O-GlcNAcylation: roles and potential therapeutic target for bone pathophysiology.

O-linked N-acetylglucosamine (O-GlcNAc) protein modification (O-GlcNAcylation) is a critical post-translational modification (PTM) of cytoplasmic and nuclear proteins. O-GlcNAcylation levels are regulated by the activity of two enzymes, O-GlcNAc transferase (OGT) and O­GlcNAcase (OGA). While OGT attaches O-GlcNAc to proteins, OGA removes O-GlcNAc from proteins. Since its discovery, researchers have demonstrated O-GlcNAcylation on thousands of proteins implicated in numerous different biological processes. Moreover, dysregulation of O-GlcNAcylation has been associated with several pathologies, including cancers, ischemia-reperfusion injury, and neurodegenerative diseases. In this review, we focus on progress in our understanding of the role of O-GlcNAcylation in bone pathophysiology, and we discuss the potential molecular mechanisms of O-GlcNAcylation modulation of bone-related diseases. In addition, we explore significant advances in the identification of O-GlcNAcylation-related regulators as potential therapeutic targets, providing novel therapeutic strategies for the treatment of bone-related disorders.

Prognostic effect of surgical treatment in elderly oral squamous cell carcinoma patients: A retrospective study.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignant tumors in head and neck. However, few studies have focused on the postoperative prognosis of elderly OSCC patients undergoing surgical resection and reconstruction. METHODS: We conducted a retrospective study of 349 patients diagnosed OSCC in the Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University from January 2016 to December 2022. Demographic and clinicopathological characteristics were recorded. Kaplan-Meier analysis was performed to identify the impact of age and reconstruction types on the prognosis of OSCC patients. Univariable regression analysis and multivariable Cox analysis were conducted to find independent prognostic factors of the younger and elderly OSCC patients. RESULTS: Among 349 OSCC patients included in this retrospective study, 241 (69.1 %) were elderly patients and 108 (30.9 %) were younger patients. The two groups were comparable according to the demographic records. The elderly group presented a better recurrence-specific prognosis than that of the younger group (RFS: p = 0.0324). There are no remarkable differences on the prognosis of different reconstructive types. Gender, current address, life habit, invasion patterns, and TNM stage were identified as independent prognostic factors of the younger and elderly OSCC patients. CONCLUSION: Elderly OSCC patients achieve a better recurrence-free survival than that of the younger patients. Meanwhile, the recurrence of OSCC patients is independent of their demographic and clinicopathological features. Elderly OSCC patients will benefit from aggressive surgical treatment as the younger patients.

Primary cutaneous anaplastic large-cell lymphoma resembling infratemporal space infection: a case report.

BACKGROUND: Primary cutaneous anaplastic large-cell lymphoma (PC-ALCL) is a rare T-cell lymphoma belonging to the CD30 + T-cell lymphoproliferative disorders. The case of PC-ALCL in the temporal region is exceedingly rare. Herein, we report a case of PC-ALCL involving the temporal region mimicking infratemporal space infection. CASE PRESENTATION: A 78-year-old woman presented to maxillofacial surgery service with a 6-month history of swelling and pain in the left side of her face. Laboratory investigations found an elevated C-reactive protein (CRP). Imaging findings showed enlarged lymph nodes and extensive thickening of subcutaneous tissue of the left temples. Based on these findings, the infratemporal space infection was suspected initially. The patient underwent incision and drainage, and we unexpectedly found no pus in the lesion area. Incisional biopsy showed necrosis and extensive involvement of the left temples by a diffuse infiltrate containing large, atypical cells. The tumor cells were positive for CD30, CD3, Ki67. They were negative for ALK (SP8), CD5, CD8, CD20 and PAX5. After considering these findings, a diagnosis of PC-ALCL was rendered. The patient was admitted to the lymphoma department for systemic chemotherapy and no relapse occurred during a follow-up period of six months. CONCLUSIONS: This report suggests that if there are suspicious intraoperative manifestations, carrying out a biopsy simultaneously, using Hematoxylin and eosin (HE) staining, and a comprehensive Immunohistochemistry (IHC) panel are essential to diagnosing PC-ALCL to prevent misdiagnosis.

Review: Protein O-GlcNAcylation regulates DNA damage response: A novel target for cancer therapy.

The DNA damage response (DDR) safeguards the stable genetic information inheritance by orchestrating a complex protein network in response to DNA damage. However, this mechanism can often hamper the effectiveness of radiotherapy and DNA-damaging chemotherapy in destroying tumor cells, causing cancer resistance. Inhibiting DDR can significantly improve tumor cell sensitivity to radiotherapy and DNA-damaging chemotherapy. Thus, DDR can be a potential target for cancer treatment. Post-translational modifications (PTMs) of DDR-associated proteins profoundly affect their activity and function by covalently attaching new functional groups. O-GlcNAcylation (O-linked-N-acetylglucosaminylation) is an emerging PTM associated with adding and removing O-linked N-acetylglucosamine to serine and threonine residues of proteins. It acts as a dual sensor for nutrients and stress in the cell and is sensitive to DNA damage. However, the explanation behind the specific role of O-GlcNAcylation in the DDR remains remains to be elucidated. To illustrate the complex relationship between O-GlcNAcylation and DDR, this review systematically describes the role of O-GlcNAcylation in DNA repair, cell cycle, and chromatin. We also discuss the defects of current strategies for targeting O-GlcNAcylation-regulated DDR in cancer therapy and suggest potential directions to address them.

Heterogeneity of molecular subtyping and therapy-related marker expression in primary tumors and paired lymph node metastases of small cell lung cancer.

The classification of molecular subtypes and the identification of targetable molecules have been proposed for small cell lung cancer (SCLC) patients. Our aim was to investigate whether the expression of these markers evaluated using lymph node (LN) metastases represents that of primary tumors. We enrolled 46 surgically resected SCLC patients' primary tumors and paired mediastinal LN metastases. The protein expression of subtype-defining markers (ASCL1, NEUROD1, POU2F3, and YAP1) and therapeutic markers (DLL3, MYC, PD-L1, and MHC I) was examined by immunohistochemistry and was correlated with clinicopathological parameters and prognoses. In primary and metastatic tumors, the expression of these markers was 78.3% and 87.0%, 50.0% and 63.0%, 13.0% and 6.5%, 17.4% and 15.2%, 84.8% and 87.0%, 17.4% and 6.5%, 50.0% and 34.8%, and 60.9% and 37.0%, respectively. Positive tumor PD-L1 expression was less present in LN metastases (p = 0.015), and the same was true for MHC I expression (p = 0.036). NEUROD1 and DLL3 expression levels in metastatic tumors were stronger (p < 0.001 and p = 0.002, respectively); conversely, POU2F3, MYC, PD-L1, and MHC I expression levels were weaker (p = 0.018, p = 0.019, p = 0.001, and p < 0.001, respectively). In 15 (32.6%) patients, we observed a change in the molecular subtyping pattern, and a higher number of neuroendocrine (NE)-high phenotype patients were diagnosed when using the LN specimens (91.3% vs. 84.8%). TNM stage and postoperative chemotherapy were independent prognostic factors in surgically resected SCLC patients, and no prognostic differences were found among molecular subtypes. This study highlights the discordance of subtype-specific proteins and therapeutic markers between SCLC primary tumors and LN metastases. Additionally, our findings have therapeutic and prognostic implications and warrant further clinical investigation.

Functional significance of O-linked N-acetylglucosamine protein modification in regulating autophagy.

Autophagy is a core molecular pathway that preserves cellular and organismal homeostasis. Being susceptible to nutrient availability and stress, eukaryotic cells recycle or degrade internal components via membrane transport pathways to provide sustainable biological molecules and energy sources. The dysregulation of this highly conserved physiological process has been strongly linked to human disease. Post-translational modification, a mechanism that regulates protein function, plays a crucial role in autophagy regulation. O-linked N-acetylglucosamine protein modification (O-GlcNAcylation), a monosaccharide post-translational modification of intracellular proteins, is essential in nutritional and stress regulatory mechanisms. O-GlcNAcylation has emerged as an essential regulatory mechanism of autophagy. It regulates autophagy throughout its lifetime by targeting the core components of the autophagy regulatory network. This review provides an overview of the O-GlcNAcylation of autophagy-associated proteins and their regulation and function in the autophagy pathway. Therefore, this article may contribute to further understanding of the role of O-GlcNAc-regulated autophagy and provide new perspectives for the treatment of human diseases.

Dynamic real-time forecasting technique for reclaimed water volumes in urban river environmental management.

In recent years, the utilization of wastewater recycling as an alternative water source has gained significant traction in addressing urban water shortages. Accurate prediction of wastewater quantity is paramount for effective urban river water resource management. There is an urgent need to develop advanced forecasting technologies to further enhance the accuracy and efficiency of water quantity predictions. Decomposition ensemble models have shown excellent predictive capabilities but are challenged by boundary effects when decomposing the original data sequence. To address this, a rolling forecast decomposition ensemble scheme was developed. It involves using a machine learning (ML) model for prediction and progressively integrating prediction outcomes into the original sequence using complementary ensemble empirical mode decomposition with adaptive noise (CEEMDAN). Long short-term memory (LSTM) is then applied for sub-signal prediction and ensemble. The ML-CEEMDAN-LSTM model was introduced for wastewater quantity prediction, compared with non-decomposed ML models, CEEMDAN-based LSTM models, and ML-CEEMDAN-based LSTM models. Three ML algorithms-linear regression (LR), gradient boosting regression (GBR), and LSTM-were examined, using real-time prediction data and historical monitoring data, with historical data selected using the decision tree method. The study used daily water volumes data from two reclaimed water plants, CH and WQ, in Beijing. The results indicate that (1) ML models varied in their selection of real-time factors, with LR performing best among ML models during testing; (2) the ML-CEEMDAN-LSTM model consistently outperformed ML models; (3) the ML-CEEMDAN-LSTM hybrid model performed better than the CEEMDAN-LSTM model across different seasons. This study offers a reliable and accurate approach for reclaimed water volumes forecasting, critical for effective water environment management.

p16 and p53 can Serve as Prognostic Markers for Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: The present study aimed to explore the expression and clinical significance of human papilloma virus-related pathogenic factors (p16, cyclin D1, p53) in patients with head and neck squamous cell carcinoma (HNSCC) and construct a predictive model. METHODS: The Cancer Genome Atlas was used to obtain clinical data for 112 patients with HNSCC. Expression of p16, p53, and cyclin D1 was quantified. We used the survival package of the R program to set the cut-off value. Values above the cut-off were considered positive, while values below the cut-off were negative. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were performed to investigate prognostic clinicopathological indicators and the expression of p16, p53, and cyclin D1. A predictive model was constructed based on the results of multifactor Cox regression analysis, and the accuracy of the predictive model was verified through final calibration analysis. Follow-up of patients with HNSCC at the Affiliated Hospital of Binzhou Medical University was conducted from 2015 to 2017, and reliability of the predictive model was validated based on follow-up data and molecular expression levels. RESULTS: According to the results, expression of p16 and p53 was significantly associated with prognosis (P < .05). The predictive model constructed based on the expression levels of p16 and p53 was useful for evaluating the prognosis of patients with HNSCC. The predictive model was validated using follow-up data obtained from the hospital, and the trend of the follow-up results was consistent with the predictive model. CONCLUSION: p16 and p53 can be used as key indicators to predict the prognosis of HNSCC patients and as critical immunohistochemical indicators in clinical practice. The survival model constructed based on p16 and p53 expression levels reliably predicts patient prognosis.

The mitochondrial regulation in ferroptosis signaling pathway and its potential strategies for cancer.

Ferroptosis is an iron-dependent regulated cell death, mainly manifested by the production of reactive oxygen species and accumulation of lipid peroxides. It is distinct from other forms of cell death with regard to morphology and biochemistry, particularly in disrupting mitochondrial function. Mitochondria are essential compartments where the organism generates energy and are closely associated with the fate of ferroptosis. Currently, researchers focus on the potential value of ferroptosis and mitochondria for overcoming drug sensitivity and assisting in cancer therapy. In this review, we summarize the main mechanisms of ferroptosis (the GPX4-realated pathway, FSP1-related pathway, and iron metabolism pathway) and the functions and regulating pathways of mitochondria (the TCA cycle, oxidative phosphorylation, mitochondrial regulation of iron ions, and mtDNA) in ferroptosis. We believe that exploring the role of mitochondria in ferroptosis will help us understand the potential regulatory mechanisms of ferroptosis in cancer and help us find new therapeutic targets.

The role of novel programmed cell death in head and neck squamous cell carcinoma: from mechanisms to potential therapies.

Head and neck squamous cell carcinoma (HNSCC) is a common oral cancer with poor prognosis and for which no targeted therapeutic strategies are currently available. Accumulating evidence has demonstrated that programmed cell death (PCD) is essential in the development of HNSCC as a second messenger. PCD can be categorized into numerous different subroutines: in addition to the two well-known types of apoptosis and autophagy, novel forms of programmed cell death (e.g., necroptosis, pyroptosis, ferroptosis, and NETosis) also serve as key alternatives in tumorigenesis. Cancer cells are not able to avoid all types of cell death simultaneously, since different cell death subroutines follow different regulatory pathways. Herein, we summarize the roles of novel programmed cell death in tumorigenesis and present our interpretations of the molecular mechanisms with a view to the development of further potential therapies.

Molecular subtypes, predictive markers and prognosis in small-cell lung carcinoma.

AIMS: A new molecular subtype classification was proposed for small-cell lung carcinoma (SCLC). We aimed to further validate the classification in various SCLC patient samples using immunohistochemistry (IHC) to highlight its clinical significance. METHODS: We analysed the protein expression of four subtype (achaete-scute family BHLH transcription factor 1 (ASCL1), neuronal differentiation 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3) and Yes1-associated transcriptional regulator (YAP1)) and two predictive markers (delta-like ligand 3 (DLL3) and MYC) using IHC in 216 specimens from 195 SCLC patients, including 21 pairs of resected biopsy tumours. Associations among molecular subtypes, clinicopathological features and prognostic implications were also explored. RESULTS: The ASCL1, NEUROD1, POU2F3, YAP1, DLL3 and MYC-positive expression rates were 70.3%, 56.9%, 14.9%, 19.0%, 75.4% and 22.6%, respectively. DLL3 expression had positive and negative associations with that of ASCL1 and POU2F3/YAP1, respectively, whereas MYC had the opposite effect. Strong associations of ASCL1 (Ρ=0.8603, p<0.0001), NEUROD1 (Ρ=0.8326, p<0.0001), POU2F3 (Ρ=0.6950, p<0.0001) and YAP1 (Ρ=0.7466, p<0.0001) expressions were detected between paired resected biopsy tumours. In addition to SCLC-A (ASCL1-dominant), SCLC-N (NEUROD1-dominant) and SCLC-P (POU2F3-dominant), unsupervised hierarchical cluster analyses identified a fourth, quadruple-negative SCLC subtype (SCLC-QN) characterised by the low expression of all four subtype-specific proteins, and 55.4% (n=108), 27.2% (n=53), 11.8% (n=23) and 5.6% (n=11) were categorised as SCLC-A, SCLC-N, SCLC-P and SCLC-QN, respectively. Significant enrichment of SCLC-P in the combined SCLC cohort was observed, and adenocarcinoma was more prevalent in SCLC-A, while large-cell neuroendocrine carcinoma was more commonly seen in SCLC-P. No survival difference was found among molecular subtypes. CONCLUSIONS: Our results provide clinical insights into the diagnostic, prognostic and predictive significance of SCLC molecular subtype classifications.

Deep learning prediction model for central lymph node metastasis in papillary thyroid microcarcinoma based on cytology.

Controversy exists regarding whether patients with low-risk papillary thyroid microcarcinoma (PTMC) should undergo surgery or active surveillance; the inaccuracy of the preoperative clinical lymph node status assessment is one of the primary factors contributing to the controversy. It is imperative to accurately predict the lymph node status of PTMC before surgery. We selected 208 preoperative fine-needle aspiration (FNA) liquid-based preparations of PTMC as our research objects; all of these instances underwent lymph node dissection and, aside from lymph node status, were consistent with low-risk PTMC. We separated them into two groups according to whether the postoperative pathology showed central lymph node metastases. The deep learning model was expected to predict, based on the preoperative thyroid FNA liquid-based preparation, whether PTMC was accompanied by central lymph node metastases. Our deep learning model attained a sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and accuracy of 78.9% (15/19), 73.9% (17/23), 71.4% (15/21), 81.0% (17/21), and 76.2% (32/42), respectively. The area under the receiver operating characteristic curve (value was 0.8503. The predictive performance of the deep learning model was superior to that of the traditional clinical evaluation, and further analysis revealed the cell morphologies that played key roles in model prediction. Our study suggests that the deep learning model based on preoperative thyroid FNA liquid-based preparation is a reliable strategy for predicting central lymph node metastases in thyroid micropapillary carcinoma, and its performance surpasses that of traditional clinical examination.

Insights into mineralogical distribution mechanism and environmental significance from geochemical behavior of sediments in the Yellow River Basin, China.

Mineralogical investigations on fluvial sedimentary sequences could provide historical environmental information on the effects of human activities and natural events. This study aims to identify the mineralogical distribution mechanism and environmental significance of sediments of the Yellow River Basin based on topographic analysis, statistics, weathering and recycling indices. In total, 107 samples were collected from sedimentary sequences in the source area, and the upper, middle, and lower reaches and analyzed for grain size, major elements, and mineral composition. The results showed that the climate conditions were cold and arid, where weak hydrolysis under continental weathering and strong erosion accelerated physical weathering. Clay minerals in the upper reaches primarily originated from the Tibetan Plateau, whereas the middle and lower reaches received input of aeolian deposits from Northern China. Quartz and feldspar in the middle and lower reaches may derive from the source area and upper reaches. Meanwhile, calcite and dolomite formed through diagenesis, with loess input from the Chinese Loess Plateau. Regarding heavy minerals, the dominant determinative factors of pyrite were post-depositional diagenesis and leaching. Hematite and amphibole primarily formed through magnetite conversion and contribution from regional sources, respectively. Moreover, the mineral distribution mechanism significantly affected the mobility and distribution of geochemical elements through diagenesis and alteration. The findings are instrumental in reconstructing the environmental evolution of large-scale watersheds across multiple climatic zones.

Molecular subtype expression and genomic profiling differ between surgically resected pure and combined small cell lung carcinoma.

A new molecular subtype classification method has been proposed for small cell lung carcinoma (SCLC). However, little is known about the differences between the pure (P-SCLC) and combined subtypes (C-SCLC). We aimed to compare the molecular subtype expression and genomic profiling in terms of clinical relevance between the two groups. 154 surgically resected SCLCs were analyzed for protein expression of four subtypes (ASCL1, NEUROD1, POU2F3, and YAP1) and two predictive markers (DLL3 and MYC) by immunohistochemistry (IHC). We also performed whole exome sequencing of 60 samples to examine genomic profiles. A total of 113 patients with P-SCLC and 41 with C-SCLC were included. In P-SCLC and C-SCLC, the expression of these markers was 78.8% and 41.5%, 98.2% and 97.6%, 42.5% and 51.2%, 38.9% and 85.4%, 85.0% and 68.3%, and 24.8% and 34.1%, respectively. ASCL1 and DLL3 were highly expressed in P-SCLC (p = 0.000 and p = 0.021, respectively), and YAP1 expression was significantly enriched in C-SCLC (p = 0.000). NGS results, including 45 P-SCLCs and 15 C-SCLCs, indicated that EGFR gene mutations were mostly observed in C-SCLCs (p = 0.000). C-SCLC showed higher CNA burden and wGII than P-SCLC (p < 0.01 and p < 0.05); conversely, P-SCLC had higher TMB burden and SDI (p < 0.05 and p < 0.05). YAP1 expression was associated with poor prognosis in P-SCLC but with favorable prognosis in C-SCLC. P-SCLC and C-SCLC are heterogeneous diseases characterized by different molecular subtype expressions and genomic profiles. Our data provide a basis for adopting histological subtype-based treatments, and further prospective studies are required to confirm our conclusions.

Expression of YT Domain Family Protein in Oral Squamous Cell Carcinoma and Its Correlation with the Prognosis.

Background: Proteins contained in the conserved YTH521-b homologous (YTH) domain, have m6A-dependent RNA binding activity. As an important part of YTH domain family proteins, YTHDF1 and YTHDF3 were shown to be associated with many cancers. This paper aimed to reveal the relationship between the expression of these two proteins and the clinical prognosis of OSCC, providing certain guidance for clinical treatment of OSCC. Methods: We detected the expression of YTHDF1 and YTHDF3 in 120 OSCC patients by immunohistochemical analysis. Statistical analysis was used to determine whether the high or low expression of these two genes was significantly associated with age, gender, histological type, clinical stage, or lymph node metastasis. The correlation curve and survival curve of the two genes were produced to evaluate the potential clinical significance. Results: We find the expression of YTHDF1 and YTHDF3 was increased in OSCC tissues compared to adjacent normal tissues. The statistical analysis showed that the expression of YTHDF1 and YTHDF3 was significantly associated with the clinical stage and histological type in OSCC patients. There was also a significant correlation between the expression of YTHDF1 and YTHDF3. A high expression of YTHDF1 and YTHDF3 was related to poor patient prognosis. Conclusion: Our findings suggest that a high expression of YTHDF1 and YTHDF3 may be related to poor patient prognosis.

Deep Learning-Based Classification and Targeted Gene Alteration Prediction from Pleural Effusion Cell Block Whole-Slide Images.

Cytopathological examination is one of the main examinations for pleural effusion, and especially for many patients with advanced cancer, pleural effusion is the only accessible specimen for establishing a pathological diagnosis. The lack of cytopathologists and the high cost of gene detection present opportunities for the application of deep learning. In this retrospective analysis, data representing 1321 consecutive cases of pleural effusion were collected. We trained and evaluated our deep learning model based on several tasks, including the diagnosis of benign and malignant pleural effusion, the identification of the primary location of common metastatic cancer from pleural effusion, and the prediction of genetic alterations associated with targeted therapy. We achieved good results in identifying benign and malignant pleural effusions (0.932 AUC (area under the ROC curve)) and the primary location of common metastatic cancer (0.910 AUC). In addition, we analyzed ten genes related to targeted therapy in specimens and used them to train the model regarding four alteration statuses, which also yielded reasonable results (0.869 AUC for ALK fusion, 0.804 AUC for KRAS mutation, 0.644 AUC for EGFR mutation and 0.774 AUC for NONE alteration). Our research shows the feasibility and benefits of deep learning to assist in cytopathological diagnosis in clinical settings.

Ionomers Modify the Selectivity of Cu-Catalyzed Electrochemical CO2 Reduction.

Electrochemical reduction of carbon dioxide (CO2 RR) to produce energy-rich fuels using copper-based electrocatalysts is widely studied as a possible solution to CO2 recycling. Ionomers are commonly used as binders to prepare catalyst-loaded electrodes, but their effects on the performance have not been fully investigated. In this study, electrochemical and operando Raman spectroscopic measurements are used to study the effects of three archetypical ionomers [Nafion, Sustainion-type XA-9, and poly(terphenyl piperidinium) (PTP)] on Cu-catalyzed CO2 reduction at high current densities (up to 200 mA cm-2 ). Nafion is found to have little influence, whereas XA-9 promotes the formation of CO over multicarbon products and PTP favors hydrogen and formate production. Charge and hydrophobicity/hydrophilicity are found to be important parameters of the ionomers. The observed effects are attributed to the charge transfer between Cu and XA-9 weakening the CO adsorption energy, whereas the hydrophilicity of PTP reduces M-H energy. This study reveals the structure-sensitive nature of the ionomer-catalyst interaction in CO2 RR.

Natural-human driving factors of groundwater salinization in a long-term irrigation area.

Salinization of groundwater is a major challenge for groundwater management in long-term irrigation areas, decoupling its complex influencing factors can provide insights for the sustainable development of irrigation areas. In this study, the natural-human driving factors of groundwater salinization in the Yinchuan Plain, a typical irrigated area, were identified using isotope analysis, information entropy, and self-organizing map. Results show that groundwater in the study area is seriously salinized with obvious spatial heterogeneity. Multiple natural conditions and frequent human activities complicate the salinization characteristics of groundwater. On this basis, four typical natural influence units of groundwater were identified, namely, an evaporation and upward leakage zone, a runoff zone, an evaporation zone, and a runoff and upward leakage zone. Information entropy was proposed to quantify the complexity of groundwater resulting from human activities: The complexity difference between densely populated areas and natural dominant areas is mainly reflected in Na+, SO42-, and Cl-. Multiple human-made drivers of complex water environment were further separated into three patterns by the SOM model: blockage-evaporation type, leakage-evaporation type, and irrigation type. The blockage of drainage ditches and obstruction of salt discharge has the highest impact on the salinization of groundwater, followed by irrigation activities and transportation losses. Water excessive stagnation caused by blockage or irrigation is the root cause of groundwater salinization in the irrigated area, and its impact is greater than that of the traditional understanding of groundwater level rise. Based on the evaluation of irrigation water quality, management initiatives for irrigated areas should prioritize dredging and maintaining a healthy soil and groundwater environment in tandem.