Tuning beneficial calcineurin phosphatase activation to counterα-synuclein toxicity in a yeast model of Parkinson’s disease

Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and mammals.Its biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated T-cells.CN is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate Cna1p.The calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.

Effect of external and internal cues on core muscle activation during the Sahrmann five-level core stability test

BACKGROUND Pain in the back or pelvis or fear of back pain may affect the timing or cocontraction of the core muscles.In both static and dynamic movements,the Sahrmann core stability test provides an assessment of core muscle activation and a person's ability to stabilize the lumbopelvic complex.Preparatory cues and images can be used to increase the activation of these muscles.To attain optimal movement patterns,it will be necessary to determine what cueing will give the most effective results for core stability.AIM To investigate the effects of external and internal cues on core muscle activation during the Sahrmann five-level core stability test.METHODS Total 68 participants(21.83±3.47 years)were randomly allocated to an external(n=35)or internal cue group(n=33).Participants performed the Sahrmann fivelevel core stability test without a cue as baseline and the five-level stability exercises with an internal or external cue.External cue group received a pressure biofeedback unit(PBU),and the internal cue group received an audio cue.A Delsys Trigno^(TM)surface electromyography unit was used for muscle activation from the rectus abdominis,external oblique,and transverse abdominis/internal oblique muscles.RESULTS Linear mixed effects model analysis showed that cueing had a significant effect on core muscle activation(P=0.001);however,there was no significant difference between cue types(internal or external)(P=0.130).CONCLUSION Both external and internal cueing have significant effects on core muscle activation during the Sahrmann five-level core stability test and the PBU does not create higher muscle activation than internal cueing.

An Efficient Boron Source Activation Strategy for the Low‑Temperature Synthesis of Boron Nitride Nanotubes

Lowering the synthesis temperature of boron nitride nanotubes(BNNTs)is crucial for their development.The primary reason for adopting a high temperature is to enable the effective activation of highmelting-point solid boron.In this study,we developed a novel approach for efficiently activating boron by introducing alkali metal compounds into the conventional MgO–B system.This approach can be adopted to form various low-melting-point AM–Mg–B–O growth systems.These growth systems have improved catalytic capability and reactivity even under low-temperature conditions,facilitating the synthesis of BNNTs at temperatures as low as 850℃.In addition,molecular dynamics simulations based on density functional theory theoretically demonstrate that the systems maintain a liquid state at low temperatures and interact with N atoms to form BN chains.These findings offer novel insights into the design of boron activation and are expected to facilitate research on the low-temperature synthesis of BNNTs.

Brain-wide activation involved in 15 mA transcranial alternating current stimulation in patients with first-episode major depressive disorder

Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely unknown.Aims To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA,delivered via the forehead and the mastoid electrodes in the human brain.Methods Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve,first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software.Results The electric field distributions of the sagittal,coronal and axial planes showed that the bilateral frontal lobes,bilateral temporal lobes,hippocampus,cingulate,hypothalamus,thalamus,amygdala,cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure.Conclusions Brain-wide activation,including the cortex,subcortical structures,cerebellum and brainstem,is involved in the 15 mA tACS intervention for first-episode major depressive disorder.Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.

Acute Inflammatory Pain Induces Sex-different Brain Alpha Activity in Anesthetized Rats Through Optically Pumped Magnetometer Magnetoencephalography

Objective Magnetoencephalography(MEG),a non-invasive neuroimaging technique,meticulously captures the magnetic fields emanating from brain electrical activity.Compared with MEG based on superconducting quantum interference devices(SQUID),MEG based on optically pump magnetometer(OPM)has the advantages of higher sensitivity,better spatial resolution and lower cost.However,most of the current studies are clinical studies,and there is a lack of animal studies on MEG based on OPM technology.Pain,a multifaceted sensory and emotional phenomenon,induces intricate alterations in brain activity,exhibiting notable sex differences.Despite clinical revelations of pain-related neuronal activity through MEG,specific properties remain elusive,and comprehensive laboratory studies on pain-associated brain activity alterations are lacking.The aim of this study was to investigate the effects of inflammatory pain(induced by Complete Freund’s Adjuvant(CFA))on brain activity in a rat model using the MEG technique,to analysis changes in brain activity during pain perception,and to explore sex differences in pain-related MEG signaling.Methods This study utilized adult male and female Sprague-Dawley rats.Inflammatory pain was induced via intraplantar injection of CFA(100μl,50%in saline)in the left hind paw,with control groups receiving saline.Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection.For MEG recording,anesthetized rats had an OPM positioned on their head within a magnetic shield,undergoing two 15-minute sessions:a 5-minute baseline followed by a 10-minute mechanical stimulation phase.Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms,generating spectrograms focused on the 4-30 Hz frequency range.Results MEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared,before and after saline/CFA injections.Mechanical stimulation elevated alpha activity in both male and female rats pre-and post-saline/CFA injections.Saline/CFA injections augmented average power in both sexes compared to pre-injection states.Remarkably,female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states.Furthermore,despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment,female rats displayed higher average power than males in the resting state after CFA injection.Conclusion These results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts.Our study exhibits sex differences in alpha activities following CFA injection,highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state.Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals.In addition,the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

基于UPLC-Q-Exactive Orbitrap MS技术的藏药“吉尼德协”体内入血成分分析研究

目的:揭示藏药“吉尼德协”在大鼠血中移行成分。方法:采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱(UPLC-Q-Exactive Orbitrap MS)技术,利用ZORBAX SB-C18柱(150 mm×2.1 mm,1.8μm),以甲醇(A)-0.1%甲酸溶液(B)为流动相进行梯度洗脱,流速为0.3 mL/min。质谱采用电喷雾电离正、负离子模式交替扫描,并自动触发采集质谱数据。运用Xcalibur、Compound Discoverer 3.0等软件,根据化合物保留时间、准分子离子峰和二级质谱信息,结合对照品及文献报道,对该复方的入血成分进行解析。结果:共鉴定了大鼠血浆中的45个化合物,包括22个原型成分和23个代谢物。结论:所建立的方法能高效、灵敏地分析藏药“吉尼德协”的入血成分,为其体内的药效物质基础和作用机制研究奠定基础。

Prognostic value of combined detection of alpha-fetoprotein,plasma prothrombin activity,and serum prealbumin in acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure(ACLF)is a liver disease based on chronic liver disease,which is significantly influenced by clinical treatment regimen and disease status,and despite the existence of multiple prognostic assessment indicators for ACLF,the overall sensitivity and accuracy are relatively low.AIM To investigate the prognostic value of the combined detection of alpha-fetoprotein(AFP),plasma prothrombin activity(PTA),and serum prealbumin(PA)in ACLF.METHODS This retrospective study included 87 patients with ACLF admitted from February 2021 to February 2023 and categorized them into the survival(n=47)and death(n=40)groups according to their clinical outcomes 3 months posttreatment.All the participants underwent AFP,PTA,and PA level measurements upon admission.Baseline data,as well as AFP,PTA,and PA levels,were comparatively analyzed.Pearson correlation coefficients were utilized to analyze the correlations of AFP,PTA,and PA with different survival outcomes in patients with ACLF.Receiver operating characteristic(ROC)curves and areas under the curves were used to evaluate the predictive value of AFP,PTA,and PA for ACLF prognosis.RESULTS AFP,PTA,and PA levels were markedly decreased in the death group than in the survival group(P<0.05).Pearson analysis indicated a positive association of the AFP,PTA,and PA levels with the survival of patients with ACLF(P<0.05).ROC curve analysis determined the sensitivity and specificity of the combined diagnosis at 91.24%and 100.00%,respectively,both of which were notably increased compared to the single-index diagnosis.The ROC of their combined diagnosis was 0.989,significantly surpassing 0.907,0.849,and 0.853 of AFP,PTA,and PA,respectively.No statistically significant variance was determined in the sensitivity and specificity of the combined diagnosis vs the single detection(P>0.05).CONCLUSION The combined detection of AFP,PTA,and PA levels demonstrates favorable diagnostic value for the short-term prognosis of patients with ACLF,featuring high sensitivity and specificity.

Acid mine drainage activation mechanism on lime-depressed pyrite flotation from copper sulfide ore

The lime-depressed pyrite from Cu differential flotation tailings with acid mine drainage(AMD)as a natural activator was recovered.The effect of AMD on lime-depressed pyrite flotation was investigated by a series of laboratory flotation tests and surface analytical techniques.Flotation test results indicated that AMD could effectively activate the pyrite flotation with a sodium butyl xanthate(SBX)collector,and a high-quality sulfur concentrate was obtained.Pulp ion concentration analysis results indicated that AMD facilitated desorption of Ca^(2+)and adsorption of Cu^(2+)on the depressed-pyrite surface.Adsorption measurements and contact angle analysis results confirmed that adding AMD improved the adsorption amount of SBX collector on the pyrite surface and increased the contact angle by 31°.Results of Raman spectroscopy and X-ray photoelectron spectroscopy analysis indicated that AMD treatment promoted the formation of hydrophobic species(S^(0) hydrophobic entity and copper sulfides)and the removal of hydrophilic calcium and iron species on the pyrite surface,which reinforced the adsorption of collector.The findings of the present research provide important theoretical basis and technical support for a cleaner production of copper sulfide ores.

Zonal activation of molecular carbon dioxide and hydrogen over dual sites Ni-Co-MgO catalyst for CO_(2) methanation:Synergistic catalysis of Ni and Co species

An in-depth mechanism in zonal activation of CO_(2)and H2molecular over dual-active sites has not been revealed yet.Here,Ni-Co-MgO was rationally constructed to elucidate the CO_(2)methanation mechanism.The abundant surface nickel and cobalt components as active sites led to strong Ni-Co interaction with charge transfer from nickel to cobalt.Notably,electron-enriched Coδ-species participated in efficient chemisorption and activation of CO_(2)to generate monodentate carbonate.Simultaneously,plentiful available Ni0sites facilitated H2dissociation,thus CO_(2)and H2were smoothly activated at zones of Coδ-species and Ni0,respectively.Detailed in situ DRIFTS,quasi situ XPS,TPSR,and DFT calculations substantiated a new formate evolution mechanism via monodentate carbonate instead of traditional bidentate carbonate based on synergistic catalysis of Coδ-species and Ni0.The zonal activation of CO_(2)and H2by tuning electron behaviors of double-center catalysts can boost heterogeneous catalytic hydrogenation performance.

Using microglia-derived extracellular vesicles to capture diversity of microglial activation phenotypes following neurological injury

Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perform immune functions similar to peripheral macrophages,they are not simply macrophages of the CNS.

The impact of maternal immune activation on the morphology and electrophysiological properties of postnatally-born neurons in the offspring

Pregnancy comes with a combination of physical changes and physiological immunosuppression that increases the susceptibility of women to pathogens and in turn,rises the prevalence of infectious diseases.

Properties of Activated Carbons from Sugarcane Leaves and Rice Straw Derived Charcoals by Activation at Low Temperature via KMnO_(4)Pre-Oxidation-Hydrolysis

Activated carbon preparation from sugarcane leaves and rice straw by carbonization(250℃–400℃)and activation at 500℃were studied.The effects of pre-oxidation,hydrolysis of derived charcoals by boiled KMnO4 aqueous solution were evaluated.The derived charcoals products were pretreated using oxidation-hydrolysis with 1–5 wt.%KMnO4 at 100℃and then activated at 500℃.The derived charcoal and activated carbon products were characterized by FTIR,XRD,SEM-EDS and BET.Iodine number and methylene blue number of derived products were also used for the analysis of the products.It was found that fabricated charcoal materials made at 350℃–400℃possess good characteristics with low content of surface functional groups and high carbon content.After pre-oxidation-hydrolysis and activation at 500℃,the resulting derived activated carbon materials from charcoals with 400℃carbonization temperature have high content of oxygen containing surface functional groups such as Mn-O,Si-O,Si-O-Si,C-O,or O-H.In addition,MnO_(2) accumulated on the surface of the derived activated carbon products.The surface area and pore volume of the activated carbon products have also increased with increasing of KMnO_(4) concentration from 1 to 3 wt.%and then decreased with 5 wt.%used during activation.Therefore,activated carbon products made by pre-oxidation-hydrolysis with 3 wt.%KMnO_(4) were used for Fe(Ⅲ)adsorption experiments.It was found that Fe(Ⅲ)adsorption on the activated carbon materials can be fitted with both the Freundlich and the Langmuir models.The calculated maximum Fe(Ⅲ)adsorption capacities of sugarcane leaves derived activated carbon and rice straw derived activated carbon products were 50.00 and 39.37 mg/g,respectively.It was shown that the effect of pre-oxidation-hydrolysis by KMnO_(4) and activation at 500℃are beneficial for activated carbon preparation with environmentally friendly and low-cost simplified operation.

Study of the reaction mechanism for preparing powdered activated coke with SO_(2)adsorption capability via one-step rapid activation method under flue gas atmosphere

In this study,the impact of different reaction times on the preparation of powdered activated carbon(PAC)using a one-step rapid activation method under flue gas atmosphere is investigated,and the underlying reaction mechanism is summarized.Results indicate that the reaction process of this method can be divided into three stages:stage I is the rapid release of volatiles and the rapid consumption of O_(2),primarily occurring within a reaction time range of 0-0.5 s;stage II is mainly the continuous release and diffusion of volatiles,which is the carbonization and activation coupling reaction stage,and the carbonization process is the main in this stage.This stage mainly occurs at the reaction time range of 0.5 -2.0 s when SL-coal is used as material,and that is 0.5-3.0 s when JJ-coal is used as material;stage III is mainly the activation stage,during which activated components diffuse to both the surface and interior of particles.This stage mainly involves the reaction stage of CO_(2)and H2O(g)activation,and it mainly occurs at the reaction time range of 2.0-4.0 s when SL-coal is used as material,and that is 3.0-4.0 s when JJ-coal is used as material.Besides,the main function of the first two stages is to provide more diffusion channels and contact surfaces/activation sites for the diffusion and activation of the activated components in the third stage.Mastering the reaction mechanism would serve as a crucial reference and foundation for designing the structure,size of the reactor,and optimal positioning of the activator nozzle in PAC preparation.

Activation of IP10/CXCR3 Signaling is Highly Coincidental with PrP^(Sc)Deposition in the Brains of Scrapie-Infected Mice

Objective To analyze the relationship between Chemokine IP10 and its receptor CXCR3 during prion infection.Methods We investigated the increases in IP10 signals,primarily localized in neurons within the brains of scrapie-infected mice,using western blotting,ELISA,co-immunoprecipitation,immunohistochemistry,immunofluorescence assays,and RT-PCR.Results Both CXCR3 levels and activation were significantly higher in the brains of scrapie-infected mice and prion-infected SMB-S15 cells.Enhanced CXCR3 expression was predominantly observed in neurons and activated microglia.Morphological colocalization of PrPC/PrPSc with IP10/CXCR3 was observed in scrapie-infected mouse brains using immunohistochemistry and immunofluorescence.immunohistochemistry(IHC)analysis of whole brain sections further revealed increased accumulation of IP10/CXCR3 specifically in brain regions with higher levels of PrPSc deposits.Co-immunoprecipitation and biomolecular interaction assays revealed the molecular interactions between PrP and IP10/CXCR3.Notably,a significantly larger amount of IP10 accumulated within prion-infected SMB-S15 cells than in the normal partner cell line,SMB-PS.Importantly,resveratrol treatment effectively suppressed prion replication in SMB-S15 cells,thereby restoring the accumulation and secretion pattern of cellular IP10 similar to that observed in SMB-PS cells.Conclusion Our data demonstrate that the activation of IP10/CXCR3 signaling in prion-infected brain tissues coincides with PrPSc deposition.Modulation of IP10/CXCR3 signaling in the brain represents a potential therapeutic target for mitigating the progression of prion diseases.

Ultra-high specific surface area activated carbon from Taihu cyanobacteria via KOH activation for enhanced methylene blue adsorption

Cyanobacteria-based activated carbon(CBAC)was successfully prepared by pyrolysis-activation of Taihu cyanobacteria.When the impregnation ratio and activated temperature were 2 and 800-C,respectively,the optimal CBACs possessed an ultra-high specific surface(2178.90 m^(2)·g^(-1))and plenty of micro-and meso-pores,as well as a high pore volume(1.01 cm^(3)·g^(-1)).Ascribed to ultra-high surface area,π-π interaction,electrostatic interaction,as well as hydrogen-bonding interactions,the CBACs displayed huge superiority in efficient dye removal.The saturated methylene blue adsorption capacity by CBACs could be as high as 1143.4 mg·g^(-1),superior to that of other reported biomass-activated carbons.The adsorption was endothermic and modeled well by the pseudo-second-order kinetic,intra-particle diffusion,and Langmuir models.This work presented the effectiveness of Taihu cyanobacteria adsorbent ascribed to its super large specific surface area and high adsorption ability.

Importance of V^(4)and optimal acid environment in the hydroxylation of inert benzene via activation of C_(sp2)-H bond

Hydroxylation of inert benzene through the activation of the C_(sp2)-H bond is a representative reaction about the transformation of C-H bonds to C-O bonds,which has far-reaching guiding significance but remains a challenging scientific problem.To overcome this problem,a series of VOx-Ga_(2)O_(3)/SiO_(2)-Al_(2)O_(3)were prepared to achieve an efficient and economical hydroxylation path of benzene to phenol.The results showed that the phenol yield was 72.89%(selectivity>98.1%)under the optimum conditions.The reason is that the C-H bond in the benzene ring is activated by heterolysis over a VOx-Ga_(2)O_(3)/SiO_(2)-Al_(2)O_(3)catalyst.Meanwhile,the introduction of aluminum(Al)and gallium(Ga)made a qualitative change in the catalyst,enhancing the electron motion and spin motion of vanadium species,resulting in the increase of V4^(+)/V5^(+)ratio.In addition,the catalyst can provide an optimal acidic environment and a threedimensional cross-linked surface structure that facilitates product diffusion.

Mo Doping and Electrochemical Activation Co-Induced Vanadium Composite as High-Rate and Long-Life Anode for Ca-Ion Batteries

Calcium-ion batteries have been considered attractive candidates for large-scale energy storage applications due to their natural abundance and low redox potential of Ca^(2+)/Ca.However,current calcium ion technology is still hampered by the lack of high-capacity and long-life electrode materials to accommodate the large Ca^(2+)(1.00Å).Herein,an amorphous vanadium structure induced by Mo doping and in-situ electrochemical activation is reported as a high-rate anode material for calcium ion batteries.The doping of Mo could destroy the lattice stability of VS4 material,enhancing the flexibility of the structure.The following electrochemical activation further converted the material into sulfide and oxides co-dominated composite(defined as MoVSO),which serves as an active material for the storage of Ca^(2+)during cycling.Consequently,this amorphous vanadium structure exhibits excellent rate capability,achieving discharge capacities of 306.7 and 149.2 mAh g^(-1)at 5 and 50 A g^(-1)and an ultra-long cycle life of 2000 cycles with 91.2%capacity retention.These values represent the highest level to date reported for calcium ion batteries.The mechanism studies show that the material undergoes a partial phase transition process to derive MoVSO.This work unveiled the calcium storage mechanism of vanadium sulfide in aqueous electrolytes and accelerated the development of high-performance aqueous calcium ion batteries.

Conversion of Lignin into Porous Carbons for High-Performance Supercapacitors via Spray Drying and KOH Activation: Structure-Properties Relationship and Reaction Mechanism

Lignin-derived porous carbons have emerged as promising electrode materials for supercapacitors.However,the challenge remains in designing and controlling their structure to achieve ideal electrochemical performance due to the complex molecular structure of lignin and its intricate chemical reactions during the activation process.In this study,three porous carbons were synthesized from lignin by spray drying and chemical activation with vary-ing KOH ratios.The specific surface area and structural order of the prepared porous carbon continued to increase with the increase of the KOH ratio.Thermogravimetric-mass spectrometry(TG-MS)was employed to track the molecular fragments generated during the pyrolysis of KOH-activated lignin,and the mechanism of the thermochemical conversion was investigated.During the thermochemical conversion of lignin,KOH facili-tated the removal of H2 and CO,leading to the formation of not only more micropores and mesopores,but also more ordered carbon structures.The pore structure exhibited a greater impact than the carbon structure on the electrochemical performance of porous carbon.The optimized porous carbon exhibited a capacitance of 256 F g-1 at a current density of 0.2 A g-1,making it an ideal electrode material for high-performance supercapacitors.

Mesoporous amorphous FeOOH-encapsulated BiO_(2–x) photocatalyst with harnessing broad spectrum toward activation of persulfate for tetracycline degradation

With the growing concern about the water environment,the advanced oxidation process of persulfate activation assisted by photocatalysis has attracted considerable attention to decompose dissolved organic micropollutants.In this work,to overcome the drawbacks of the photocatalytic activity reduction caused by the photo-corrosion of non-stoichiometric BiO_(2–x),a novel material with amorphous FeOOH in situ grown on layered BiO_(2–x) to form a core-shell structure similar to popcorn chicken-like morphology was produced in two simple and environmentally beneficial steps.Through a series of degradation activity tests of hybrid materials under different conditions,the as-prepared materials exhibited remarkable degradation activity and stability toward tetracycline in the FeOOH@BiO_(2–x)/Vis/PS system due to the synergism of photocatalysis and persulfate activation.The results of XRD,SEM,TEM,XPS,FTIR,and BET show that the loading of FeOOH increases the specific surface area and active sites appreciably;the heterogeneous structure formed by FeOOH and BiO_(2–x) is more favorable to the effective separation of photogenerated carriers.The optimal degradation conditions were at a catalyst addition of 0.7 g·L^(–1),a persulfate concentration of 1.0 g·L^(–1),and an initial pH of 4.5,at which the degradation rate could reach 94.7%after 90 min.The influence of typical inorganic anions on degradation was also examined.ESR studies and radical quenching experiments revealed that·OH,SO_(4)^(-)·,and·O_(2)^(-)were the principal active species generated during the degradation of tetracycline.The results of the 1,10-phenanthroline approach proved that the effect of dissolved iron ions on the tetracycline degradation was limited,and the interfacial reaction that occurs on the active sites on the material's surface was a critical factor.This work provides a novel method for producing efficient broad-spectrum Bismuth-based composite photocatalysts and photocatalytic-activated persulfate synergistic degradation of tetracycline.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.