Clinical efficacy of EUS-guided celiac plexus neurolysis versus EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain relief in advanced pancreatic cancer: A long-term retrospective study.

Background and Objective: To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (125I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer. Methods: We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-125I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups. Results: EUS-CPN and 125I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-125I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-125I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure. Conclusions: Both EUS-CPN and EUS-125I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-125I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential.

BACKGROUND: Up until now, no research has been reported on the association between the clinical growth rate of multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and computed tomography (CT) imaging characteristics. Our study sought to examine the correlation between them, with the objective of distinguishing unique features of MCRNLMP from renal cysts and exploring effective management strategies. AIM: To investigate optimal management strategies of MCRNLMP. METHODS: We retrospectively collected and analyzed data from 1520 patients, comprising 1444 with renal cysts and 76 with MCRNLMP, who underwent renal cyst decompression, radical nephrectomy, or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution. Detection of MCRNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology. RESULTS: Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP. Precisely, it comprises 1.48% of all cases involving simple renal cysts, 5.26% of those with complex renal cysts, and a noteworthy 12.11% of renal tumors coexisting with renal cysts, indicating a statistically significant difference (P = 0.001). Moreover, MCRNLMP constituted a significant 22.37% of the patient population whose cysts demonstrated a rapid growth rate of ≥ 2.0 cm/year, whereas it only represented 0.66% among those with a growth rate below 2.0 cm/year. Of the 76 MCRNLMP cases studied, none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis. In the remaining 67 patients, who were actively monitored over a 3-year postoperative period, only one showed suspicious recurrence on CT scans. CONCLUSION: MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators. In treating MCRNLMP, partial nephrectomy is preferred, while radical nephrectomy should be minimized. After surgery, active monitoring is advisable to prevent unnecessary nephrectomy.

3D-Bioprinted Hepar-on-a-Chip Implanted in Graphene-Based Plasmonic Sensors.

Precise three-dimensional (3D) bioprinting designs enable the fabrication of unique structures for 3D-cell culture models. There is still an absence of real-time detection tools to effectively track in situ 3D-cell performance, hindering a comprehensive understanding of disease progression and drug efficacy assessment. While numerous bioinks have been developed, few are equipped with internal sensors capable of accurate detection. This study addresses these challenges by constructing a 3D-bioprinted hepar-on-a-chip embedded with graphene quantum dot-capped gold nanoparticle-based plasmonic sensors, featuring strong surface-enhanced Raman scattering (SERS) enhancement, biostability, and signal consistency. Such an integrated hepar-on-a-chip demonstrates excellent capability in the secretion of liver function-related proteins and the expression of drug metabolism and transport-related genes. Furthermore, the on-site detection of cell-secreted biomarker glutathione transferase α (GST-α) was successfully achieved using the plasmonic probe, with a dynamic linear detection range of 20-500 ng/mL, showcasing high anti-interference and specificity for GST-α. Ultimately, this integrated hepar-on-a-chip system offers a high-quality platform for monitoring liver injury.

Laryngopharyngeal reflux disease: Updated examination of mechanisms, pathophysiology, treatment, and association with gastroesophageal reflux disease.

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

Immune microenvironment of human papillomavirus-positive head and neck squamous cell carcinoma.

OBJECTIVES: Research progress of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) based on immune microenvironment. METHODS: This article preliminarily discusses the composition of immune microenvironment components and immune therapy and elaborates and analyzes the involvement and impact of T cells, B cells, natural killer (NK) cells, tumor-associated fibroblasts, and bone marrow-derived suppressor cells in HPV-positive HNSCC on tumor progression and prognosis. Furthermore, the application of immune-related therapies in HPV-positive HNSCC is explored. RESULTS: It is found that immune microenvironment research plays an important role in the pathogenesis and treatment of HPV-positive HNSCC. CONCLUSIONS: Immune microenvironment research as an important means to explore tumors has played an important role in the study of HPV-positive HNSCC. We describe the biological significance of important components of HNSCC immune microenvironment by analyzing the effects of HNSCC immune microenvironment components and immunotherapy on HPV-positive HNSCC. May to provide new strategies for experimental research and clinical prevention and treatment of this disease.

Silicone oil as a corneal lubricant to reduce corneal edema and improve visualization during vitrectomy.

AIM: To evaluate the efficacy and safety of silicone oil (SO) as a corneal lubricant to improve visualization during vitrectomy. METHODS: Patients who underwent vitreoretinal surgery were divided into two groups. Group 1 was operated on with initial SO (Oxane 5700) as a corneal lubricant. Group 2 was operated on with initial lactated ringer's solution (LRS) and then replaced with SO as required. Fundus clarity was scored during the surgery. Fluorescein staining was performed to determine the damage to corneal epithelium. RESULTS: Totally 114 eyes of 114 patients were included. Single SO use maintained a clear cornea and provided excellent visualization of surgical image. In group 1, the fundus clarity was grade 3 in 41/45 eyes and grade 2 in 4/45 eyes. In group 2, corneal edema frequently occurred after initial LRS use. The fundus clarity was grade 3 in 19/69 eyes, 2 in 37/69 eyes and 1 in 13/69 eyes (P<0.05). SO was applied in 29 eyes of initial LRS use with subsequent corneal edema, which eliminated the corneal edema in 26 eyes. Corneal fluorescein staining score in group 1 was 0 in 28 eyes, 1 in 11 eyes and 2 in 6 eyes, and 40, 20 and 9, respectively, in group 2 (all P>0.05). CONCLUSION: The use of SO as a corneal lubricant is effective and safe for preserving and improving corneal clarity and providing clear surgical field during vitrectomy.

Exploring ecological effects of arsenic and cadmium combined exposure on cropland soil: from multilevel organisms to soil functioning by multi-omics coupled with high-throughput quantitative PCR.

Arsenic (As) and cadmium (Cd) pose potential ecological threats to cropland soils; however, few studies have investigated their combined effects on multilevel organisms and soil functioning. Here, we used collembolans and soil microbiota as test organisms to examine their responses to soil As and Cd co-contamination at the gene, individual, and community levels, respectively, and further uncovered ecological relationships between pollutants, multilevel organisms, and soil functioning. At the gene level, collembolan transcriptome revealed that elevated As concentrations stimulated As-detoxifying genes AS3MT and GST, whereas the concurrent Cd restrained GST gene expression. At the individual level, collembolan reproduction was sensitive to pollutants while collembolan survival wasn't. At the community level, significant but inconsistent correlations were observed between the biodiversity of different soil keystone microbial clusters and soil As levels. Moreover, soil functioning related to nutrient (e.g., carbon, nitrogen, phosphorus, and sulfur) cycles was inhibited under As and Cd co-exposure only through the mediation of plant pathogens. Overall, these findings suggested multilevel bioindicators (i.e., AS3MT gene expression in collembolans, collembolan reproduction, and biodiversity of soil keystone microbial clusters) in cropland soils co-contaminated with As and Cd, thus improving the understanding of the ecotoxicological impact of heavy metal co-contamination on soil ecosystems.

Pulmonary artery aneurysm protruding into the bronchus as an endobronchial mass: A case report.

BACKGROUND: Pulmonary artery (PA) aneurysms are usually diagnosed radiographically and present as small or large lesions resembling inflammation or a neoplasm on chest radiography. It has rarely been reported as an endobronchial mass. CASE SUMMARY: We report the case of a 64-year-old man who presented with recurrent hemoptysis. Bronchoscopy revealed a tumorous protrusion blocking the right middle lobe bronchus, which was confirmed to be a PA aneurysm using endobronchial ultrasound bronchoscopy and computed tomography angiography. CONCLUSION: Although endobronchial PA aneurysms are rare, bronchoscopists need to add this lesion to the list of endobronchial masses for which a biopsy is to be assiduously avoided.

Knockdown of LINC01087 inhibits gastric cancer malignant behavior by regulating the miR-135a-5p/CAAP1 axis.

Long noncoding RNAs play important roles in the occurrence and development of many malignant cancers. This study focuses on the effects of LINC01087 on gastric cancer and its underlying mechanism. In the present study, LINC01087 and CAAP1 were found to be upregulated, and miR-135a-5p was diminished in gastric cancer specimens and cells. Inhibition of LINC01087 resulted in cell proliferation inhibition and induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-3 and caspase-9. An investigation of the signaling pathway revealed that the effects on proliferation and apoptosis following LINC01087 knockdown were mediated by suppression of CAAP1. Furthermore, application of a miR-135a-5p inhibitor or overexpression of CAAP1 could attenuate the apoptotic effect achieved by LINC01087 inhibition, confirming the involvement of miR-135a-5p/CAAP1 signaling in the occurrence of gastric cancer. In conclusion, the LINC01087/miR-135a-5p/CAAP1 axis modulates gastric cancer tumorigenesis and pathogenesis and presents new insight into gastric cancer targeted therapy.

Functional reconstruction of the impaired cortex and motor function by hMGEOs transplantation in stroke.

Stroke is the leading cause of death and long-term disability worldwide. But treatments are not available to promote functional recovery, and efficient therapies need to be investigated. Stem cell-based therapies hold great promise as potential technologies to restore function in brain disorders. Loss of GABAergic interneurons after stroke may result in sensorimotor defects. Here, by transplanting human brain organoids resembling the MGE domain (human MGE organoids, hMGEOs) derived from human induced pluripotent stem cells (hiPSCs) into the infarcted cortex of stroke mice, we found that grafted hMGEOs survived well and primarily differentiated into GABAergic interneurons and significantly restored the sensorimotor deficits of stroke mice for a long time. Our study offers the feasibility of stem cell replacement therapeutics strategy for stroke.

Periosteum-derived mesenchymal stem cell alleviates renal fibrosis through mTOR-mediated Treg differentiation.

BACKGROUND: Mesenchymal stem cells (MSCs) are the hotspots of cellular therapy due to their low immunogenicity, potent immunoregulation, and unique renoprotection. The present study aimed to investigate the effects of periosteum-derived MSCs (PMSCs) in ischemia-reperfusion (IR)-mediated renal fibrosis. METHODS: Using cell proliferation assay, flow cytometry, immunofluorescence, and histologic analysis, the differences in cell characteristics, immunoregulation, and renoprotection of PMSCs were compared to the bone marrow-derived MSCs (BMSCs), the most frequently studied stem cells in cellular therapy. In addition, the mechanism of PMSC renoprotection was investigated by 5' end of the RNA transcript sequencing (SMART-seq) and mTOR knockout mice. RESULTS: The proliferation and differentiation capabilities of PMSCs were stronger than those of BMSCs. Compared with BMSCs, the PMSCs exerted a better effect on alleviating renal fibrosis. Meanwhile, the PMSCs more effectively promote Treg differentiation. Treg exhaustion experiment indicated that Tregs exerted an important effect on inhibiting renal inflammation and acted as a critical mediator in PMSC renoprotection. Additionally, SMART-seq results implied that the PMSCs promoted Treg differentiation, possibly via the mTOR pathway. In vivo and in vitro experiments showed that PMSC inhibited mTOR phosphorylation of Treg. After mTOR knockout, the PMSCs failed to promote Treg differentiation. CONCLUSIONS: Compared with BMSCs, the PMSCs exerted stronger immunoregulation and renoprotection that was mainly attributed to PMSC promotion for Treg differentiation by inhibiting the mTOR pathway.

Cerebral organoids transplantation repairs infarcted cortex and restores impaired function after stroke.

Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke. Months later, we found that the grafted organoids survived well in the infarcted core, differentiated into target neurons, repaired infarcted tissue, sent axons to distant brain targets, and integrated into the host neural circuit and thereby eliminated sensorimotor defect behaviors of stroke mice, whereas transplantation of dissociated single cells from organoids failed to repair the infarcted tissue. Our study offers a new strategy for reconstructing infarcted tissue via organoids transplantation thereby reversing stroke-induced disability.

Siraitia grosvenorii (Swingle) C. Jeffrey: Research Progress of Its Active Components, Pharmacological Effects, and Extraction Methods.

Siraitia grosvenorii (Swingle) C. Jeffrey, a perennial vine of the Cucurbitaceae family, is a unique medicine food homology species from China. S. grosvenorii can be used as a natural sweetener in the food industry and as a traditional medicine for moistening the lungs, quenching a cough, smoothing the intestines, and relieving constipation. Additionally, the fruits, roots, stems, and leaves of S. grosvenorii are rich in active ingredients, and have pharmacological effects such as immune regulation, hypoglycemia, and antioxidant, hepatoprotective, and antitumor effects, etc. Therefore, S. grosvenorii has broad application prospects in the pharmaceutical industry. This paper reviews the bioactive components, pharmacological effects, and extraction methods of S. grosvenorii, summarizes them, and proposes their future development directions. This current overview highlights the value of S. grosvenorii. By documenting the comprehensive information of S. grosvenorii, the review aims to provide the appropriate guidelines for its future in-depth development and the utilization of S. grosvenorii resources for their roles as active ingredient (triterpenoids, flavonoids, and polysaccharides, etc.) sources in the food industry and in the development of functional foods.

Application of Hi-C technology in three-dimensional genomics research and disease pathogenesis analysis.

3D genomics aims to investigate the spatial structure of chromatin in the nucleus on the basis of genomic sequences, gene structures and relevant regulatory elements. The spatial organization of chromosomes is fundamental for gene expression regulation. Recent advances of high-throughput chromosome conformation capture (Hi-C) technology and its derivatives, has enabled capture of chromatin architecture with high resolution. In this review, we summarize the development and applications of various technologies of 3D genomes in disease research, particularly in the elucidation of pathogenic mechanisms in cancers and other systemic disorders.

Heterogeneity in the immune microenvironment of bone metastasis in driver-positive non-small cell lung cancer.

Mutations in epidermal growth factor receptor and anaplastic lymphoma kinase are common driver events in non-small cell lung cancer (NSCLC), which are associated with a high frequency of bone metastases (BMs). While the bone marrow represents a specialized immune microenvironment, the immune repertoire of BMs remains unknown. Considering the higher incidence of BMs in driver gene-positive NSCLCs, and the unique biology of the bone, herein, we assessed the infiltrating immune cells and T cell receptor (TCR) profile of BMs in driver-positive NSCLCs. Immune profile of BMs in driver gene-positive NSCLC were assessed in 10 patients, where 6 had driver gene-positive mutation. TCR and bulk RNA sequencing were performed on malignant bone samples. The diversity and clonality of the TCR repertoire were analyzed. The cellular components were inferred from bulk gene expression profiles computationally by CIBERSORT. Although BMs were generally regarded as immune-cold tumors, immune cell composition analyses showed co-existence of cytotoxic and suppressor immune cells in driver-positive BM samples, as compared to primary lung. Analysis of the TCR repertoire indicated a trend of higher diversity and similar clonality in the driver-positive compared with the driver-negative subsets. In addition, we identified two cases that showed the opposite response to immune checkpoint blockade. A comparison of these two patients' BM samples showed more highly amplified clones, fewer M2 macrophages and more activated natural killer cells in the responder. In summary, BMs in NSCLC are heterogeneous in their immune microenvironment, which might be related to differential clinical outcomes to immune checkpoint blockade.

Wheat Selenium-binding protein TaSBP-A enhances cadmium tolerance by decreasing free Cd2+ and alleviating the oxidative damage and photosynthesis impairment.

Cadmium, one of the toxic heavy metals, robustly impact crop growth and development and food safety. In this study, the mechanisms of wheat (Triticum aestivum L.) selenium-binding protein-A (TaSBP-A) involved in response to Cd stress was fully investigated by overexpression in Arabidopsis and wheat. As a cytoplasm protein, TaSBP-A showed a high expression in plant roots and its expression levels were highly induced by Cd treatment. The overexpression of TaSBP-A enhanced Cd-toleration in yeast, Arabidopsis and wheat. Meanwhile, transgenic Arabidopsis under Cd stress showed a lower H2O2 and malondialdehyde content and a higher photochemical efficiency in the leaf and a reduction of free Cd2+ in the root. Transgenic wheat seedlings of TaSBP exhibited an increment of Cd content in the root, and a reduction Cd content in the leaf under Cd2+ stress. Cd2+ binding assay combined with a thermodynamics survey and secondary structure analysis indicated that the unique CXXC motif in TaSBP was a major Cd-binding site participating in the Cd detoxification. These results suggested that TaSBP-A can enhance the sequestration of free Cd2+ in root and inhibit the Cd transfer from root to leaf, ultimately conferring plant Cd-tolerance via alleviating the oxidative stress and photosynthesis impairment triggered by Cd stress.

Hepar-on-a-sensor-platform with hybridization chain reaction amplification strategy to intuitively monitor the hepatoxicity of natural compounds.

The irrational use of natural compounds in the treatment of diseases can lead to serious side effects, especially hepatoxicity, and its toxic effects are usually cumulative and imperceptible. Therefore, an accurate sensing platform is urgently needed to monitor the hepatotoxicity of natural compounds. Here, we deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and a thorough validation was adopted to evaluate the bioprinted hepatic constructs. The engineered hepar-platform was then employed to access its biological response toward Emodin (EM) and Triptolide (TP), two typical hepatotoxic natural compounds. Subsequently, we integrated it with a robust fluorescent sensor based on hybridization chain reaction amplification strategy (HCR) to monitor the early hepatotoxic biomarker - glutathione-S-transferase-alpha (GST-α) secreted by this 3D constructs. Our study was the first attempt to construct an accurate hepar-on-a-sensor platform that could effectively detect GST-α for monitoring the hepatoxic effects of natural compounds. The limit of detection of the platform was 0.3 ng ml-1 and the accuracy of this platform was verified by enzyme linked immunosorbent assay. Furthermore, the variation of GST-α induced by EM and TP was consistent with hepatotoxicity studies, thus providing an important application value for evaluating the hepatotoxicity of natural compounds. STATEMENT OF SIGNIFICANCE: 1. We deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and elucidated the essential reasons why hybrid bioinks more suitable for 3D extrusion from biomaterials itself. Also, a thorough validation associated with a series of important proteins and genes involved in liver cell metabolism was adopted to evaluate the bioprinted hepatic constructs accurately 2. Glutathione-S-transferase-alpha is a soluble trace biomarker for acute hepatotoxic injury, the hepatotoxic effects of natural compounds on the secretion of GST-α has not been reported to date. We integrated our 3D hepar-platform with recognition molecules-aptamers and HCR amplification strategy to monitor the variation of GST-α, aiming at developing a robust and stable fluorescent biosensing platform to monitor the hepatoxicity of natural compounds.

Supramolecular self-assembled AIE molecules are used in the search for target proteins in norcantharidin.

Norcantharidin (NCTD), a demethylated derivative of cantharidin, is an anticancer active component in traditional Chinese medicine. At present, the main methods for finding its target proteins are pharmacological methods and biophysical screening, which cannot achieve the purpose of efficient and accurate screening. Here we established a new analytical method for specific fishing and assisted imaging for norcantharidin target proteins. For the AIE supramolecule probe, the benzophenone azide (BPA) fluorescent nanoparticles with strong AIE properties were encapsulated in biocompatible DSPE-PEG that covalently coupled with NCTD (named BPA@NCTD NPs). The target proteins of NCTD can be captured by BPA@NCTD NPs, and then be detected to investigate the potential signaling pathways. The screened differential proteins were analysed through the protein and signaling pathway database, and multiple signaling pathways were obtained and verified. The mechanism of norcantharidin in inhibiting the migration and invasion of A549 cells through the P53 signaling pathway was confirmed by Western blot experiments. Our research showed that AIE supramolecule probe BPA@NCTD NPs has the dual functions of specific screening of A549 cells target proteins and biological imaging, which not only offers a good anti-fluorescence quenching ability for the dynamic imaging process of NCTD, but also provides a novel and efficient specific method for efficient analysis of target proteins and signal pathways.

Variation in pollution status, sources, and risks of soil heavy metals in regions with different levels of urbanization.

Soil heavy metal (HM) pollution is an increasing threat to ecosystem integrity and human health with rapid urbanization. Nevertheless, how soil HMs vary with the process of urbanization remains unclear. Here we used index evaluation, spatial analysis, and a positive matrix factorization (PMF) model to determine the pollution characteristics and sources of eight soil HMs (Mn, Cr, Cu, Zn, As, Cd, Pb, and Ni) among regions with different urbanization levels (urban area, suburb, and ecoregion) in Baoding City, Northern China. We also assessed the risks posed to the ecosystem and human health using risk assessment models. The results indicated that the mean levels of Cu, Zn, As, Cd, and Pb in the study area exceeded the soil environmental quality standards by 10.7 %, 10.7 %, 12.5 %, 23.2 %, and 3.57 %, respectively. A pronounced regional spatial distribution was discovered with high levels in suburban areas. Both the geo-accumulation index and potential ecological risk index revealed significantly higher HM contamination in suburban areas than in urban or ecoregion areas. Source apportionment based on the PMF model and correlation analysis showed that soil HMs in suburban areas primarily originated from agricultural activity, industrial sources, and natural sources. Those in urban soils originated from industrial sources, urban traffic, and natural sources, whereas those in ecoregions derived from natural sources and agricultural activity. The complex sources of soil HMs in suburban areas resulted in the highest carcinogenic risks to children health, followed by the ecoregion, but not in urban areas. This study identified the differences in pollution levels, sources, and risks of soil HMs among regions with different urbanization levels and can guide future efforts to mitigate and manage soil HM pollution during urbanization.