Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

Analysis of gravity wave activity during stratospheric sudden warmings in the northern hemisphere

Due to the significant changes they bring to high latitude stratospheric temperature and wind,stratospheric sudden warmings(SSWs)can have an impact on the propagation and energy distribution of gravity waves(GWs).The variation characteristics of GWs during SSWs have always been an important issue.Using temperature data from January to March in 2014−2016,provided by the Constellation Observing System for Meteorology,Ionosphere and Climate(COSMIC)mission,we have analyzed global GW activity at 15−40 km in the Northern Hemisphere during SSW events.During the SSWs that we studied,the stratospheric temperature rose in one or two longitudinal regions in the Northern Hemisphere;the areas affected extended to the east of 90°W.During these SSWs,the potential energy density(E_(p)of GWs expanded and covered a larger range of longitude and altitude,exhibiting an eastward and downward extension.The E_(p)usually increased,while partially filtered by the eastward zonal winds.When zonal winds weakened or turned westward,E_(p)began to strengthen.After SSWs,the E_(p)usually decreased.These observations can serve as a reference for analyzing the interaction mechanism between SSWs and GWs in future work.

The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways

Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.

Apatinib and gamabufotalin co-loaded lipid/Prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis

Due to the non-targeted release and low solubility of anti-gastric cancer agent,apatinib(Apa),a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects.In order to avoid these drawbacks,lipid-film-coated Prussian blue nanoparticles(PB NPs)with hyaluronan(HA)modification was used for Apa loading to improve its solubility and targeting ability.Furthermore,anti-tumor compound of gamabufotalin(CS-6)was selected as a partner of Apawith reducing dosage for combinational gastric therapy.Thus,HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue.In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor(VEGFR)and matrix metalloproteinase-9(MMP-9).In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects.In summary,we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer(GC)therapy.

Using cemented paste backfill to tackle the phosphogypsum stockpile in China:A down-to-earth technology with new vitalities in pollutant retention and CO_(2) abatement

Phosphogypsum(PG),a hard-to-dissipate by-product of the phosphorus fertilizer production industry,places strain on the biogeochemical cycles and ecosystem functions of storage sites.This pervasive problem is already widespread worldwide and requires careful stewardship.In this study,we review the presence of potentially toxic elements(PTEs)in PG and describe their associations with soil properties,anthropogenic activities,and surrounding organisms.Then,we review different ex-/in-situ solutions for promoting the sustainable management of PG,with an emphasis on in-situ cemented paste backfill,which offers a cost-effective and highly scalable opportunity to advance the value-added recovery of PG.However,concerns related to the PTEs'retention capacity and long-term effectiveness limit the implementation of this strategy.Furthermore,given that the large-scale demand for ordinary Portland cement from this conventional option has resulted in significant CO_(2) emissions,the technology has recently undergone additional scrutiny to meet the climate mitigation ambition of the Paris Agreement and China's Carbon Neutrality Economy.Therefore,we discuss the ways by which we can integrate innovative strategies,including supplementary cementitious materials,alternative binder solutions,CO_(2) mineralization,CO_(2) curing,and optimization of the supply chain for the profitability and sustainability of PG remediation.However,to maximize the co-benefits in environmental,social,and economic,future research must bridge the gap between the feasibility of expanding these advanced pathways and the multidisciplinary needs.

Scheme Based on Multi-Level Patch Attention and Lesion Localization for Diabetic Retinopathy Grading

Early screening of diabetes retinopathy(DR)plays an important role in preventing irreversible blindness.Existing research has failed to fully explore effective DR lesion information in fundus maps.Besides,traditional attention schemes have not considered the impact of lesion type differences on grading,resulting in unreasonable extraction of important lesion features.Therefore,this paper proposes a DR diagnosis scheme that integrates a multi-level patch attention generator(MPAG)and a lesion localization module(LLM).Firstly,MPAGis used to predict patches of different sizes and generate a weighted attention map based on the prediction score and the types of lesions contained in the patches,fully considering the impact of lesion type differences on grading,solving the problem that the attention maps of lesions cannot be further refined and then adapted to the final DR diagnosis task.Secondly,the LLM generates a global attention map based on localization.Finally,the weighted attention map and global attention map are weighted with the fundus map to fully explore effective DR lesion information and increase the attention of the classification network to lesion details.This paper demonstrates the effectiveness of the proposed method through extensive experiments on the public DDR dataset,obtaining an accuracy of 0.8064.

Electro-spraying/spinning: A novel battery manufacturing technology

Lithium-ion battery(LIB) industry seems to have met its bottle neck in cutting down producing costs even though much efforts have been put into building a complete industrial chain. Actually, manufacturing methods can greatly affect the cost of battery production. Up to now, lithium ion battery producers still adopt manufacturing methods with cumbersome sub-components preparing processes and costly assembling procedures, which will undoubtedly elevate the producing cost. Herein, we propose a novel approach to directly assemble battery components(cathode, anode and separator) in an integrated way using electro-spraying and electro-spinning technologies. More importantly, this novel battery manufacturing method can produce LIBs in large scale, and the products show excellent mechanical strength, flexibility, thermal stability and electrolyte wettability. Additionally, the performance of the as-prepaed Li Fe PO_(4)||graphite full cell produced by this new method is comparable or even better than that produced by conventional manufacturing approach. In brief, this work provides a new promising technology to prepare LIBs with low cost and better performance.

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy

AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.

Ambient-Condition Strategy for Production of Hollow Ga_(2)O_(3)@rGO Crystalline Nanostructures Toward Efficient Lithium Storage

Crystallineγ-Ga_(2)O_(3)@rGO core-shell nanostructures are synthesized in gram scale,which are accomplished by a facile sonochemical strategy under ambient condition.They are composed of uniformγ-Ga_(2)O_(3)nanospheres encapsulated by reduced graphene oxide(rGO)nanolayers,and their formation is mainly attributed to the existed opposite zeta potential between the Ga_(2)O_(3)and rGO.The as-constructed lithium-ion batteries(LIBs)based on as-fabricatedγ-Ga_(2)O_(3)@rGO nanostructures deliver an initial discharge capacity of 1000 mAh g^(-1)at 100 mA g^(-1)and reversible capacity of 600 mAh g^(-1)under 500 mA g^(-1)after 1000 cycles,respectively,which are remarkably higher than those of pristineγ-Ga_(2)O_(3)with a much reduced lifetime of 100 cycles and much lower capacity.Ex situ XRD and XPS analyses demonstrate that the reversible LIBs storage is dominant by a conversion reaction and alloying mechanism,where the discharged product of liquid metal Ga exhibits self-healing ability,thus preventing the destroy of electrodes.Additionally,the rGO shell could act robustly as conductive network of the electrode for significantly improved conductivity,endowing the efficient Li storage behaviors.This work might provide some insight on mass production of advanced electrode materials under mild condition for energy storage and conversion applications.

Anomalous{1012}tensile twinning and subsequent detwinning in a friction stir processed carbon fiber-reinforced Mg composite

1.Main text Owing to their low density and high specific strength,magnesium alloys and magnesium-based composites have great potential as structure metal materials in applications where lightweight matters[1–4].Deformation twins[5],especially the{1012}tension twins(also called tensile or extension twins)with a low critical resolved shear stress(CRSS)[6],are commonly observed in Mg alloys.They can provide the much-needed deformation along the c-axis in their hcp structure resulting from the very few easily activated slip systems in this crystal structure[7].The tensile twinning activation usually follows the macroscopic Schmid factor law[2],i.e.,the twin variant with the highest Schmid factor occurs,and it only appears when its Schmid factor is positive.

Safety and efficacy comparison of remimazolam and propofol for intravenous anesthesia during gastroenteroscopic surgery of older patients:A meta-analysis

BACKGROUND Remimazolam is characterized by rapid action and inactive metabolites.It is used as the general anesthetic for many clinical surgeries.In this study,we performed a meta-analysis to evaluate whether remimazolam is superior to propofol for gastroenteroscopy in older patients.AIM To compare the adverse events and efficacy of remimazolam and propofol during gastroenteroscopy in older adults.METHODS The PubMed,Web of Science,the Cochrane Library databases were queried for the relevant key words"remimazolam,""and propofol,""and gastrointestinal endoscopy or gastroscopy."The search scope was"Title and Abstract,"and the search was limited to human studies and publications in English.Seven studies wherein remimazolam and propofol were compared were included for the metaanalysis.RESULTS We selected seven randomized controlled trials involving 1445 cases for the analysis.Remimazolam reduced the hypotension(relative risk,RR=0.44,95%CI:0.29-0.66,P=0.000),respiratory depression(RR=0.46,95%CI:0.30-0.70,P=0.000),injection pain(RR=0.12,95%CI:0.05-0.25,P=0.000),bradycardia(RR=0.37,95%CI:0.24-0.58,P=0.000),and time to discharge[weighted mean difference(WMD)=-0.58,95%CI:-0.97 to-0.18,P=0.005],compared to those after propofol administration.No obvious differences were observed for postoperative nausea and vomiting(RR=1.09,95%CI:0.97-1.24,P=0.151),dizziness(RR=0.77,95%CI:0.43-1.36,P=0.361),successful sedation rate(RR=0.96,95%CI:0.93-1.00,P=0.083),or the time to become fully alert(WMD=0.00,95%CI:-1.08-1.08,P=0.998).CONCLUSION Remimazolam appears to be safer than propofol for gastroenteroscopy in older adults.However,further studies are required to confirm these findings.

Covalent Organic Framework with 3D Ordered Channel and Multi-Functional Groups Endows Zn Anode with Superior Stability

Achieving a highly robust zinc(Zn)metal anode is extremely important for improving the performance of aqueous Zn-ion batteries(AZIBs)for advancing“carbon neutrality”society,which is hampered by the uncontrollable growth of Zn dendrite and severe side reactions including hydrogen evolution reaction,corrosion,and passivation,etc.Herein,an interlayer containing fluorinated zincophilic covalent organic framework with sulfonic acid groups(COF-S-F)is developed on Zn metal(Zn@COF-S-F)as the artificial solid electrolyte interface(SEI).Sulfonic acid group(-SO_(3)H)in COF-S-F can effectively ameliorate the desolvation process of hydrated Zn ions,and the three-dimensional channel with fluoride group(-F)can provide interconnected channels for the favorable transport of Zn ions with ion-confinement effects,endowing Zn@COF-S-F with dendrite-free morphology and suppressed side reactions.Consequently,Zn@COF-S-F symmetric cell can stably cycle for 1,000 h with low average hysteresis voltage(50.5 m V)at the current density of 1.5 m A cm^(-2).Zn@COF-S-F|Mn O_(2)cell delivers the discharge specific capacity of 206.8 m Ah g^(-1)at the current density of 1.2 A g^(-1)after 800 cycles with high-capacity retention(87.9%).Enlightening,building artificial SEI on metallic Zn surface with targeted design has been proved as the effective strategy to foster the practical application of high-performance AZIBs.

Broadband high-efficiency dielectric metalenses based on quasi-continuous nanostrips

Benefiting from the abrupt phase changes within subwavelength thicknesses,metasurfaces have been widely applied for lightweight and compact optical systems.Simultaneous broadband and high-efficiency characteristics are highly attractive for the practical implementation of metasurfaces.However,current metasurface devices mostly adopt discrete micro/nano structures,which rarely realize both merits simultaneously.In this paper,dielectric metasurfaces composed of quasi-continuous nanostrips are proposed to overcome this limitation.Via quasi-continuous nanostrips metasurface,a normal focusing metalens and a superoscillatory lens overcoming the diffraction limit are designed and experimentally demonstrated.The quasi-continuous metadevices can operate in a broadband wavelength ranging from 450 nm to 1000nm and keep a high power efficiency.The average efficiency of the fabricated metalens reaches 54.24%,showing a significant improvement compared to the previously reported metalenses with the same thickness.The proposed methodology can be easily extended to design other metadevices with the advantages of broadband and high-efficiency in practical optical systems.

Heterogeneous Image Knowledge Driven Visual Perception

Dear Editor,This letter is concerned with visual perception closely related to heterogeneous images.Facing the huge challenge brought by different image modalities,we propose a visual perception framework based on heterogeneous image knowledge,i.e.,the domain knowledge associated with specific vision tasks,to better address the corresponding visual perception problems.

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.

CFD modeling of gas−liquid flow phenomenon in lead smelting oxygen-enriched side-blown furnace

A validated numerical model was established to simulate gas−liquid flow behaviors in the oxygen-enriched side-blown bath furnace.This model included the slip velocity between phases and the gas thermal expansion effect.Its modeling results were verified with theoretical correlations and experiments,and the nozzle-eroded states in practice were also involved in the analysis.Through comparison,it is confirmed that the thermal expansion effect influences the flow pattern significantly,which may lead to the backward motion of airflow and create a potential risk to production safety.Consequently,the influences of air injection velocity and furnace width on airflow behavior were investigated to provide operating and design guidance.It is found that the thin layer melt,which avoids high-rate oxygen airflow eroding nozzles,shrinks as the injection velocity increases,but safety can be guaranteed when the velocity ranges from 175 to 275 m/s.Moreover,the isoline patterns and heights of thin layers change slightly when the furnace width increases from 2.2 to 2.8 m,indicating that the furnace width shows a limited influence on production safety.

A Nonlinear Explicit Model of A Non-Circular Subsea Tunnel-Liner System with An FGM Inverted Arch Under Mechanical Loading and Fire Fields

This paper proposes an explicit scheme to analyze the failure of a subsea polyhedral tunnel-liner system with an inverted arch under mechanical loading and fire fields.The thin-walled liner is made of Functionally Graded Materials(FGMs),which may improve the stability behavior of the tunnel-liner system.Hydrostatic pressure is inevitable in the liner since underground water may penetrate the cracks of the tunnel,and reach the outer surface of the liner.In addition,an elevated temperature loading is taken into account,considering that fire may occur in the tunnel-liner system.Under the combination of mechanical loading and thermal loading,the liner deforms into a single-lobe shape,which is depicted by a trigonometric function.The total potential energy is expressed quantitatively after the energy approach and thin-walled shell theory are used.The minimum potential energy is obtained when the critical buckling occurs.The critical buckling pressure is calculated,which considers the effect of the thermal field.The present analytical prediction is subsequently compared precisely with other closed-form solutions.Finally,the effects of several parameters,such as the geometric shapes,temperature variations,and volume fraction indices,are discussed to further survey the buckling performance of the nonlinear buckling of an FGM polyhedral liner with an inverted arch.One may address a polyhedral liner with fewer polyhedral sides,and a lower volume fraction index is recommended to rehabilitate cracked tunnels in engineering applications.

Attention-Based Residual Dense Shrinkage Network for ECG Denoising

Electrocardiogram(ECG)signal is one of the noninvasive physiological measurement techniques commonly usedin cardiac diagnosis.However,in real scenarios,the ECGsignal is susceptible to various noise erosion,which affectsthe subsequent pathological analysis.Therefore,the effective removal of the noise from ECG signals has becomea top priority in cardiac diagnostic research.Aiming at the problem of incomplete signal shape retention andlow signal-to-noise ratio(SNR)after denoising,a novel ECG denoising network,named attention-based residualdense shrinkage network(ARDSN),is proposed in this paper.Firstly,the shallow ECG characteristics are extractedby a shallow feature extraction network(SFEN).Then,the residual dense shrinkage attention block(RDSAB)isused for adaptive noise suppression.Finally,feature fusion representation(FFR)is performed on the hierarchicalfeatures extracted by a series of RDSABs to reconstruct the de-noised ECG signal.Experiments on the MIT-BIHarrhythmia database and MIT-BIH noise stress test database indicate that the proposed scheme can effectively resistthe interference of different sources of noise on the ECG signal.

Novel damage constitutive models and new quantitative identification method for stress thresholds of rocks under uniaxial compression

Four key stress thresholds exist in the compression process of rocks,i.e.,crack closure stress(σ_(cc)),crack initiation stress(σ_(ci)),crack damage stress(σ_(cd))and compressive strength(σ_(c)).The quantitative identifications of the first three stress thresholds are of great significance for characterizing the microcrack growth and damage evolution of rocks under compression.In this paper,a new method based on damage constitutive model is proposed to quantitatively measure the stress thresholds of rocks.Firstly,two different damage constitutive models were constructed based on acoustic emission(AE)counts and Weibull distribution function considering the compaction stages of the rock and the bearing capacity of the damage element.Then,the accumulative AE counts method(ACLM),AE count rate method(CRM)and constitutive model method(CMM)were introduced to determine the stress thresholds of rocks.Finally,the stress thresholds of 9 different rocks were identified by ACLM,CRM,and CMM.The results show that the theoretical stress−strain curves obtained from the two damage constitutive models are in good agreement with that of the experimental data,and the differences between the two damage constitutive models mainly come from the evolutionary differences of the damage variables.The results of the stress thresholds identified by the CMM are in good agreement with those identified by the AE methods,i.e.,ACLM and CRM.Therefore,the proposed CMM can be used to determine the stress thresholds of rocks.