Failure mechanism and infrared radiation characteristic of hard siltstone induced by stratification effect

The deformation in sedimentary rock induced by train loads has potential threat to the safe operation of tunnels. This study investigated the influence of stratification structure on the infrared radiation and temporal damage mechanism of hard siltstone. The uniaxial compression tests, coupled with acoustic emission(AE) and infrared radiation temperature(IRT) were conducted on siltstones with different stratification effects. The results revealed that the stratigraphic structure significantly affects the stress-strain response and strength degradation characteristics. The mechanical parameters exhibit anisotropy characteristics, and the stratification effect exhibits a negative correlation with the cracking stress and peak stress. The failure modes caused by the stratification effect show remarkable anisotropic features, including splitting failure(Ⅰ: 0°-22.50°, Ⅱ: 90°), composite failure(45°), and shearing failure(67.50°). The AE temporal sequences demonstrate a stepwise response characteristic to the loading stress level. The AE intensity indicates that the stress sensitivity of shearing failure and composite failure is generally greater than that of splitting failure. The IRT field has spatiotemporal migration and progressive dissimilation with stress loading and its dissimilation degree increases under higher stress levels. The stronger the stratification effect, the greater the dissimilation degree of the IRT field. The abnormal characteristic points of average infrared radiation temperature(AIRT) variance at local stress drop and peak stress can be used as early and late precursors to identify fracture instability. Theoretical analysis shows that the competitive relationship between compaction strengthening and fracturing damage intensifies the dissimilation of the infrared thermal field for an increasing stress level. The present study provides a theoretical reference for disaster warnings in hard sedimentary rock mass.

Microdynamic mechanical properties and fracture evolution mechanism of monzogabbro with a true triaxial multilevel disturbance method

The far-field microdynamic disturbance caused by the excavation of deep mineral resources and underground engineering can induce surrounding rock damage in high-stress conditions and even lead to disasters.However,the mechanical properties and damage/fracture evolution mechanisms of deep rock induced by microdynamic disturbance under three-dimensional stress states are unclear.Therefore,a true triaxial multilevel disturbance test method is proposed,which can completely simulate natural geostress,excavation stress redistribution(such as stress unloading,concentration and rotation),and subsequently the microdynamic disturbance triggering damaged rock failure.Based on a dynamic true triaxial test platform,true triaxial microdynamic disturbance tests under different frequency and amplitudes were carried out on monzogabbro.The results show that increasing amplitude or decreasing frequency diminishes the failure strength of monzogabbro.Deformation modulus gradually decreases during disturbance failure.As frequency and amplitude increase,the degradation rate of deformation modulus decreases slightly,disturbance dissipated energy increases significantly,and disturbance deformation anisotropy strengthens obviously.A damage model has been proposed to quantitatively characterize the disturbance-induced damage evolution at different frequency and amplitude under true triaxial stress.Before disturbance failure,the micro-tensile crack mechanism is dominant,and the micro-shear crack mechanism increases significantly at failure.With the increase of amplitude and frequency,the micro-shear crack mechanism increases.When approaching disturbance failure,the acoustic emission fractal dimension changes from a stable value to local large oscillation,and finally increases sharply to a high value at failure.Finally,the disturbance-induced failure mechanism of surrounding rock in deep engineering is clearly elucidated.

Antagonism effect of residual S triggers the dual-path mechanism for water oxidation

Transition metal chalcogenides(TMCs)are recognized as pre-catalysts,and their(oxy)hydroxides derived from electrochemical reconstruction are the active species in the water oxidation.However,understanding the role of the residual chalcogen in the reconstructed layer is lacking in detail,and the corresponding catalytic mechanism remains controversial.Here,taking Cu_(1-x)Co_(x)S as a platform,we explore the regulating effect and existence form of the residual S doped into the reconstructive layer for oxygen evolution reaction(OER),where a dual-path OER mechanism is proposed.First-principles calculations and operando~(18)O isotopic labeling experiments jointly reveal that the residual S in the reconstructive layer of Cu_(1-x)Co_(x)S can wisely balance the adsorbate evolution mechanism(AEM)and lattice oxygen oxidation mechanism(LOM)by activating lattice oxygen and optimizing the adsorption/desorption behaviors at metal active sites,rather than change the reaction mechanism from AEM to LOM.Following such a dual-path OER mechanism,Cu_(0.4)Co_(0.6)S-derived Cu_(0.4)Co_(0.6)OSH not only overcomes the restriction of linear scaling relationship in AEM,but also avoids the structural collapse caused by lattice oxygen migration in LOM,so as to greatly reduce the OER potential and improved stability.

Regarding the Regulatory Sandbox Route and Mechanism for Governance of Artificial Intelligence

The main challenge in AI governance today is striking a balance between controlling AI dangers and fostering AI innovation.Regulators in a number of nations have progressively extended the regulatory sandbox,which was first implemented in the banking sector,to AI governance in an effort to reduce the conflict between regulation and innovation.The AI regulatory sandbox is a new and feasible route for AI governance in China that not only helps to manage the risks of technology application but also prevents inhibiting AI innovation.It keeps inventors'trial-and-error tolerance space inside the regulatory purview while offering a controlled setting for the development and testing of novel AI that hasn't yet been put on the market.By providing full-cycle governance of AI with the principles of agility and inclusive prudence,the regulatory sandbox offers an alternative to the conventional top-down hard regulation,expost regulation,and tight regulation.However,the current system also has inherent limitations and practical obstacles that need to be overcome by a more rational and effective approach.To achieve its positive impact on AI governance,the AI regulatory sandbox system should build and improve the access and exit mechanism,the coordination mechanism between the sandbox and personal information protection,and the mechanisms of exemption,disclosure,and communication.

Classification of musical hallucinations and the characters along with neural-molecular mechanisms of musical hallucinations associated with psychiatric disorders

BACKGROUND Musical hallucinations(MH)involve the false perception of music in the absence of external stimuli which links with different etiologies.The pathomechanisms of MH encompass various conditions.The etiological classification of MH is of particular importance and offers valuable insights to understand MH,and further to develop the effective treatment of MH.Over the recent decades,more MH cases have been reported,revealing newly identified medical and psychiatric causes of MH.Functional imaging studies reveal that MH activates a wide array of brain regions.An up-to-date analysis on MH,especially on MH comorbid psychiatric conditions is warranted.AIM To propose a new classification of MH;to study the age and gender differences of MH in mental disorders;and neuropathology of MH.METHODS Literatures searches were conducted using keywords such as“music hallucination,”“music hallucination and mental illness,”“music hallucination and gender difference,”and“music hallucination and psychiatric disease”in the databases of PubMed,Google Scholar,and Web of Science.MH cases were collected and categorized based on their etiologies.The t-test and ANOVA were employed(P<0.05)to compare the age differences of MH different etiological groups.Function neuroimaging studies of neural networks regulating MH and their possible molecular mechanisms were discussed.RESULTS Among the 357 yielded publications,294 MH cases were collected.The average age of MH cases was 67.9 years,with a predominance of females(66.8%females vs 33.2%males).MH was classified into eight groups based on their etiological mechanisms.Statistical analysis of MH cases indicates varying associations with psychiatric diagnoses.CONCLUSION We carried out a more comprehensive review of MH studies.For the first time according to our knowledge,we demonstrated the psychiatric conditions linked and/or associated with MH from statistical,biological and molecular point of view.

Instability mechanism of mining roadway passing through fault at different angles in kilometre-deep mine and control measures of roof cutting and NPR cables

The angle α between the fault strike and the axial direction of the roadway produces different damage characteristics. In this paper, the research methodology includes theoretical analyses, numerical simulations and field experiments in the context of the Daqiang coal mine located in Shenyang, China. The stability control countermeasure of "pre-splitting cutting roof + NPR anchor cable"(PSCR-NPR) is simultaneously proposed. According to the different deformation characteristics of the roadway, the faults are innovatively classified into three types, with α of type I being 0°-30°, α of type II being 30°-60°, and α of type III being 60°-90°. The full-cycle stress evolution paths during mining roadway traverses across different types of faults are investigated by numerical simulation. Different pinch angles α lead to high stress concentration areas at different locations in the surrounding rock. The non-uniform stress field formed in the shallow surrounding rock is an important reason for the instability of the roadway. The pre-cracked cut top shifted the high stress region to the deep rock mass and formed a low stress region in the shallow rock mass. The high prestressing NPR anchor cable transforms the non-uniform stress field of the shallow surrounding rock into a uniform stress field. PSCR-NPR is applied in the fault-through roadway of Daqiang mine. The low stress area of the surrounding rock was enlarged by 3-7 times, and the cumulative convergence was reduced by 45%-50%. It provides a reference for the stability control of the deep fault-through mining roadway.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

Deep Insight of Design,Mechanism,and Cancer Theranostic Strategy of Nanozymes

Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction conditions,good stability,and suitable for large-scale production.Recently,with the cross fusion of nanomedicine and nanocatalysis,nanozyme-based theranostic strategies attract great attention,since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects.Thus,various nanozymes have been developed and used for tumor therapy.In this review,more than 270 research articles are discussed systematically to present progress in the past five years.First,the discovery and development of nanozymes are summarized.Second,classification and catalytic mechanism of nanozymes are discussed.Third,activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory,machine learning,biomimetic and chemical design.Then,synergistic theranostic strategy of nanozymes are introduced.Finally,current challenges and future prospects of nanozymes used for tumor theranostic are outlined,including selectivity,biosafety,repeatability and stability,in-depth catalytic mechanism,predicting and evaluating activities.

Recent advances in cobalt phosphide-based materials for electrocatalytic water splitting:From catalytic mechanism and synthesis method to optimization design

Electrochemical water splitting has long been considered an effective energy conversion technology for trans-ferring intermittent renewable electricity into hydrogen fuel,and the exploration of cost-effective and high-performance electrocatalysts is crucial in making electrolyzed water technology commercially viable.Cobalt phosphide(Co-P)has emerged as a catalyst of high potential owing to its high catalytic activity and durability in water splitting.This paper systematically reviews the latest advances in the development of Co-P-based materials for use in water splitting.The essential effects of P in enhancing the catalytic performance of the hydrogen evolution reaction and oxygen evolution reaction are first outlined.Then,versatile synthesis techniques for Co-P electrocatalysts are summarized,followed by advanced strategies to enhance the electrocatalytic performance of Co-P materials,including heteroatom doping,composite construction,integration with well-conductive sub-strates,and structure control from the viewpoint of experiment.Along with these optimization strategies,the understanding of the inherent mechanism of enhanced catalytic performance is also discussed.Finally,some existing challenges in the development of highly active and stable Co-P-based materials are clarified,and pro-spective directions for prompting the wide commercialization of water electrolysis technology are proposed.

Preliminary discussion on the ignition mechanism of exploding foil initiators igniting boron potassium nitrate

Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ignition mechanism of EFIs directly igniting pyrotechnics.An oscilloscope,a photon Doppler velocimetry,and a plasma spectrum measurement system were employed to obtain information of electric characteristics,impact pressure,and plasma temperature.The results of the electric characteristics and the impact pressure were inconsistent with ignition results.The only thing that the ignition success tests had in common was that their plasma all had a relatively long period of high-temperature duration(HTD).It eventually concludes that the ignition mechanism in this research is the microconvection heat transfer rather than the shock initiation,which differs from that of exploding foil initiators detonating explosives.Furthermore,the methods for evaluating the ignition success of semiconductor bridge initiators are not entirely applicable to the tests mentioned in this paper.The HTD is the critical parameter for judging the ignition success,and it is influenced by two factors:the late time discharge and the energy of the electric explosion.The longer time of the late time discharge and the more energy of the electric explosion,the easier it is to expand the HTD,which improves the probability of the ignition success.

Recent research progress in the mechanism and suppression of fusion welding-induced liquation cracking of nickel based superalloys

Nickel-based superalloys are extensively used in the crucial hot-section components of industrial gas turbines,aeronautics,and astronautics because of their excellent mechanical properties and corrosion resistance at high temperatures.Fusion welding serves as an effective means for joining and repairing these alloys;however,fusion welding-induced liquation cracking has been a challenging issue.This paper comprehensively reviewed recent liquation cracking,discussing the formation mechanisms,cracking criteria,and remedies.In recent investigations,regulating material composition,changing the preweld heat treatment of the base metal,optimizing the welding process parameters,and applying auxiliary control methods are effective strategies for mitigating cracks.To promote the application of nickel-based superalloys,further research on the combination impact of multiple elements on cracking prevention and specific quantitative criteria for liquation cracking is necessary.

Hybrid model for BOF oxygen blowing time prediction based on oxygen balance mechanism and deep neural network

The amount of oxygen blown into the converter is one of the key parameters for the control of the converter blowing process,which directly affects the tap-to-tap time of converter. In this study, a hybrid model based on oxygen balance mechanism (OBM) and deep neural network (DNN) was established for predicting oxygen blowing time in converter. A three-step method was utilized in the hybrid model. First, the oxygen consumption volume was predicted by the OBM model and DNN model, respectively. Second, a more accurate oxygen consumption volume was obtained by integrating the OBM model and DNN model. Finally, the converter oxygen blowing time was calculated according to the oxygen consumption volume and the oxygen supply intensity of each heat. The proposed hybrid model was verified using the actual data collected from an integrated steel plant in China, and compared with multiple linear regression model, OBM model, and neural network model including extreme learning machine, back propagation neural network, and DNN. The test results indicate that the hybrid model with a network structure of 3 hidden layer layers, 32-16-8 neurons per hidden layer, and 0.1 learning rate has the best prediction accuracy and stronger generalization ability compared with other models. The predicted hit ratio of oxygen consumption volume within the error±300 m^(3)is 96.67%;determination coefficient (R^(2)) and root mean square error (RMSE) are0.6984 and 150.03 m^(3), respectively. The oxygen blow time prediction hit ratio within the error±0.6 min is 89.50%;R2and RMSE are0.9486 and 0.3592 min, respectively. As a result, the proposed model can effectively predict the oxygen consumption volume and oxygen blowing time in the converter.

Molecular Mechanism and Molecular Design of Lubricating Oil Antioxidants

To overcome the limitations of traditional experimental“trial and error”methods in lubricant additive design,a new molecular design method based on molecular structure parameters is established here.The molecular mechanism of the antioxidant reaction of hindered phenol,diphenylamine,and alkyl sulfide are studied via molecular simulations.Calculation results show that the strong electron-donating ability and high hydrogen-donating activity of the antioxidant molecule and the low hydrogen-abstracting activity of free radicals formed after dehydrogenation are the internal molecular causes of the shielding of phenol and diphenylamine from scavenging peroxy free radicals,and the strong electron-donating ability is the internal molecular cause of the high activity of thioether in decomposing alkyl hydrogen peroxide.Based on this antioxidant molecular mechanism,a molecular design rule of antioxidant is proposed,namely“high EHOMO,large Q(S),low bond dissociation energy BDE(O—H)and BDE(N—H)”.Two new antioxidants,PAS-I and PAS-II,are designed and prepared by chemical bonding of hindered phenol,diphenylamine,and sulfur atoms.Experimental results show that these antioxidants both have excellent antioxidant effects in lubricating oil,and that PAS-II is the superior antioxidant,consistent with theoretical predictions.

Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

Efficient Unsupervised Image Stitching Using Attention Mechanism with Deep Homography Estimation

Traditional feature-based image stitching techniques often encounter obstacles when dealing with images lackingunique attributes or suffering from quality degradation. The scarcity of annotated datasets in real-life scenesseverely undermines the reliability of supervised learning methods in image stitching. Furthermore, existing deeplearning architectures designed for image stitching are often too bulky to be deployed on mobile and peripheralcomputing devices. To address these challenges, this study proposes a novel unsupervised image stitching methodbased on the YOLOv8 (You Only Look Once version 8) framework that introduces deep homography networksand attentionmechanisms. Themethodology is partitioned into three distinct stages. The initial stage combines theattention mechanism with a pooling pyramid model to enhance the detection and recognition of compact objectsin images, the task of the deep homography networks module is to estimate the global homography of the inputimages consideringmultiple viewpoints. The second stage involves preliminary stitching of the masks generated inthe initial stage and further enhancement through weighted computation to eliminate common stitching artifacts.The final stage is characterized by adaptive reconstruction and careful refinement of the initial stitching results.Comprehensive experiments acrossmultiple datasets are executed tometiculously assess the proposed model. Ourmethod’s Peak Signal-to-Noise Ratio (PSNR) and Structure Similarity Index Measure (SSIM) improved by 10.6%and 6%. These experimental results confirm the efficacy and utility of the presented model in this paper.

Antibacterial mechanism of kojic acid and tea polyphenols against Escherichia coli O157:H7 through transcriptomic analysis

Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans.The previous found that a combination of kojic acid and tea polyphenols exhibited better activity against E.coli O157:H7 than using either alone.This study aimed to explore responses underlying the antibacterial mechanisms of kojic acid and tea polyphenols from the gene level.The functional enrichment analysis by comparing kojic acid and tea polyphenols individually or synergistically against E.coli O157:H7 found that acid resistance systems in kojic acid were activated,and the cell membrane and genomic DNA were destructed in the cells,resulting in“oxygen starvation”.The oxidative stress response triggered by tea polyphenols inhibited both sulfur uptake and the synthesis of ATP,which affected the bacteria's life metabolic process.Interestingly,we found that kojic acid combined with tea polyphenols hindered the uptake of iron that played an essential role in the synthesis of DNA,respiration,tricarboxylic acid cycle.The results suggested that the iron uptake pathways may represent a novel approach for kojic acid and tea polyphenols synergistically against E.coli O157:H7 and provided a theoretical basis for bacterial pathogen control in the food industry.

An Underwater Target Detection Algorithm Based on Attention Mechanism and Improved YOLOv7

For underwater robots in the process of performing target detection tasks,the color distortion and the uneven quality of underwater images lead to great difficulties in the feature extraction process of the model,which is prone to issues like error detection,omission detection,and poor accuracy.Therefore,this paper proposed the CER-YOLOv7(CBAM-EIOU-RepVGG-YOLOv7)underwater target detection algorithm.To improve the algorithm’s capability to retain valid features from both spatial and channel perspectives during the feature extraction phase,we have added a Convolutional Block Attention Module(CBAM)to the backbone network.The Reparameterization Visual Geometry Group(RepVGG)module is inserted into the backbone to improve the training and inference capabilities.The Efficient Intersection over Union(EIoU)loss is also used as the localization loss function,which reduces the error detection rate and missed detection rate of the algorithm.The experimental results of the CER-YOLOv7 algorithm on the UPRC(Underwater Robot Prototype Competition)dataset show that the mAP(mean Average Precision)score of the algorithm is 86.1%,which is a 2.2%improvement compared to the YOLOv7.The feasibility and validity of the CER-YOLOv7 are proved through ablation and comparison experiments,and it is more suitable for underwater target detection.

Deep tectonics and seismogenic mechanisms of the seismic source zone of the Jishishan M_(s)6.2 earthquake on December 18,2023,at the northeast margin of the Tibetan Plateau

On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong earthquakes to occur through the release of overlying rigid crustal stresses.However,it is unlikely that an earthquake of comparable or larger magnitude would occur in the short term(e.g.,in one year)at the Jishishan east margin fault.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.