Expression Analysis of Retinal G Protein-coupled Receptor and its Correlation with Regulation of the Balance between Proliferation and Aberrant Differentiation in Cutaneous Squamous Cell Carcinoma.

Retinal G protein-coupled receptor (RGR), a photosensitive protein, functions as a retinal photoisomerase under light conditions in humans. Cutaneous squamous cell carcinoma (cSCC) is linked to chronic ultraviolet exposure, which suggests that the photoreceptor RGR may be associated with tumorigenesis and progression of squamous cell carcinoma (SCC). However, the expression and function of RGR remain uncharacterized in SCC. This study analysed RGR expression in normal skin and in lesions of actinic keratosis, Bowen's disease and invasive SCC of the skin with respect to SCC initiation and development. A total of 237 samples (normal skin (n = 28), actinic keratosis (n = 42), Bowen's (n = 35) and invasive SCC (n = 132) lesions) were examined using immunohistochemistry. Invasive SCC samples had higher expression of RGR protein than the other samples. A high immunohistochemical score for RGR was associated with increased tumour size, tumour depth, Clark level, factor classification, and degree of differentiation and a more aggressive histological subtype. In addition, RGR expression was inversely correlated with involucrin expression and positively correlated with proliferating cell nuclear antigen (PCNA) and Ki67 expression. Furthermore, RGR regulates SCC cell differentiation through the PI3K-Akt signalling pathway, as determined using molecular biology approaches in vitro, suggesting that high expression of RGR is associated with aberrant proliferation and differentiation in SCC.

A pan-cancer analysis of RGR opsin expression and its downregulation associated with poor prognosis in glioma.

Retinal G protein-coupled receptor (RGR) serves a retinal photoisomerase function to mediate retinoid metabolism and visual chromophore regeneration in the human eyes. Retinoids display critical functions in cell proliferation, differentiation, and apoptosis. Abnormal retinoid metabolism may contribute to tumor development. However, in human tumor tissues, the expression of RGR remains uncharacterized. Herein, we performed the analysis of RGR expression in 620 samples from 24 types of tumors by immunohistochemistry (IHC) and 33 cancer types from the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases by bioinformatic analyses. Furthermore, the biological role of RGR in glioma cells was investigated using molecular biology approaches in vitro. Notably, we found that brain lower grade glioma (LGG), in contrast to other tumor types, had the highest median score of IHC and RNA level of RGR expression. Survival analysis showed that low RGR expression was associated with worse overall survival in LGG (p<0.0001). RGR expression levels in glioma were also associated with pathological subtypes, grades, and isocitrate dehydrogenase (IDH) mutations. Moreover, its molecular function was closely associated with cadherin-related family member 1 (CDHR1), a tumor suppressive protein in glioma, suggesting that RGR might negatively regulate the tumorigenesis and progression of LGG through interacting with CDHR1. Our findings provide new insight into the role of RGR in human cancer, especially in glioma.

A novel cadmium detoxification pathway in Tri-spine horseshoe crab (Tachypleus tridentatus): A 430-million-years-ago organism.

Marine and intertidal heavy metal pollution has been a major concern in recent years. Tachypleus tridentatus has existed on earth for more than 430 million years. It has suffered a sharp decline in population numbers caused by environmental pollution and anthropogenic disturbance for almost 40 years. However, the effects of heavy metal pollution on juvenile T. tridentatus have not been reported. Here we show the mechanism of cadmium (Cd) detoxification in juvenile T. tridentatus using integrated antioxidant indexes and transcriptomic and metabolomic analysis. High Cd2+ concentration caused oxidative stress in juvenile T. tridentatus. The hazards increase with increasing Cd2+ concentration in juvenile T. tridentatus. Transcriptomics and metabolomics analyses concluded that high Cd2+ concentration resulted in the imbalance of glycerophospholipid metabolism in juvenile T. tridentatus to detoxify Cd. Our results offer a rationale for protective measures and further studies of heavy metal stress in T. tridentatus.

Ecotoxicological risk of antibiotics and their mixtures to aquatic biota with the DGT technique in sediments.

Antibiotics are emerging contaminants and widely used in human healthcare, livestock, and aquaculture. The toxicity posed by antibiotics and their mixtures in sediments depends on their bioavailability. Now, the bioavailability of organic materials can be determined accurately by the diffusive gradients in thin films (DGT) technique. This technique was used for the first time ever in this study to evaluate in detail the integral toxicity of antibiotics in sediments to aquatic biota. Zhelin Bay was selected as a case study, because it is the largest mariculture area in eastern Guangdong, South China. Two antibiotics, chlortetracycline (CTC) (A) and sulfachlorpyridazine (SCP), were detected at average concentrations of 2.83 and 1.14 ng/ml, respectively. The other fifteen antibiotics were undetectable. The single risk assessment based on the risk quotient (RQ) of CTC and SCP shows that a relatively low risk has occurred. After this careful assessment of probabilistic ecotoxicological risks, the combined toxicity of antibiotic mixtures (CTC and SCP) clearly indicates that the toxicity probability of surface sediments to aquatic organisms was relatively low (0.23%).

Heavy metal(loid)s in multiple media within a mussel mariculture area of Shangchuan Island, China: Partition, transfer and health risks.

Limited research has been conducted on the heavy metal (loid) (HM) exchanges among seawater, sediments and cultured mussels in mariculture areas. To determine the impacts of mussel mariculture on the transfer and risks of HMs in coastal environments, samples of seawater, sediments and cultured mussels from a typical mariculture area in the South China Sea were analysed. The logarithmic partition coefficients of sediment/water indicated that HMs were preferentially retained by sediments. There were relatively low ecological risks in mussel raft mariculture areas. Principal component analysis and correlation analysis revealed the influences of terrestrial input and ocean circulation on the HMs in seawater, and the bioaccumulation factors reflected the possible accumulation of HMs in seawater by cultured mussels. Mussel farming was the indirect source of HMs in sediments, and the biochemical processes of cultured mussels promoted the transfer and accumulation of HMs into sediments. Health risk assessment revealed that children were more susceptible than adults, and Cd, As and Cr were among the threatening elements. Nonetheless, the health risks that were possibly caused by the daily consumption of farmed mussels were still within safe limits. Thus, the potential pollution remediation and biomonitoring functions of mussel aquaculture in coastal water environments will be further studied in the future.

Risk on assessment of 15 REEs and mixtures by DGT in Songhua River system sediments of China's largest old industrial base.

Rare earth elements (REEs) are increasingly used in the high-tech sectors in the world and are therefore called burgeoning contaminants. As diffusive gradients in thin films (DGT) can be used to assess the bioavailability of inorganic matters, in this paper, we evaluated, for the first time, the ecotoxicology risks of REEs and their mixtures in river sediments of China's old industrial base by DGT. During our research, taking the Songhua River system (SRS) as an example, we detected its surficial sediments, of which the DGT-labile concentration of REEs (∑REEs) was 2.07-8.76 µg/L. As for the single toxicity, the risk quotient (RQ) values of Y at all sites were significantly greater than 1; while the values of Nd and Pr in some upstream reaches were all significantly greater than the threshold (1), indicating that these adverse effects of single REEs were not neglected. In terms of the combined toxicity of REEs mixtures, we carried out an assessment of the risks of probabilistic ecotoxicology, which showed that the SRS superficial sediments had a low probability of toxicity to aquatic organisms (0.54%).

A new method for estimating sedimental integrated toxicity of heavy metal mixtures to aquatic biota: a case study.

The existing methods of measuring combined toxicity of heavy metal mixtures in environment do not fully consider three major factors (i.e., number of heavy metal species, aquatic biota, all investigated sites as an entity). Herein, a new method named joint probabilistic risk (JPR) method is proposed for evaluating the combined toxicity of heavy metal mixtures to aquatic biota. In this new method, the above three factors are fully taken into account. In order to evaluate the feasibility of the new method, the Pearl River Estuary (PRE) is selected as a case study. Concentrations of heavy metals (Cd, Pb, Cr, Ni, Cu, and Zn) in surface sediments of PRE are investigated and toxic equivalent factors (TEFs) of these heavy metals are calculated. Based on TEFs, sedimental concentrations of heavy metals of PRE are converted to Cd toxic equivalent concentration (Cdeq), while the Cd toxicity data (Cdto) are extracted from the literature. The probability density curves for Cdeq and Cdto are constructed and the overlap area is quantified as 0.2497. This indicates that the surface sediments of PRE have a 24.97% probability of toxic effect towards aquatic biota. Finally, this new method is validated by two indirect methods of mERMq and mPELq.

Nonmetric multidimensional scaling and adverse effects on aquatic biota of polycyclic aromatic hydrocarbons in sediments: A case study of a typical aquaculture wetland, China.

Aquaculture wetlands, particularly those located within urban areas, are fragile ecosystems which are generally heavily impacted by urban and aquaculture activities. However, there are, to date, no reports on adverse effects related to polycyclic aromatic hydrocarbons (PAHs) in sediments from aquaculture wetlands in metropolitan areas. The characterization, sources, and incidence of adverse effects on aquatic biota of PAHs were studied in the riverine and estuarine sediments of the Rongjiang River in an aquaculture wetland in Chaoshan metropolis. The total PAH concentrations varied from 46.0 to 1665.2 ng/g (dry weight), with a mean of 246.4 ng/g, indicating lower concentrations than those of other comparable rivers and estuaries worldwide. High-molecular-weight PAHs were the major PAH species, with fluorene, benzo(b)fluoranthene, and benzo(a)pyrene as the dominant components. These PAHs are likely to be mainly derived from oil and coal/biomass combustion. Probability risk assessment indicated a moderate PAH ecological risk in the Rongjiang River and its estuary (RJE). Accordingly, a comprehensive management plan should be established to ensure sustainable aquaculture wetlands.

Bioaccumulation of polycyclic aromatic hydrocarbons (PAHs) in wild marine fish from the coastal waters of the northern South China Sea: Risk assessment for human health.

Little data are available on polycyclic aromatic hydrocarbons (PAHs) in marine fish associated with oil and gas activities from the South China Sea (SCS). Twenty-one wild marine fish species from the northern South China Sea were collected for analysis of the presence of polycyclic aromatic hydrocarbons (PAHs). The total concentration of the PAHs (∑16PAHs) ranged from 199 to 606 ng·g-1 d.w., indicating moderate contamination. PAHs in fish species found in the Pearl River Delta (PRD) were significantly higher than those from the Yachen (YC) gas fields (p < 0.05). Planktivorous fish exhibited significantly higher concentrations of PAHs than carnivorous and omnivorous fish (p < 0.05). The PAHs were dominated by three ring compounds. Source identification analyses indicated that the PAH pollution originated from petroleum inputs. The cancer and non-cancer risk assessments concluded that the probable risk associated with the intake of PAHs via fish consumption is minimal. Long-term monitoring is necessary to determine the ecological impacts of PAHs associated with oil and gas activities.

Bioaccessibilities and health implications of heavy metals in exposed-lawn soils from 28 urban parks in the megacity Guangzhou inferred from an in vitro physiologically-based extraction test.

This study focused on characterizing the oral bioaccessibilities and human health risks of eight heavy metals (Cd, Pb, Cr, Ni, Cu, Zn, Fe, and Mn) in surface-exposed lawn soils from 28 urban parks in Guangzhou. The physiologically-based extraction test (PBET) method was used to assess bioavailability (in gastric and intestinal phases) and human health risk was assessed via statistical modelling (carcinogenic risk assessment, hazard quotients and hazard indices). Mean bioaccessibilities of Cd, Pb, Cr, Ni, Cu, Zn, Fe, and Mn from all soil samples were 50.90 ± 17.67%, 5.81 ± 1.67%, 7.12 ± 3.24%, 17.91 ± 18.34%, 11.93 ± 2.88%, 34.33 ± 10.02%, 1.68 ± 0.48%, 26.71 ± 5.06%, respectively. The concentrations of most heavy metals were higher in the gastric phase, except for Cr and Ni which remained higher in the intestinal phase. Principal component analysis revealed that the bioaccessibilities of the heavy metals could be split into three groupings, based on the urban park of soil origin. The carcinogenic risk probabilities for Pb and Cr were under the acceptable level (< 1 × 10-4) for both adults and children. The hazard quotient and hazard index values indicated no significant risk of non-carcinogenic effects to children or adults exposed to Guangzhou urban park soils. This research will help inform further risk assessment and management of heavy metal contaminants in urban environments.

Bioaccessibility and human health implications of heavy metals in different trophic level marine organisms: A case study of the South China Sea.

This study investigated the total concentrations and bioaccessibility of heavy metals in edible tissues and trophic levels of 12 marine organism species in the South China Sea. The results were used to estimate health risks to humans. Of the heavy metals detected, nickel (Ni) was present at the highest concentrations, followed in descending, order by iron (Fe), zinc (Zn), manganese (Mn), chromium (Cr), copper (Cu), cadmium (Cd) and lead (Pb). Cd had the highest percentage bioaccessibility (61.91%). There were no correlations between log-transformed total metal concentrations and trophic level values, nor between log-transformed bioaccessibility metal concentrations and trophic level values. This indicates there is no biomagnification among these trace metals. The carcinogenic risk probabilities for Pb and Cr to urban and rural residents were below the acceptable level (< 1â€¯× 10-4). The target hazard quotient (THQ) value for each metal and the total THQ values for all metals studied indicated no significant risk of non-carcinogenic effects to urban and rural residents from consuming marine organisms from the South China Sea.

Contamination, Fractionation and Biological Risk Related to Metals in Surface Sediments from the Largest Deep Freshwater Lake in China.

The toxicity and mobility of metals in the environment are driven by their specific chemical forms and binding states. However, heavy metal fractionation in sediments from plateau deep lakes in China is rare. This study analyzed surface sediments collected from Fuxian Lake, the largest deep freshwater lake in China; parameters examined included total metal concentrations, chemical partitioning, and biological risk assessment. The average total concentrations (mg/kg) were 7.9 for Cd, 97.6 for Pb, 102.8 for Cr, 60.8 for Ni, 73.6 for Cu, and 112.9 for Zn; these levels were significantly higher than their corresponding background values. Cd was preferentially associated with the acid-soluble fraction; significant portions of the Pb, Cr, Ni, Cu, and Zn were mainly associated with the residual fractions. Overall, surface sediments of Fuxian Lake were associated with a 21% incidence of toxicity based on the mean effects range-median quotient. Cd was mainly at high or very high risk levels, and Cu and Zn were mainly at medium or high risk levels based on the risk assessment code (RAC).

Polycyclic Aromatic Hydrocarbons (PAHs) in Exposed-Lawn Soils from 28 Urban Parks in the Megacity Guangzhou: Occurrence, Sources, and Human Health Implications.

Polycyclic aromatic hydrocarbons (PAHs) in urban soils may pose a serious threat to human health via oral ingestion, dermal absorption, and particulate inhalation, especially in public parks and playgrounds, with children and senior citizens showing the highest susceptibility. Several studies have been undertaken identifying PAHs in urban soils, but no studies to date have assessed PAHs in urban parks, in particular in exposed-lawn soils. In recent decades, unprecedented rates of urbanization and industrialization in China have resulted in significant levels of urban environmental pollution. However, concentrations, sources, and the health risk associated with PAH exposure via urban park lawn soils in China remain unknown. The concentrations, sources, and health risk of exposure to 16 PAHs in surface-exposed lawn soils were studied in 28 urban parks in Guangzhou. Concentrations of Σ16PAHs ranged from 76.44 to 890.85 ng/g with a mean of 286.11 ng/g. PAH composition was mostly characterized by 2- and 4-ring PAHs in most sampling parks; Nap, Flua, Pyr, Phe, and Chr were the dominant constituents. Principle component analysis coupled with multivariate linear regression indicated that vehicular and coal combustion emissions contributed to 50.53 and 49.46% of PAHs in Guangzhou's urban park soils, respectively. Total cancer risk (TCR) analysis found that 22 parks (accounting for 78.57% total parks) designed for children's use and general-use park areas presented a potentially high risk (>1 × 10-4) for all users.

Fuzzy comprehensive assessment of heavy metals and Pb isotopic signature in surface sediments from a bay under serious anthropogenic influences: Daya Bay, China.

The fuzzy comprehensive assessment was undertaken to evaluate the marine sediment quality in Daya Bay, China based on the monitoring data of 2015 and China National Standard for Marine Sediment Quality (GB 18668-2002). The results demonstrated that the average metal concentrations (mg/kg) were 0.08 (Cd), 51.30 (Pb), 91.30 (Cr), 29.63 (Cu), 143.42 (Zn), 0.03 (Hg), and 7.31 (As), which were clearly higher with respect to their corresponding background values. Cr was the major pollutant based weight matrices calculated. Taken as whole, the membership degree of class I was a range from 0.65 to 1, suggesting that the marine sediment quality in Daya Bay belongs to class I. Pb stable isotopic analysis coupled with geographic information system (GIS) approach showed the sedimentary Pb mainly originated from petrochemical industry at northwest coast of Daya Bay.

Probabilistic risk assessment of microplastics on aquatic biota in coastal sediments.

As an emerging form of pollution, microplastic contamination of the coastal ecosystems is one of the world's most pressing environmental concerns. Coastal sediments have been polluted to varying degrees by microplastics, and their ubiquitous presence in sediments poses a threat to marine organisms. However, there is currently no ecological risk assessment of microplastics on aquatic biota in sediments. This study, for the first time, established a new procedure to evaluate the toxicity of microplastics on aquatic biota in sediments, based on the probabilistic risk assessment (PRA) concept. The choice of Zhelin Bay as the case study site was based on its severe pollution status. The average content of microplastics in the sediments of Zhelin Bay was 2054.17 items kg-1 dry weight, and these microplastics consisted of 46 different species. Microplastics in sediments exist in five different forms, with the film form being the main composition, and the majority of microplastics have particle sizes ranging from 100 to 500 µm. Correlation analysis (CA) reveals significant negative correlations between microplastic abundance, and Al2O3 and SiO2. The toxicity of microplastics, based on the PRA concept, suggests that Zhelin Bay surface sediments had a low probability (3.43%) of toxic effects on aquatic biota.

Environmental and dietary exposure to 24 polycyclic aromatic hydrocarbons in a typical Chinese coking plant.

Polycyclic aromatic hydrocarbons (PAHs), known for their health risks, are prevalent in the environment, with the coking industry being a major source of their emissions. To bridge the knowledge gap concerning the relationship between environmental and dietary PAH exposure, we explore this complex interplay by investigating the dietary exposure characteristics of 24 PAHs within a typical Chinese coking plant and their association with environmental pollution. Our research revealed Nap and Fle as primary dietary contaminants, emphasizing the significant influence of soil and atmospheric pollution on PAH exposure. We subjected our data to non-metric multidimensional scaling (NMDS), Spearman correlation analysis, Lasso regression, and Weighted Quantile Sum (WQS) regression to delve into this multifaceted phenomenon. NMDS reveals that dietary PAH exposure, especially within the high molecular weight (HMW) group, is common both within and around the coking plant. This suggests that meals prepared within the plant may be contaminated, posing health risks to coking plant workers. Furthermore, our assessment of dietary exposure risk highlights Nap and Fle as the primary dietary contaminants, with BaP and DahA raising concerns due to their higher carcinogenic potential. Our findings indicate that dietary exposure often exceeds acceptable limits, particularly for coking plant workers. Correlation analyses uncover the dominant roles of soil and atmospheric pollution in shaping dietary PAH exposure. Soil contamination significantly impacts specific PAHs, while atmospheric pollution contributes to others. Additionally, WQS regression emphasizes the substantial influence of soil and drinking water on dietary PAHs. In summary, our study sheds light on the dietary exposure characteristics of PAHs in a typical Chinese coking plant and their intricate interplay with environmental factors. These findings underscore the need for comprehensive strategies to mitigate PAH exposure so as to safeguard both human health and the environment in affected regions.

Differential response of two ferritin subunit genes (VpFer1 and VpFer2) from Venerupis philippinarum following pathogen and heavy metals challenge.

As a principal extracellular iron storage molecule, ferritin plays an important role in the iron-withholding strategy of innate immunity and detoxification system. In this study, we cloned and characterized another ferritin from Venerupis philippinarum (designated as VpFer2), in addition to one previously reported (VpFer1). VpFer2 possessed all the conserved features critical for the fundamental structure and function of ferritin H subunit. VpFer1 and VpFer2 mRNA were both found to be most abundantly expressed in hepatopancreas. Vibrio challenge could significantly up-regulate the mRNA expression of VpFers, and VpFer2 showed more sensitive to Vibrio anguillarum infection. For heavy metals exposure, the expression level of VpFer1 was significantly induced by Cd at 48 h, but kept relatively constant after exposure to Cu. With regards to VpFer2, the expression level dropped significantly at 24 h, then began to increase to the peak value at 48 h under Cd exposure, while Cu exposure constantly depressed the expression level of VpFer2 throughout the time course. Similarly, VpFer2 seemed to be more sensitive to heavy metals exposure than VpFer1 as its mRNA level changed by higher magnitudes. All these results suggested that VpFers may be important proteins involved in host immune defense and heavy metals detoxification. The diverse expression patterns of VpFers demonstrated that VpFer2 was an early and sensitive responder to environmental stress in V. philippinarum.

The anthropogenic effects on organic matter in sediment core based on Bayesian mixing model: a case study of Daya Bay.

Sediment is an important carrier of evidence about environmental evolution which receives huge volumes of organic material originated from both anthropogenic and natural sources. In this study, based on sedimentary chronology, the vertical trends of particle size distribution, total organic carbon (TOC), total nitrogen (TN), and their stable isotopes (δ13C, δ15N) in the sediment core of the nuclear power sea in southwest Daya Bay were analyzed, and the distribution characteristics and contribution ratios of different sources of organic matter in the sedimentary environment over the past 70 years were resolved using a Bayesian mixing model (MixSIAR). TOC, TN, δ13C, and δ15N ranged from 0.89 to 1.56%, 0.09 to 0.2%, - 22.3 to - 20.6‰, and 4.38 to 6.51‰, respectively. The organic matter in the sediment is controlled by a mixture of terrestrial input and marine autochthonous, the proportion of organic matter from terrestrial sources increases, while that from marine sources decreases in the sediment core, which persists from 1960 to 2000, yet organic matter from marine sources still dominates. The first signs of increased primary productivity occurred in 1960, and it was primarily due to agricultural activity. After the 1980s, the rapid increase in population around Daya Bay, the construction of nuclear power plants, the rise of aquaculture, and the quick expansion of industrial bases were all major factors that changed the ecological environment of Daya Bay.

Metal Biological Enrichment Capacities, Distribution Patterns, and Health Risk Implications in Sea Bass (Lateolabrax japonicus).

Seabass (Lateolabrax japonicus) is a major aquacultured fish species worldwide. The bioconcentration, bioaccumulation, and biomagnification of metals in water, sediments, and commercial feed were investigated in L. japonicus from an aquaculture pond in the Pearl River Delta of South China. Aluminum (Al), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), and lead (Pb) were determined in the dorsal muscle, viscera, backbone, gill, and stomach contents of L. japonicus. The gill and stomach contents had higher levels of bioconcentration of most metals than other parts of fish. Based on the bioaccumulation factor, the gill and backbone exhibited the highest accumulation of Zn, while the viscera had the highest capacity to accumulate Cu. The mean biomagnification factor values exceeded for As in dorsal muscle, for Cu in the viscera, for Cr and Pb in the gill, and for Al, Cr, Fe, Cu, and Pb in the stomach contents, indicating efficient bioaccumulation from commercial feed and their habitat. Non-metric multidimensional scaling analysis revealed two groups that resulted from the accumulation of metals in various parts of L. japonicus. Moreover, health risk assessment indicated that no notable adverse health effects occurred from the ingestion of L. japonicus.

Impact assessment of human activities on resources of juvenile horseshoe crabs in Hainan coastal areas, China.

The booming coastal zone economy poses increasing anthropogenic threats to marine life and habitats. Using the endangered living fossil horseshoe crab (HSC) as an example, we quantified the intensity of various anthropogenic pressures along the coast of Hainan Island, China, and for the first time assessed their impact on the distribution of juvenile HSCs through a field survey, remote sensing, spatial geographic modeling, and machine learning methods. The results indicate that the Danzhou Bay needs to be protected as a priority based on species and anthropogenic pressure information. Aquaculture and port activities dramatically impact the density of HSCs and therefore be managed priority. Finally, a threshold effect between total, coastal residential, and beach pressure and the density of juvenile HSCs were detected, which indicates the need for a balance between development and conservation as well as the designation of suitable sites for the construction of marine protected areas.