Immunogenic hypofractionated radiotherapy sensitising head and neck squamous cell carcinoma to anti-PD-L1 therapy in MDSC-dependent manner.

BACKGROUND: Enhancing the response rate of immunotherapy will aid in the success of cancer treatment. Here, we aimed to explore the combined effect of immunogenic radiotherapy with anti-PD-L1 treatment in immunotherapy-resistant HNSCC mouse models. METHODS: The SCC7 and 4MOSC2 cell lines were irradiated in vitro. SCC7-bearing mice were treated with hypofractionated or single-dose radiotherapy followed by anti-PD-L1 therapy. The myeloid-derived suppressive cells (MDSCs) were depleted using an anti-Gr-1 antibody. Human samples were collected to evaluate the immune cell populations and ICD markers. RESULTS: Irradiation increased the release of immunogenic cell death (ICD) markers (calreticulin, HMGB1 and ATP) in SCC7 and 4MOSC2 in a dose-dependent manner. The supernatant from irradiated cells upregulated the expression of PD-L1 in MDSCs. Mice treated with hypofractionated but not single-dose radiotherapy were resistant to tumour rechallenge by triggering ICD, when combined with anti-PD-L1 treatment. The therapeutic efficacy of combination treatment partially relies on MDSCs. The high expression of ICD markers was associated with activation of adaptive immune responses and a positive prognosis in HNSCC patients. CONCLUSION: These results present a translatable method to substantially improve the antitumor immune response by combining PD-L1 blockade with immunogenic hypofractionated radiotherapy in HNSCC.

Human biomonitoring of heavy metals exposure in different age- and gender-groups based on fish consumption patterns in typical coastal cities of China.

The study aimed to investigate heavy metals (HMs) concentrations in human hair based on fish consumption patterns in Qingdao, Xiamen, and Zhoushan. The (HMs) concentrations were determined using acid digestion and an inductively coupled plasma mass spectrometer (ICP-MS, NexION 300X, PerkinElmer). The associated health risks were investigated using risk assessment models described by the United States Environmental Protection Agency (USEPA). The order of fish HMs concentration in Qingdao was CdCrCu>Pb>Cr>As>Cd in all three study areas. The hair Zn concentration in 28 % of the studied population exceeded the safety standards. Overall, the hair HMs concentration was found to be high in middle-aged groups (19-45 and 45-59), and the hair HMs concentrations were high, especially in the case of females. A significant correlation was noticed between hair As (0.119; p < 0.05), Cr (0.231; p < 0.05),) and Cu (0.117; p < 0.05),) and fish consumption frequency. High Odd ratios (>2) were noticed for As, Cu and Zn in high fish-eating frequency. A significant non-carcinogenic risk was noticed in human Cr exposure (1.10E+00) in Xiamen, and the hazard index values indicated non-carcinogenic risk in Xiamen and Zhoushan. The carcinogenic risk for human As exposure (2.50E-05-7.09E-03) indicated a significant cancer risk.

Impacts of Mercury Exposure Levels and Sources on the Demethylation of Methylmercury Through Human Gut Microbiota.

This study aims to investigate methylmercury (MeHg) demethylation processes in human gut. Here, we determined the compositions and MeHg demethylation rates of gut microbiota in residents from different Hg exposure levels (Wanshan (WS) town and Yangtou (YT) town) and different Hg exposure sources (Zhuchang (ZC) town and YT town) regions. MeHg and inorganic Hg exposure levels in residents of WS town were significantly higher than those of YT and ZC town. Desulfovibrio and Methanogens, which related to Hg methylation/demethylation, showed significantly higher abundance in WS and ZC, comparing with YT. In vitro experiments demonstrated that human intestinal microbiota could degrade MeHg directly. Besides, gut microbiota in WS and ZC exhibited significantly higher demethylation rates than YT, suggesting Desulfovibrio and Methanogens may play important roles in intestinal MeHg demethylation. This study highlights Hg exposure levels and sources may affect demethylation efficiency of gut microbiota, which provides new insights for MeHg demethylation processes in human body.

Compound-Specific Stable Isotope Analysis Provides New Insights for Tracking Human Monomethylmercury Exposure Sources.

Monomethylmercury (MMHg) exposure can induce adverse neurodevelopmental effects in humans and is a global environmental health concern. Human exposure to MMHg occurs predominately through the consumption of fishery foods and rice in Asia, but it is challenging to quantify these two exposure sources. Here, we innovatively utilized MMHg compound-specific stable isotope analyses (MMHg-CSIA) of the hair to quantify the human MMHg sources in coastal and inland areas, where fishery foods and rice are routinely consumed. Our data showed that the fishery foods and rice end members had distinct Δ199HgMMHg values in both coastal and inland areas. The Δ199HgMMHg values of the human hair were comparable to those of fishery foods but not those of rice. Positive shifts in the δ202HgMMHg values of the hair from diet were observed in the study areas. Additionally, significant differences in δ202Hg versus Δ199Hg were detected between MMHg and inorganic Hg (IHg) in the human hair but not in fishery foods and rice. A binary mixing model was developed to estimate the human MMHg exposures from fishery foods and rice using Δ199HgMMHg data. The model results suggested that human MMHg exposures were dominated (>80%) by fishery food consumption and were less affected by rice consumption in both the coastal and inland areas. This study demonstrated that the MMHg-CSIA method can provide unique information for tracking human MMHg exposure sources by excluding the deviations from dietary surveys, individual MMHg absorption/demethylation efficiencies, and the confounding effects of IHg.

Geochemical cycle of mercury associated with wet deposition and inflows in a subalpine wetland.

Subalpine wetland is a mercury (Hg) sensitive ecosystem, but there is poor understanding of Hg behavior in this typical wetland. Here, distribution and speciation of Hg in waters of a subalpine wetland (Dajiuhu) in China were investigated, and an initial model of the Hg geochemical cycle in the wetland was established based on Hg mass balance calculations. Concentrations of both total Hg (THg, 9.52 ± 6.61 ng L-1) and total methyl mercury (TMeHg, 0.34 ± 0.44 ng L-1) in the waters during the wet season were higher than in the dry season. The majority of THg was in dissolved form whereas most TMeHg was in particle form. The geochemical models suggested that, due to the wet deposition and surface runoff, the input of THg and TMeHg into the wetland in the wet season (222 and 2.74 g year-1, respectively) was higher than that in the dry season (57.9 and 1.15 g year-1, respectively). The output of THg and TMeHg from the wetland underground runoff in the wet season was estimated to be 154 and 2.51 g year-1, respectively, and in the dry season was 15.9 and 0.43 g year-1, respectively. Other losses of Hg were due to volatilization of Hg0 from the sediment water (30.5 and 12.5 g year-1 in the wet and dry seasons, respectively). The flux of the settling of particulate Hg in the wet season was higher than that in the dry season. The fluxes of Hg diffusion from the porewater were relatively low in comparison to the fluxes of inflows and wet deposition. The flux of oxidation was higher than reduction, while the flux of methylation was higher than demethylation. These results indicated that the elevated levels of THg and MeHg in the Dajiuhu wetland are a consequence of rainfall and surface runoff inputs.

Prodrug-Based Versatile Nanomedicine for Enhancing Cancer Immunotherapy by Increasing Immunogenic Cell Death.

Nanoparticle-based tumor immunotherapy has emerged to show great potential for simultaneously regulating the immunosuppressive tumor microenvironment, reducing the unpleasant side effects, and activating tumor immunity. Herein, an excipient-free glutathione/pH dual-responsive prodrug nanoplatform is reported for immunotherapy, simply by sequentially liberating 5-aminolevulinic acid and immunogenically inducing doxorubicin drug molecules, which can leverage the acidity and reverse tumor microenvironment. The obtained nanoplatform effectively boosts the immune system by promoting dendritic cell maturation and reducing the number of immune suppressive immune cells, which shows the enhanced adjunctive effect of anti-programmed cell death protein 1 therapy. Overall, the prodrug-based immunotherapy nanoplatform may offer a reliable strategy for improving synergistic antitumor efficacy.

Expression of inositol polyphosphate 4-phosphatase type II and the prognosis of oral squamous cell carcinoma.

Inositol polyphosphate 4-phosphatase type II (INPP4B) is a phosphoinositide phosphatase that plays complex roles in the pathogenesis of different tumors. We aimed to explore the expression, clinicopathological significance, and prognostic value of INPP4B in oral squamous cell carcinoma (OSCC). Tissue microarrays that included samples from 176 primary OSCCs, 42 normal mucosae, and 69 dysplastic tissues were used for immunostaining analyses of INPP4B protein. Aperio ScanScope CS scanner and aperio quantification software were used to scan the microarrays and score the staining, respectively. We also evaluated the correlation between INPP4B expression and clinical parameters, pathological grades, node-positive status, and immune-related markers. Expression of INPP4B was statistically significantly upregulated in human primary OSCC tissues compared with dysplastic and normal tissues. Additionally, we found that patients with strong expression of INPP4B had a statistically significantly poorer overall survival than patients with weak expression of INPP4B. Furthermore, our study indicated that expression of INPP4B in OSCC was positively associated with expression of p-S6Ser235/236 , p-CADSer1859 , and certain immune checkpoints (B7-H4, Galectin-9). Therefore, INPP4B may be an independent prognostic indicator for patients with OSCC, in which it might function as an oncoprotein.

Early forest-fire detection using scanning polarization lidar.

As forest terrain is complex, containing leaves and other obstacles, it is difficult to distinguish the signal of forest-fire smoke when using single-channel lidar. To address this difficulty, a scanning micropulse polarization lidar system is developed, and a new method to detect forest fires is proposed in this study. Based on the characteristics of the depolarization ratio of in-scene obstacles, a matrix is constructed to remove obstacle signals, which in turn reduces the misidentification rate. Artificial forest-fire tests are carried out to verify the correctness of the proposed method and the feasibility of early forest-fire detection using the scanning polarization lidar system. In the working mode, the developed polarizing lidar system can locate a forest fire within three minutes with the proposed method. The experimental results show that forest fires can be accurately detected in real time when using scanning polarization lidar.

Risks related to heavy metal pollution in urban construction dust fall of fast-developing Chinese cities.

Urban construction is a major contributor to air pollution, but few studies have examined heavy metal pollution in urban areas caused by construction dust fall. We measured the concentrations of Cr, Ni, Cu, Zn, Pb, Cd, and Hg and particle size distribution in dust fall from various construction activities in seven fast-developing cities in China and conducted a health risk assessment. Mean metal concentrations in construction dust fall were on the order of Zn (246.3 mg/kg) > Cr (94.2 mg/kg) > Pb (56.5 mg/kg) > Cu (53.6 mg/kg) > Ni (22.8 mg/kg) > Cd (0.68 mg/kg) > Hg (0.08 mg/kg). Cu and Zn were positively correlated in areas of subway and building construction, and Pb and Cd were positively correlated in areas of road construction, likely because of the materials specific to these activities. Enrichment factors for heavy metals at all sampling sites were on the order of Cd (10.4) > Zn (6.37) > Cu (4.25) > Pb (3.84) > Hg (2.41) > Cr (2.02) > Ni (1.32). The enrichment factors for all metals except Zn indicated that heavy metal pollution was highest in road construction, followed by building and subway construction. Non-carcinogenic risks to children (hazard index >1) were 1.01-1.08 in four of the seven sampling sites, indicating possible risk from deposition of construction dust fall. In contrast, the hazard index for adults was <1 at the seven cities and total carcinogenic risks (<1 × 10-6) were at acceptable levels. An integrated ecological risk assessment demonstrated that heavy metal particles in construction dust fall in two of the cities (Shijiazhuang and Qingdao) were likely to be suspended in the atmosphere. Our study of heavy metal pollution in construction dust fall provides data on ecological and human health impacts and suggests that extensive measures are required to control construction dust fall in China.

Profiles, source identification and health risks of potentially toxic metals in pyrotechnic-related road dust during Chinese New Year.

Potentially toxic metal (PTM) pollution in road dust is of great concern, however, our understanding of PTMs released by pyrotechnic displays and their adverse impacts on human health in road dust is limited. Here, we studied PTM pollution levels and Pb isotope signatures in pyrotechnic ash and road dust (aged dust and pyrotechnic-influenced dust) samples from eight cities in China during Chinese New Year and carried out a human health risk assessment. Pyrotechnic ash had higher values of Cr, Co, Ni, Cu, Zn, As, Sr and Pb but lower values of Mn and Cd than Chinese background soil. Pyrotechnic-influenced dust had significantly higher Cu and Cr values than aged dust, with enrichment of Sr, Cu, Pb, Cr and Ni in road dust after pyrotechnic displays. Both 208Pb/206Pb and Sr values were used to confirm the presence of pyrotechnic ash in road dust. A positive matrix factorization demonstrated that pyrotechnic events contributed 70.1%, 50.4%, 36.6% and 35.5% of the Sr, Cu, Cr and Pb values to these road dust, respectively. We found that non-carcinogenic and carcinogenic risks related to PTMs in road dust were at safe levels during the Chinese New Year, although both risks were elevated following pyrotechnic events. Typically, PTM pollutants related to pyrotechnic events contributed 33.99% to non-carcinogenic and 21.83% to carcinogenic risks, suggesting that more attention needs to be paid to this source of PTM pollution in China. Current results improve our understanding of PTM pollution in pyrotechnic-influenced road dust and health risks related to pyrotechnic displays in China.

Novel Lidar algorithm for horizontal visibility measurement and sea fog monitoring.

Traditionally, Klett and Fernald inversion estimates an initial value using the slope method for horizontal visibility, which causes inversion uncertainty. We proposed an algorithm to retrieve the extinction coefficient and visibility distribution information from scanning Lidar to overcome instability due to initial atmospheric extinction coefficient choice and assuming the Lidar ratio. Numerical simulations showed that extinction coefficient maximum relative was much larger for inhomogeneous atmosphere using the Klett method, reaching 0.31. In contrast, it is only 0.049 using the proposed algorithm. Experimental showed that the proposed algorithm and scanning Lidar system provide very high stability and accuracy, can work in different weather conditions and monitor sea fog evolution over real time, and is suitable for various situations with different visibility.

Economic benefit of ecological remediation of mercury pollution in southwest China 2007-2022.

Methylmercury (MeHg) exposure via rice consumption poses health risk to residents in mercury contaminated areas, such as the Wanshan Hg mining area (WSMA) in southwest China. Making use of the published data for WSMA, this study developed a database of rice MeHg concentrations for different villages in this region for the years of 2007, 2012, 2017, and 2019. The temporal changes of human MeHg exposure, health effects, and economic benefits under different ecological remediation measures were then assessed. Results from this study revealed a decrease of 3.88 µg/kg in rice MeHg concentration and a corresponding reduction of 0.039 µg/kg/d in probable daily intake of MeHg in 2019 compared to 2007 on regional average in the WSMA. Ecological remediation measures in this region resulted in the accumulated economic benefits of $38.7 million during 2007-2022, of which 84 % was from pollution source treatment and 16 % from planting structure adjustment. However, a flooding event in 2016 led to an economic loss of $2.43 million (0.38 % of regional total Gross Domestic Product). Planting structure adjustment generates the greatest economic benefits in the short term, whereas pollution source treatment maximizes economic benefits in the long term and prevents the perturbations from flooding event. These findings demonstrate the importance of ecological remediation measures in Hg polluted areas and provide the foundation for risk assessment of human MeHg exposure via rice consumption.

Mercury sources, transport, and transformation in rainfall-runoff processes: Mercury isotope approach.

Mercury (Hg) in runoff water poses significant ecological risks to aquatic ecosystems that can affect organisms. However, accurately identifying the sources and transformation processes of Hg in runoff water is challenging due to complex natural conditions. This study provides a comprehensive investigation of Hg dynamics in water from rainfall to runoff. The Hg isotope fractionation in water was characterized, which allows accurate quantification of Hg sources, transport, and transformations in rainfall-runoff processes. Δ200Hg and corrected Δ199Hg values can serve as reliable tracers for identifying Hg sources in the runoff water and the variation of δ202Hg can be explained by Hg transformation processes. During runoff migration processes, Hg from rainfall is rapidly absorbed on the land surface, while terrestrial Hg entering the water by the dissolution process becomes the primary component of dissolved mercury (DHg). Besides the dissolution and adsorption, microbial Hg(II) reduction and demethylation of MeHg were dominant processes for DHg in the runoff water that flows through the rice paddies, while photochemical Hg(II) reduction was the dominant process for DHg in the runoff water with low water exchange rates. Particulate Hg (PHg) in runoff water is dominantly originated by the terrestrial material and derived from the dissolution and adsorption process. Tracking sources and transformations of Hg in runoff water during the rainfall-runoff process provides a basis for studying Hg pollution in larger water bodies under complex environmental factors.

Spatial Distribution, Pollution, and Ecological Risk Assessment of Metal(loid)s in Multiple Spheres of the Shennongjia Alpine Critical Zone, Central China.

The development of Earth's critical zone concept has strengthened the capacity of environmental science to better solve real-world problems, such as metal(loid) pollution in the remote alpine areas. The selected metal(loid) contents in soil, moss, and water were investigated to explore the geochemical distribution patterns, pollution levels, and potential ecological risks of metal(loid)s in the Shennongjia (SNJ) alpine critical zone of central China. The distribution of metal(loid)s in different spheres had horizontal and vertical differences. The maximum V, Ni, and Zn contents in water occurred at the sampling sites close to the Hohhot-Beihai Highway, while Dajiuhu Lake had the maximum Cu, Cr, and Mn contents. Most metal(loid) contents in the mosses showed an increasing trend from the northeast low-altitude area to the southwest high-altitude area, while As, Co, V, Ni, Cr, and Zn in soil decreased significantly with altitude and were enriched near the service areas and the highway. The contents of water Co and Ni, soil Cu and Mn, and moss As were evenly distributed and showed no significant differences with altitude. The enrichment factors, pollution index, Nemerow integrated pollution index, geo-accumulation index, heavy metal pollution index, contamination factor, and potential ecological risk index (PERI) were used to assess the pollution levels and ecological risks of SNJ soil, water, and atmosphere. The overall pollution levels of SNJ soil, moss, and water were low to moderate, low, and low, respectively. Soil V, Cu, Zn, moss As, Co, V, and Dajiuhu Lake water Mn were the main pollution factors. The ecological risks in the three spheres of the SNJ alpine critical zone were low to moderate, and As, Co, and V were the most critical potential ecological risk factors. The metal(loid)s pollution problem caused by the continuous development of tourism needs further attention.

Mercury isotope compositions in seawater and marine fish revealed the sources and processes of mercury in the food web within differing marine compartments.

Anthropogenic activities and climate change have significantly increased mercury (Hg) levels in seawater. However, the processes and sources of Hg in differing marine compartments (e.g. estuary, marine continental shelf (MCS) or pelagic area) have not been well studied, which makes it difficult to understand Hg cycling in marine ecosystems. To address this issue, the total Hg (THg) concentration, methylmercury (MeHg) concentration and stable Hg isotopes were determined in seawater and fish samples collected from differing marine compartments of the South China Sea (SCS). The results showed that the estuarine seawater exhibited substantially higher THg and MeHg concentrations than those in the MCS and pelagic seawater. Significantly negative δ202Hg (-1.63‰ ± 0.42‰) in estuarine seawater compared with that in pelagic seawater (-0.58‰ ± 0.08‰) may suggest watershed input and domestic sewage discharge of Hg in the estuarine compartment. The Δ199Hg value in estuarine fish (0.39‰ ± 0.35‰) was obviously lower than that in MCS (1.10‰ ± 0.54‰) and pelagic fish (1.15‰ ± 0.46‰), which showed that relatively little MeHg photodegradation occurred in the estuarine compartment. The Hg isotope binary mixing model based on Δ200Hg revealed that approximately 74% MeHg in pelagic fish is derived from atmospheric Hg(II) deposition, and over 60% MeHg in MCS fish is derived from sediments. MeHg sources for estuarine fish may be highly complex (e.g. sediment or riverine/atmospheric input) and further investigations are warranted to clarify the contribution of each source. Our study showed that Hg stable isotopes in seawater and marine fish can be used to identify the processes and sources of Hg in different marine compartments. This finding is of great relevance to the development of marine Hg food web models and the management of Hg in fish.

Combining of C, N and specific Hg stable isotopes to track bioaccumulation of monomethylmercury in coastal and freshwater seafood.

Human exposure to monomethylmercury (MMHg) through seafood consumption is a global concern. This study investigates the potential sources and processes of MMHg in seafood of coastal and freshwater areas through combing of δ13C, δ15N, and specific Hg (including MMHg and inorganic Hg (IHg)) isotopes. The results showed that δ13C and δ15N values exhibit different patterns in coastal and freshwater species. Δ199HgMMHg/δ202HgMMHg values suggested that coastal and freshwater seafood undergo similar aqueous MMHg photodegradation processes. The Δ199HgMMHg values could distinguish that, coastal fish absorb MMHg from water column whereas coastal shellfish absorb MMHg mainly from sediment. The positive values of Δ199HgIHg in seafood could reflect in vivo MMHg demethylation and IHg reabsorption. Positive correlation between δ15N and Δ199HgIHg indicated that aquatic organisms in various trophic levels may have different MMHg demethylation efficiency. We proposed that combining of multiple isotopes can provide overall profiles on aquatic MMHg biogeochemical cycle and bioaccumulation.

Application of Pb Isotopes and REY Patterns in Tracing Heavy Metals in Farmland Soils from the Upper-Middle Area of Yangtze River.

Farmland heavy metal pollution-caused by both human activity and natural processes-is a major global issue. In the current study, principal component analysis (PCA), cluster analysis (CA), rare earth elements and yttrium (REY) analysis, and isotope fingerprinting were combined to identify sources of heavy metal pollution in soil from different farmland types in the upper-middle area of the Yangtze River. The concentrations of Zn and Cu were found to be higher in the vegetable base and tea plantation soil compared with their concentrations in the orangery soil. On the other hand, greater accumulation of Cd and Pb was observed in the orangery soil versus the vegetable base and tea plantation soils. Influenced by the type of bedrock, REY was significantly enriched in the orangery soil and depleted in the vegetable base soil, as compared with the tea plantation soil. The Pb isotopic compositions of the tea plantation (1.173-1.193 for 206Pb/207Pb and 2.070-2.110 for 208Pb/206Pb) and vegetable base (1.181-1.217 for 206Pb/207Pb and 2.052-2.116 for 208Pb/206Pb) soils were comparable to those of coal combustion soil. The compositions of 206Pb/207Pb (1.149-1.170) and 208Pb/206Pb (2.121-2.143) in the orangery soil fell between those observed in soils obtained from coal combustion and ore smelting sites. Using the IsoSource model, the atmospheric Pb contributions of the vegetable base, tea plantation, and orangery soils were calculated to be 66.6%, 90.1%, and 82.0%, respectively, and the bedrock contributions of Pb were calculated to be 33.3%, 9.90%, and 18.1%, respectively. Based on the PCA, CA, and REY results, as well as the Pb isotope model, it appears that heavy metals in the orangery soil may be derived from atmospheric deposition and bedrock weathering, while heavy metals in the vegetable base and tea plantation soils may be derived from mining and the use of fertilizer.

Heavy metals in fish, rice, and human hair and health risk assessment in Wuhan city, central China.

The current study investigated the concentration of heavy metals (HMs) in human hair associated with fish and rice consumption in Wuhan City, central China. The mean values of As in 8/10 fish species exceeded the food safety standard of 0.015 mg/kg. The mean values (mg/kg) of HMs in rice followed a descending order of Zn (13.7)> Cu (1.9)>Cr (0.51)>As (0.11) >Cd (0.08) >Pb (0.04). The ascending order of HMs for male hair was Cd < As < Cr < Pb < Cu < Zn, while As < Cd < Cr < Pb < Cu < Zn for female. 30% of hair Cr and 22% of hair Zn contents exceeded the recommended values. The middle age (19-44) and adult (45-59) groups were the most vulnerable group, as the concentration for most elements was high in these age groups. A significant correlation was found between fish-eating frequency and hair Zn (r = 0.213; p < 0.05), and As (r = 0.204; p < 0.05). High odd ratios were found in a population with high fish-eating frequency, especially for Pb (7.19), As (3.1), Zn (3.83), and Cd (3.7). A significant non-carcinogenic risk was associated with Cr exposure through consuming herbivores, filter feeders, and omnivorous fish. The cancer risk values of Cd exposure (1.54E-04) via rice consumption and As exposure (1.25E-04) via consumption of omnivores fish indicate precautionary measures.

Bioengineering of BRAF and COX2 inhibitor nanogels to boost the immunotherapy of melanoma via pyroptosis.

Glutathione-responsive nanogels (CDNPs) crosslinked via crosslinker DBHD with the BRAF inhibitor dabrafenib and the COX2 inhibitor celecoxib were fabricated. The CDNPs can effectively induce tumor cell pyroptosis to activate robust antitumor immunity. Additionally, CDNPs combined with αPD-1 antibody greatly inhibited tumor growth in a melanoma mouse model with a prolonged survival time.

Trace mercury migration and human exposure in typical mercury-emission areas by compound-specific stable isotope analysis.

Anthropogenic mercury (Hg) emissions have increased significantly since the Industrial Revolution, resulting in severe health impacts to humans. The consumptions of fish and rice were primary human methylmercury (MeHg) exposure pathways in Asia. However, the lifecycle from anthropogenic Hg emissions to human MeHg exposure is not fully understood. In this study, a recently developed approach, termed MeHg Compound-Specific Isotope Analysis (CSIA), was employed to track lifecycle of Hg in four typical Hg-emission areas. Distinct Δ199Hg of MeHg and inorganic Hg (IHg) were observed among rice, fish and hair. The Δ199Hg of MeHg averaged at 0.07 ± 0.15 ‰, 0.80 ± 0.55 ‰ and 0.43 ± 0.29 ‰ in rice, fish and hair, respectively, while those of IHg averaged at - 0.08 ± 0.24 ‰, 0.85 ± 0.43 ‰ and - 0.28 ± 0.68 ‰. In paddy ecosystem, Δ199Hg of MeHg in rice showed slightly positive shifts (∼0.2 ‰) from those of IHg, and comparable Δ199Hg of IHg between rice grain and raw/processed materials (coal, Hg ore, gold ore and sphalerite) were observed. Simultaneously, it was proved that IHg in fish muscle was partially derived from in vivo demethylation of MeHg. By a binary model, we estimated the relative contributions of rice consumption to human MeHg exposure to be 84 ± 14 %, 58 ± 26 %, 52 ± 20 % and 34 ± 15 % on average in Hg mining area, gold mining area, zinc smelting area and coal-fired power plant area, respectively, and positive shifts of δ202HgMeHg from fish/rice to human hair occurred during human metabolic processes. Therefore, the CSIA approach can be an effective tool for tracking Hg biogeochemical cycle and human exposure, from which new scientific knowledge can be generated to support Hg pollution control policies and to protect human health.