BACKGROUND:The prognosis for patients with esophageal squamous cell carcinoma (ESCC) is poor, mainly due to the immunosuppressive tumor microenvironment (TME). However, the underlying mechanism and strategies to reverse this immunosuppressive TME remain to be clarified. PURPOSE:This study aimed to identify key factors contributing to ESCC immunosuppressive TME, to investigate the regulatory role of diosmetin (DIOS), and to explore its potential in enhancing the anti-PD-1 therapy efficacy. METHODS:Bioinformatics analysis identified the key factors affecting the ESCC immune microenvironment. Cell proliferation, transwell migration, invasion, tube formation, spheroid sprouting and Chick chorioallantoic membrane (CAM) assays evaluated the effect of DIOS on angiogenesis. Transcriptomic sequencing clarified the mechanism of DIOS in ESCC cells and HUVECs. Molecular docking, Cellular thermal shift assay (CETSA), pull down and Surface plasmon resonance (SPR) assays detected the binding of DIOS to target proteins. Finally, the combined effect of DIOS and anti-PD-1 antibody was explored in vivo. RESULTS:Angiogenesis and CD8+T cell suppression were key contributors to ESCC immunosuppression. DIOS suppressed angiogenesis in ESCC cells via the AURKB/AKT/STAT4/PDGFC axis and in HUVECs stimulated by ESCC CM via the JAK1/STAT1/PDGFC pathway. Clinically, high PDGFC was associated with poor prognosis and limited immune checkpoint blockade efficacy in ESCC patients. Meanwhile, DIOS promoted both T cell adhesion and migration, as well as the killing capacity of CD8⁺T cells. Furthermore, anti-CD8 antibody attenuated the anti-tumor effect of DIOS. Notably, the combination of DIOS with anti-PD-1 antibody inhibited the growth of ESCC without causing significant kidney toxicity. CONCLUSION:This study demonstrates for the first time that the natural compound DIOS dually suppresses tumor angiogenesis and enhances CD8⁺T cell function. And the combination of DIOS with anti-PD-1 antibody enhanced anti-tumor efficacy in ESCC. These findings provide a novel strategy for developing low-toxicity immunotherapy combinations based on natural products.

Digestive tract tumors represent a substantial global public health challenge, accounting for elevated morbidity and mortality rates. Perineural invasion (PNI), the spread of tumor cells along nerve fibers, has emerged as a key driver of aggressiveness and a poor prognosis. This study systematically reviews the complex, underexplored interplay between PNI and antitumor immunity in gastrointestinal cancers. By analyzing immune-related components (the programmed cell death protein 1/programmed death ligand 1 axis, T cell subsets, tumor-associated macrophages, and other immune checkpoints), it reveals PNI disrupts immune balance: It suppresses T-cell activity via programmed death ligand 1/programmed cell death protein 1 binding, skews T-cell differentiation to reduce antitumor efficacy and boost immunosuppression, and polarizes macrophages to aid tumor progression. These findings provide novel insights into how PNI reshapes the tumor immune microenvironment and promotes metastatic behavior, establishing a framework for prioritizing immunotherapeutic targets to inform precision treatment strategies.

This commentary critically appraises Chen et al, who delineate the nuclear factor kappa B (NF-κB)-microRNA-136 (miR-136)-programmed cell death protein 11 (PDCD11) axis in Helicobacter pylori (H. pylori)-associated gastric carcinogenesis and propose H. pylori-induced miR-136 as a potential biomarker for early gastric cancer (GC). The study's major strength lies in its multi-level validation - clinical specimen analysis, in vitro assays, and in vivo models - which collectively support a model in which H. pylori activates NF-κB to upregulate miR-136, and miR-136 in turn suppresses PDCD11 to promote GC cell proliferation, migration, and tumorigenicity. These findings lend experimental weight to the inflammation → molecular alteration → carcinogenesis paradigm and identify a novel axis for early intervention. Nonetheless, important mechanistic and methodological gaps limit translational readiness. Mechanistically, the work does not dissect how specific H. pylori virulence factors trigger NF-κB activation, nor does it define the downstream effectors and signaling cascades through which PDCD11 loss drives malignant phenotypes. Furthermore, this study did not detect the apoptotic properties of the PDCD11 protein. The study also omits an analysis of why miR-136 function may vary across histological subtypes. At the methodological level, in vitro validation was confined to only two GC cell lines. It lacked models representing the early stages of gastric mucosal transformation, which hinders the study's ability to unravel the temporal dynamics of miR-136 function and its subtype specificity. Additionally, the experimental result figures of this study contain several flaws in terms of labeling, completeness, and consistency, which may interfere with readers' accurate understanding of the results. To advance clinical translation, future studies should clarify the precise molecular links between H. pylori components and NF-κB activation, elucidate the downstream pathways of PDCD11, and investigate the heterogeneity of miR-136 across different pathological subtypes. Furthermore, conducting robust validation in multicenter, larger-scale cohorts and establishing expanded cellular models that include gastric mucosal cells and subtype-representative cell lines will also be essential tasks. Despite these limitations, by identifying a targetable regulatory axis and providing directions for in-depth mechanistic and translational research on miR-136 as an early diagnostic and therapeutic target, this study still makes a meaningful contribution to research on H. pylori-associated GC.

Background Perineural invasion (PNI) represents a uniquely distinctive pathway for tumor metastasis, but its underlying molecular mechanisms and therapy remain unclear.Methods Bioinformatics analysis and transcriptomic sequencing were first employed to investigate the involvement of the BDNF/TrkB axis in the ESCC PNI, which was validated with ESCC cells co-cultured with a dorsal root ganglia system (ESCC/DRG model), a mouse PNI model, and ESCC tissues, mainly using microscopic imaging, IVIS Spectrum in vivo imaging, Western blot (WB), and immunohistochemistry (IHC). Additionally, transcriptomic sequencing and WB were conducted to analyze the downstream molecular mechanisms of the BDNF/TrkB axis. Similar experiments were applied to investigate the role of Deguelin in ESCC PNI. Deguelin's interaction with BDNF was assessed using computational docking, pull-down assays, cellular thermal shift assays, surface plasmon resonance (SPR) and WB. Its inhibitory effects on the ESCC PNI were further evaluated through rescue experiments, where BDNF overexpression was used to counteract Deguelin's activity.Results The BDNF/TrkB axis is closely associated with the PNI in ESCC. This pathway plays a pivotal role in driving PNI progression via Akt signaling. Deguelin was identified as an effective inhibitor of PNI in ESCC. Mechanistically, BDNF was revealed to be a key binding target of Deguelin, which disrupts PNI development by modulating the BDNF/TrkB/Akt axis. Notably, overexpression of BDNF can counteract Deguelin's inhibitory effects on ESCC growth and PNI progression.Conclusion The BDNF/TrkB axis promotes the progression of ESCC PNI, and Deguelin inhibits ESCC PNI by targeting this axis, enhancing the understanding of PNI's molecular mechanisms and offering new therapeutic options.

This commentary provides a critical evaluation of the study by Wang et al , which focuses on rhapontin activating colonic nuclear factor erythroid 2-related factor 2 (NRF2) to explore its therapeutic potential for Parkinson’s disease (PD)-associated gastrointestinal dysfunction. The commentary acknowledges the academic value of the study: It has not only validated intestinal NRF2 as a therapeutic target for PD but also provided experimental support for the “enteric pathology hypothesis”. However, several key gaps remain unresolved in the study. At the gut microbiota level, the exploration of the causal relationship of the microbiota is insufficient, with no validation conducted via methods such as fecal microbiota transplantation; additionally, it fails to systematically integrate the gut-brain axis with PD and does not assess the impact of rhapontin on the composition or function of the gut microbiota. At the pathway mechanism level, it lacks an analysis of the crosstalk between NRF2 and other rhapontin-targeted pathways, including nuclear factor kappa-B, mitogen-activated protein kinase, adenosine monophosphate-activated protein kinase, and sirtuin 1. At the experimental method level, the behavioral testing methods for PD mouse models and the limitations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse models need attention. Additionally, certain flaws exist in some experimental result figures. Furthermore, this commentary puts forward improvement suggestions for the study. Future research should prioritize multi-omics analysis, encompassing combined metabolomics and metagenomics detection, while conducting mechanistic validation of NRF2-interacting molecules (KEAP1 and p62). In addition, it is necessary to improve refined behavioral tests, focusing on incorporating cognitive function and anxiety-related assessment items.

The tumor microenvironment plays a crucial role in tumor angiogenesis, yet the mechanism by which the microenvironment promotes tumor angiogenesis in esophageal squamous cell carcinoma (ESCC) is unclear. Here, transcriptomics revealed that IL-8 was the most significantly upregulated in HUVECs induced by ESCC cell supernatants, and the JAK3/STAT5A pathway was activated to regulate IL-8 during this process. Moreover, targeting JAK3 suppressed ESCC angiogenesis. Notably, dihydroartemisinin (DHA) directly targeted JAK3 and inhibited ESCC CM-induced HUVECs angiogenesis and the ESCC angiogenesis in vivo, similar to the clinical drugs Avastin or Apatinib. Mechanistically, STAT5A transcriptionally regulated IL-8, which could be inhibited by DHA. Besides, DHA inhibited ESCC angiogenesis through JAK3/STAT5A/IL-8 signaling in vivo and in vitro, and JAK3 blockade alleviated its effect. In conclusion, these findings demonstrate a critical role of the JAK3/STAT5A/IL-8 pathway in regulating ESCC angiogenesis, and DHA is an effective drug for targeting JAK3 against ESCC angiogenesis, providing a research basis and a new strategy for anti-ESCC angiogenesis therapy.

The study by Yang et al presents a comprehensive investigation into the therapeutic potential of curcumin for gastric cancer (GC). Using network pharmacology, the researchers identified 48 curcumin-related genes, 31 of which overlap with GC targets. Key genes, including ESR1 , EGFR , CYP3A4 , MAPK14 , CYP1A2 , and CYP2B6 , are linked to poor survival in GC patients. Molecular docking confirmed strong binding affinity of curcumin to these genes. In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823 , suggesting its therapeutic potential in GC through multiple targets and pathways.

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.

Perineural invasion (PNI), a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread, has the capacity to extend well beyond the primary tumor site, infiltrating distant regions devoid of lymphatic or vascular structures. PNI often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of cancers. Despite its clinical significance, the underlying molecular mechanisms of PNI remain elusive, complicating the development of specific and efficacious diagnostic and therapeutic strategies. In the realm of cancer research, non-coding RNAs (ncRNAs) have attracted considerable attention due to their multifaceted roles and cancer-specific expression profiles, positioning them as promising candidates for applications in cancer diagnostics, prognostics, and treatment. Among the various types of ncRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have emerged as influential players in PNI. Their involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic resistance. Our study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in cancer. This comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

Brain-derived neurotrophic factor (BDNF) is a predominant neurotrophic factor in the brain, indispensable for neuronal growth, synaptic development, neuronal repair, and hippocampal neuroplasticity. Among its genetic variants, the BDNF Val66Met polymorphism is widespread in the population and has been associated with the onset and aggravation of diverse pathologies, including metabolic conditions like obesity and diabetes, cardiovascular ailments, cancer, and an array of psychiatric disorders. Psychiatric disorders constitute a broad category of mental health issues that influence mood, cognition, and behavior. Despite advances in research and treatment, challenges persist that hinder our understanding and effective intervention of these multifaceted conditions. Achieving and maintaining stable body weight is pivotal for overall health and well-being, and the relationship between psychiatric conditions and body weight is notably intricate and reciprocal. Both weight gain and loss have been linked to varying mental health challenges, making the disentanglement of this relationship critical for crafting holistic treatment strategies. The BDNF Val66Met polymorphism's connection to weight fluctuation in psychiatric patients has garnered attention. This review investigated the effects and underlying mechanisms by which the BDNF Val66Met polymorphism moderates body weight among individuals with psychiatric disorders. It posits the polymorphism as a potential biomarker, offering prospects for improved monitoring and therapeutic approaches for mental illnesses.

Cisplatin (CDDP) is the first-line drug in the clinical treatment of esophageal squamous cell carcinoma (ESCC), which has severe nephrotoxicity. Diosmetin (DIOS) can protect kidney from oxidative damage, however, its function in ESCC is unknown. This study aims to explore the effect and mechanism of DIOS on ESCC and its combined effect with CDDP. Herein, we found that DIOS significantly inhibited the progression of ESCC in vitro and in vivo. Furthermore, the anti-tumor effect of DIOS was not statistically different from that of CDDP. Mechanically, transcriptomics revealed that DIOS inhibited the E2F2/RRM2 signaling pathway. The transcriptional regulation of RRM2 by E2F2 was verified by luciferase assay. Moreover, docking model, CETSA, pull-down assay and CDK2 inhibitor assay confirmed that DIOS directly targeted CDK2, leading to significant suppression of ESCC. Additionally, the patient-derived xenografts (PDX) model showed that the combination of DIOS and CDDP significantly inhibited the growth of ESCC. Importantly, the combined treatment with DIOS and CDDP significantly reduced the mRNA expression levels of kidney injury biomarkers KIM-1 and NGAL in renal tissue, as well as the levels of blood urea nitrogen, serum creatinine and blood uric acid compared to the single treatment with CDDP. In conclusion, DIOS could be an effective drug and a potential chemotherapeutic adjuvant for ESCC treatment. Furthermore, DIOS could reduce the nephrotoxicity of CDDP to some extent.

MicroRNA (miRNA), a non‑coding single‑stranded RNA molecule with a length of 21‑25 nucleotides transcripts, has been identified to play important roles in tumorigenesis and shows great potential applications in cancer diagnosis, prognosis and therapy. Brain derived neurotrophic factor (BDNF) is a member of the nerve growth factor family and usually serves as a biomarker in neurological and neuropsychiatric diseases for diagnosis and treatment by regulating its high‑affinity receptor TrkB (Tyrosine Kinase Receptor B). Abnormal expression of BDNF is also closely related to the development of cancer, cancer‑related pain and depression. However, little significant progress has been made in the application of BDNF in cancers. Recent studies have shown that the expression of BDNF is directly regulated by a cluster of miRNAs. This review concluded and discussed the role and mechanism of miRNAs targeting BDNF in cancers, and provided novel insights into the diagnosis and therapy of cancer in the future.

Purpose: Esophageal squamous carcinoma (ESCC) with a high incidence in China, lacks effective therapeutic targets. Phosphoglycerate dehydrogenase (PHGDH) is a key enzyme in serine biosynthesis. However, the biological role of PHGDH in ESCC has not been revealed. Methods: The expression of PHGDH in ESCC was investigated by UALCAN. The relationship between PHGDH expression and its prognostic value was analyzed by Kaplan-Meier and univariate Cox regression. Further, the potential functions of PHGDH involved in ESCC were explored through DAVID database and GSEA software. In addition, the expression of PHGDH was verified in ESCC. Then, the effects of PHGDH knockdown on ESCC were evaluated in vitro and in vivo by cell proliferation, clone formation, cell cycle, apoptosis, tube formation assays and ESCC cells derived xenograft model. In addition, western blotting and immunohistochemistry were used to detect the expression of Wnt/beta-catenin pathway which was associated with PHGDH. Results: Bioinformatics analysis found that PHGDH was highly expressed in ESCC, and meaningfully, patients with high PHGDH expression had a poor prognosis. Moreover, the overexpression of PHGDH was verified in ESCC. Afterwards, PHGDH knockdown inhibited the cell proliferation, induced cell cycle arrest and apoptosis in ESCC cells, and inhibited the angiogenesis of HUVECs induced by ESCC conditioned medium, as well as inhibited the growth of xenograft tumor. Mechanistically, PHGDH knockdown inhibited Wnt/beta-catenin signaling pathway in ESCC. Conclusion: High expression of PHGDH predicts a poor prognosis for ESCC. PHGDH knockdown inhibits ESCC progression by suppressing Wnt/beta-catenin signaling pathway, indicating that PHGDH might be a potential target for ESCC therapy.

Background: Perineural invasion (PNI) is a malignant metastatic mode of tumors and has been reported in many tumors including esophageal cancer (EC). However, the role of PNI in EC has been reported differently. This systematic review and meta-analysis aims to focus on the role of PNI in EC. Methods: Eight databases of CNKI, VIP, Wanfang, Scopus, Wiley, ISI, PubMed, and EBSCO are used for literature search. The association of PNI with gender, pathological stages of T and N (pT and pN), lymphovascular invasion (LVI), lymph node metastasis, 5-year overall survival (OS), and 5-year disease-free survival (DFS) was examined in the meta-analysis by Revman5.0 Software. The pooled OR/HR and 95% CI were used to assess the risk and prognostic value. Results: Sixty-nine published studies were screened for analysis of PNI in EC. The incidence of PNI in esophageal squamous carcinoma (ESCC) and esophageal adenocarcinoma (EAC) was different, but not statistically significant (p > 0.05). The PNI-positive patients had a significantly higher risk of pT stage (OR = 3.85, 95% CI = 2.45-6.05, p < 0.00001), pN stage (OR = 1.86, 95% CI = 1.52-2.28, p < 0.00001), LVI (OR = 2.44, 95% CI = 1.55-3.85, p = 0.0001), and lymph node metastasis (OR = 2.87, 95% CI = 1.56-5.29, p = 0.0007). Furthermore, the cumulative analysis revealed a significant correlation between PNI and poor OS (HR = 1.37, 95% CI = 1.24-1.51, p < 0.0001), as well as poor DFS (HR = 1.55, 95% CI = 1.38-1.74, p < 0.0001). Conclusion: PNI occurrence is significantly related to tumor stage, LVI, lymph node metastasis, OS, and DFS. These results indicate that PNI can serve as an indicator of high malignant degree and poor prognosis in EC.

Background Perineural invasion (PNI) is a malignant metastatic mode of tumors and has been reported in many tumors including esophageal cancer (EC). However, the role of PNI in EC has been reported differently. This systematic review and meta-analysis aims to focus on the role of PNI in EC. Methods Eight databases of CNKI, VIP, Wanfang, Scopus, Wiley, ISI, PubMed, and EBSCO are used for literature search. The association of PNI with gender, pathological stages of T and N (pT and pN), lymphovascular invasion (LVI), lymph node metastasis, 5-year overall survival (OS), and 5-year disease-free survival (DFS) was examined in the meta-analysis by Revman5.0 Software. The pooled OR/HR and 95% CI were used to assess the risk and prognostic value. Results Sixty-nine published studies were screened for analysis of PNI in EC. The incidence of PNI in esophageal squamous carcinoma (ESCC) and esophageal adenocarcinoma (EAC) was different, but not statistically significant (p > 0.05). The PNI-positive patients had a significantly higher risk of pT stage (OR = 3.85, 95% CI = 2.45–6.05, p < 0.00001), pN stage (OR = 1.86, 95% CI = 1.52–2.28, p < 0.00001), LVI (OR = 2.44, 95% CI = 1.55–3.85, p = 0.0001), and lymph node metastasis (OR = 2.87, 95% CI = 1.56–5.29, p = 0.0007). Furthermore, the cumulative analysis revealed a significant correlation between PNI and poor OS (HR = 1.37, 95% CI = 1.24–1.51, p < 0.0001), as well as poor DFS (HR = 1.55, 95% CI = 1.38–1.74, p < 0.0001). Conclusion PNI occurrence is significantly related to tumor stage, LVI, lymph node metastasis, OS, and DFS. These results indicate that PNI can serve as an indicator of high malignant degree and poor prognosis in EC.

Dihydroartemisinin (DHA) is an active metabolite of artemisinin and its derivatives (ARTs), and it is an effective clinical drug widely used to treat malaria. Recently, the anticancer activity of DHA has attracted increasing attention. Nevertheless, there is no systematic summary on the anticancer effects of DHA. Notably, studies have shown that DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stress. In this review, we comprehensively summarized the latest progress regarding the anticancer activities of DHA in cancer. Importantly, the underlying anticancer molecular mechanisms and pharmacological effects of DHA in vitro and in vivo are the focus of our attention. Interestingly, new methods to improve the solubility and bioavailability of DHA are discussed, which greatly enhance its anticancer efficacy. Remarkably, DHA has synergistic anti-tumor effects with a variety of clinical drugs, and preclinical and clinical studies provide stronger evidence of its anticancer potential. Moreover, this article also gives suggestions for further research on the anticancer effects of DHA. Thus, we hope to provide a strong theoretical support for DHA as an anticancer drug.

文化素质教育课程是本科教育的重要教学环节之一,它既是培育大学生人文精神和科学精神的基础教育平台,也是课程思政的天然载体.开展致癌因素和肿瘤预防课程,对于培养在校大学生疾病预防的理念意义重大.本研究采用微视频结合雨课堂的方式开展致癌因素和肿瘤预防课程思政实践,使课程思政内容和专业内容有机融合,极大地培养了学生的文化自信、爱国情怀、科学精神和人文素养,达到了课程思政立德树人的根本目的.

Drug repositioning is a better way to cancer drug discovery. As a common used oral contraceptive, Levonorgestrel (LNG) was found to play important anticancer roles in several cancers, but its role in human esophageal squamous cell carcinoma (ESCC) was little known. Using ESCC cell line of Ec1 and human normal esophageal epithelial cell line of Het-1A, this study was aim to investigate the effect and molecular mechanism of LNG on the ESCC. The results showed that LNG inhibit the cell proliferation; LNG also induced the cell apoptosis of ESCC related to mitochondrial apoptotic pathway for its disruption of mitochondrial capacity and upregulation of cleaved-Caspase 3 and the declining of the ratio of Bcl-2/Bax; LNG can inhibit the cell migration of ESCC with the E-cadherin overexpression. The anticancer effect of LNG on ESCC mainly associated with Wnt/β-catenin signaling pathway through up-regulation the phosphorylation level of β-catenin. At last, the study declared that LNG combined with cisplatin (CDDP) significantly suppressed the proliferation of Ec1. In conclusions, the LNG serves as efficient anticancer drug in ESCC cells and maybe used for drug repositioning to adjunctive therapy ESCC.

As a novel lactate-derived post-translational modification (PTM), lysine lactylation (Kla) is involved in diverse biological processes, and participates in human tumorigenesis. Identification of Kla substrates with their exact sites is crucial for revealing the molecular mechanisms of lactylation. In contrast with labor-intensive and time-consuming experimental approaches, computational prediction of Kla could provide convenience and increased speed, but is still lacking. In this work, although current identified Kla sites are limited, we constructed the first Kla benchmark dataset and developed a few-shot learning-based architecture approach to leverage the power of small datasets and reduce the impact of imbalance and overfitting. A maximum 11.7% (0.745 versus 0.667) increase of area under the curve (AUC) value was achieved in contrast to conventional machine learning methods. We conducted a comprehensive survey of the performance by combining 8 sequence-based features and 3 structure-based features and tailored a multi-feature hybrid system for synergistic combination. This system achieved >16.2% improvement of the AUC value (0.889 versus 0.765) compared with single feature-based models for the prediction of Kla sites in silico. Taken few-shot learning and hybrid system together, we present our newly designed predictor named FSL-Kla, which is not only a cutting-edge tool for Kla site profile but also could generate candidates for further experimental approaches. The webserver of FSL-Kla is freely accessible for academic research at http://kla.zbiolab.cn/.

Carbonyl stress is caused by active carbonyl compounds. Abnormal metabolism will produce high concentration of active carbonyl substances, leading to carbonyl stress, thus inducing cell damage or apoptosis. It is important to find effective markers for carbonyl stress level and find therapeutic or palliative drugs. Peroxynitrite (ONOO-), as a kind of important reactive oxygen species, can be produced under a variety of pathological conditions. Hydrogen sulfide (H2S) has been known as antioxidant agent, anti-inflammatory et al. However, the protective effect of H2S and the level of ONOO- in endothelial cell apoptosis during carbonyl stress kept unknown. Herein, for address it, we reported the first single-molecule fluorescent probe (SZ) is capable of detecting ONOO- and H2S in Endothelial cell. The probe SZ shows good selectivity and low detection limit to ONOO- and H2S. More importantly, probe SZ may be a useful tool for evaluating and confirming the protective effects of endogenous H2S in Endothelial cell during carbonyl stress.