Effects of CYP3A5*3 genetic polymorphisms on the pharmacokinetics of perampanel in Chinese pediatric patients with epilepsy.

PURPOSE: This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. RESULTS: The plasma concentration showed a linear correlation with the daily dose taken ( r  = 0.17; P  < 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5 ±â€…297.1 vs. 633.8 ±â€…305.5 µg/ml; P  = 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2 ±â€…1.7 vs. 3.8 ±â€…2.0; P  = 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8 ±â€…293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1 ±â€…165.6 ng/ml and 260.0 ±â€…36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8 ±â€…285.6 vs. 433.0 ±â€…227.2 ng/ml; P  = 0.042). CONCLUSION: The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.

Cyclic cryotherapy with vitamin D facilitates early rehabilitation after total knee arthroplasty.

Objective: This study aimed to evaluate the efficacy of cyclic cryotherapy and vitamin D administration on early rehabilitation after total knee arthroplasty (TKA), as its efficacy remains unclear. Methods: We divided 150 patients (three groups) who underwent TKA into those treated with or without cyclic cryotherapy and vitamin D. Results: Compared with patients who did not receive cyclic cryotherapy, those who received postoperative cyclic cryotherapy and vitamin D supplementation had significantly higher American Knee Society Scores (AKSS) on postoperative day (POD) 7 and at 1 month postoperatively; higher visual analogue scale (VAS) values on POD1-3 and POD7; reduced thigh swelling on POD3 and POD7; increased range of motion (ROM) on POD3, POD7, and at 1 month postoperatively; and reduced postoperative length of stay (PLOS). However, no significant difference in patient satisfaction was observed between the patient groups. At 1 and 3 months postoperatively, patients administered cyclic cryotherapy and vitamin D had significantly higher AKSS, ROM, and vitamin D levels than those who did not receive vitamin D. No perioperative complications such as surgical site infection, skin frostbite, or vitamin D intoxication were observed. Conclusion: Cyclic cryotherapy post-TKA had short-term advantages in terms of AKSS, VAS, thigh swelling, ROM, PLOS, and accelerated rehabilitation, but did not improve patient satisfaction. Cyclic cryotherapy combined with vitamin D improved AKSS and ROM at 1 and 3 months postoperatively.

Deep brain stimulation for pediatric pantothenate kinase-associated neurodegeneration with status dystonicus: A case report and literature review.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is a type of inherited metabolic disorder caused by mutation in the PANK2 gene. The metabolic disorder mainly affects the basal ganglia region and eventually manifests as dystonia. For patients of dystonia, their dystonic symptom may progress to life-threatening emergency--status dystonicus. OBJECTIVE: We described a case of a child with PKAN who had developed status dystonicus and was successfully treated with deep brain stimulation (DBS). Based on this rare condition, we analysed the clinical features of PKAN with status dystonicus and reviewed the reasonable management process of this condition. CONCLUSION: This case confirmed the rationality of choosing DBS for the treatment of status dystonicus. Meanwhile, we found that children with classic PKAN have a cluster of risk factors for developing status dystonicus. Once children diagnosed with similar neurodegenerative diseases are under status dystonicus, DBS can be active considered because it has showed high control rate of this emergent condition.

Flexible nanoimprint lithography enables high-throughput manufacturing of bioinspired microstructures on warped substrates for efficient III-nitride optoelectronic devices.

III-nitride materials are of great importance in the development of modern optoelectronics, but they have been limited over years by low light utilization rate and high dislocation densities in heteroepitaxial films grown on foreign substrate with limited refractive index contrast and large lattice mismatches. Here, we demonstrate a paradigm of high-throughput manufacturing bioinspired microstructures on warped substrates by flexible nanoimprint lithography for promoting the light extraction capability. We design a flexible nanoimprinting mold of copolymer and a two-step etching process that enable high-efficiency fabrication of nanoimprinted compound-eye-like Al2O3 microstructure (NCAM) and nanoimprinted compound-eye-like SiO2 microstructure (NCSM) template, achieving a 6.4-fold increase in throughput and 25% savings in economic costs over stepper projection lithography. Compared to NCAM template, we find that the NCSM template can not only improve the light extraction capability, but also modulate the morphology of AlN nucleation layer and reduce the formation of misoriented GaN grains on the inclined sidewall of microstructures, which suppresses the dislocations generated during coalescence, resulting in 40% reduction in dislocation density. This study provides a low-cost, high-quality, and high-throughput solution for manufacturing microstructures on warped surfaces of III-nitride optoelectronic devices.

[Bupleuri Radix-Paeoniae Radix Alba medicated plasma exerts effects on HepG2 hepatoma cells by regulating miR-1297/PTEN signaling axis].

The present study aimed to investigate the effect and mechanism of Bupleuri Radix-Paeoniae Radix Alba medicated plasma on HepG2 hepatoma cells by regulating the microRNA-1297(miR-1297)/phosphatase and tensin homologue deleted on chromosome 10(PTEN) signaling axis. Real-time quantitative PCR(RT-qPCR) was carried out to determine the mRNA levels of miR-1297 and PTEN in different hepatoma cell lines. The dual luciferase reporter assay was employed to verify the targeted interaction between miR-1297 and PTEN. The cell counting kit-8(CCK-8) was used to detect cell proliferation, and the optimal concentration and intervention time of the medicated plasma were determined. The cell invasion and migration were examined by Transwell assay and wound healing assay. Cell cycle distribution was detected by PI staining, and the apoptosis of cells was detected by Annexin V-FITC/PI double staining. The mRNA levels of miR-1297, PTEN, protein kinase B(Akt), and phosphatidylinositol 3-kinase(PI3K) were determined by RT-qPCR. Western blot was employed to determine the protein levels of PTEN, Akt, p-Akt, caspase-3, caspase-9, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). The results showed that HepG2 cells were the best cell line for subsequent experiments. The dual luciferase reporter assay confirmed that miR-1297 could bind to the 3'-untranslated region(3'UTR) in the mRNA of PTEN. The medicated plasma inhibited the proliferation of HepG2 cells, and the optimal intervention concentration and time were 20% and 72 h. Compared with the blank plasma, the Bupleuri Radix-Paeoniae Radix Alba medicated plasma, miR-1297 inhibitor, miR-1297 inhibitor + medicated plasma all inhibited the proliferation, invasion, and migration of HepG2 cells, increased the proportion of cells in the G_0/G_1 phase, decreased the proportion of cells in the S phase, and increased the apoptosis rate. The medicated plasma down-regulated the mRNA levels of miR-1297, PI3K, and Akt and up-regulated the mRNA level of PTEN. In addition, it up-regulated the protein levels of PTEN, Bax, caspase-3, and caspsae-9 and down-regulated the protein levels of p-Akt, p-PI3K, and Bcl-2. In conclusion, Bupleuri Radix-Paeoniae Radix Alba medicated plasma can inhibit the expression of miR-1297 in HepG2 hepatoma cells, promote the expression of PTEN, and negatively regulate PI3K/Akt signaling pathway, thereby inhibiting the proliferation and inducing the apoptosis of HepG2 cells.

PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous tumor lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It has higher aggressiveness and metastasis than other subtypes, with limited effective therapeutic strategies, leading to a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target. This review summarizes the PI3K/AKT/mTOR signaling pathway activation mechanism in TNBC and discusses the relationship between its activation and various TNBC subtypes. We also report the latest clinical studies on kinase inhibitors related to this pathway for treating TNBC. Our review discusses the issues that need to be addressed in the clinical application of these inhibitors.

Pylorus-preserving gastrectomy for early gastric cancer.

Pylorus-preserving gastrectomy (PPG) has been widely accepted as a function-preserving gastrectomy for middle-third early gastric cancer (EGC) with a distal tumor border at least 4 cm proximal to the pylorus. The procedure essentially preserves the function of the pyloric sphincter, which requires to preserve the upper third of the stomach and a pyloric cuff at least 2.5 cm. The suprapyloric and infrapyloric vessels are usually preserved, as are the hepatic and pyloric branches of the vagus nerve. Compared with distal gastrectomy, PPG has significant advantages in preventing dumping syndrome, body weight loss and bile reflux gastritis. The postoperative complications after PPG have reached an acceptable level. PPG can be considered a safe, effective, and superior choice in EGC, and is expected to be extensively performed in the future.

Fully digital workflow of occlusal reconstruction treatment in a patient with congenital dentition defects.

OBJECTIVE: Occlusal reconstruction is a critical intervention for patients with dental hard tissue defects, temporomandibular joint (TMJ) disorders, and jaw position abnormalities. Clinical efficiency and outcomes of these procedures have improved with advances in digital technologies. This case report aims to illustrate a comprehensive digital workflow for occlusal reconstruction in a patient with congenital dentition defects, emphasizing the application of digital technologies to enhance treatment outcomes. CLINICAL CONSIDERATIONS: A 28-year-old woman with previously installed porcelain-fused-to-metal bridge restorations presented with a fractured prosthesis and TMJ symptoms. A multidisciplinary approach was adopted involving the use of digital facebow, intraoral scanners, digital smile design, and CAD/CAM technologies. The process included the extraction of defective restorations, temporary restorations to refine jaw position, and final permanent restorations. The digital workflow facilitated precise diagnostics and treatment, culminating in the successful installation of permanent restorations. Regular follow-ups at one- and three-months post-treatment confirmed stable occlusal function and high patient satisfaction. CONCLUSIONS: This case report showcases the potential of multiple digital technologies to streamline complex dental treatments and achieve high-quality results. CLINICAL SIGNIFICANCE: The integration of digital technologies in occlusal reconstruction treatments offers significant benefits in terms of precision, patient comfort, and esthetic outcomes.

Metabolic Heterogeneity and Potential Immunotherapeutic Responses Revealed by Single-Cell Transcriptomics of Breast Cancer.

BACKGROUND: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated. METHODS: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out. RESULTS: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity.

Radiologic Evaluation of Uncinate Processes of the Cervical Spine and the Relationship Between the Uncinate Process and Vertebral Artery: Implication in Anterior Cervical Spine Surgery.

OBJECTIVE: To determine the relationship between the uncinate process (UP) and vertebral artery (VA) from a radiologic view and to confirm the surgical safety margin to minimize the risk of VA injury during anterior cervical approaches. METHODS: We retrospectively reviewed computed tomography angiography of 205 patients by using a contrast-enhanced computed tomography angiography protocol of the VA. Four kinds of images were simultaneously reconstructed to measure all the parameters associated with VA and UP of cervical spine. RESULTS: The shortest distance from the UP's tip to the VA's medial border (P < 0.001) was at the C-6 level (2.9 ± 0.9 mm on the left and 3.2 ± 1.3 mm on the right), and the longest distance (P < 0.001) was at the C-3 level on both sides. The distance between UP's tip and the medial border of the ipsilateral VA was statistically significantly different at each cervical level, and the right distance was larger than the left (P < 0.05). We found the height of UP gradually increased from C-3 to C5-level and then decreased from C-5 to C-7 level for both sides. The mean distance between the medial borders of left UP and left VA was on average 7.5 ± 1.4 mm. The diameter of VA was on average 3.4 ± 0.6 mm on the left side and 3.2 ± 0.7 mm on the right. The diameter of the VA was statistically significantly different on both sides, and the left side was larger than the right (P < 0.05). CONCLUSIONS: Detailed radiologic anatomy of VA and UP was reviewed in this study. A deep understanding of the correlation between the UP and VA is essential to perform anterior cervical spine surgery safely and ensure adequate spinal canal decompression.

RNA polymerase I subunit D activated by Yin Yang 1 transcription promote cell proliferation and angiogenesis of colorectal cancer cells.

This study aims to explore possible effect of RNA polymerase I subunit D (POLR1D) on proliferation and angiogenesis ability of colorectal cancer (CRC) cells and mechanism herein. The correlation of POLR1D and Yin Yang 1 (YY1) expressions with prognosis of CRC patients in TCGA database was analyzed. Quantitative realtime polymerase chain reaction (qRT-PCR) and Western blot were applied to detect expression levels of POLR1D and YY1 in CRC cell lines and CRC tissues. SW480 and HT- 29 cells were transfected with si-POLR1D or pcDNA3.1-POLR1D to achieve POLR1D suppression or overexpression before cell migration, angiogenesis of human umbilical vein endothelial cells were assessed. Western blot was used to detect expressions of p38 MAPK signal pathway related proteins and interaction of YY1 with POLR1D was confirmed by dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). TCGA data showed that both POLR1D and YY1 expressions were up-regulated in CRC patients. High expression of POLR1D was associated with poor prognosis of CRC patients. The results showed that POLR1D and YY1 were highly expressed in CRC cell lines. Inhibition or overexpression of POLR1D can respectively suppress or enhance proliferation and angiogenesis of CRC cells. YY1 inhibition can suppress CRC progression and deactivate p38 MAPK signal pathway, which can be counteracted by POLR1D overexpression. JASPAR predicted YY1 can bind with POLR1D promoter, which was confirmed by dual luciferase reporter gene assay and ChIP. YY1 transcription can up-regulate POLR1D expression to activate p38 MAPK signal pathway, thus promoting proliferation and angiogenesis ability of CRC cells.

Lnc-Clic5 as a sponge for miR-212-5p to inhibit cow barn PM2.5-induced apoptosis in rat alveolar macrophages.

Particulate matter 2.5 (PM2.5) is a highly hazardous airborne particulate matter that poses a significant risk to humans and animals. Urban airborne particulate matter contributes to the increased incidence and mortality of respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), in humans. However, the specific mechanism by which PM2.5 affects animals in barn environments is yet to be elucidated. In this study, we investigated the effect of exposure to cow barn PM2.5 on rat alveolar macrophages (NR8383) and found that it induced apoptosis via the miR-212-5p/RASSF1 pathway. We found that lnc-Clic5 expression was downregulated in NR8383 cells exposed to cow barn PM2.5. Lnc-Clic5 plays a competitive endogenous RNA (ceRNA) regulatory role by sponging miR-212-5p to attenuate the regulation of RASSF1. Moreover, lnc-Clic5 overexpression inhibited NR8383 apoptosis by targeting the miR-212-5p/RASSF1 pathway. Co-treatment with miR-212-5p and lnc-Clic5 in the presence of cow barn PM2.5 revealed that lnc-Clic5 reversed NR8383 cell apoptosis induced by PM2.5 when miR-212-5p was overexpressed. These findings contribute to the study of ncRNAs and ceRNAs regulating PM2.5-induced apoptosis in animal farms, provide therapeutic targets for lung macrophage apoptosis, and may be useful for further evaluating the toxicological effects of PM2.5 in farmhouses on the respiratory systems of humans and animals.

Guest water-induced structural transformation and spin-crossover variation of a two-dimensional Hofmann-type compound.

In this paper, we report a two-dimensional (2D) Hofmann-type spin-crossover coordination polymer [FeII(o-NTrz)2PtII(CN)4]·H2O (o-NTrz = 4-(o-nitrobenzyl)imino-1,2,4-triazole). Due to the remarkable configurational flexibility of triazole-based ligand, the porous structure of this compound can be reversibly regulated by the loss of guest water molecules as a consequence of rotation of o-NTrz. The 180° reorientation of the o-nitrobenzyl moiety not only induces a response of gate-closing/opening of the porous framework but also significantly modulates the spin transition temperature. The present investigation highlights the potential of Hofmann-type SCO compounds with flexible ligands in exploring unusual physical and chemical phenomena.

Seeking a quantum advantage with trapped-ion quantum simulations of condensed-phase chemical dynamics.

Simulating the quantum dynamics of molecules in the condensed phase represents a longstanding challenge in chemistry. Trapped-ion quantum systems may serve as a platform for the analog-quantum simulation of chemical dynamics that is beyond the reach of current classical-digital simulation. To identify a 'quantum advantage' for these simulations, performance analysis of both analog-quantum simulation on noisy hardware and classical-digital algorithms is needed. In this Review, we make a comparison between a noisy analog trapped-ion simulator and a few choice classical-digital methods on simulating the dynamics of a model molecular Hamiltonian with linear vibronic coupling. We describe several simple Hamiltonians that are commonly used to model molecular systems, which can be simulated with existing or emerging trapped-ion hardware. These Hamiltonians may serve as stepping stones towards the use of trapped-ion simulators for systems beyond the reach of classical-digital methods. Finally, we identify dynamical regimes in which classical-digital simulations seem to have the weakest performance with respect to analog-quantum simulations. These regimes may provide the lowest hanging fruit to make the most of potential quantum advantages.

An autocatalytic CRISPR-Cas amplification effect propelled by the LNA-modified split activators for DNA sensing.

CRISPR-Cas systems with dual functions offer precise sequence-based recognition and efficient catalytic cleavage of nucleic acids, making them highly promising in biosensing and diagnostic technologies. However, current methods encounter challenges of complexity, low turnover efficiency, and the necessity for sophisticated probe design. To better integrate the dual functions of Cas proteins, we proposed a novel approach called CRISPR-Cas Autocatalysis Amplification driven by LNA-modified Split Activators (CALSA) for the highly efficient detection of single-stranded DNA (ssDNA) and genomic DNA. By introducing split ssDNA activators and the site-directed trans-cleavage mediated by LNA modifications, an autocatalysis-driven positive feedback loop of nucleic acids based on the LbCas12a system was constructed. Consequently, CALSA enabled one-pot and real-time detection of genomic DNA and cell-free DNA (cfDNA) from different tumor cell lines. Notably, CALSA achieved high sensitivity, single-base specificity, and remarkably short reaction times. Due to the high programmability of nucleic acid circuits, these results highlighted the immense potential of CALSA as a powerful tool for cascade signal amplification. Moreover, the sensitivity and specificity further emphasized the value of CALSA in biosensing and diagnostics, opening avenues for future clinical applications.

Complying with ISO 26262 and ISO/SAE 21434: A Safety and Security Co-Analysis Method for Intelligent Connected Vehicle.

A cyber-physical system (CPS) integrates communication and automation technologies into the operational processes of physical systems. Nowadays, as a complex CPS, an intelligent connected vehicle (ICV) may be exposed to accidental functional failures and malicious attacks. Therefore, ensuring the ICV's safety and security is crucial. Traditional safety/security analysis methods, such as failure mode and effect analysis and attack tree analysis, cannot provide a comprehensive analysis for the interactions between the system components of the ICV. In this work, we merge system-theoretic process analysis (STPA) with the concept phase of ISO 26262 and ISO/SAE 21434. We focus on the interactions between components while analyzing the safety and security of ICVs to reduce redundant efforts and inconsistencies in determining safety and security requirements. To conquer STPA's abstraction in describing causal scenarios, we improved the physical component diagram of STPA-SafeSec by adding interface elements. In addition, we proposed the loss scenario tree to describe specific scenarios that lead to unsafe/unsecure control actions. After hazard/threat analysis, a unified risk assessment process is proposed to ensure consistency in assessment criteria and to streamline the process. A case study is implemented on the autonomous emergency braking system to demonstrate the validation of the proposed method.

One-pot green solid-state synthesis of Cu2O/microcrystalline cellulose composite with high anti-pathogenic activity.

Cuprous oxide (Cu2O) is proven as an excellent anti-harmful microbial material. However, the liquid and vapor pha5se preparation methods reported so far hardly make pure Cu2O-containing composites and suffer environmental issues caused by chemical reducing agents with multiple processing steps. This work develops a facile one-pot solid-state sintering method to synthesize Cu2O/microcrystalline cellulose (MCC) composite via the thermal decomposition and oxidation-reduction reactions where copper formate was reduced by MCC. The Cu2O/MCC composite exhibits superior purity, dispersibility, stability, high yield, and high efficacy of antibacterial and antiviral properties, e.g., against E. coli, S. aureus, and Equine Arteritis Viral. This work utilizes elegantly the strong reducing capability of cellulose to develop an environmentally benign method to prepare high-purity Cu2O-polymer composites with low cytotoxicity and cost, which can be incorporated readily into other substrate materials to form various forms of anti-harmful microbial materials widely used in public health care products. In addition, the preparation of Cu2O-containing composites based on the reducing capability of cellulose is also expected to be applied to other cellulose-based materials for the loading of Cu2O particles.

Comprehensive insight into mercury contamination in atmospheric, terrestrial and aquatic ecosystems surrounding a typical antimony-coal mining district.

This study comprehensively investigated mercury (Hg) contents of various environmental compartments in a typical antimony-coal mining area with intensive industrial activities over the past 120 years to analyze Hg environmental behaviors and evaluate Hg risks. The total mercury (THg) contents in river water, sediments, soils, PM10, dust falls, vegetables and corns were 1.16 ± 0.63 µg/L, 2.01 ± 1.64 mg/kg, 1.87 ± 3.88 mg/kg, 7.87 ± 18.68 ng/m3, 13.01 ± 14.53 mg/kg, 0.30 ± 0.34 mg/kg and 3.11 ± 0.51 µg/kg, respectively. The δ202Hg values in soils and dust falls were - 1.58 ∼ 0.12‰ and 0.25 ∼ 0.30‰, respectively. Environmental samples affected by industrial activities in the Xikuangshan (XKS) presented higher THg and δ202Hg values. Binary mixing model proved that atmospheric deposition with considerable Hg deposition flux (0.44 ∼ 6.40, 3.12 ± 2.20 mg/m2/y) in the XKS significantly contributed to Hg accumulations on surface soils. Compared with soils, sediments with more frequent paths and higher burst probabilities presented higher dynamic Hg risks. Children were faced higher health risk of multiple Hg exposure than adults. Furthermore, the health risk of THg by consuming leaf vegetables deserved more attention. These findings provided scientific basis for managing Hg contamination.

Real-time detection of 20 amino acids and discrimination of pathologically relevant peptides with functionalized nanopore.

Precise identification and quantification of amino acids is crucial for many biological applications. Here we report a copper(II)-functionalized Mycobacterium smegmatis porin A (MspA) nanopore with the N91H substitution, which enables direct identification of all 20 proteinogenic amino acids when combined with a machine-learning algorithm. The validation accuracy reaches 99.1%, with 30.9% signal recovery. The feasibility of ultrasensitive quantification of amino acids was also demonstrated at the nanomolar range. Furthermore, the capability of this system for real-time analyses of two representative post-translational modifications (PTMs), one unnatural amino acid and ten synthetic peptides using exopeptidases, including clinically relevant peptides associated with Alzheimer's disease and cancer neoantigens, was demonstrated. Notably, our strategy successfully distinguishes peptides with only one amino acid difference from the hydrolysate and provides the possibility to infer the peptide sequence.