Integrated Physiologic and Proteomic Analyses Reveal the Molecular Mechanism of Navicula sp. in Response to Ultraviolet Irradiation Stress.

With the continuous development of space station construction, space ecosystem research has attracted increasing attention. However, the complicated responses of different candidate plants and algae to radiation stress remain unclear. The present study, using integrated physiologic and proteomic analyses, was carried out to reveal the molecular mechanism of Navicula sp. in response to ultraviolet (UV) irradiation stress. Under 12~24 h of high-dose UV irradiation conditions, the contents of chlorophyll and soluble proteins in Navicula sp. cells were significantly higher than those in the control and 4~8 h of low-dose UV irradiation groups. The activity of catalase (CAT) increased with the extension of irradiation time, and the activity of superoxide dismutase (SOD) decreased first and then increased. Furthermore, differential volcano plot analysis of the proteomic data of Navicula sp. samples found only one protein with a significant difference. Differential protein GO analysis unveiled that UV irradiation can activate the antioxidant system of Navicula sp. and further impact photosynthesis by affecting the photoreaction and chlorophyll synthesis of Navicula sp. The most significant differences in KEGG pathway analysis were also associated with photosynthesis. The above results indicate that Navicula sp. has good UV radiation resistance ability by regulating its photosynthetic pigment content, photosynthetic activity, and antioxidant system, making it a potential candidate for the future development of space ecosystems.

The Role of TGF-ß/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with high incidence and mortality, accounting for approximately 90% of liver cancer. The development of HCC is a complex process involving the abnormal activation or inactivation of multiple signaling pathways. Transforming growth factor-ß (TGF-ß)/Small mothers against decapentaplegic (SMAD) signaling pathway regulates the development of HCC. TGF-ß activates intracellular SMADs protein through membrane receptors, resulting in a series of biological cascades. Accumulating studies have demonstrated that TGF-ß/SMAD signaling plays multiple regulatory functions in HCC. However, there is still controversy about the role of TGF-ß/SMAD in HCC. Because it involves different pathogenic factors, disease stages, and cell microenvironment, as well as upstream and downstream relationships with other signaling pathways. This review will summary the regulatory mechanism of the TGF-ß/SMAD signaling pathway in HCC, involving the regulation of different pathogenic factors, different disease stages, different cell populations, microenvironments, and the interaction with microRNAs. In addition, we also introduced small molecule inhibitors, therapeutic vaccines, and traditional Chinese medicine extracts based on targeting the TGF-ß/SMAD signaling pathway, which will provide future research direction for HCC therapy targeting the TGF-ß/SMAD signaling pathway.

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma.

BACKGROUND: Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM. METHODS: OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L :: AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR. RESULTS: In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L :: AHI1 and GRIK1::NSDHL , which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction. CONCLUSIONS: Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.

The regulatory metabolic networks of the Brassica campestris L. hairy roots in response to cadmium stress revealed from proteome studies combined with a transcriptome analysis.

Brassica campestris L., a cadmium (Cd) hyperaccumulating herbaceous plant, is considered as a promising candidate for the bioremediation of Cd pollution. However, the molecular mechanisms regulating these processes remain unclear. The present work, using proteome studies combined with a transcriptome analysis, was carried out to reveal the response mechanisms of the hairy roots of Brassica campestris L. under Cd stress. Significant tissue necrosis and cellular damage occurred, and Cd accumulation was observed in the cell walls and vacuoles of the hairy roots. Through quantitative proteomic profiling, a total of 1424 differentially expressed proteins (DEPs) were identified, and are known to be enriched in processes including phenylalanine metabolism, plant hormone signal transduction, cysteine and methionine metabolism, protein export, isoquinoline alkaloid biosynthesis and flavone biosynthesis. Further studies combined with a transcriptome analysis found that 118 differentially expressed genes (DEGs) and their corresponding proteins were simultaneously up- or downregulated. Further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the 118 shared DEGs and DEPs indicated their involvement in calcium, ROS and hormone signaling-mediated response, including regulation of carbohydrate and energy metabolism, biosynthesis of GSH, PCs and phenylpropanoid compounds that play vital roles in the Cd tolerance of Brassica campestris L. Our findings contribute to a better understanding of the regulatory networks of Brassica campestris L. under Cd stress, as well as provide valuable information on candidate genes (e.g., BrPAL, BrTAT, Br4CL, BrCDPK, BrRBOH, BrCALM, BrABCG1/2, BrVIP, BrGCLC, BrilvE, BrGST12/13/25). These results are of particular importance to the subsequent development of promising transgenic plants that will hyperaccumulate heavy metals and efficient phytoremediation processes.

Establishment of hairy root system of transgenic IRT1 brassica campestris L. and preliminary study of its effect on cadmium enrichment.

Cadmium (Cd) is the main heavy metal pollutant in soil. The combination of genetic engineering technology and Rizobium rhizogenes mediated technology can effectively improve the enrichment efficiency of heavy metals in super accumulators and reduce soil heavy metal pollution. In this study, the transgenic hairy root system containing the IRT1 gene of Cd hyperaccumulator-Brassica campestris L. was successfully constructed by the R. rhizogenes mediated method (IRT1 gene come from Arabidopsis thaliana). The hairy roots of each subculture can grow stably within 6 weeks, and IRT1 gene will not be lost within 50 subcultures., which is detected using PCR method. The results of Cd enrichment experiments showed that after treatment with 100 µmol/L Cd for 14 days, the growth state of transgenic IRT1 hairy roots only showed slight browning. Also, the accumulation value of Cd reached 331.61 µg/g and the enrichment efficiency of transgenic IRT1 hairy roots was 13.8% higher than that of wild-type hairy roots. Western blotting results showed that the expression of IRT1 protein in transgenic hairy roots was significantly higher than that of wild-type hairy roots under Cd stress. The above results indicated that the overexpression of IRT1 gene can help B. campestris L. hairy roots to effectively cope with Cd stress and improve its ability to enrich Cd.

In this study, the transgenic hairy root system containing the IRT1 gene of Cd hyperaccumulator-Brassica campestris L. was successfully constructed by the Rizobium rhizogenes mediated method. At the same time, the growth state and cadmium enrichment efficiency of transgenic hairy roots under different concentrations of Cd stress were studied. Overexpression of IRT1 gene can effectively improve the tolerance of hairy root to Cd. The enrichment efficiency of transgenic IRT1 hairy roots was 13.8% higher than that of wild-type hairy roots. The transgenic IRT1 hairy root system established in this study can be used as a reliable experimental model for the study of Cd adsorption mechanism, and can be further regenerated to obtain transgenic IRT1 B. campestris L. plants for the study of heavy metal Cd pollution remediation.

Cancer Stem Cell Biomarkers in the Nervous System.

Cancer stem cells (CSCs) have been increasingly recognized in recent years. CSCs from human neural tumors are one of the root causes of metastatic tumor progression, therapeutic resistance and recurrence. However, there is a lack of comprehensive literature that systematically consolidates the biomarkers specific to CSCs in neurological cancers. Therefore, this review provides a comprehensive summary of cancer stem cell (CSC) biomarkers for neurological tumors such as glioma, meningioma, medulloblastoma and neurofibroma. It also points out the possible functions of these biomarkers in diagnosis, treatment and prognosis, providing a broader perspective. First, we quantitatively screened key words such as CSCs, biomarkers, and expression by bibliometric analysis and clarified the intrinsic connections between the key words. Then, we describe the CSC biomarkers of major neurological tumors and their pathway mechanisms, and provide an in-depth analysis of the commonalities and differences with the biomarkers of non-CSCs. In addition, many studies have shown that antipsychotic drugs can inhibit tumor growth and reduce the expression of CSC biomarkers, which facilitates targeted therapy against tumors in the nervous system. Therefore, this study will focus on the biomarkers of CSCs in the nervous system, hoping to provide guidance for future in-depth exploration and monitoring of neurological tumors for clinical applications.

Effects of Fertilizer on the Quality and Traceability of Tibet highland Barley (Hordeum vulgare L.): A Diagnosis Using Nutrients and Mineral Elements.

Production areas influence the quality of highland barley (Hordeum vulgare L.), and fertilization levels may be associated with the origin traceability of highland barley. As the main object of the study, a collection of highland barley was planted in different areas in Tibet, China, to explore the effect of fertilizer on the quality and traceability of highland barley. We carried out field experiments with and without fertilizer treatment (using urea and diamine phosphate). Highland barley was distinguished by nutrient and mineral element contents in combination with chemometric methods. The results indicated that fertilizer treatment significantly affected some mineral element contents in highland barley and improved the accuracy of highland barley traceability. The combination of nutrients and mineral elements could distinguish highland barley from those raised in other areas due to influence of growing environment. P, K, Fe, and Cu provided a great contribution to the classification of highland barley. Thus, the combination of nutrients and mineral elements can be used as a powerful tool to track highland barley, indicating that fertilization treatment should be considered when tracing highland barley.

Metagenomic study of the gut microbiota associated with cow milk consumption in Chinese peri-/postmenopausal women.

Cow milk consumption (CMC) and alterations of gut bacterial composition are proposed to be closely related to human health and disease. Our research aims to investigate the changes in human gut microbial composition in Chinese peri-/postmenopausal women with different CMC habits. A total of 517 subjects were recruited and questionnaires about their CMC status were collected; 394 subjects were included in the final analyses. Fecal samples were used for studying gut bacterial composition. All the subjects were divided into a control group (n = 248) and a CMC group (n = 146) according to their CMC status. Non-parametric tests and LEfSe at different taxonomic levels were used to reveal differentially abundant taxa and functional categories across different CMC groups. Relative abundance (RA) of one phylum (p_Actinobacteria), three genera (g_Bifidobacterium, g_Anaerostipes, and g_Bacteroides), and 28 species diversified significantly across groups. Specifically, taxa g_Anaerostipes (p < 0.01), g_Bacteroides (p < 0.05), s_Anaerostipes_hadrus (p < 0.01), and s_Bifidobacterium_pseudocatenulatum (p < 0.01) were positively correlated with CMC levels, but p_Actinobacteria (p < 0.01) and g_Bifidobacterium (p < 0.01) were negatively associated with CMC levels. KEGG module analysis revealed 48 gut microbiome functional modules significantly (p < 0.05) associated with CMC, including Vibrio cholerae pathogenicity signature, cholera toxins (p = 9.52e-04), and cephamycin C biosynthesis module (p = 0.0057), among others. In conclusion, CMC was associated with changes in gut microbiome patterns including beta diversity and richness of some gut microbiota. The alterations of certain bacteria including g_Anaerostipes and s_Bifidobacterium_pseudocatenulatum in the CMC group should be important for human health. This study further supports the biological value of habitual cow milk consumption.

Surfactant-assisted alkaline pretreatment and enzymatic hydrolysis of Miscanthus sinensis for enhancing sugar recovery with a reduced enzyme loading.

Surfactants play a vital role in the delignification and saccharification of lignocellulosic biomass. A strategy for coupling surfactant-assisted alkaline pretreatment (SAP) with surfactant-assisted enzymatic hydrolysis (SEH) has been proposed for improving sugar recovery from a potential energy crop, Miscanthus sinensis. Poly (ethylene glycol) 2000 (PEG 2000) was found to be more efficient in SAP than in other tested surfactants. Compositional and structural analysis revealed that the SAP process with 1% of PEG 2000 produced more efficient lignin removal and microstructure disruption of the pretreated sample, thus indicating much higher reducing sugar yields of 544.4-601.2 mg/g compared to the samples that were untreated or pretreated by alkali alone. Moreover, SEH with 1% Tween 80, which could block the lignin-enzyme interactions, produced a substantial reduction of 33.3% in the enzyme loading to achieve a higher sugar recovery from the SAP sample.

Rapid and Visual RPA-Cas12a Fluorescence Assay for Accurate Detection of Dermatophytes in Cats and Dogs.

Dermatophytosis, an infectious disease caused by several fungi, can affect the hair, nails, and/or superficial layers of the skin and is of global significance. The most common dermatophytes in cats and dogs are Microsporum canis and Trichophyton mentagrophytes. Wood's lamp examination, microscopic identification, and fungal culture are the conventional clinical diagnostic methods, while PCR (Polymerase Chain Reaction) and qPCR (Quantitative PCR) are playing an increasingly important role in the identification of dermatophytes. However, none of these methods could be applied to point-of-care testing (POCT). The recent development of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) based diagnostic platform promises a rapid, accurate, and portable diagnostic tool. In this paper, we present a Cas12a-fluorescence assay to detect and differentiate the main dermatophytes in clinical samples with high specificity and sensitivity. The Cas12a-based assay was performed with a combination of recombinase polymerase amplification (RPA). The results could be directly visualized by naked eyes under blue light, and all tested samples were consistent with fungal culture and sequencing results. Compared with traditional methods, the RPA-Cas12a-fluorescence assay requires less time (about 30 min) and less complicated equipment, and the visual changes can be clearly observed with naked eyes, which is suitable for on-site clinical diagnosis.

A Review of Current Bacterial Resistance to Antibiotics in Food Animals.

The overuse of antibiotics in food animals has led to the development of bacterial resistance and the widespread of resistant bacteria in the world. Antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) in food animals are currently considered emerging contaminants, which are a serious threat to public health globally. The current situation of ARB and ARGs from food animal farms, manure, and the wastewater was firstly covered in this review. Potential risks to public health were also highlighted, as well as strategies (including novel technologies, alternatives, and administration) to fight against bacterial resistance. This review can provide an avenue for further research, development, and application of novel antibacterial agents to reduce the adverse effects of antibiotic resistance in food animal farms.

Land-use changes and ecosystem services under different scenarios in Nansi Lake Basin, China.

Ecosystem services (ESs) have been affected drastically by rapid urban sprawl and significant land-use changes (LUC) in Nansi Lake Basin (NLB) in China. Based on land-use data with a 30-m resolution from 1990 to 2015, we analyzed the process of LUC by atlas analysis and explored the impacts of LUC on ecological service value (ESV) under urban sprawl. The results showed that water area and buildup land increased significantly from 1990 to 2015. The area of cultivated land, forests, grassland, and unutilized land decreased. Land transfer mainly occurred between cultivated land, water area, and grassland. The total amount of land transfer was 4830.64 km2, and the average transfer rate is 185.79 km2/year in 26 years. The most obvious transfer occurred in period IV. The increased buildup land was mainly transferred from cultivated land. The total urban sprawl in the NLB was 1623.37 km2 in the past 26 years, with an average expansion rate of 62.44 km2/year, with the fastest sprawl in period IV. Tengzhou city was the most prominent area of expansion. Its ESV increased by 5.73 × 107 US$ with an increased rate of 2.21 × 106 US$/year. The annual total value of regulating and supporting services in the first-level ESs in the NLB accounted for 54.8 and 25.2% of the total ESV in all years, which were the primary types of ESs. Water area, forests, and cultivated land were the principal contributors to ESV changes. In conclusion, urban sprawl had a significant negative effect on ESV changes. Urban sprawl, water area, forests, and cultivated land were all sensitive factors for ESV changes.

Enhanced Cadmium Accumulation and Tolerance in Transgenic Hairy Roots of Solanum nigrum L. Expressing Iron-Regulated Transporter Gene IRT1.

Solanum nigrum L., a hyperaccumulator of cadmium (Cd), is regarded as a promising candidate for phytoremediation of heavy metal pollution. In the present study, the hairy roots of Solanum nigrum L. were selected as a model plant system to study the potential application of Iron-regulated Transporter Gene (IRT1) for the efficient phytoremediation of Cd pollution. The transgenic hairy roots of Solanum nigrum L. expressing the IRT1 gene from Arabidopsis thaliana were successfully obtained via the Agrobacterium tumegaciens-mediated method. Expression of IRT1 reduced Cd stress-induced phytotoxic effects. Significantly superior root growth, increased antioxidant enzyme activities, decreased reactive oxygen species (ROS) levels, and less cell apoptosis were observed in the transgenic hairy roots of Solanum nigrum L. compared to the wild-type lines under Cd stress. Enhanced Cd accumulation was also carried out in the transgenic hairy roots compared to the control (886.8 µg/g vs. 745.0 µg/g). These results provide an important understanding of the Cd tolerance mechanism of transgenic IRT1 hairy roots of Solanum nigrum L., and are of particular importance to the development of a transgenic candidate for efficient phytoremediation process.

A Two-Step Ferric Chloride and Dilute Alkaline Pretreatment for Enhancing Enzymatic Hydrolysis and Fermentable Sugar Recovery from Miscanthus sinensis.

A two-step process was proposed to enhance enzymatic hydrolysis of Miscanthus sinensis based on a comparative study of acid/alkaline pretreatments. Ferric chloride pretreatment (FP) effectively removed hemicellulose and recovered soluble sugars, but the enzymatic hydrolysis was not efficient. Dilute alkaline pretreatment (ALP) resulted in much better delignification and stronger morphological changes of the sample, making it more accessible to enzymes. While ALP obtained the highest sugar yield during enzymatic hydrolysis, the soluble sugar recovery from the pretreatment stage was still limited. Furthermore, a two-step ferric chloride and dilute alkaline pretreatment (F-ALP) has been successfully developed by effectively recovering soluble sugars in the first FP step and further removing lignin of the FP sample in the second ALP step to improve its enzymatic hydrolysis. As a result, the two-step process yielded the highest total sugar recovery (418.8 mg/g raw stalk) through the whole process.

Enhanced Enzymatic Hydrolysis of Pennisetum alopecuroides by Dilute Acid, Alkaline and Ferric Chloride Pretreatments.

In this study, effects of different pretreatment methods on the enzymatic digestibility of Pennisetum alopecuroides, a ubiquitous wild grass in China, were investigated to evaluate its potential as a feedstock for biofuel production. The stalk samples were separately pretreated with H2SO4, NaOH and FeCl3 solutions of different concentrations at 120 °C for 30 min, after which enzymatic hydrolysis was conducted to measure the digestibility of pretreated samples. Results demonstrated that different pretreatments were effective at removing hemicellulose, among which ferric chloride pretreatment (FCP) gave the highest soluble sugar recovery (200.2 mg/g raw stalk) from the pretreatment stage. In comparison with FCP and dilute acid pretreatment (DAP), dilute alkaline pretreatment (DALP) induced much higher delignification and stronger morphological changes of the biomass, making it more accessible to hydrolysis enzymes. As a result, DALP using 1.2% NaOH showed the highest total soluble sugar yield through the whole process from pretreatment to enzymatic hydrolysis (508.5 mg/g raw stalk). The present work indicates that DALP and FCP have the potential to enhance the effective bioconversion of lignocellulosic biomass like P. alopecuroides, hence making this material a valuable and promising energy plant.

Comparative Transcriptome Analysis of the Molecular Mechanism of the Hairy Roots of Brassica campestris L. in Response to Cadmium Stress.

Brassica campestris L., a hyperaccumulator of cadmium (Cd), is considered a candidate plant for efficient phytoremediation. The hairy roots of Brassica campestris L are chosen here as a model plant system to investigate the response mechanism of Brassica campestris L. to Cd stress. High-throughput sequencing technology is used to identify genes related to Cd tolerance. A total of 2394 differentially expressed genes (DEGs) are identified by RNA-Seq analysis, among which 1564 genes are up-regulated, and 830 genes are down-regulated. Data from the gene ontology (GO) analysis indicate that DEGs are mainly involved in metabolic processes. Glutathione metabolism, in which glutathione synthetase and glutathione S-transferase are closely related to Cd stress, is identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A Western blot shows that glutathione synthetase and glutathione S-transferase are involved in Cd tolerance. These results provide a preliminary understanding of the Cd tolerance mechanism of Brassica campestris L. and are, hence, of particular importance to the future development of an efficient phytoremediation process based on hairy root cultures, genetic modification, and the subsequent regeneration of the whole plant.

Estimation of the benchmark dose of urinary cadmium as the reference level for renal dysfunction: a large sample study in five cadmium polluted areas in China.

BACKGROUND: Itai-itai disease primarily results from cadmium (Cd) exposure and is known as one of the four major pollution diseases in Japan. Cd pollution is more serious in several areas of China than in Japan. However, there is still a lack of information regarding the threshold level of Cd exposure for the adverse health effects in the general Chinese population. This study aims to evaluate the reference value of urinary Cd (UCd) for renal dysfunction in a Chinese population as the benchmark dose lower confidence limit (BMDL) based on a large sample survey. METHODS: A total of 6103 participants who lived in five Cd polluted areas of China participated in this study. We analyzed UCd levels as a biomarker of exposure and urinary ß2-microglobulin (Uß2-MG) levels as a renal tubular effect biomarker. The BMD studies were performed using BMD software. The benchmark response (BMR) was defined as a 10% additional risk above the background. RESULTS: There was a positive correlation between the UCd levels and the prevalence of Uß2-MG. The BMD of UCd for Uß2-MG was estimated for each province. The findings showed that the BMD levels were related to the participants' geographic region, which may be partially due to the large differences in Cd exposure level, ethnic group, lifestyle and diet of the sample population in these study areas. The reference level of UCd for the renal effects was further evaluated by combining the five sets of data from all 6103 subjects. The overall BMDLs of UCd for Uß2-MG with an excess risk of 10% were 2.00 µg/g creatinine (µg/g cr) in males and 1.69 µg/g cr in females, which were significantly lower than the World Health Organization (WHO) threshold level of 5 µg/g cr for Cd-related renal effects. CONCLUSIONS: The selection of the sample population and geographic region affected the BMDL evaluation. Based on the findings of this survey of a large sample population, the UCd BMDLs for Uß2-MG in males with BMRs at 10% were 2.00 µg/g cr. The BMD was slightly lower in females, which indicated that females may be relatively more sensitive to Cd exposure than males.

Cadmium contamination of rice from various polluted areas of China and its potential risks to human health.

A total of 484 rice samples were collected from five polluted areas in China to investigate the cadmium (Cd) contamination of rice and its potential health risks. The mean Cd contents of analyzed rice samples obtained from different areas ranged from 0.149 to 0.189 mg·kg(-1). Cd concentrations in more than 18% of rice samples exceeded the maximum allowable Cd concentration, and the highest level of 41.1% was observed in samples from Hezhang, Guizhou, which was characterized by serious Cd pollution. Target hazard quotient (THQ) values of 1.5 to 7.8 from rice intake indicated a significant non-carcinogenic health risk for humans, particularly for highly exposed consumers. Children are more at risk than adults, as indicated by the higher THQs. Moreover, carcinogenic risks of Cd from rice intake for average and high consumers in the selected areas were two to three and four to eight greater, respectively, than the threshold value recommended by the International Commission on Radiological Protection.

Body burden of cadmium and its related factors: a large-scale survey in China.

A survey of more than 6000 participants from four distinct non-polluted and polluted regions in China was conducted to evaluate the body burden of cadmium (Cd) on the Chinese populations using urinary Cd (UCd) as a biomarker. The findings revealed that the UCd level was 1.24 µg/g creatinine (µg/g cr) for the sample population from non-polluted Shanghai, and the UCd levels exceeded 5 µg/g cr, which is the health-based exposure limit set by the World Health Organization (WHO), in 1.1% of people. The mean UCd levels in moderately polluted (Hubei and Liaoning) and highly polluted areas (Guizhou) were 4.69 µg/g cr, 3.62 µg/g cr and 6.08 µg/g cr, respectively, and these levels were 2.9 to 4.9 times the levels observed in Shanghai. Notably, the UCd levels exceeded the recently updated human biomonitoring II values (i.e., intervention or "action level") in 44.8%-87.9% of people from these areas compared to only 5.1%-21.4% of people in Shanghai. The corresponding prevalence of elevated UCd levels (>WHO threshold, 5 µg/g cr) was also significantly higher (30.7% to 63.8% vs. 1.1%), which indicates that elevated Cd-induced health risks to residents in these areas. Age and region were significant determinants for UCd levels in a population, whereas gender did not significantly influence UCd.