ligands,and the capacity for carbon sequestration using transmission electron microscopy,thermogravimetric,x-ray photoelectron spectroscopy,and wet-chemical disposal.Furthermore,spherical aberration-corrected scanning transmission electron microscopy–electron energy loss spectroscopy and Mossbauer spectra have been carried out to demonstrate the spatial heterogeneity of A-HA/Fe(hydr)oxides and reveal the relationship between the increase in Fe-phase crystallinity and redox sensitivity and the accumulation of organic carbon.Additionally,the dynamics of soil structures on a microscale,distribution of carbon–iron microdomains,and the cementing-gluing effect can be observed in the constructing nonliving anthropogenic soils,confirming that the formation of stable aggregates is an effective approach to achieving organic carbon indirect protection.We propose that exogenous organic carbon inputs,specifically A-HA,could exert a substantial but hitherto unexplored effect on the geochemistry of iron–carbon turnover and sequestration in anoxic water/solid soils and sediments.展开更多
Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).How...Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral bioavailability.In addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse effects.Therefore,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with antibodies.Further,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic effects.Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy.In this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),etc.The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.:82074129,82004073,82204666,and 82374073)the Science and Technology Planning Project of Sichuan Province,China(Grant Nos.:2022JDJQ0061,2022ZYD0087,2022YFS0607,2022YFS0635,and 2022YFS0635-B1)+1 种基金the Joint Project of Xuzhou District People's Government and Southwest Medical University,China(Grant No.:2021XZXNYD01)Science and Technology Planning Project of Yibin City,China(Grant Nos.:2022NY020,2021ZYY009,and 2021ZYY005).
文摘Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxymatrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mechanism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological prediction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-kB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in acceleratingMKdifferentiation and thrombopoiesis via the STING/NF-kB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.
基金the financial support by the National Key Research and Development Program of China(No.2022YFD1500100)the National Natural Science Foundation of China(No.52279034)+5 种基金the Outstanding Youth Project of Heilongjiang Province,China(No.JQ2021D001)the Young Longjiang Scholar,China,the Science and Technology Project of Henan Province,China(No.252102321157)the Scientific Research Foundation for Doctoral Talents at Shangqiu Normal University,China(No.700125017)the Natural Science Foundation of Heilongjiang Province,China(No.LH2022D003)the Heilongjiang Postdoctoral Fund,China(No.LBH-Z21037)the Science and Technology Project of Henan Province,China(No.252102110185)。
文摘Rice yield in the black soil region of Northeast China has been declining due to severe soil fertility degradation caused by both biotic and abiotic factors.Artificial humic substance(A-HS)has attracted much attention due to its high cost-effectiveness and great potential to improve soil fertility.However,the specific effects of A-HS on nutrient contents in rice nursery soils remain unclear.This study systematically investigated the effects of rational application of A-HS on soil nutrient turnover and yield and analyzed the changes in soil nutrients and microbial communities at Qianfeng Farm,Northeast China.The results indicated that the application of A-HS significantly increased soil dissolved organic matter and nutrient contents in the native and seedling soils.In addition,the root growth and yield of the seedlings at maturity were effectively promoted.More interestingly,the application of A-HS significantly altered plant growth-promoting rhizobacteria,such as Noviherbaspirillum,Klebsiella,and Pedobacter,improving natural barrier formation and soil nutrient conversion.It could be concluded that A-HS significantly enhanced crop nutrient uptake and accumulation by altering soil bacterial communities.In general,the application of A-HS could be profitable and sustainable in rice production.The current study from multiple aspects provides valuable insights into the benefits of A-HS in promoting crop growth and development,which could have important implications for agriculture and food security.
基金financially supported by the Fundamental Research Funds for the Central Universities,North Minzu University(No.2020KYQD18)the Key Research and Development Program(Talents Introduction Project)of Ningxia(No.2021BEB04027)+1 种基金the Fundamental Research Funds for the Central Universities,North Minzu University(No.2021KJCX04)the Natural Science Foundation of Ningxia Province(No.2022AAC05033)
文摘With the rapid development of flexible equipment,high-energy/-power requirements have been proposed for energy storage devices.Nevertheless,the poor conductivities of metallic oxides and their low levels of transmission of electrons/ions hinder their widespread application.Here,a sandwich-structured Co_(3)O_(4)-Fe_(3)O_(4)(CFO) composite with binder-free was synthesized on a carbon cloth substrate via co-precipitation and partial ion exchange.The appropriate substitution of Co_(3)O_(4)with Fe_(3)O_(4)is favorable in promoting the rapid transfer of electrolyte ions and alleviating changes in volume during the electrochemical studies.When the duration of the substitution reaction is 20 min,the obtained electrode delivers a maximum specific capacitance of 1196.2 Fg^(-1)at a current density of 1 A g^(-1)and a superior capacity retention of~71%when the current density varies from 1to 30 Ag^(-1).Furthermore,the fabricated CFO//activated carbon flexible all-solid-state supercapacitor exhibits arespective maximum energy and power density of 68.7Wh kg^(-1)and 16,000 W kg^(-1)and excellent flexibility.It also displays a specific capacity retention of 81.3%under four continuous bending states at a current density of 6A g^(-1)over 10,000 cycles.These remarkable electrochemical char ac teristics suggest that the sandwich-structured CFO composite displays considerable potential for application in flexible high-energy/-power supercapacitors.
基金the Sichuan Provincial Science and Technology Department Project under Grant 2019YFN0104the Yibin Science and Technology Plan Project under Grant 2021GY008the Sichuan University of Science and Engineering Postgraduate Innovation Fund Project under Grant Y2022154.
文摘As a distributed machine learning method,federated learning(FL)has the advantage of naturally protecting data privacy.It keeps data locally and trains local models through local data to protect the privacy of local data.The federated learning method effectively solves the problem of artificial Smart data islands and privacy protection issues.However,existing research shows that attackersmay still steal user information by analyzing the parameters in the federated learning training process and the aggregation parameters on the server side.To solve this problem,differential privacy(DP)techniques are widely used for privacy protection in federated learning.However,adding Gaussian noise perturbations to the data degrades the model learning performance.To address these issues,this paper proposes a differential privacy federated learning scheme based on adaptive Gaussian noise(DPFL-AGN).To protect the data privacy and security of the federated learning training process,adaptive Gaussian noise is specifically added in the training process to hide the real parameters uploaded by the client.In addition,this paper proposes an adaptive noise reduction method.With the convergence of the model,the Gaussian noise in the later stage of the federated learning training process is reduced adaptively.This paper conducts a series of simulation experiments on realMNIST and CIFAR-10 datasets,and the results show that the DPFL-AGN algorithmperforms better compared to the other algorithms.
基金supported by National Natural Science Foundation of China(Nos.51672056 and 51702063)Natural Science Foundation of Heilongjiang(LC2018004)+1 种基金China Postdoctoral Science Foundation(2018M630340)the Fundamental Research Funds for the Central University(HEUCFD201732)
文摘Lithium/potassium ion capacitors(LICs/PICs) have been proposed to bridge the performance gap between high-energy batteries and high-power capacitors.However,their development is hindered by the choice,electrochemical performance,and preparation technique of the battery-type anode materials.Herein,a nitrogen and phosphorus dual-doped multilayer graphene(NPG) material is designed and synthesized through an arc discharge process,using low-cost graphite and solid nitrogen and phosphorus sources.When employed as the anode material,NPG exhibits high capacity,remarkable rate capability,and stable cycling performance in both lithium and potassium ion batteries.This excellent electrochemical performance is ascribed to the synergistic effect of nitrogen and phosphorus doping,which enhances the electrochemical conductivity,provides a higher number of ion storage sites,and leads to increased interlayer spacing.Full carbon-based NPG‖LiPF6‖active carbon(AC) LICs and NPG‖KPF6‖AC PICs are assembled and show excellent electrochemical performance,with competitive energy and power densities.This work provides a route for the large-scale production of dual-doped graphene as a universal anode material for high-performance alkali ion batteries and capacitors.
基金supported by the financial support from the National Natural Science Foundation of China(21571040)the Young Top-Notch Talent of National Ten Thousand Talent Program+1 种基金Heilongjiang Touyan Innovation Team ProgramFundamental Research Funds for the Central Universities。
文摘It is highly desirable to design and synthesize two-dimensional nanostructured electrode materials with high electrical conductivity,large electrolyte-accessible surface area and more exposed active sites for energy storage applications.Herein,MXene/Co Al-LDH heterostructure has been prepared through electrostatic ordered hetero-assembly of monolayer MXene and edge-rich Co Al-LDH nanosheets in a faceto-face manner on molecular-scale for supercapacitor applications.Benefiting from the unique structure,strong interfacial interaction and synergistic effects between MXene and Co Al-LDH nanosheets,the electrical conductivity and exposed electrolyte-accessible active sites are significantly enhanced.The asprepared MXene/Co Al-LDH-80%(ML-80)film exhibits high volumetric capacity of 2472 C cm-3 in 3 M KOH electrolyte with high rate capability of 70.6%at 20 A g-1.Notably,to the best of our knowledge,the high volumetric capacity is the highest among other previously reported values for supercapacitors in aqueous electrolytes.Furthermore,our asymmetric supercapacitor device fabricated with ML-80 and MXene/graphene composite as cathode and anode,respectively,exhibits impressive volumetric energy density of 85.4 Wh L-1 with impressive cycling stability of 94.4%retention ratio after 30,000 continuous charge/discharge cycles.
基金the financial support by Open Research Fund of State Key Laboratory of Geomechanics and Geotechnical Engineering,Institute of Rock and Soil Mechanics,Chinese Academy of Sciences(No.Z019005)the Longjiang Scholars for young scientist。
文摘Nowadays,iron ions as a ubiquitous heavy metal pollutant are gradually concerned and the convenient and quick removal of excessive iron ions in groundwater has become a major challenge for the safety of drinking water.In this study,boron-doped biochar(B-BC)was successfully prepared at various preparation conditions with the addition of boric acid.The as-prepared material has a more developed pore structure and a larger specific surface area(up to 897.97 m2/g).A series of characterization results shows that boric acid effectively activates biochar,and boron atoms are successfully doped on biochar.Compared with the ratio of raw materials,the pyrolysis temperature has a greater influence on the amount of boron doping.Based on Langmuir model,the maximum adsorption capacity of 800 B-BC1:2 at25℃,40℃,55℃ are 50.02 mg/g,95.09 mg/g,132.78 mg/g,respectively.Pseudo-second-order kinetic model can better describe the adsorption process,the adsorption process is mainly chemical adsorption.Chemical complexation,ions exchange,and co-precipitation may be the main mechanisms for Fe2+removal.
基金the financial support of this study by the Ph.D.Student Research and Innovation Fund of the Fundamental Research Funds for the Central Universities(grant number GK6530260034)the National Natural Science Foundation of China(grant numbers:51572052)。
文摘Urea oxidation is a significant reaction for utilizing urea-rich wastewater or human urine as sustainable power sources which can ease the water eutrophication while generate electricity. A direct urea-hydrogen peroxide fuel cell is a new kind of fuel cell employing urea as fuel and hydrogen peroxide as oxidant which possesses a larger cell voltage. Herein, this work tries to promote the kinetics process of urea oxidation by preparing low-cost and high-efficient NiCo2S4 nanowires modified carbon sponge electrode. The carbon sponge used in this work with a similar three-dimensional multi-channel structure to Ni foam, is prepared by carbonizing recycled polyurethane sponge which is also a process of recycling waste. The performance of the prepared catalyst in an alkaline solution is investigated in a three-electrode system.With the introduction of Co element to the catalyst, a reduced initial urea oxidation potential and a high performance are obtained. Furthermore, a direct urea-hydrogen peroxide fuel cell is assembled using the NiCo2S4 nanowires modified carbon sponge anode. Results indicate that the prepared catalyst provides a chance to solve the current problems that hinder the development of urea electrooxidation(high initial urea oxidation potential, low performance, and high electrode costs).
文摘A hot primary-air pipe system is the bridge connecting an air-preheater with a coal mill in power generation stations.The effective geometrical configuration of the pipe network greatly affects the air flow distribution and consequently influences the safe and economic operation of milling systems in power stations.In order to improve the properties of the air flow,in the present work the SIMPLEC method is used to simulate numerically the flow field for the original layout of the system.As a result,the internal mechanisms influencing the uneven pressure drop in each branch are explored and three optimization schemes are proposed accordingly.The numerical results indicate that,for the original layout,the local pressure drop of the tee section accounts for approximately 74%of the total drop of the system,with other pressure drops depending on the specific branch considered.It is shown that after optimization,a roughly balanced flow resistance and flow rate can be obtained.Compared with the original layout,the pressure drop relating to different branches is significantly reduced.
基金supported by the National Natural Science Foundation of China(Nos.51702063,51672056)Natural Science Foundation of Heilongjiang Province(No.LC2018004)+2 种基金China Postdoctoral Science Foundation(Nos.2018M630340,2019T120254)the Fundamental Research Funds for the Central University(No.3072019CF1006)the support from the Starting Research Fund from Harbin Normal University(No.XKB201420)。
文摘MXene-based electrode materials exhibit favorable supercapacitor performance in sulfuric acid due to praised pseudocapacitance charge storage mechanism.However,self-stacking of conventional MXene electrodes severely restricts their electrochemical performance,especially at high loading.Herein,a flexible cross-linked porous Ti3C2Tx-MXene-reduced graphene oxide(Ti3C2Tx-RGO)film is skillfully designed and synthesized by microscopic explosion of graphene oxide(GO)at sudden high te mperature.The generated chamber structure between layers could hold a few of electrolyte,leading to a close-fitting reaction at interlayer and avoiding complex ions transmission paths.The Ti3C2Tx-RGO film displayed a preferable rate performance than that of pure Ti3C2Tx film and a high capacitance of 505 F/g at 2 mV/s.Furthermore,the uniform intralayer structure and unique energy storage process lead to thicknessindependenct electrochemical performances.This work provides a simple and feasible improvement approach for the design of MXene-based electrodes,which can be spread other electrochemical systems limited by ions transport,such as metal ions batteries and catalysis.
基金supported by the National Natural Science Foundation of China(51702063,51672056)Natural Science Foundation of Heilongjiang(LC2018004)+1 种基金China Postdoctoral Science Foundation(2018M630340,2019T120254)the Fundamental Research Funds for the Central University。
文摘Sodium ion batteries and capacitors have demonstrated their potential applications for next-generation low-cost energy storage devices.These devices’s rate ability is determined by the fast sodium ion storage behavior in electrode materials.Herein,a defective TiO2@reduced graphene oxide(M-TiO2@rGO)self-supporting foam electrode is constructed via a facile MXene decomposition and graphene oxide self-assembling process.The employment of the MXene parent phase exhibits distinctive advantages,enabling defect engineering,nanoengineering,and fluorine-doped metal oxides.As a result,the M-TiO2@rGO electrode shows a pseudocapacitance-dominated hybrid sodium storage mechanism.The pseudocapacitance-dominated process leads to high capacity,remarkable rate ability,and superior cycling performance.Significantly,an M-TiO2@rGO//Na3 V2(PO4)3 sodium full cell and an M-TiO2@rGO//HPAC sodium ion capacitor are fabricated to demonstrate the promising application of M-TiO2@rGO.The sodium ion battery presents a capacity of 177.1 mAh g-1 at 500 mA g-1 and capacity retention of 74%after 200 cycles.The sodium ion capacitor delivers a maximum energy density of 101.2 Wh kg-1 and a maximum power density of 10,103.7 W kg-1.At 1.0 A g-1,it displays an energy retention of 84.7%after 10,000 cycles.
基金supported by the National Natural Science Foundation of China(51672056)Excellent Youth Project of Natural Science Foundation of Heilongjiang Province of China(YQ2019B002)+1 种基金China Postdoctoral Science Foundation(2018M630307 and 2019T120220)Fundamental Research Funds for the Central Universities(HEUCFD201732)。
文摘Aqueous rechargeable zinc ion batteries are very attractive in large-scale storage applications,because they have high safety,low cost and good durability.Nonetheless,their advancements are hindered by a dearth of positive host materials(cathode)due to sluggish diffusion of Zn2+in the solid inorganic frameworks.Here,we report a novel organic electrode material of poly 3,4,9,10-perylentetracarboxylic dianhydride(PPTCDA)/graphene aerogel(GA).The 3D interconnected porous architecture synthesized through a simple solvothermal reaction,where the PPTCDA is homogenously embedded in the GA nanosheets.The self-assembly of PPTCDA/GA coin-type cell will not only significantly improve the durability and extend lifetime of the devices,but also reduce the electronic waste and economic cost.The self-assembled structure does not require the auxiliary electrode and conductive agent to prepare the electrode material,which is a simple method for preparing the coin-type cell and a foundation for the next large-scale production.The PPTCDA/GA delivers a high capacity of≥200 m Ah g^–1 with the voltage of 0.0~1.5 V.After 300 cycles,the capacity retention rate still close to 100%.The discussion on the mechanism of Zn2+intercalation/deintercalation in the PPTCDA/GA electrode is explored by Fourier transform infrared spectrometer(FT-IR),X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS)characterizations.The morphology and structure of PPTCDA/GA are examined by scanning electron microscopy(SEM)and transmission electron microscopy(TEM).
基金This study was supported by the National Natural Science Foundation of China(51702063 and 51672056)Natural Science Foundation of Heilongjiang(LC2018004)+1 种基金China Postdoctoral Science Foundation(2018M630340,2019T120254)the Fundamental Research Funds for the Central University.
文摘Lithium-sulfur batteries attract lots of attention due to their high specific capacity,low cost,and environmental friendliness.However,the low sulfur utilization and short cycle life extremely hinder their application.Herein,we design and fabricate a three-dimensional electrode by a simple filtration method to achieve a high-sulfur loading.Biomass porous carbon is employed as a current collector,which not only enhances the electronic transport but also effectively limits the volume expansion of the active material.Meanwhile,an optimized carboxymethyl cellulose binder is chosen.The chemical bonding restricts the shuttle effect,leading to improved electrochemical performance.Under the ultrahigh sulfur load of 28mg/cm2,the high capacity of 18mAh/cm2 is still maintained,and stable cycling performance is obtained.This study demonstrates a viable strategy to develop promising lithium-sulfur batteries with a three-dimensional electrode,which promotes sulfur loading and electrochemical performance.
基金the support of the National Natural Science Foundation of China (No.51971099)the Analytical and Testing Center, HUST。
文摘To overcome the disadvantages of inhomogeneous microstructures and poor mechanical properties of additively manufactured Ti-6Al-4V alloys,a novel technique of hybrid deposition and synchronous micro-rolling is proposed.The micro-rolling leads to equiaxed prior β grains,thin discontinuous intergranular α,and equiaxed primary α,in contrast to the coarse columnar prior β grains without the application of micro-rolling.The recrystallization by micro-rolling results in discontinuous intergranular α via the mechanism of strain and interface-induced grain boundary migration.The evolution of α globularization,driven by a solute concentration gradient,starts from the sub-boundary until the formation of equiaxed primary α.Simultaneous strengthening and toughening are achieved,which means an increase in yield strength,ultimate tensile strength,fracture elongation,and work hardening rate.The formation of α recrystallization leads to more fine grain boundaries to strengthen the yield strength,and the improvement of ductility is due to the better-coordinated deformation ability of discontinuous intergranular α and equiaxed primary α.As a result,the fracture mode in micro-rolling changes from intergranular type to transgranular type.
基金the National Natural Science Foundation of China(51572052)the Natural Science Foundation of Heilongjiang Province of China(LC2015004)+2 种基金the China Postdoctoral Science Special Foundation(2015T80329)the Major Project of Science and Technology of Heilongjiang Province(GA14A101)the Project of Research and Development of Applied Technology of Harbin(2014DB4AG016)
文摘ZnCo_2O_4 nanocluster particles(NCPs) were prepared through a designed hydrothermal method, with the assistance of a surfactant, sodium dodecyl benzene sulfonate. The crystalline structure and surface morphology of ZnCo_2O_4 were investigated by XRD, XPS, SEM, TEM, and BET analyses. The results of SEM and TEM suggest a clear nanocluster particle structure of cubic ZnCo_2O_4(*100 nm in diameter), which consists of aggregated primary nanoparticles(*10 nm in diameter), is achieved. The electrochemical behavior of synthesized ZnCo_2O_4 NCPs was investigated by galvanostatic discharge/charge measurements and cyclic voltammetry. The ZnCo_2O_4 NCPs exhibit a high reversible capacity of 700 mAh g^(-1) over 100 cycles under a current density of 100 mA g^(-1) with an excellent coulombic efficiency of 98.9% and a considerable cycling stability. This work demonstrates a facile technique designed to synthesize ZnCo_2O_4 NCPs which show great potential as anode materials for lithium ion batteries.
基金supported by the Fundamental Research Funds for the Central Universities (HEUCF201403018)the Heilongjiang Postdoctoral Fund (LBHZ13059)+1 种基金the China Postdoctoral Science Foundation (2014M561332)the National Natural Science Foundation of China (21403044)
文摘A novel plastic/multi-walled carbon nanotube（MWNTs）-nickel（Ni）-platinum（Pt） electrode（PMNP） is prepared by chemical-reducing Pt onto the surface of Ni film covered plastic/MWNTs（PM） substrate. The MWNTs are adhered by a piece of commercial double faced adhesive tape on the surface of plastic paper and the Ni film is prepared by a simple electrodeposition method. The morphology and phase structure of the PMNP electrode are characterized by scanning electron microscopy,transmission electron microscope and X-ray diffractometer. The catalytic activity of the PMNP electrode for Na BH4 electrooxidation is investigated by means of cyclic voltammetry and chronoamperometry. The catalyst combines tightly with the plastic paper and exhibits a good stability. MWNTs serve as both conductive material and hydrogen storage material and the Ni film and Pt are employed as electrochemical catalysts. The PMNP electrode exhibits a high electrocatalytic performance and the oxidation current density reaches to 10.76 A/（mg·cm） in 0.1 mol/dm3 Na BH4at0 V,which is much higher than those in the previous reports. The using of waste plastic reduces the discarding of white pollution and consumption of metal resources.
基金supported by the National Natural Science Foundation of China(Nos.82173668,82260676)Jiangxi Provincial Natural Science Foundation(20232BAB216131,China)+2 种基金the Scientific and Technological Key Projects of Guangdong Province(Nos.2021B1111110003,2019B020202002,China)the Science and Technology Projects of Ganzhou(202101094462,China)the Start-Up Foundation of Gannan Medical University(No.QD202144-2067,China).
文摘Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators(e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges,including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result,the design of new epigenetic modulators(e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging(Hy T) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review,we aim to provide an in-depth illustration of new degrading strategies(2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.
基金supported by Foundation of Ministry of Science and Technology of China(2022YFC2304203)National Natural Science Foundation of China(Nos.82073689,82273762 and 81973183)+1 种基金National Natural Science Foundation of Guangdong Province(No.2024A1515010642,China)Science and Technology Program of Guangzhou(No.201904010380,China).
文摘Cervical cancer,the most common gynecological malignancy,significantly and adversely af-fects women’s physical health and well-being.Traditional surgical interventions and chemotherapy,while potentially effective,often entail serious side effects that have led to an urgent need for novel therapeutic methods.Photothermal therapy(PTT)has emerged as a promising approach due to its ability to minimize damage to healthy tissue.Connecting a biothiol detection group to PTT-sensitive molecules can improve tumor targeting and further minimize potential side effects.In this study,we developed a near-infrared fluorescence(NIRF)/photoacoustic(PA)dual-mode probe,S-NBD,which demonstrated robust PTT per-formance.This innovative probe is capable of activating NIRF/PA signals to enable the detection of bio-thiols with high emission wavelength(838 nm)and large Stokes shift(178 nm),allowing for in vivo monitoring of cancer cells.Additionally,the probe achieved an outstanding photothermal conversion ef-ficiency of 67.1%.The application of laser irradiation(660 nm,1.0 W/cm^(2),5 min)was able to achieve complete tumor ablation without recurrence.In summary,this seminal study presents a pioneering NIRF/PA dual-mode dicyanoisophorone-based probe for biothiol imaging,incorporating features from PTT for the first time.This pioneering approach achieves the dual objectives of improving tumor diagnosis and treatment.
基金supported by the Outstanding Youth Project of Heilongjiang Province(JQ2021D001)the National Natural Science Foundation of China(52279034)the National Key Research and Development Program of China(2022YFD1500100).
文摘Fe(hydr)oxides have a substantial impact on the structure and stability of soil organic carbon(SOC)pools and also drive organic carbon turnover processes via reduction–oxidation reactions.Currently,many studies have paid much attention to organic matter–Fe mineral–microbial interactions on SOC turnover,while there is few research on how exogenous carbon addition abiotically regulates the intrinsic mechanisms of Fe-mediated organic carbon conversion.The study investigated the coupling process of artificial humic acid(A-HA)and Fe(hydr)oxide,the mechanism of inner-sphere ligands,and the capacity for carbon sequestration using transmission electron microscopy,thermogravimetric,x-ray photoelectron spectroscopy,and wet-chemical disposal.Furthermore,spherical aberration-corrected scanning transmission electron microscopy–electron energy loss spectroscopy and Mossbauer spectra have been carried out to demonstrate the spatial heterogeneity of A-HA/Fe(hydr)oxides and reveal the relationship between the increase in Fe-phase crystallinity and redox sensitivity and the accumulation of organic carbon.Additionally,the dynamics of soil structures on a microscale,distribution of carbon–iron microdomains,and the cementing-gluing effect can be observed in the constructing nonliving anthropogenic soils,confirming that the formation of stable aggregates is an effective approach to achieving organic carbon indirect protection.We propose that exogenous organic carbon inputs,specifically A-HA,could exert a substantial but hitherto unexplored effect on the geochemistry of iron–carbon turnover and sequestration in anoxic water/solid soils and sediments.
基金This work was supported by the National Natural Science Foundation of China(No.82173668)Scientific Research Project of High-Level Talents(No.C1034335,China)in Southern Medical University of ChinaThousand Youth Talents Program(No.C1080094,China)from the Organization Department of the CPC Central Committee,China.
文摘Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral bioavailability.In addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse effects.Therefore,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with antibodies.Further,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic effects.Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy.In this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),etc.The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.
