Biomimetic natural biomaterials for tissue engineering and regenerative medicine:new biosynthesis methods,recent advances,and emerging applications

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Facile synthesis of hierarchical NaX zeolite from natural kaolinite for efficient Knoevenagel condensation

Zeolite catalysts have found extensive applications in the synthesis of various fine chemicals.However,the micropores of zeolites impose diffusion limitations on bulky molecules,greatly reducing the catalytic efficiency.Herein,we explore an economic and environmentally friendly method for synthesizing hierarchical NaX zeolite that exhibits improved catalytic performance in the Knoevenagel condensation reaction for producing the useful fine chemical 2-cyano-3-phenylacrylate.The synthesis was achieved via a low-temperature activation of kaolinite and subsequent in-situ transformation strategy without any template or seed.Systematic characterizations reveal that the synthesized NaX zeolite has both intercrystalline and intra-crystalline mesopores,smaller crystal size,and larger external specific surface area compared to commercial NaX zeolite.Detailed mechanism investigations show that the inter-crystalline mesopores are generated by stacking smaller crystals formed from in-situ crystallization of the depolymerized kaolinite,and the intra-crystalline mesopores are inherited from the pores in the depolymerized kaolinite.This synthesis strategy provides an energy-saving and effective way to construct hierarchical zeolites,which may gain wide applications in fine chemical manufacturing.

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

Natural Disaster Risk Monitoring for Immovable Cultural Relics Based on Digital Twin

Natural disaster risk monitoring is an important task for disaster prevention and reduction.In the case of immovable cultural relics,however,the feedback mechanism,risk factors,monitoring logic,and monitoring indicators of natural disaster risk monitoring are complex.How to achieve intelligent perception and monitoring of natural disaster risk for immovable cultural relics has always been a focus and a challenge for researchers.Based on the analysis of the concepts and issues related to the natural disaster risk of immovable cultural relics,this paper proposes a framework for natural disaster risk monitoring for immovable cultural relics based on the digital twin.This framework focuses on risk monitoring,including the physical entities of natural disaster risk for immovable cultural relics,monitoring indicators,and virtual entity construction.A platform for monitoring the natural disaster risk of immovable cultural relics is proposed.Using the Puzhou Ancient City Site as a test bed,the proposed concept can be used for monitoring the natural disaster risk of immovable cultural relics at different scales.

DNA G-Quadruplexes as Targets for Natural Product Drug Discovery

DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

New insights into the deposition of natural gas hydrate on pipeline surfaces:A molecular dynamics simulation study

Natural gas hydrate(NGH)can cause pipeline blockages during the transportation of oil and gas under high pressures and low temperatures.Reducing hydrate adhesion on pipelines is viewed as an efficient way to prevent NGH blockages.Previous studies suggested the water film can greatly increase hydrate adhesion in gas-dominant system.Herein,by performing the molecular dynamics simulations,we find in water-dominant system,the water film plays different roles in hydrate deposition on Fe and its corrosion surfaces.Specifically,due to the strong affinity of water on Fe surface,the deposited hydrate cannot convert the adsorbed water into hydrate,thus,a water film exists.As water affinities decrease(Fe>Fe_(2)O_(3)>FeO>Fe_(3)O_(4)),adsorbed water would convert to amorphous hydrate on Fe_(2)O_(3)and form the ordered hydrate on FeO and Fe_(3)O_(4)after hydrate deposition.While absorbed water film converts to amorphous or to hydrate,the adhesion strength of hydrate continuously increases(Fe<Fe_(2)O_(3)<FeO<Fe_(3)O_(4)).This is because the detachment of deposited hydrate prefers to occur at soft region of liquid layer,the process of which becomes harder as liquid layer vanishes.As a result,contrary to gas-dominant system,the water film plays the weakening roles on hydrate adhesion in water-dominant system.Overall,our results can help to better understand the hydrate deposition mechanisms on Fe and its corrosion surfaces and suggest hydrate deposition can be adjusted by changing water affinities on pipeline surfaces.

Natural Products Improve Organ Microcirculation Dysfunction Following Ischemia/Reperfusion-and Lipopolysaccharide-Induced Disturbances:Mechanistic and Therapeutic Views

Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and thrombosis.These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and platelets.In clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances.Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory disturbances.In recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals.In 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,respectively.This review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue injury.Based on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.

Simultaneous purification of minor components in natural products using twin-column recycling chromatography with a step solvent gradient

The isolation of minor components from complex natural product matrices presents a significant challenge in the field of purification science due to their low concentrations and the presence of structurally similar compounds.This study introduces an optimized twin-column recycling chromatography method for the efficient and simultaneous purification of these elusive constituents.By introducing water at a small flowing rate between the twin columns,a step solvent gradient is created,by which the leading edge of concentration band would migrate at a slower rate than the trailing edge as it flowing from the upstream to downstream column.Hence,the band broadening is counterbalanced,resulting in an enrichment effect for those minor components in separation process.Herein,two target substances,which showed similar peak position in high performance liquid chromatography(HPLC)and did not exceed 1.8%in crude paclitaxel were selected as target compounds for separation.By using the twin-column recycling chromatography with a step solvent gradient,a successful purification was achieved in getting the two with the purity almost 100%.We suggest this method is suitable for the separation of most components in natural produces,which shows higher precision and recovery rate compared with the common lab-operated separation ways for natural products(thin-layer chromatography and prep-HPLC).

Natural vibration and critical velocity of translating Timoshenko beam with non-homogeneous boundaries

In most practical engineering applications,the translating belt wraps around two fixed wheels.The boundary conditions of the dynamic model are typically specified as simply supported or fixed boundaries.In this paper,non-homogeneous boundaries are introduced by the support wheels.Utilizing the translating belt as the mechanical prototype,the vibration characteristics of translating Timoshenko beam models with nonhomogeneous boundaries are investigated for the first time.The governing equations of Timoshenko beam are deduced by employing the generalized Hamilton's principle.The effects of parameters such as the radius of wheel and the length of belt on vibration characteristics including the equilibrium deformations,critical velocities,natural frequencies,and modes,are numerically calculated and analyzed.The numerical results indicate that the beam experiences deformation characterized by varying curvatures near the wheels.The radii of the wheels play a pivotal role in determining the change in trend of the relative difference between two beam models.Comparing the results unearths that the relative difference in equilibrium deformations between the two beam models is more pronounced with smaller-sized wheels.When the two wheels are of equal size,the critical velocities of both beam models reach their respective minima.In addition,the relative difference in natural frequencies between the two beam models exhibits nonlinear variation and can easily exceed 50%.Furthermore,as the axial velocities increase,the impact of non-homogeneous boundaries on modal shape of translating beam becomes more significant.Although dealing with non-homogeneous boundaries is challenging,beam models with non-homogeneous boundaries are more sensitive to parameters,and the differences between the two types of beams undergo some interesting variations under the influence of non-homogeneous boundaries.

Sustainable, thermoplastic and hydrophobic coating from natural cellulose and cinnamon to fabricate eco-friendly catering packaging

Non-degradable polymers cause serious environmental pollution problem,such as the widely-used while unrecyclable coatings which significantly affect the overall degradation performance of products.It is imperative and attractive to develop biodegradable functional coatings.Herein,we proposed a novel strategy to successfully prepare biodegradable,thermoplastic and hydrophobic coatings with high transparence and biosafety by weakening the interchain interactions between cellulose chain.The natural cellulose and cinnamic acid were as raw materials.Via reducing the degree of polymerization(DP)of cellulose and regulating the degree of substitution(DS)of cinnamate moiety,the obtained cellulose cinnamate(CC)exhibited not only the thermalflow behavior but also good biodegradability,which solves the conflict between the thermoplasticity and biodegradability in cellulose-based materials.The glass transition temperature(T_(g))and thermalflow temperature(T_(f))of the CC could be adjusted in a range of 150–200℃ and 180–210℃,respectively.The CC with DS<1.2 and DP≤100 degraded more than 60%after an enzyme treatment for 7 days,and degraded more than 80%after a composting treatment for 42 days.Furthermore,CC had no toxicity to human epidermal cells even at a high concentration(0.5 mg mL^(-1)).In addition,CC could be easily fabricated into multifunctional coating with high hydrophobicity,thermal adhesion and high transparence.Therefore,after combining with cellophane and paperboard,CC coating with low DP and DS could be used to prepare fully-biodegradable heat-sealing packaging,art paper,paper cups,paper straws and food packaging boxes.

Modelling analysis embodies drastic transition among global potential natural vegetations in face of changing climate

Potential natural vegetation(PNV)is a valuable reference for ecosystem renovation and has garnered increasing attention worldwide.However,there is limited knowledge on the spatio-temporal distributions,transitional processes,and underlying mechanisms of global natural vegetation,particularly in the case of ongoing climate warming.In this study,we visualize the spatio-temporal pattern and inter-transition procedure of global PNV,analyse the shifting distances and directions of global PNV under the influence of climatic disturbance,and explore the mechanisms of global PNV in response to temperature and precipitation fluctuations.To achieve this,we utilize meteorological data,mainly temperature and precipitation,from six phases:the Last Inter-Glacial(LIG),the Last Glacial Maximum(LGM),the Mid Holocene(MH),the Present Day(PD),2030(20212040)and 2090(2081–2100),and employ a widely-accepted comprehensive and sequential classification sy–stem(CSCS)for global PNV classification.We find that the spatial patterns of five PNV groups(forest,shrubland,savanna,grassland and tundra)generally align with their respective ecotopes,although their distributions have shifted due to fluctuating temperature and precipitation.Notably,we observe an unexpected transition between tundra and savanna despite their geographical distance.The shifts in distance and direction of five PNV groups are mainly driven by temperature and precipitation,although there is heterogeneity among these shifts for each group.Indeed,the heterogeneity observed among different global PNV groups suggests that they may possess varying capacities to adjust to and withstand the impacts of changing climate.The spatio-temporal distributions,mutual transitions and shift tendencies of global PNV and its underlying mechanism in face of changing climate,as revealed in this study,can significantly contribute to the development of strategies for mitigating warming and promoting re-vegetation in degraded regions worldwide.

Research progress of CO_(2) capture and mineralization based on natural minerals

Natural minerals,such as kaolinite,halloysite,montmorillonite,attapulgite,bentonite,sepiolite,forsterite,and wollastonite,have considerable potential for use in CO_(2) capture and mineralization due to their abundant reserves,low cost,excellent mechanical prop-erties,and chemical stability.Over the past decades,various methods,such as those involving heat,acid,alkali,organic amine,amino sil-ane,and ionic liquid,have been employed to enhance the CO_(2) capture performance of natural minerals to attain high specific surface area,a large number of pore structures,and rich active sites.Future research on CO_(2) capture by natural minerals will focus on the full utiliza-tion of the properties of natural minerals,adoption of suitable modification methods,and preparation of composite materials with high specific surface area and rich active sites.In addition,we provide a summary of the principle and technical route of direct and indirect mineralization of CO_(2) by natural minerals.This process uses minerals with high calcium and magnesium contents,such as forsterite(Mg_(2)SiO_(4)),serpentine[Mg_(3)Si_(2)O(OH)_(4)],and wollastonite(CaSiO_(3)).The research status of indirect mineralization of CO_(2) using hydro-chloric acid,acetic acid,molten salt,and ammonium salt as media is also introduced in detail.The recovery of additives and high-value-added products during the mineralization process to increase economic benefits is another focus of future research on CO_(2) mineralization by natural minerals.

Stabilizing perovskite precursors with the reductive natural amino acid for printable mesoscopic perovskite solar cells

Solution processability significantly advances the development of highly-efficient perovskite solar cells.However,the precursor solution tends to undergo irreversible degradation reactions,impairing the device performance and reproducibility.Here,we utilize a reductive natural amino acid,Nacetylcysteine(NALC),to stabilize the precursor solution for printable carbon-based hole-conductorfree mesoscopic perovskite solar cells.We find that I_(2) can be generated in the aged solution containing methylammonium iodide(MI) in an inert atmosphere and speed up the MA-FA^(+)(formamidinium) reaction which produces large-size cations and hinders the formation of perovskite phase.NALC effectively stabilizes the precursor via its sulfhydryl group which reduces I_(2) back to I^(-)and provides H^(+).The NALC-stabilized precursor which is aged for 1440 h leads to devices with a power conversion efficiency equivalent to 98% of that for devices prepared with the fresh precursor.Furthermore,NALC improves the device power conversion efficiency from 16.16% to 18.41% along with enhanced stability under atmospheric conditions by modifying grain boundaries in perovskite films and reducing associated defects.

Rapid discovery of a novel “green” and natural GST inhibitor for sensitizing hepatocellular carcinoma to Cisplatin by visual screening strategy

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen“green”natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by downregulating GST expression.Considering the high GST levels in HCC patients,this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Stand dynamics of old-growth hemlock forests in central Bhutan are shaped by natural disturbances

Understanding how past disturbances have influenced the development of forests is critical for deciphering their current structure and composition and forecasting future changes.In this study,dendrochronological methods were applied to uncover the disturbance history of old-growth hemlock-dominated forests in central Bhutan.Analysis of tree-ring samples from two old-growth hemlock stands,located in two different topographic settings,identified the importance of gap-phase dynamics in facilitating recruitment and growth releases and producing complex,multi-aged structure s over time.One site showed evidence of a near stand-replacing disturbance in the late 1700s,while the other showed no evide nce of high-severity disturbance at any time over the last 400 years.At both sites low-to medium-severity disturbances,some of which appear to be associated with cyclones originating in the Bay of Bengal,dominated the disturbance regime.The hemlock stands exhibited a significant positive association between cyclone occurrence and growth release events and between recruitment pulses and growth release events.From 1800 to 1970 there was an increase in recruitment of angiosperm tree species at most sites and a corresponding decline in conifer recruitment.Over the past 50 years there has been little new recruitment;this may be due to light limitation in the understory from shade-tolerant angiosperms and bamboo in the lower strata of these stands.Significant variations in disturbance dynamics and recruitment were observed across the study sites,suggesting that other factors,such as topography and climate,may be influencing long-term stand development patterns.This study highlights the complex interplay between historical disturbance regimes and tree recruitment in shaping the age and size structures of old-growth hemlock forests in central Bhutan.It also provides new insights into the dynamics of these forests that can be used to support effective forest conservation and management in the future.

Natural variation in the cytochrome c oxidase subunit 5B OsCOX5B regulates seed vigor by altering energy production in rice

Seed vigor is a crucial trait for the direct seeding of rice.Here we examined the genetic regulation of seed vigor traits in rice,including germination index(GI)and germination potential(GP),using a genome-wide association study approach.One major quantitative trait locus,qGI6/qGP6,was identified simultaneously for both GI and GP.The candidate gene encoding the cytochrome c oxidase subunit 5B(OsCOX5B)was validated for qGI6/qGP6.The disruption of OsCOX5B caused the vigor traits to be significantly lower in Oscox5b mutants than in the japonica Nipponbare wild type(WT).Gene co-expression analysis revealed that OsCOX5B influences seed vigor mainly by modulating the tricarboxylic acid cycle process.The glucose levels were significantly higher while the pyruvic acid and adenosine triphosphate levels were significantly lower in Oscox5b mutants than in WT during seed germination.The elite haplotype of OsCOX5B facilitates seed vigor by increasing its expression during seed germination.Thus,we propose that OsCOX5B is a potential target for the breeding of rice varieties with enhanced seed vigor for direct seeding.

Formation of Natural Melanin/TiO_(2) Nanostructure Hybrids with Enhanced Optical,Thermal and Magnetic Properties as a Soft Material

The natural Melanin/TiO_(2) was synthesized by the use of ultrasonication under UV radiation.The influence of natural melanin on the structural,optical and thermal properties of TiO_(2) nanoparticles was investigated by using Fourier transform infrared spectroscopy,thermogravimetric analysis and UV-Vis spectroscopy.It was observed that incorporating natural melanin on TiO_(2) nanoparticles(TiO_(2)-Mel)occurred at 2.01 eV with a low value of Urbach energy around 100 meV indicating improvement in the crystalline structure.Magnetic measurement at room temperature showed diamagnetic behavior.Furthermore,thermal results showed that TiO_(2)-Mel is stable even at temperatures up to 400℃.According to the results obtained by the thermal stability of melanin with titanium dioxide,it can be a good candidate in many applications such as solar cells and optoelectronics.

OSDA-free synthesis of FeZSM-22 zeolite from natural minerals for n-octane hydroisomerization

A seed-directed approach to synthesizing Fe ZSM-22 zeolite without organic structure directing agent(OSDA)was developed by using Fe-rich diatomite as all aluminum and iron sources.The Fe ZSM-22zeolite with optimal crystallinity and purity can be obtained by systematically adjusting feed composition and synthesis conditions.Characterizations show that Fe ZSM-22 zeolite synthesized with OSDA-free owns high crystallinity,obvious thin needle-shaped morphology and high Bronsted/Lewis acid ratio.Significantly,when used for n-octane hydroisomerization reaction,its derived catalyst exhibits the best catalytic performance reflected by the highest selectivity to C_(8)isomers compared to the two reference catalysts prepared based on a Fe-containing and a Fe-free ZSM-22 synthesized through an OSDA-directed route from natural diatomite and conventional chemicals,respectively.This work provides an alternative route to sustainably synthesizing heteroatomic zeolites with high performance.

Energy Design and Optimization of Greenhouse by Natural Convection

This study addresses the pressing need for energy-efficient greenhouse management by focusing on the innovative application of natural ventilation.The primary objective of this study is to evaluate various ventilation strategies to enhance energy efficiency and optimize crop production in agricultural greenhouses.Employing advanced numerical simulation tools,the study conducts a comprehensive assessment of natural ventilation’s effectiveness under real-world conditions.The results underscore the crucial role of the stack effect and strategic window positioning in greenhouse cooling,providing valuable insights for greenhouse designers.Our findings shed light on the significant benefits of optimized ventilation and also offer practical implications for improving greenhouse design,ensuring sustainable and efficient agricultural practices.The study demonstrated energy savings in cooling from November to April,with a maximum saving of 680 kWh in March,indicating the effectiveness of strategically positioning windows to leverage the stack effect.This approach enhances plant growth and reduces the need for costly cooling systems,thereby improving overall energy efficiency and lowering operational expenses.

Natural variation of GmFNSII-2 contributes to drought resistance by modulating enzyme activity in soybean

As an essential crop that provides vegetable oil and protein,soybean(Glycine max(L.)Merr.)is widely planted all over the world.However,the scarcity of water resources worldwide has seriously impacted on the quality and yield of soybean.To address this,exploring excellent genes for improving drought resistance in soybean is crucial.In this study,we identified natural variations of GmFNSII-2(flavone synthase II)significantly affect the drought resistance of soybeans.Through sequence analysis of GmFNSII-2 in 632 cultivated and 44 wild soybeans nine haplotypes were identified.The full-length allele GmFNSII-2^(C),but not the truncated allele GmFNSII-2^(A) possessing a nonsense nucleotide variation,increased enzyme activity.Further research found that GmDREB3,known to increase soybean drought resistance,bound to the promoter region of GmFNSII-2^(C).GmDREB3 positively regulated the expression of GmFNSII-2^(C),increased flavone synthase abundance and improved the drought resistance.Furthermore,a singlebase mutation in the GmFNSII-2^(C) promoter generated an additional drought response element(CCCCT),which had stronger interaction strength with GmDREB3 and increased its transcriptional activity under drought conditions.The frequency of drought-resistant soybean varieties with Hap 1(Pro:GmFNSII-2^(C))has increased,suggesting that this haplotype may be selected during soybean breeding.In summary,GmFNSII-2^(C) could be used for molecular breeding of drought-tolerant soybean.