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Mapping Wastewater Pathogens and Their Associated Environmental and Public Health Risk Factors: A Systematic Review and Meta-Analysis.

BACKGROUND: Wastewater-based epidemiology (WBE) has emerged as a critical tool for public health surveillance, yet its application across diverse pathogens and geographical settings remains inconsistent. This systematic review synthesizes global evidence on wastewater surveillance to identify associated risk factors. METHODS: Following PRISMA 2020 guidelines (PROSPERO: CRD420261297382), a systematic search was conducted across PubMed, Scopus, Google Scholar, and Web of Science for studies published between 2000 and 2025. RESULTS: Thirty-nine peer-reviewed studies were included. The evidence base is geographically skewed toward the European Region (48.7%) and the Americas (23.1%), with significant underrepresentation in LMICs. Viruses were the primary biological target (89.7%), followed by bacteria (7.7%) and parasites (2.6%). A proportion meta-analysis of 31 eligible studies demonstrated a pooled wastewater pathogen detection prevalence of 62% (95% CI: 47.5-74.6%), with the European Region yielding the highest regional estimate (73%) and the African Region the lowest (8.3%). Conventional PCR and sequencing methods showed higher pooled detection rates (92.4% and 90.1%, respectively) than RT-qPCR (47.9%). CONCLUSION: WBE provides a robust early-warning system indicating a need for broader pathogen diversity, incorporating bacterial and parasitic surveillance and expansion into rural and resource-limited regions.

Contamination

Selective and sensitive colorimetric sensing of carbosulfan based on BiO2-x/Bi2O2.75 nanosheets with excellent haloperoxidase-like activity.

The development of colorimetric methods based on directly inhibiting nanozyme activity for pesticide detection has attracted considerable attention. In this study, we report a novel colorimetric sensing strategy utilizing BiO2-x/Bi2O2.75 nanosheets (BiO2-x/Bi2O2.75 NSs) with haloperoxidase (HPO)-like activity for the rapid and sensitive detection of carbosulfan (CBS) in foods. Oxygen-vacancy-rich BiO2-x/Bi2O2.75 NSs with HPO-like activity were rationally constructed. Kinetic studies revealed a remarkable Michaelis-Menten constant (Km) of 0.014 mM for I-, indicating a higher affinity for iodide ions than other reported HPO-like nanozymes, as evidenced by its lower Km. Under acidic conditions, CBS tends to be hydrolyzed to produce reductive sulfide species, which directly inhibit the iodoperoxidase-like activity of BiO2-x/Bi2O2.75 NSs, enabling selective detection with a limit of detection (LOD) of 0.18 μg/mL and a linear range of 0.20-100 μg/mL. When the concentration of interfering pesticides and substances was 5 times that of CBS, the sensor remained unaffected, exhibiting excellent stability and specificity. This work contributes to the detection of CBS in complex food matrices, bridging the application gap of HPO-like nanozymes in pesticide detection and providing a promising method for food safety detection.

Colorimetry

Metabolomic differences in the Ophiura sarsii complex from the Yellow Sea Cold Water Mass and Bering Sea Cold Pool.

Metabolomics provides a functional readout of cellular physiology and can reveal metabolite-level differences associated with environmental and evolutionary contexts. Here, we used GC-MS- and LC-MS-based metabolomics to characterize metabolic profiles of the Ophiura sarsii complex from the Yellow Sea Cold Water Mass (YSCWM) and the Bering Sea Cold Pool (BSCP). This metabolomics analysis identified 398 LC-MS/MS and 87 GC-MS/MS differential metabolites (DEMs). Marked metabolic differences were observed between the two taxa, involving antioxidant-related metabolites, central carbon-related intermediates, osmolyte-associated compounds, and membrane lipid components. O. sarsii vadicola from the YSCWM showed higher levels of glutathione, glucose, citric acid, D-ribulose 5-phosphate, and unsaturated lipid-related metabolites, indicating differences in antioxidant-related and energy-associated metabolic profiles. By contrast, O. sarsii from the BSCP was characterized by higher levels of sugar alcohols, particularly myo-inositol, together with differences in membrane lipid-associated metabolites. These results provide metabolomics-based evidence for metabolite-level physiological differences between two members of the O. sarsii complex sampled from the Yellow Sea Cold Water Mass and the Bering Sea Cold Pool, while the relative contributions of lineage divergence and site-specific environmental variation remain to be tested experimentally.

Metabolomics

Functional neuroimaging subtypes of obsessive-compulsive disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) exhibits substantial clinical heterogeneity that may reflect underlying neurobiological diversity. Neuroimaging-based subtyping may advance precision psychiatry by identifying biologically distinct subgroups with differential treatment responses. This study systematically synthesized evidence from functional neuroimaging subtyping studies in OCD to identify reproducible neurobiological subtypes, characterize their clinical profiles, and establish a consensus-based classification framework. We reviewed 40 original studies employing machine learning, clustering, normative modeling, or classification approaches, encompassing approximately 8,150 patients. Consensus clustering identified three reproducible neurobiological subtypes. The Limbic-Hyperactive subtype, comprising approximately 40% of patients, exhibited amygdala and insula hyperconnectivity, elevated anxiety levels, predominant contamination and washing symptoms, and favorable response to cognitive-behavioral therapy. The Fronto-Striatal-Hypoconnected subtype, comprising approximately 35% of patients, demonstrated reduced orbitofrontal-striatal connectivity, cognitive inflexibility, predominant checking and ordering symptoms, and a favorable response to selective serotonin reuptake inhibitors. The Global-Disrupted subtype, comprising approximately 25% of patients, exhibited widespread connectivity disruption, greater symptom severity, and poor treatment response. Support vector machine classification achieved 81.5% accuracy for subtype assignment, though classification of OCD versus healthy controls showed limited generalizability in multisite settings (AUC 0.567-0.673). These findings support a neuroimaging-based framework for personalized treatment selection but require prospective validation.

Humans

Influenza as a Less Commonly Recognized Cause of Hemophagocytic Lymphohistiocytosis: A Systematic Review of Case Reports and Case Series.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory condition that can be triggered by viral infections. However, influenza is not commonly recognized as a cause of HLH, and there is no comprehensive synthesis of influenza-associated HLH in the literature to guide clinicians. We conducted a systematic search of Pubmed and Embase to identify case reports and case series on influenza-associated HLH, and included 29 articles involving 47 patients. Their age ranged from 2 months to 72 years. 67% were males. Influenza A accounted for 91.3% of the cases, predominantly H1N1 (90.2%). All patients had fever, 60% had anemia, 69.7% had thrombocytopenia, 46.6% had leukopenia, 61.3% had splenomegaly, 71.4% had hypertriglyceridemia, and 94.7% had elevated ferritin levels. 97.6% had hemophagocytosis on biopsy. Antiviral therapy was administered in 89.5% of patients. HLH-directed therapy included corticosteroids (77%), intravenous immunoglobulin (36%), and etoposide (23.1%). Intensive care was required in 95.2% of cases. Overall survival was 53.2%. Survival rate was 50% among patients who received either antiviral therapy alone or HLH-directed therapy alone, compared with 65.4% among those who received both. Further studies are necessary to establish standardized diagnostic and therapeutic protocols for influenza-associated HLH.

Humans

Genome-wide scans reveal candidate genes associated with wing morph differentiation in Tetrix japonica.

Wing dimorphism is an important dispersal-related trait in insects, but its genomic basis remains poorly understood in pygmy grasshoppers. Here, we integrated genome-wide single-nucleotide polymorphism (SNP) analyses, population structure inference, selection scans, and functional annotation to investigate genomic differentiation between long- and short-winged Tetrix japonica. Principal component analysis (PCA), ADMIXTURE, and phylogenetic analyses revealed weak genome-wide separation between morphs, indicating differentiation on a largely shared genetic background. Genome-wide scans based on the fixation index (FST), nucleotide diversity ratios, and Tajima's D, using 50-kb non-overlapping windows and empirical top-5% outlier thresholds, identified multiple candidate regions across seven chromosomes. The broader long- and short-winged candidate sets spanned 9.35 Mb and 9.37 Mb and directly overlapped 82 and 77 genes, respectively. Candidate genes were associated with signaling/hormone regulation, membrane transport, metabolism, cytoskeletal organization, extracellular matrix structure, and development. Short-winged candidate genes were significantly enriched for ABC-type transporter activity and ATP hydrolysis activity. Because all individuals originated from a single laboratory-maintained population with weak genome-wide structure, these regions should be regarded as candidate loci from a screening-stage analysis that require validation in independent populations and by functional assays, rather than as confirmed targets of selection.

Animals

Malaria rapid diagnostic tests: performance, pitfalls, and progress.

PURPOSE OF REVIEW: Malaria rapid diagnostic tests (RDTs) have revolutionized malaria diagnosis in endemic settings. RDTs are simple to use and accurate for clinical cases, although sensitivity is reduced at parasite densities below 200 parasites/μl. However, increasing prevalence of hrp2/3 gene deletions in certain areas threaten utility of histidine-rich protein 2 (HRP2)-based RDTs, and lingering HRP2 antigenemia can generate false-positive results after parasite clearance. This review summarizes current performance of malaria RDTs, threats to their validity, and recent innovations to improve their performance and continued role in malaria diagnosis. RECENT FINDINGS: Most World Health Organization (WHO) prequalified RDTs perform well for clinical diagnosis, with only occasional exceptions, including a recently reported issue affecting several countries. RDT sensitivity is generally related to malaria transmission intensity, with higher proportions of false-negative results in lower-transmission areas. Newly prequalified lactate dehydrogenase (pLDH)-based RDTs perform well for both Plasmodium falciparum in areas with >5% hrp2/3 gene deletions and for Plasmodium vivax diagnosis. Several point-of-care alternatives to RDTs, including micro-fluidic devices, hemozoin-detecting devices, and automated hematology analyzers, have shown promising results in small studies, but require larger-scale trials before widespread use. SUMMARY: RDTs remain a critical tool in clinical diagnosis of malaria, and newer pLDH-based tests perform well in areas where hrp2/3 gene deletions threaten validity of HRP2-based RDTs.

Humans

Three-dimensional porous nano-hydroxyapatite@gelatin composite as efficient adsorbent for uranyl ion removal from low-level radioactive wastewater.

The contamination of water resources by uranyl (UO22+) ions poses significant environmental and health risks, requiring the development of efficient and sustainable remediation strategies. Adsorption-based techniques have emerged as promising approaches in the field of UO22+ removal, but the design of cost-effective, high-capacity, and environmentally friendly adsorbents remains challenging. In this study, a three-dimensional porous nano-hydroxyapatite@gelatin (nHAP@Ge) composite was synthesized through glutaraldehyde cross-linking, combining the structural stability of Ge with the high uranium affinity of nHAP. The optimized nHAP@Ge, with a nHAP:Ge mass ratio of 1:0.5, exhibited exceptional UO22+ removal efficiency (97 %), along with high adsorption capacity (364.03 mg/g). Systematic characterizations using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, and X-ray photoelectron spectroscopy (XPS) methods revealed that the porous structure and surface functional groups (-OH, Ca2+, and PO43-) of the material synergistically contributed to binding UO22+ species. Furthermore, the incorporation of nHAP into the Ge framework resulted in enhanced thermal stability while significantly improving the UO22+ adsorption performance. This work presents a scalable, eco-friendly, and recyclable strategy for the effective treatment of uranium-contaminated water, with potential applications in nuclear wastewater treatment and environmental remediation.

Adsorption

Biallelic Variants in ATP1A4 Are Associated with Oligoasthenoteratozoospermia and Male Infertility.

Male infertility, often caused by structural and functional sperm defects, remains genetically unexplained in a substantial proportion of cases. ATP1A4 encodes a testis-specific isoform of the Na+, K+-ATPase, a membrane enzyme crucial for maintaining cellular ionic homeostasis. Previous studies on Atp1a4 knockout mice have demonstrated severe defects in sperm motility and flagellar architecture; however, the contribution of ATP1A4 variants to human male reproduction remains to be elucidated. In this study, we identified compound biallelic variants in ATP1A4, a missense variant (c.2578 T>A, p.Tyr860Asn) and a frameshift variant (c.2582del, p.Gly861Aspfs*5), in a patient presenting with severe oligoasthenoteratozoospermia. Both variants markedly affected ATP1A4 protein expression. Morphological analyses revealed coiled and folded flagella, disrupted mitochondrial sheaths, and irregular head morphology in the patient's spermatozoa. Expression profiling revealed that ATP1A4 was highly enriched in post-meiotic spermatids and localized along the entire flagellum of mature sperm in both humans and mice, indicating a critical role in flagellar assembly and structural integrity. Notably, intracytoplasmic sperm injection (ICSI) in this patient resulted in low fertilization efficiency and failed implantation, suggesting a potential adverse impact of ATP1A4 deficiency on sperm functional competence beyond motility. These findings broaden the genetic spectrum of oligoasthenoteratozoospermia and highlight ATP1A4 as a potential gene associated with human male infertility.

Male

Application of causal discovery of factors driving dissolved oxygen in estuarine environments.

Dissolved oxygen (DO) concentrations in estuarine bottom waters are a manifestation of multiple, interacting physical and biogeochemical processes, yet identifying their independent contributions remains challenging. Here, we analyze monthly water quality monitoring data from eight stations across Long Island Sound from 1994 to 2022 using a causal discovery framework (PCMCI+) and transformation of forcing variables. Our goal is to identify and isolate variables that causally influence bottom DO and improve predictive models by minimizing overfitting and multicollinearity. PCMCI+ reveals surface-layer temperature as the most important and consistent negative driver of bottom DO, followed by stratification. Wind events exhibit only brief relief by advection and mixing, while river discharge shows no direct causal link to DO, making it less influential than previously thought. Biogeochemical variables, including chlorophyll-a (Chl-a), nitrate and nitrite, and particulate carbon, influence DO through both contemporaneous and time-lagged pathways, often with signs that shift depending on the process. The derived models were evaluated by comparing skill scores, mean squared error, and Akaike Information Criterion. Both model types perform well, with coefficient of determination values exceeding 0.90 at multiple stations using only 3-5 predictors. Our analysis reveals that the best causal predictors are surface-layer temperature, stratification, Chl-a, and particle carbon. This approach provides a scalable framework for improving prediction models and understanding the mechanistic links that control the seasonal variability of DO in estuarine systems.

Estuaries

Are there any common effects in preclinical models of micro- and nanoplastic (MNP) exposure? A systematic review.

Micro- and nanoplastics (MNPs) are emerging contaminants detected in food sources and the marine food chain, raising concerns about human health. Although no causal relationship has been established between MNP exposure and specific diseases, growing evidence suggests adverse developmental, behavioral, cognitive and biochemical effects. This systematic review synthesized evidence from common preclinical neurotoxicology models, including C. elegans, D. rerio, D. melanogaster, in vitro systems and rodents, to identify convergent developmental, behavioral and biochemical outcomes. The protocol was preregistered in OSF, followed PRISMA-P guidelines, applied PICOS criteria, and assessed methodological quality using the European Commission's ToxRTool. Overall, 185 studies were included. Consistent findings showed impaired survival and disrupted development across all models. Behavioral alterations affecting anxiety, memory, learning, sociability and locomotor activity were also consistently reported. In addition, numerous studies identified disruptions in the serotonergic (5-HT) system, including changes in neurotransmitter levels, transporters and metabolic enzymes. Despite methodological heterogeneity, these findings indicate that MNP exposure produces reproducible neurodevelopmental and neurochemical alterations across experimental models. Future studies should improve methodological harmonization, strengthen cross-model comparability and identify robust biomarkers and key mechanisms underlying MNP-induced neurotoxicity, facilitating translation to human health risk assessment frameworks.

Animals

The association between normalized creatinine-to-cystatin C ratio and incident circadian syndrome in middle-aged and older adults: a national cohort study.

BACKGROUND: Evidence on the association between the normalized creatinine-to-cystatin C ratio (NCCR) and Circadian Syndrome (CircS) in the general population remains scarce. This study aimed to investigate this relationship using data from middle-aged and elderly participants in the China Health and Retirement Longitudinal Study (CHARLS). METHODS: We conducted a cross-sectional analysis of 5,981 participants (2011 wave) and a prospective cohort analysis of 2,053 participants (2015 wave, median follow-up 4.0 years). CircS was defined as a cluster including elevated blood pressure, dyslipidemia, hyperglycemia, abdominal obesity, depression, and abnormal sleep duration. RESULTS: During follow-up, 552 participants developed incident CircS. A significant inverse association was observed: the risk of new-onset CircS progressively decreased with higher baseline NCCR levels. After adjusting for multiple confounders, each standard deviation increase in NCCR was associated with a 40% reduced odds of CircS (adjusted odds ratio = 0.60, 95% confidence interval: 0.48 to 0.75). Subgroup and dose-response analyses confirmed the robustness of this inverse relationship. CONCLUSIONS: In conclusion, a lower NCCR is independently associated with an elevated risk of developing CircS. These findings support NCCR's role as a practical serum indicator of sarcopenia and implicate muscle loss as a potentially key underlying pathway in the pathogenesis of Circadian Syndrome.

Humans

Comparative analysis of genomic variations among different Cdo1 paralogs for salinity-adaptation in oysters.

Under rapid climate change and anthropogenic activities, oysters, a global aquaculture species, are subjected to exacerbated culturing environments, especially for those living in in-shore estuarine species, such as Suminoe oysters Crassostrea ariakensis. This study aims to investigate the molecular mechanisms of salinity adaptation of C. ariakensis. We performed an expression genome-wide association study (eGWAS) to compare genetic regulation among 5 paralogous copies of a key salinity-related gene, cysteine dioxygenase 1 (Cdo1). A total of 40 significant eSNPs with 82 adjacent eGenes were identified in 2 copies (Cdo1_26639 and Cdo1_1666). We identified only trans-eSNPs for Cdo1_26639 and more cis-eSNPs for Cdo1_1666, and different eGenes for these 2 Cdo1 copies, which indicated that the expressional regulation of these paralogs may undergo distinct pathways. We identified 3 eGenes that exhibited identical expression patterns with Cdo1_26639 and Cdo1_1666, including 6-Pgdh, Trapp and tandem copy of Cdo1_27337. The expression correlation between Cdo1 copies and eGenes was enhanced under salinity stresses, suggesting the crucial role of eGenes in regulating Cdo1's expression in response to salinity changes. Our results provide comprehensive identification and comparison of eSNPs across different paralogous copies of one gene, along with insights into the molecular mechanisms underlying salinity tolerance, and genetic markers for breeding salinity-resistant oysters.

Animals

Transabdominal lumbar approach (TALA) versus retroperitoneal approach for robot-assisted renal surgery: a prospective randomised controlled trial.

PURPOSE: Common robotic nephrectomy approaches access the kidney via transperitoneal (TP) or retroperitoneal (RP) routes, each with distinct trade-offs. We developed the transabdominal lumbar approach (TALA), combining advantages of both accesses with improved visualisation and strategic trocar placement, and compared it with conventional RP in a prospective randomised controlled trial using technique-oriented intraoperative endpoints. METHODS: In this single-centre, prospective, open-label RCT, 40 patients were randomised to TALA (n = 18) or conventional RP (n = 22). Eligible patients were ≥ 18 years with a renal tumour or non-functional kidney requiring robot-assisted total or partial nephrectomy. Exclusions included prior surgery on the affected kidney, renal vein tumour thrombus, and pregnancy. Both groups were followed for 30 days. The primary endpoint was time from first skin incision to renal artery identification. RESULTS: TALA achieved a median time saving of 16 min compared to conventional RP (38 vs. 54 min, p = 0.001). Perioperative safety was comparable between groups, with three patients (7.5%) experiencing Clavien-Dindo grade III-IV complications. CONCLUSIONS: TALA met its primary endpoint with a significantly shorter time to renal artery identification than conventional RP access, and improving perceived surgical exposure and instrument handling.

Humans

Impact of climate change on pediatric health outcomes.

Climate change has become one of the most critical health issues globally in the twenty-first century with children bearing the disproportionate burden of the burden since they are more vulnerable than adults because of their physiological, behavioral, and developmental capacities. It is a systematic review that rates the evidence of the relationship between climatic exposures such as heat, air-pollution, and extreme weather events and pediatric health outcomes. The number of peer-reviewed studies involved was 23 published in 2000-2025, which represented different geographic areas and study designs and assessed acute and chronic health outcomes. The Newcastle-Ottawa Scale and the ROBINS-I tool were used to evaluate the methodological quality, and the majority of the studies had low to moderate risks of bias. The narrative synthesis shows that there are always links between air pollutants especially PM2.5, NO2 and O3 and respiratory morbidity, prevalence of asthma and hospitalization of children. Amplified temperatures as well as heat waves were associated with increased cases of heat illness, dehydration, and febrile state in infants and young children. There were elevated cases of diarrheal and vector-related infections, especially in low-resource settings, which were linked to extreme weather events especially floods. Although the overall results were similar, significant differences in the regions and methods were found, and low-income countries show little evidence. In addition, exposures as analyzed in most studies were usually considered individually, which may have underestimated the cumulative or compound climate risks.

Humans

Analyzing salinity tolerance in grass carp (Ctenopharyngodon idella): Insights from genome-wide association study and genomic selection.

Grass carp (Ctenopharyngodon idella) is one of the most widely cultured freshwater fish species globally. However, the expansion of its farming scale faces severe limitation owing to freshwater scarcity; therefore, the development of strains with greater salinity tolerance is key for expanding production using brackish water resources. To investigate the genetic basis of salinity tolerance in grass carp, a genome-wide association study (GWAS) was conducted using 200 individuals representing extreme phenotypes, namely salinity-tolerant and salinity-sensitive groups. In total, 17 single nucleotide polymorphisms (SNPs) related to salinity tolerance were detected, which were distributed across 11 chromosomes. Through gene annotation, 38 candidate genes were obtained from these loci. Enrichment analysis revealed these candidate genes are primarily implicated in key biological processes, including osmotic regulation, energy metabolism, and stress responses. Analyses of different SNP densities revealed that the 5 K SNP density panel can balance prediction accuracy and computational efficiency. The BayesA model achieved the highest prediction accuracy under the GWAS_Evenly selection strategy, with substantial reductions in mean absolute error and mean square error. This study reveals the genetic mechanisms of salinity tolerance in grass carp, which might be optimized through genomic selection, and provides insights for selectively breeding new varieties with greater salinity tolerance.

Animals

Prevalence of Theileria luwenshuni in goats (Capra hircus) on Tarama Island, Okinawa, Japan.

Caprine theileriosis is an economically important tick-borne disease caused by various Theileria species, particularly Theileria lestoquardi, Theileria luwenshuni, and Theileria uilenbergi, in goats (Capra hircus). Goat farming plays an economically and culturally important role on Tarama Island, Okinawa, Japan. Because goats on the island are mainly managed under an extensive grazing system, tick infestation is common. However, Theileria infections have not previously been investigated in goats on Tarama Island. To address this, archived DNA samples prepared from blood collected from 44 goats on Tarama Island were screened using a universal PCR assay targeting 18S rRNA sequences of Theileria and Babesia species. Two DNA samples were positive, and sequencing analysis of the amplicons identified T. luwenshuni. To further investigate the epidemiology of T. luwenshuni on Tarama Island, blood samples were subsequently collected from 96 goats across 19 farms. From each blood sample, a thin blood smear was prepared and genomic DNA was extracted. Microscopic examination of Diff-Quik-stained smears detected intraerythrocytic Theileria-like organisms in 35 (36.5%) goats. In addition, screening of DNA samples using a newly developed T. luwenshuni-specific PCR assay detected 77 (80.2%) positive goats, and the subsequent sequencing analysis confirmed the PCR results. Given that T. luwenshuni can cause severe disease in small ruminants, our findings highlight the importance of managing T. luwenshuni infection in goats on Tarama Island.

Animals

Characterization of ZIC5 expression in esophageal squamous cell carcinoma and its association with patient survival.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy known for its aggressive nature and poor prognosis. The present study aimed to investigate the expression levels and clinical importance of the Zic family member 5 (ZIC5) gene in ESCC. Gene expression data and survival information obtained from The Cancer Genome Atlas and Gene Expression Omnibus were utilized. In 176 patients with surgically resected ESCC, immunohistochemical analysis was conducted to validate the expression of ZIC5 protein in cancerous and adjacent tissues. The findings of the present study revealed a significant upregulation of ZIC5 in ESCC compared with normal tissues (P<0.05), which was further corroborated by immunohistochemistry exhibiting a notable association between ZIC5 expression and clinical parameters such as tumor size, invasion depth, lymph node metastasis and TNM staging (P<0.05). Survival analysis further indicated that high ZIC5 expression was an independent prognostic factor for poor outcomes in patients with ESCC (hazard ratio=1.519; 95% CI: 1.017-2.269; P<0.05). In addition, bioinformatic analyses predicted that hsa-microRNA-212-5p may regulate ZIC5 mRNA and gene enrichment analysis suggested that ZIC5 may facilitate ESCC progression through involvement in the cell cycle and DNA repair pathways. In conclusion, ZIC5 is highly expressed in ESCC and associated with a poor prognosis, indicating its potential as a therapeutic target and biomarker for ESCC management. Further studies are warranted to elucidate the precise mechanisms underlying the role of ZIC5 in ESCC progression.

ESCC