Feasibility of an artificial intelligence system for tumor response evaluation.

PURPOSE: The objective of this study was to evaluate the feasibility of using Artificial Intelligence (AI) to measure the long-diameter of tumors for evaluating treatment response. METHODS: Our study included 48 patients with lung-specific target lesions and conducted 277 measurements. The radiologists recorded the long-diameter in axial imaging plane of the target lesions for each measurement. Meanwhile, AI software was utilized to measure the long-diameter in both the axial imaging plane and in three dimensions (3D). Statistical analyses including the Bland-Altman plot, Spearman correlation analysis, and paired t-test to ascertain the accuracy and reliability of our findings. RESULTS: The Bland-Altman plot showed that the AI measurements had a bias of -0.28 mm and had limits of agreement ranging from - 13.78 to 13.22 mm (P = 0.497), indicating agreement with the manual measurements. However, there was no agreement between the 3D measurements and the manual measurements, with P < 0.001. The paired t-test revealed no statistically significant difference between the manual measurements and AI measurements (P = 0.497), whereas a statistically significant difference was observed between the manual measurements and 3D measurements (P < 0.001). CONCLUSIONS: The application of AI in measuring the long-diameter of tumors had significantly improved efficiency and reduced the incidence of subjective measurement errors. This advancement facilitated more convenient and accurate tumor response evaluation.

A base-mediated aerobic oxidative synthesis of cyclopent-2-enol derivatives from doubly activated cyclopropanes and substituted acetonitriles.

We report here that polysubstituted cyclopent-2-enols can be constructed by the one-pot reaction of doubly activated cyclopropanes and α-EWG substituted acetonitriles under mild basic conditions via a domino-ring-opening-cyclization/deacylation/oxidation sequence. Moreover, the synthetic applications of these cyclopent-2-enols have been demonstrated in the late-stage derivatization into functionalized cyclopentapyrimidin-4-ones and 2-hydroxy cyclopentanones with good yields.

Novel synthesis of fused spiro piperidone-cyclopropanes from cyclopropyl amides and electron-deficient alkenes.

We report here that a series of bridged O,O-ketal fused spiro piperidone-cyclopropane derivatives 3 can be constructed with excellent yields and good diastereoselectivity by the one-pot reaction of 1-acylcyclopropanecarboxamides 1 with electron-deficient alkene 2a (EWG = CHO) via the domino process involving [4 + 2] annulation/intermolecular electrophilic addition/intramolecular cyclization. Furthermore, reactions of 1 with 2b/2c (EWG = CN, COOMe), leading to spiro piperidone-cyclopropane derivatives 4 or 5 by base catalyst selection, were also presented.

Neuronal Modulators from the Coral-Associated Fungi Aspergillus candidus.

Three new p-terphenyl derivatives, named 4″-O-methyl-prenylterphenyllin B (1) and phenylcandilide A and B (17 and 18), and three new indole-diterpene alkaloids, asperindoles E-G (22-24), were isolated together with eighteen known analogues from the fungi Aspergillus candidus associated with the South China Sea gorgonian Junceela fragillis. The structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic analysis, and DFT/NMR and TDDFT/ECD calculations. In a primary cultured cortical neuronal network, the compounds 6, 9, 14, 17, 18 and 24 modulated spontaneous Ca2+ oscillations and 4-aminopyridine hyperexcited neuronal activity. A preliminary structure-activity relationship was discussed.

Genetic Mapping and Nucleotide Diversity of Two Powdery Mildew Resistance Loci in Melon (Cucumis melo).

Powdery mildew (PM) significantly and negatively affects the yield and quality of melon (Cucumis melo) worldwide. Race 2F is the predominant physiological race of the pathogen Podosphaera xanthii in many regions. We used accessions PMR 6 (P1; resistant to PM) and M1-7 (P2; susceptible to PM) to analyze the inheritance of resistance to PM (race 2F). The ratio between resistant and susceptible individuals fits a Mendelian segregation ratio of 13:3 in a total of 256 F2 individuals and 1:1 in BC1P2. The resistance to PM in PMR 6 was governed by two genes: a dominant (AA) gene with an epistatic effect and a recessive gene (bb). Only individuals with aaBB or aaBb genotypes were susceptible to PM. Two PM resistance loci, Pm2.1 and pm12.1, were mapped on chromosomes 2 and 12 by bulked segregant analysis and secondary mapping by quantitative trait loci analysis with 18 markers. A new marker-assisted selection system to identify melon genotypes resistant or susceptible to PM was developed and tested in 93 melon accessions. Nucleotide diversity (π) and fixation index (Fst) for the two PM resistance loci were estimated using resequencing data of 336 melons from three groups: C. melo subsp. agrestis, Cucumis melo subsp. melo, and the intermediate type. The lowest π was observed in C. melo ssp. agrestis, and the highest Fst value was between C. melo ssp. agrestis and C. melo ssp. melo. The findings provide a promising tool that can be used to accelerate breeding for durable resistance to PM.

[Study on lipid-lowering mechanism of active peptide DP17 from Eupolyphaga steleophaga in hyperlipidemia rats].

The aim of this paper was to investigate the mechanism of the active peptide DP17 of Eupolyphaga steleophaga in the treatment of hyperlipidemia rats. HPLC and MADIL-TOF/TOF-MS were used for the amino acid sequence analysis and solid-phase synthesis on the active peptide of E. steleophaga which were obtained by biomimetic enzymatic hydrolysis, separation and purification. The hyperlipidemia model was established by feeding with high-fat diet.Twenty days later, the rats in the blank group and the model group were given the saline and the rats in remaining groups were given the corresponding drugs by oral administration. After administration for 4 weeks, the levels of triglyceride(TG), total cholesterol(TC) and low density lipoprotein(LDL) in serum, the levels of TG, TC, adenosine monophosphate(AMP), adenosine triphosphate(ATP) in liver tissues and TG in feces were detected, respectively. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of liver tissues. The Real-time fluorescence quantitative PCR method was used to detect the expression of acetyl coa carboxylase(ACC) and hydroxymethylglutaryl-coa reductase(HMGCR) mRNA in liver tissues. The expression of mammalian target of rapamycin(mTORC1) protein and adenosine 5'-monophosphate-activated protein kinase(AMPK) in liver tissues were detected by Western blot. The analysis showed that the amino acid sequence of active peptide from E. steleophaga was DAVPGAGPAGCHPGAGP(DP17). The results of pharmacological experiments showed that after oral administration of DP17 in rats, the levels of TG, TC and LDL in serum as well as TG and TC levels in liver tissues were significantly decreased(P<0.05), while the levels of AMP, ATP in liver tissues and TG content in feces were significantly increased(P<0.05); the liver steatosis of rats was significantly relieved; the expression of ACC, HMGCR mRNA and mTORC1 protein in liver tissues were significantly reduced, while the expression of AMPK phosphorylated protein was significantly increased(P<0.05). DP17, the active peptide of E. steleophag can significantly reduce lipid accumulation in liver tissues, and it may play a role in reducing blood lipids by regulating the energy metabolism balance in the body and activating AMPK/mTOR signaling pathway.

An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL/COMPASS-like complexes.

PIWI-interacting RNA (piRNA) silences the transposons in germlines or induces epigenetic modifications in the invertebrates. However, its function in the mammalian somatic cells remains unknown. Here we demonstrate that a piRNA derived from Growth Arrest Specific 5, a tumor-suppressive long non-coding RNA, potently upregulates the transcription of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a proapoptotic protein, by inducing H3K4 methylation/H3K27 demethylation. Interestingly, the PIWIL1/4 proteins, which bind with this piRNA, directly interact with WDR5, resulting in a site-specific recruitment of the hCOMPASS-like complexes containing at least MLL3 and UTX (KDM6A). We have indicated a novel pathway for piRNAs to specially activate gene expression. Given that MLL3 or UTX are frequently mutated in various tumors, the piRNA/MLL3/UTX complex mediates the induction of TRAIL, and consequently leads to the inhibition of tumor growth.

Identification of MGMT promoter methylation sites correlating with gene expression and IDH1 mutation in gliomas.

O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation was reported to be an independent prognostic and predictive factor in glioma patients who received temozolomide treatment. However, the predictive value of MGMT methylation was recently questioned by several large clinical studies. The purpose of this study is to identify MGMT gene promoter CpG sites or region whose methylation were closely correlated with its gene expression to elucidate this contradictory clinical observations. The methylation status for all CpG dinucleotides in MGMT promoter and first exon region were determined in 42 Chinese glioma patients, which were then correlated with MGMT gene expression, IDH1 mutation, and tumor grade. In whole 87 CpG dinucleotides analyzed, three distinct CpG regions covering 28 CpG dinucleotides were significantly correlated with MGMT gene expression; 10 CpG dinucleotides were significantly correlated with glioma classification (p < 0.05). Isocitrate dehydrogenase 1 (IDH1) mutation and MGMT gene hypermethylation significantly co-existed, but not for MGMT gene expression. The validation cohort of gliomas treated with standard of care and comparison of the CpGs we identified with the current CpGs used in clinical setting will be very important for gliomas individual medicine in the future.

The allele frequency of CYP2A6*4 in four ethnic groups of China.

The CYP2A6*4 allele, characterized as the whole deletion of this gene, is closely associated with nicotine dependence, cancer susceptibility, and drug responsiveness. The frequency of this molecular variant differs across populations. Although genetic polymorphisms of CYP2A6*4 and its functional results have been reported in Chinese Han population, the allele frequency of CYP2A6*4 was largely unknown in other Chinese ethnic population. In this study, we investigated the allele frequency of CYP2A6*4 in four main ethnic groups of China based on our newly developed quantitative real-time PCR assay. The frequencies of the CYP2A6*4 allele were 7.9%, 15%, 0% and 2% in Han (N=120), Uighur (N=100), Bouyei (N=100) and Tibetan (N=100) (P<0.0001), respectively. This work greatly expanded our understanding of the distribution of CYP2A6*4 in Chinese population and provided more information of different ethnic population's smoking behavior and also in disease susceptibility and drug response.

Genetic alterations of PIK3CA and tumor response in patients with locally advanced cervical squamous cell carcinoma treated with cisplatin-based concurrent chemoradiotherapy.

OBJECTIVE: The objective of this study was to investigate the predictive value of common genetic alterations of PI3K/AKT/mTOR and Ras/Raf/MAPK pathways in patients with locally advanced cervical squamous cell carcinoma (LACSCC) treated with cisplatin-based concurrent chemoradiotherapy (CCRT). METHODS: Patients with LACSCC, treated at a single institution with CCRT were eligible for this retrospective study. A total of sixty pre-treatment tumor biopsies were retrieved. Somatic mutations were detected by pyrosequencing and CNV was determined by quantitative realtime PCR. The association of genetic alterations with clinicopathological characteristics and treatment response were analyzed. RESULTS: Patients without genetic alterations (mutations or amplification) of PIK3CA had a significantly higher response rate than patients with these alterations (p=0.006). In the logistic regression analysis, PIK3CA genetic alterations retained an independent factor in predicting response to CCRT. CONCLUSIONS: Somatic mutations and copy number amplification of PIK3CA were associated with response to CCRT in patients with cervical squamous cell carcinoma.

A multiplex allele-specific real-time PCR assay for screening of ESR1 mutations in metastatic breast cancer.

BACKGROUND: Acquired resistance to endocrine-based therapies occurs in virtually all estrogen receptor-α (ERα, encoded by ESR1) positive breast cancer patients. The underlying molecular mechanism is attributed to the activating mutations in ESR1. These mutations provide an exciting opportunity for the development of new antagonists that specifically inhibit the mutant proteins. Therefore, accurate detection of ESR1 mutations is of critical importance in clinical practice. MATERIALS AND METHODS: We carried out a single tube, multiplex allele-specific real-time PCR assay for the detection of four ESR1 mutations (Y537S, Y537C, Y537N, and D538G). RESULTS: The assay was found to be highly specific and sensitive. With this assay, as low as 1% mutant DNA template in wild type DNA could be detected. Fifteen DNA samples were prepared from archived formalin-fixed paraffin-embedded metastatic breast cancer biopsies. They were further screened with this assay, and three samples were identified as ESR1 mutant. The results were validated with pyrosequencing and complete concordance was observed between the two assays. CONCLUSION: The multiplex allele-specific real-time PCR assay provides a rapid and reliable diagnostic tool for accurate detection of ESR1 mutations. This procedure may be used in the clinical treatment of breast cancer.

[Study on the Supercontinuum Generation with Femtosecond Pulse in Photonic Crystal Fiber].

Physical mechanism of supercontinuum generation in photonic crystal fiber by femtosecond laser pulse has been investigated experimentally. In this study, we used the tunable output wavelength Ti: sapphire optical parametric amplifier as the pump source and the fiber spectrometer acquired the spectrogram of supercontinuum generation in photonic crystal fiber under different power and wavelength conditions, then we normalized the spectrograms and make a comparison of them. PCF supercontinuum differences affected by physical mechanisms were analyzed. We found that when increasing the incident pump pulse power, the spectral width will be gradually widened, there are more peaks, part of the energy will transfer in to the short-wave- length region; as long as it reaches a certain intensity, width of supercontinuum finally saturated, the shape of supercontinuum was also stabilized. As the incident power was settled at 300 milliwatt and the length of PCF was settled at 105 millimeter, experimental results show that width and shape of supercontinuum are affected by the wavelength of pump pulse, in the range of 760 to 840 nm, there appears more and more peaks with the increase of incident wavelength; at anomalous dispersion the spectrogram of supercontinuum generation will be more flat and more wider as the wavelength of pump pulse closer to zero point.

Differential regulation of myosin X movements by its cargos, DCC and neogenin.

Myosin X (Myo X), also known as MYO10, is an unconventional actin-based motor protein that plays an important role in filopodium formation. Its intra-filopodia movement, an event tightly associated with the function of Myo X, has been extensively studied. However, how the motor activity of Myo X and the direction of its movements are regulated remains largely unknown. In our previous study, we demonstrated that DCC (for 'deleted in colorectal carcinoma') and neogenin (neogenin 1, NEO1 or NGN), a family of immunoglobin-domain-containing transmembrane receptors for netrins, interact with Myo X and that DCC is a cargo of Myo X to be delivered to the neurites of cultured neurons. Here, we provide evidence for DCC and neogenin as regulators of Myo X. DCC promotes movement of Myo X along basal actin filaments and enhances Myo-X-mediated basal filopodium elongation. By contrast, neogenin appears to suppress Myo X movement on the basal side, but increases its movement towards the apical and dorsal side of a cell, promoting dorsal filopodium formation and growth. Further studies have demonstrated that DCC, but not neogenin, enhances integrin-mediated tyrosine phosphorylation of focal adhesion kinase and basal F-actin reorganization, providing a cellular mechanism underlying their distinct effects on Myo X. These results thus demonstrate differential regulatory roles on Myo X activity by its cargo proteins, DCC and neogenin, revealing different cellular functions of DCC and neogenin.

Myosin X regulates netrin receptors and functions in axonal path-finding.

Netrins regulate axon path-finding during development, but the underlying mechanisms are not well understood. Here, we provide evidence for the involvement of the unconventional myosin X (Myo X) in netrin-1 function. We find that Myo X interacts with the netrin receptor deleted in colorectal cancer (DCC) and neogenin, a DCC-related protein. Expression of Myo X redistributes DCC to the cell periphery or to the tips of neurites, whereas its silencing prevents DCC distribution in neurites. Moreover, expression of DCC, but not neogenin, stimulates Myo X-mediated formation and elongation of filopodia, suggesting that Myo X function may be differentially regulated by DCC and neogenin. The involvement of Myo X in netrin-1 function was further supported by the effects of inhibiting Myo X function in neurons. Cortical explants derived from mouse embryos expressing a motor-less Myo X exhibit reduced neurite outgrowth in response to netrin-1 and chick commissural neurons expressing the motor-less Myo X, or in which Myo X is silenced using microRNA (miRNA), show impaired axon projection in vivo. Taken together, these results identify a novel role for Myo X in regulating netrin-1 function.

Single tube genotyping of CYP2A6 gene deletion based on copy number determination by quantitative real-time PCR.

The CYP2A6*4 allele, characterized as the whole deletion of this gene, is closely associated with nicotine dependence, cancer susceptibility, and drug responsiveness. It has long been a significant challenge for pharmacogenetics scientists to develop a reliable method to detect this molecular variant due to its high homology with its homologous genes CYP2A6 and CYP2A3 in the clinical setting. Here, we introduce a quantitative real-time PCR assay that specifically amplifies CYP2A6 by designing a specific set of primers and the probe, which effectively prevent the amplification of the CYP2A7 and CYP2A13 alleles. CYP2A6 gene copy numbers were normalized to albumin (ALB) which was co-amplified simultaneously in a single-tube duplex reaction and at a setting as the internal reference gene. The established assay was validated with a selection of previously genotyped DNA samples, which harbored none, one or two CYP2A6 gene copies. The results were in complete concordance with previously published data and no overlap between the three groups was observed. Further analysis of a cohort of 120 samples revealed high specificity and sensitivity of this assay as demonstrated by the agreement of determined gene copy numbers in all of the cases. In conclusion, this novel assay allows reliable and sensitive detection of the CYP2A6 gene deletion, which will be useful for pharmacogenetics studies and routine clinical settings.

Single tube genotyping of TYMS 1494del6 polymorphism in the Chinese Han population by duplex scorpion primers.

BACKGROUND: The development of pharmacogenomics has created an urgent need for robust molecular characterization. And it has become a challenge to develop suitable detecting methods for routine clinical use. AIM: The aim of the current study is to develop a simple and reliable TYMS 1494del6 polymorphism genotyping assay by duplex scorpion primers in the Chinese Han population. METHOD: We evaluated the performance of the duplex scorpion primer assay in the genotyping of TYMS 1494del6 polymorphism and screened 54 DNA samples of the Chinese Han population. The results were further validated by pyrosequencing. RESULTS: The duplex scorpion primer assay showed high specificity and accuracy for genotyping TYMS 1494del6 polymorphism. Complete concordance was observed between the duplex scorpion primer assay and pyrosequencing. The frequency of the TYMS +6 bp allele was 34% and the -6 bp allele was 66% in 54 Chinese Han population DNA samples. CONCLUSION: The duplex scorpion primer assay provides a rapid, reliable and high-throughput method to genotype TYMS 1494del6 polymorphism in the Chinese Han population.

Markov Progressive Framework, a Universal Paradigm for Modeling Long Videos.

Compared to images, video, as an increasingly mainstream visual media, contains more semantic information. For this reason, the computational complexity of video models is an order of magnitude larger than their image-level counterparts, which increases linearly with the square number of frames. Constrained by computational resources, training video models to learn long-term temporal semantics end-to-end is quite a challenge. Currently, the main-stream method is to split a raw video into clips, leading to incomplete fragmentary temporal information flow and failure of modeling long-term semantics. To solve this problem, in this paper, we design the Markov Progressive framework (MaPro), a theoretical framework consisting of the progressive modeling method and a paradigm model tailored for it. Inspired by natural language processing techniques dealing with long sentences, the core idea of MaPro is to find a paradigm model consisting of proposed Markov operators which can be trained in multiple sequential steps and ensure that the multi-step progressive modeling is equivalent to the conventional end-to-end modeling. By training the paradigm model under the progressive method, we are able to model long videos end-to-end with limited resources and ensure the effective transmission of long-term temporal information. We provide detailed implementations of this theoretical system on the mainstream CNN- and Transformer-based models, where they are modified to conform to the Markov paradigm. The theoretical paradigm as a basic model is the lower bound of the model efficiency. With it, we further explore more sophisticated designs for CNN and Transformer-based methods specifically. As a general and robust training method, we experimentally demonstrate that it yields significant performance improvements on different backbones and datasets. As an illustrative example, the proposed method improves the SlowOnly network by 4.1 mAP on Charades and 2.5 top-1 accuracy on Kinetics. And for TimeSformer, MaPro improves its performance on Kinetics by 2.0 top-1 accuracy. Importantly, all these improvements are achieved with a little parameter and computation overhead. We hope the MaPro method can provide the community with new insight into modeling long videos.

Research and experimental verification of lightweight loader rims.

The safety performance and structural stiffness of a rim, which is the main load-bearing structure of the loader during operation, influence the overall performance, stability, and braking capabilities of the machine. In the industry, researchers are currently pursuing lightweight and high-strength rims as a primary objective. A low weight not only enhances machinery fuel efficiency but also aligns with societal demands for sustainable development, energy conservation, and emission reduction. In this article, multiobjective optimization analysis on rims composed of three different materials is performed, and the relationships between various optimization parameters and target parameters are established using the results of response surface construction. Multiobjective genetic algorithms are utilized to derive various optimization plans, which are subsequently evaluated through static analysis, fatigue analysis, and weight loss analysis. The final optimization plan is determined based on the calculation results while considering production costs. Field tests are conducted on the optimized rims under various working conditions to verify the test results, evaluate the reliability of the finite element analysis results, and confirm the safety of the optimized rim.

Dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology.

Background: Alzheimer's disease (AD) is an age-related neurodegenerative disorder with no effective interventions for curing or modifying its progression. However, emerging research suggests that vitamin A in the diet may play a role in both the prevention and treatment of AD, although the exact mechanisms are not fully understood. Objectives: This study aims to investigate the dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology shedding light on its potential as a dietary intervention for AD prevention and treatment. Methods: The APP/PS1-AD mouse model was employed and divided into three dietary groups: vitamin A-deficient (VAD), normal vitamin A (VAN), and vitamin A-supplemented (VAS) for a 12-week study. Neurobehavioral functions were assessed using the Morris Water Maze Test (MWM). Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of Diamine Oxidase (DAO), D-lactate, IL-6, IL-1ß, and TNF-a cytokines. Serum vitamin A levels were analyzed via LC-MS/MS analysis. Immunohistochemical analysis and morphometry were performed to evaluate the deposition of Aß in brain tissue. The gut microbiota of APP/PS1 mice was analyzed using 16S rRNA sequencing analysis. Additionally, transcriptomic analysis was conducted on intestinal tissue from APP/PS1 mice. Results: No significant changes in food intake and body weight were observed among the groups. However, the VAD and VAS groups showed reduced food intake compared to the VAN group at various time points. In terms of cognitive function, the VAN group performed better in the Morris Water Maze Test, indicating superior learning and memory abilities. The VAD and VAS groups exhibited impaired performance, with the VAS group performing relatively better than the VAD group. Serum vitamin A concentrations differed significantly among the groups, with the VAS group having the highest concentration. Aß levels were significantly higher in the VAD group compared to both the VAN and VAS groups. Microbial analysis revealed that the VAS and VAN groups had higher microbial diversity than the VAD group, with specific taxa characterizing each group. The VAN group was characterized by taxa such as Actinohacteriota and Desulfovibrionaceae, while the VAD group was characterized by Parabacteroides and Tannerellaceae. The VAS group showed similarities with both VAN and VAD groups, with taxa like Desulfobacterota and Desulfovibrionaceae being present. The VAD vs. VAS, VAD vs. VAN, and VAS vs. VAN comparisons identified 571, 313, and 243 differentially expressed genes, respectively, which associated with cellular and metabolic processes, and pathway analysis revealed enrichment in pathways related to chemical carcinogenesis, drug metabolism, glutathione metabolism, and immune-related processes. The VAD group exhibited higher levels of D-lactate, diamine oxidase, and inflammatory cytokines (TNF-a, IL-1ß, IL-6) compared to the VAN and VAS groups. Conclusion: Dietary vitamin A supplementation modulates the gut microbiota, intestinal permeability, inflammatory factors, and Aß protein formation, offering insights into the pathogenesis of AD and potential therapeutic avenues for further exploration. This research highlights the intricate interplay between diet, gut microbiota, and neurodegenerative processes, emphasizing the importance of dietary interventions in managing AD-related pathologies.

Two-Dimensional MoS2-Based Anisotropic Synaptic Transistor for Neuromorphic Computing by Localized Electron Beam Irradiation.

Neuromorphic computing, a promising solution to the von Neumann bottleneck, is paving the way for the development of next-generation computing and sensing systems. Axon-multisynapse systems enable the execution of sophisticated tasks, making them not only desirable but essential for future applications in this field. Anisotropic materials, which have different properties in different directions, are being used to create artificial synapses that can mimic the functions of biological axon-multisynapse systems. However, the restricted variety and unadjustable conductive ratio limit their applications. Here, it is shown that anisotropic artificial synapses can be achieved on isotropic materials with externally localized doping via electron beam irradiation (EBI) and purposefully induced trap sites. By employing the synapses along different directions, artificial neural networks (ANNs) are constructed to accomplish variable neuromorphic tasks with optimized performance. The localized doping method expands the axon-multisynapse device family, illustrating that this approach has tremendous potentials in next-generation computing and sensing systems.