Identification and characterization of FpRco1 in regulating vegetative growth and pathogenicity based on T-DNA insertion in Fusarium pseudograminearum

Fusarium pseudograminearum is a devastating pathogen that causes Fusarium crown rot(FCR)in wheat and poses a significant threat to wheat production in terms of grain yield and quality.However,the mechanism by which F.pseudograminearum infects wheat remains unclear.In this study,we aimed to elucidate these mechanisms by constructing a T-DNA insertion mutant library for the highly virulent strain WZ-8A of F.pseudograminearum.By screening this mutant library,we identified nine independent mutants that displayed impaired pathogenesis in barley leaves.Among these mutants,one possessed a disruption in the gene FpRCO1 that is an ortholog of Saccharomyces cerevisiae RCO1,encoding essential component of the Rpd3S histone deacetylase complex in F.pseudograminearum.To further investigate the role of FpRCO1 in F.pseudograminearum,we employed a split-marker approach to knock out FpRCO1 in F.pseudograminearum WZ-8A.FpRCO1 deletion mutants exhibit reduced vegetative growth,conidium production,and virulence in wheat coleoptiles and barley leaves,whereas the complementary strain restores these phenotypes.Moreover,under stress conditions,the FpRCO1 deletion mutants exhibited increased sensitivity to NaCl,sorbitol,and SDS,but possessed reduced sensitivity to H_(2)O_(2)compared to these characteristics in the wild-type strain.RNA-seq analysis revealed that deletion of FpRCO1 affected gene expression(particularly the downregulation of TRI gene expression),thus resulting in significantly reduced deoxynivalenol(DON)production.In summary,our findings highlight the pivotal role of FpRCO1 in regulating vegetative growth and development,asexual reproduction,DON production,and pathogenicity of F.pseudograminearum.This study provides valuable insights into the molecular mechanisms underlying F.pseudograminearum infection in wheat and may pave the way for the development of novel strategies to combat this devastating disease.

Establishment and validation of a predictive model for peripherally inserted central catheter-related thrombosis in patients with liver cancer

BACKGROUND Peripherally inserted central catheters(PICCs)are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy,nutrition,and other medications.However,PICC-related thrombosis is a serious complication that can lead to morbidity and mortality in this patient population.Several risk factors have been identified for the development of PICC-related thrombosis,including cancer type,stage,comorbidities,and catheter characteristics.Understanding these risk factors and developing a predictive model can help healthcare providers identify high-risk patients and implement preventive measures to reduce the incidence of thrombosis.AIM To analyze the influencing factors of PICC-related thrombosis in hospitalized patients with liver cancer,construct a predictive model,and validate it.METHODS Clinical data of hospitalized patients with liver cancer admitted from January 2020 to December 2023 were collected.Thirty-five cases of PICC-related thrombosis in hospitalized patients with liver cancer were collected,and 220 patients who underwent PICC placement during the same period but did not develop PICC-related thrombosis were randomly selected as controls.A total of 255 samples were collected and used as the training set,and 77 cases were collected as the validation set in a 7:3 ratio.General patient information,case data,catheterization data,coagulation indicators,and Autar Thrombosis Risk Assessment Scale scores were analyzed.Univariate and multivariate unconditional logistic regression analyses were performed on relevant factors,and the value of combined indicators in predicting PICC-related thrombosis in hospitalized patients with liver cancer was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed statistically significant differences(P<0.05)in age,sex,Karnofsky performance status score(KPS),bedridden time,activities of daily living impairment,parenteral nutrition,catheter duration,distant metastasis,and bone marrow suppression between the thrombosis group and the non-thrombosis group.Other aspects had no statistically significant differences(P>0.05).Multivariate regression analysis showed that age≥60 years,KPS score≤50 points,parenteral nutrition,stage III to IV,distant metastasis,bone marrow suppression,and activities of daily living impairment were independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer(P<0.05).Catheter duration of 1-6 months and catheter duration>6 months were protective factors for PICC-related thrombosis(P<0.05).The predictive model for PICC-related thrombosis was obtained as follows:P predictive probability=[exp(Logit P)]/[1+exp(Logit P)],where Logit P=age×1.907+KPS score×2.045+parenteral nutrition×9.467+catheter duration×0.506+tumor-node-metastasis(TNM)staging×2.844+distant metastasis×2.065+bone marrow suppression×2.082+activities of daily living impairment×13.926.ROC curve analysis showed an area under the curve(AUC)of 0.827(95%CI:0.724-0.929,P<0.001),with a corresponding optimal cut-off value of 0.612,sensitivity of 0.755,and specificity of 0.857.Calibration curve analysis showed good consistency between the predicted occurrence of PICC-related thrombosis and actual occurrence(P>0.05).ROC analysis showed AUCs of 0.888 and 0.729 for the training and validation sets,respectively.CONCLUSION Age,KPS score,parenteral nutrition,TNM staging,distant metastasis,bone marrow suppression,and activities of daily living impairment are independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer,while catheter duration is a protective factor for the disease.The predictive model has an AUC of 0.827,indicating high predictive accuracy and clinical value.

Lower extremity peripherally inserted central catheter placement ectopic to the ascending lumbar vein:A case report

BACKGROUND Peripherally inserted central catheters(PICCs)are an essential infusion route for oncology patients receiving intravenous treatments,but lower extremity veni-puncture is the preferred technique for patients with superior vena cava syndrome(SVCS).We report the case of a patient with a lower extremity PICC ectopic to the ascending lumbar vein,to indicate and verify PICC catheterisation in the lower extremity is safe and feasible.And hope to provide different per-spectives for clinical PICC venipuncture to get the attention of peers.CASE SUMMARY On 24 August 2022,a 58-year-old male was admitted to our department due to an intermittent cough persisting for over a month,which worsened 10 d prior.Imaging and laboratory investigations suggested the patient with pulmonary malignancy and SVCS.Chemotherapy was not an absolute contraindication in this patient.Lower extremity venipuncture is the preferred technique because administering upper extremity venous transfusion to patients with SVCS can exacerbate oedema in the head,neck,and upper extremities.The patient and his family were informed about the procedure,and informed consent was obtained.After successful puncture and prompt treatment,the patient was discharged,experiencing some relief from symptoms.CONCLUSION Inferior vena cava catheterisation is rare and important for cancer patients with SVCS,particularly in complex situations involving ectopic placement.

Researchers Develop New Tools for Precise Large DNA Insertions

GAO Caixia’s group from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences(CAS)has developed a new genome editing technology that achieves efficient and precise targeted insertion of large DNA segments in plants.The new technology,called prime editing-mediated recombination of opportune targets(PrimeRoot),combines an optimized dual-ePPE editor protein previously published by the group with a highly efficient tyrosine site-specific recombinase,Cre.It can achieve one-step,precise targeted insertion of large DNA segments in rice and maize with an efficiency up to 6%and has been used to successfully insert DNA segments up to 11.1 kb.

Esophageal inserted subclavian catheter:a rare complication

Central venous catheterization(CVC) is an invasive procedure for administering fluids,nutrients,and drugs;monitoring central venous pressure;performing pulmonary artery catheterization;and placing transvenous pacemakers in intensive care units and all specialties,from anesthesia to emergency medicine,for the treatment of trauma and hemodynamically unstable pediatric and adult patients.[1,2]Complications have been observed in more than 15% of patients who underwent CVC.Mechanical,infectious,and thrombotic complications have been reported in 5%–19%,5%–26%,and 2%–26% of patients,respectively.[3] Malposition,on the other hand,is common in subclavian catheter insertion and is usually associated with an initially misplaced guidewire.[4]

A Novel Insertion Solution for the Travelling Salesman Problem

The studypresents theHalfMax InsertionHeuristic (HMIH) as a novel approach to solving theTravelling SalesmanProblem (TSP). The goal is to outperform existing techniques such as the Farthest Insertion Heuristic (FIH) andNearest Neighbour Heuristic (NNH). The paper discusses the limitations of current construction tour heuristics,focusing particularly on the significant margin of error in FIH. It then proposes HMIH as an alternative thatminimizes the increase in tour distance and includes more nodes. HMIH improves tour quality by starting withan initial tour consisting of a ‘minimum’ polygon and iteratively adding nodes using our novel Half Max routine.The paper thoroughly examines and compares HMIH with FIH and NNH via rigorous testing on standard TSPbenchmarks. The results indicate that HMIH consistently delivers superior performance, particularly with respectto tour cost and computational efficiency. HMIH’s tours were sometimes 16% shorter than those generated by FIHand NNH, showcasing its potential and value as a novel benchmark for TSP solutions. The study used statisticalmethods, including Friedman’s Non-parametric Test, to validate the performance of HMIH over FIH and NNH.This guarantees that the identified advantages are statistically significant and consistent in various situations. Thiscomprehensive analysis emphasizes the reliability and efficiency of the heuristic, making a compelling case for itsuse in solving TSP issues. The research shows that, in general, HMIH fared better than FIH in all cases studied,except for a few instances (pr439, eil51, and eil101) where FIH either performed equally or slightly better thanHMIH. HMIH’s efficiency is shown by its improvements in error percentage (δ) and goodness values (g) comparedto FIH and NNH. In the att48 instance, HMIH had an error rate of 6.3%, whereas FIH had 14.6% and NNH had20.9%, indicating that HMIH was closer to the optimal solution. HMIH consistently showed superior performanceacross many benchmarks, with lower percentage error and higher goodness values, suggesting a closer match tothe optimal tour costs. This study substantially contributes to combinatorial optimization by enhancing currentinsertion algorithms and presenting a more efficient solution for the Travelling Salesman Problem. It also createsnew possibilities for progress in heuristic design and optimization methodologies.

Enhancing hydrogen evolution and oxidation kinetics through oxygen insertion into nickel lattice

Nickel-based materials,including metallic Ni and Ni oxide,have been widely studied in the exploration of non-precious-metal hydrogen electrocatalysts,but neither pure Ni nor NiO is ideal for the hydrogen evolution reaction(HER)and hydrogen oxidation reaction(HOR).In this paper,an oxygen insertion strategy was applied on nickel to regulate its hydrogen electrocatalytic performance,and the oxygen-inserted nickel catalyst was successfully obtained with the assistance of tungsten dioxide support(denoted as O-Ni/WO_(2)).The partial insertion of oxygen in Ni maintains the face-centered cubic arrangement of Ni atoms,simultaneously expanding the lattice and increasing the lattice spacing.Consequently,the adsorption strength of^(*)H and^(*)OH on Ni is optimized,thus resulting in superior electrocatalytic performance of0-Ni/WO_(2)in alkaline HER/HOR.The Tafel slope of O-Ni/WO_(2)@NF for HER is 56 mV dec^(-1),and the kinetic current density of O-Ni/WO_(2)for HOR reaches 4.85 mA cm^(-2),which is ahead of most currently reported catalysts.Our proposed strategy of inserting an appropriate amount of anions into the metal lattice could provide more possibilities for the design of high-performance catalysts.

An efficient method for constructing a random insertional mutant library for forward genetics in Nannochloropsis oceanica

Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.

Velamentous Cord Insertion: Interest of Antenatal Diagnosis and Review of the Literature

Velamentous insertion of the umbilical cord corresponds to the insertion of the cord directly on amniotic membranes. It is a rare situation whose frequency varies from 0.5% to 1.69% of single pregnancies. It must be diagnosed during the morphological ultrasound of the 2nd trimester, actively looking for the association with a vasa previa, due to the risk of fetal haemorrhagic threat. We report an antenatal diagnosis of velamentous cord insertion and its management with literature review.

Tubular Heat Enhancement Using Twisted Tape Inserts with Large Holes

Heat augmentation techniques play a vital role in the heating and cooling processes in industries,including solar collectors and many applications that utilize heat exchangers.Several studies are based on inserting fillers inside the tubes to enhance heat transfer.This investigation considered the effects of twisted tapes with large holes on a tubular heat exchanger’s(HX)heat transmission,pressure drop,and thermal boosting factor.In the experimental section,counter-swirl flow generators used twisted tapes with pairs of 1.0 cm-diameter holes and changes in porosity(Rp)at 1.30%and 2.70%.In the experiments,air was utilized as a working fluid in a tube with a circular cross-section.The turbulent flow was considered,with Reynolds numbers(Re)domain from 4800 to 9500,and a boundary condition with a uniform wall heat flux was constructed.The findings expound that when the number of holes rose,the Nusselt number(Nu),the factor of friction(f),and the thermal enhancement factor(η)all increased as well.Additionally,as the friction factor increased,the Nusselt number of the tape-equipped tube was noticeably higher.Additionally,it was discovered that the friction factor was between 70%and 94%lower than the values of the tube without tape,while the(Nu)was between 87%and 97%higher than the conventional tube values.The maximum value ofηis 89%.According to the experimental results,empirical correlations for Nu,f,andηwere also generated.

Treatment of benign rectal stricture caused by repeated anal insertion by endoscopy and balloon dilation:A case report

BACKGROUND Benign rectal strictures can be categorized as primary(disease-related)and secondary(surgical anastomosis-related).Secondary strictures arise from surgical complications,whereas primary strictures have diverse etiologies,including various inflammatory conditions.Benign strictures are usually managed by surgery and endoscopy.We present an unusual etiology of benign rectal stricture caused by the repeated insertion of foreign objects into the rectum for sexual purposes,resulting in rectal injury and subsequent chronic inflammation.CASE SUMMARY A 53-year-old man presented to the outpatient clinic of the Colorectal Surgery Department with symptoms of chronic constipation and bloody stools.The patient previously experienced rectal injury due to foreign object insertion for sexual purposes.Colonoscopy revealed benign circumferential narrowing of the rectum.He underwent treatment by endoscopic argon plasma coagulation and balloon dilation and follow-up as an outpatient for 4 months.A colonoscopy at the end of the follow-up period revealed no evidence of rectal stricture relapse.CONCLUSION A history of rectal injury,followed by chronic inflammation,should be considered in patients with benign rectal strictures.Management with endoscopic argon plasma coagulation and balloon dilation can prevent the need for surgical resection of benign rectal strictures.

Genetic Analysis of a Small Grain Mutant Induced by T-DNA Insertion in Rice

[Objective] The aim of this study is to understand the genetic characteristics of a grain shape mutant and its possible role in genetic improvement of grain yield in rice. [Method] On the basis of the collection of T-DNA tag lines, the progeny of homozygous plants carrying T-DNA insertion were screened for mutants with mutated phenotypes. The genetic analysis of the mutant and test for the linkage between the mutated phenotype and the T-DNA insertion were carried out to determine its genetic characteristics. [Result] In the present study, a grain shape mutant induced by T-DNA insertion in rice was identified, which showed small grain. Genetic analysis of the mutant showed that the two types of phenotype, normal and small grain in the segregating populations derived from the T-DNA heterozygotes, fit the ratio of 3∶1. Test for Basta resistance showed that all the mutants were resistant while the normal plants segregated for resistant and susceptible by the ratio of 2∶1. The results indicated that the mutant phenotype cosegregated with Bar gene. The small grain mutant caused by T-DNA insertion was confirmed by PCR amplification aiming at T-DNA. [Conclusion] The grain shape mutant is useful for isolation of the tagged gene and genetic improvement in rice.

Studies on rice seed quality through analysis of a large- scale T-DNA insertion population

A rice （Oryza sativa） T-DNA insertion population, which included more than 63 000 independent transgenic lines and 8 840 identified flanking sequence tags （FSTs） that were mapped onto the rice genome, was developed to systemi- cally study the rice seed quality control. Genome-wide analysis of the FST distribution showed that T-DNA insertions were positively correlated with expressed genes, but negatively with transposable elements and small RNAs. In addition, the recovered T-DNAs were preferentially located at the untranslated region of the expressed genes. More than 11 000 putative homozygous lines were obtained through multi-generations of planting and resistance screening, and measurement of seed quality of around half of them, including the contents of starch, amylose, protein and fat, with a nondestructive near-infrared spectroscopy method, identified 551 mutants with unique or multiple altered param- eters of seed quality. Analysis of the corresponding FSTs showed that genes participating in diverse functions, including metabolic processes and transcriptional regulation, were involved, indicating that seed quality is regulated by a complex network.

基于重测序鉴定耐盐转基因大豆事件外源T-DNA整合位点及特异性检测

[目的]转基因大豆事件L8014是本研究前期利用农杆菌介导的大豆子叶节高效遗传转化技术体系,将来源于山菠菜的基因BADH导入大豆(Glycine max)‘Williams 82’而获得具有良好耐盐(1.5%NaCl)性状的转基因大豆(该材料已经完成环境释放试验)。T-DNA插入位点侧翼序列的获得与分析对于转基因事件的安全评价及应用非常重要,本文旨在明确该转基因大豆材料的分子特征及其检测方法,以进一步推进安全评价。[方法]利用Southern杂交检测转基因大豆外源基因的拷贝数;基于基因组重测序技术,采用BWA(Burrows-Wheeler-Alignment)方法将重测序数据与T-DNA序列以及大豆基因组序列进行比对分析。[结果]T-DNA在大豆基因组10号染色体上的基因组区间3925017—3926022位点,插入方式为反向插入;结合PCR扩增技术获得外源T-DNA整合位点的左、右边界侧翼序列,基于该序列建立了转BADH基因大豆事件L8014的特异性PCR检测方法。[结论]本研究获得了转基因事件的整合位点及侧翼序列,方法快速、结果可靠,为转基因大豆及其衍生产品的检测提供了技术支撑。

T-DNA transfer and integration as a tool for insertional mutagenesis in the taxol-producing fungus

Agrobacterium tumefaciens-mediated DNA transiormation method was applied to transform Noclulisporium sylviforme fusant HDF-68, a taxol-produeing fungus. We constructed a binary vector pBI121-43 canting a hygromycin-resistant gene cassette between the right and left borders of T-DNA, Optimal co-cultivation of N.sylviforrne with A. tumefaciens containing pBI121-43 led to 110- 130 hygromycin-resistant transformants per＂ million eonidia. Putative transformants were found to be mitotically stable. The molecular analysis of transformants demonstrated the random integration of single copy of the T-DNA into the host genome. This transformation system serves as a basic tool for insertional mutagenesis in N. sylviforme fusant HDF-68, and the development of such svstem lays a solid foundation for constructing high-yied gene engineering strain and clarifying taxol biosynthesis pathway in this fungus.

Regulation of AtbZIP1 Gene Expression by T-DNA Insertion in Arabidopsis thaliana

bZIP transcription factor family is one of the largest groups of the plant transcription factor families and plays an important role in plant growth and adaption to the abiotic stresses. In this study, two AtbZIP1 mutant Arabidopsis （bzipl） were used with T-DNA inserted into two different sites, designated as SALK-556773 and SALK-660942, in order to identify different effects on AtbZIP1 gene expression by different T-DNA insertion sites. PCR and RT-PCR results revealed that T-DNA insertion in CDS region could effectively inhibit AtbZIP1 gene expression, while T-DNA insertion in 3＇-UTR couldn＇t. The phenotype analysis further confirmed the differences and showed that T-DNA insertion in CDS region decreased plants＇ drought resistance, while in 3＇-UTR couldn＇t. The phenotype assays also suggested that AtbZIP1 held pivotal roles in plant response to drought stress.

Isolation of T-DNA flanking plant DNA from T-DNAinsertional embryo-lethal mutants of Arabidopsis thaliana by plasmid rescue technique

Three T-DNA insertional embryonic lethal mutants from NASC (The Nottingham Arabidopsis Stock Center)were first checked with their segregation ratio of abortive and normal seeds and the copy number of T-DNA insertion. The N4081 mutant has a segregation ratio of 1:3.04in average and one T-DNA insertion site according to our assay It was therefore chosen for further analysis. To isolate the joint fragment of T-DNA and plan DNA, the plasmid rescue technique waJs used. pEL-7, one of plasmids from left border of T-DNA, which contained pBR322 was selected from ampicillin plate. The T-DNA fragment of pEL-7 was checked by restriction enzyme analysis and Southern Blot. Restriction analysis confirmed the presence of known sites of EcoRI, PstI and PvuII on it.For confirming the presence of flanking plant DNA in this plasmid, pEL-7 DNA was labeled and hybridized with wild type and mutant plant DNA. The Southern Blot indicated the hybridization band in both of them. Furthermore, the junction of T-DNA/plant DNA was subcloned into bluescript SK+ and sequenced by Applied Biosystem 373A Sequencer. The results showed the 822 bp fragment contained a 274 bp sequence, which is 99.6%homolog (273bp/274 bp) to Ti plasmid pTi 15955 DNA.Ten bp of left 25 bp border repeat were also found in the juction of T-DNA and Plant DNA.Taken together, pEL-7 should contain a joint fragment of T-DNA and flanking plant DNA. This plasmid DNA could be used for the isolation of plant gene, which will be helpful to elucidate the relationship between gene function and plant embryo development.

Identification of T-DNA Inserted Mutant Gene Transcription by Using Real-time PCR in Arabidopsis

AtERF4 （ethylene response factor） is a negative regulator in jasmonic acid mediated signal transduction pathway and ethylene mediated signal transduction pathway of Arabidopsis. It could respond to abscisic acid （ABA） and ethylene stimulus ATSYR1 gene encodes a syntaxin localizing at the plasma membrane in Arabidopsis, which can be induced by abiotic stress. To identify mutation lines for gene functional analysis, real-time PCR was employed to detect the expression level of AtERF4 and ATSYR1 in homozygous T-DNA insertion mutant line, respectively. Real-time PCR is a powerful tool which can be used to detect steady-state mRNA levels specifically, sensitively and reproducibly. Comparing to other forms of quantitative RT-PCR, the amount of amplified products can be detected by real-time PCR instantly and thus is a preferable alternative. In this study, RNA with T-DNA inserting into exon could be detected in AtERF4 knock-out mutation line. The results indicated that AtERF4 had been trucked in transcription level. On the other hand, T-DNA inserting into the promoter of gene ATSYR1 had no effect on reducing the expression level ofATSYR1 gene. Further molecular and phenotype studies now are ongoing to clarify the potential consequences of AtERF4 and ATSYR1 deficiency in Arabidopsis

Relationships between distribution characteristics of ceramic fragments and anti-penetration performance of ceramic composite bulletproof insert plates

Through quantitative statistics and morphological characterization of ceramic fragments for ceramic composite bulletproof insert plates(CCBIPs),distribution characteristics of ceramic fragments within a specific size range were analyzed for different Armor Piercing Incendiary(API)and shot times.To quantitatively evaluate the effect of energy absorption for ceramic plates,a model of energy absorption during penetration for CCBIPs was established based on statistics of the size distribution of ceramic fragments(SDCF).Variation in the SDCF and its influence on energy absorption for CCBIPs were investigated.The results indicate that the distribution feature of ceramic fragments in the range of 0.25-2.25 mm is Gaussian distribution.Compared with Type 56 of API(56-API),ceramic fragments formed by 53-API with higher kinetic energy possess more quantity and more concentrated distribution,whose average equivalence size decreases by 6.5%,corresponding to increasing by 83.9%of estimated energy absorption.Besides,the ability of CCBIPs to resist the third shot is significantly weakened,whose estimated energy absorption decreases by 58.8%compared with the first shot.More concentrated distribution and fewer fragments are formed after the third shot,the average equivalence size of ceramic fragments increases by 6.9%,which may attribute to the micro-cracks induced by the previous two shots.

Health Monitoring of Milling Tool Inserts Using CNN Architectures Trained by Vibration Spectrograms

In-process damage to a cutting tool degrades the surface􀀀nish of the job shaped by machining and causes a signi􀀀cant􀀀nancial loss.This stimulates the need for Tool Condition Monitoring(TCM)to assist detection of failure before it extends to the worse phase.Machine Learning(ML)based TCM has been extensively explored in the last decade.However,most of the research is now directed toward Deep Learning(DL).The“Deep”formulation,hierarchical compositionality,distributed representation and end-to-end learning of Neural Nets need to be explored to create a generalized TCM framework to perform eciently in a high-noise environment of cross-domain machining.With this motivation,the design of dierent CNN(Convolutional Neural Network)architectures such as AlexNet,ResNet-50,LeNet-5,and VGG-16 is presented in this paper.Real-time spindle vibrations corresponding to healthy and various faulty con􀀀gurations of milling cutter were acquired.This data was transformed into the time-frequency domain and further processed by proposed architectures in graphical form,i.e.,spectrogram.The model is trained,tested,and validated considering dierent datasets and showcased promising results.