Wildfire-related PM2.5 and cause-specific cancer mortality.

Wildfires have devastating effects on society and public health. However, little evidence from population-based cohort has been performed to analyze the relationship of wildfire-related PM2.5, an important component of wildfire smoke, with cancer-specific mortality. We aimed to explore this relationship and identify vulnerable populations in UK with lower levels of wildfire-related PM2.5 exposure. The study consisted of 492394 participants (age: 38-73 years) recruited by UK Biobank during 2004-2010. The cumulative wildfire-related PM2.5 within 10 kilometers of residence over three years was used as exposure, which was assessed by chemical transport and machine learning models. A time-varying Cox regression was utilized to explore the relationship of exposure with diverse cancer-specific mortality outcomes. Subgroup analyses of a range of potential modifiers were performed. Each 10 µg/m3 increment of 3-year cumulative exposure was related to a 0.4 % greater risk of total cancer (95 %CI: 1.001-1.007), a 1.1 % greater risk of lung cancer (95 %CI: 1.004-1.018), and a 2.7 % greater risk of lip, oral cavity and pharynx (LOP) cancer (95 %CI: 1.005-1.049). Higher vulnerability in the wildfire-related PM2.5-lung cancer relationship was found among participants being retired than those with other employment status. Even lower levels of exposure to PM2.5 from wildfires were related to elevated mortality risks for cancer from total, lung, LOP, highlighting the importance of wildfire prevention and control. Further investigations are warranted to enrich and extend existing knowledge in this field.

The role of heterotrophic plasticity in coral response to natural low-light environments.

Coastal darkening is emerging as a global threat to fringing reefs. While some reef-building corals exhibit resistance to low-light environments, the mechanisms behind this resistance, particularly the role of coral hosts, remain inadequately understood. Here, we investigated variations in underwater photosynthetically active radiation (PAR) and employed the Bayesian stable isotope mixing model (MixSIAR) to estimate the contributions of autotrophic (i.e., dissolved inorganic matter, DIM) and heterotrophic sources (i.e., particulate organic matter, POM, and dissolved organic matter, DOM) to the nutrition of the reef coral Galaxea fascicularis on the Luhuitou turbid reef in the northern South China Sea. Our findings revealed that the heterotrophic contribution to coral nutrition increased to 58.5% with decreasing PAR and that the heterotrophic contribution was significantly negatively correlated with δ13C difference between host and symbiont (δ13Ch-s). Moreover, we observed significant seasonal variations in the respective contributions of POM and DOM to coral nutrition, linked to the sources of these nutrients, demonstrating that G. fascicularis can selectively ingest POM and DOM based on their bioavailability to enhance its heterotrophic contribution. This heterotrophic plasticity improved the low-light resistance of G. fascicularis and contributed to its prominence within coral communities. However, with a low-light threshold of approximately 3.73% of the surface PAR for G. fascicularis, our results underscore the need for effective strategies to mitigate low-light conditions on nearshore turbid reefs. In summary, our study highlights the critical role of heterotrophic plasticity in coral responses to natural low-light environments, suggesting that some reef-building corals with such plasticity could become dominant or resilient species in the context of coastal darkening.

Micro plastic driving changes in the soil microbes and lettuce growth under the influence of heavy metals contaminated soil.

Microplastics (MPs) have garnered global attention as emerging contaminants due to their adaptability, durability, and robustness in various ecosystems. Still, studies concerning their combination with heavy metals (HMs), their interactions with soil biota, and how they affect soil physiochemical properties and terrestrial plant systems are limited. Our study was set to investigate the combined effect of HMs (cadmium, arsenic, copper, zinc and lead) contaminated soil of Tongling and different sizes (T1 = 106 µm, T2 = 50 µm, and T3 = 13 µm) of polystyrene microplastics on the soil physiochemical attributes, both bacterial and fungal diversity, compositions, AMF (arbuscular mycorrhizal fungi), plant pathogens in the soil, and their effect on Lactuca sativa by conducting a greenhouse experiment. According to our results, the combination of HMs and polystyrene microplastic (PS-MPs), especially the smaller PS-MPs (T3), was more lethal for the lettuce growth, microbes and soil. The toxicity of combined contaminants directly reduced the physio-biochemical attributes of lettuce, altered the lettuce's antioxidant activity and soil health. T3 at the final point led to a significant increase in bacterial and fungal diversity. In contrast, overall bacterial diversity was higher in the rhizosphere, and fungal diversity was higher in the bulk soil. Moreover, the decrease in MPs size played an important role in decreasing AMF and increasing both bacterial and fungal pathogens, especially in the rhizosphere soil. Functional prediction was found to be significantly different in the control treatment, with larger MPs compared to smaller PS-MPs. Environmental factors also played an important role in the alteration of the microbial community. This study also demonstrated that the varied distribution of microbial populations could be an ecological indicator for tracking the environmental health of soil. Overall, our work showed that the combination of HMs and smaller sizes of MPs was more lethal for the soil biota and lettuce and also raised many questions for further studying the ecological risk of PS-MPs and HMs.

Effects of cadmium on the intestinal health of the snail Bradybaena ravida Benson.

The heavy metal cadmium (Cd) is a toxic and bioaccumulative metal that can be enriched in the tissues and organs of living organisms through the digestive tract. However, more research is needed to determine whether food-sourced Cd affects the homeostasis of host gut microflora. In this study, the snail Bradybaena ravida (Benson) was used as a model organism fed with mulberry leaves spiked with different concentrations of Cd (0, 0.052, 0.71, and 1.94 mg kg-1). By combining 16S rRNA high-throughput sequencing with biochemical characterization, it was found that there were increases in the overall microbial diversity and abundances of pathogenic bacteria such as Corynebacterium, Enterococcus, Aeromonas, and Rickettsia in the gut of B. ravida after exposure to Cd. However, the abundances of potential Cd-resistant microbes in the host's gut, including Sphingobacterium, Lactococcus, and Chryseobacterium, decreased with increasing Cd concentrations in the mulberry leaves. In addition, there was a significant reduction in activities of energy, nutrient metabolism, and antioxidant enzymes for gut microbiota of snails treated with high concentrations of Cd compared to those with low ones. These findings highlight the interaction of snail gut microbiota with Cd exposure, indicating the potential role of terrestrial animal gut microbiota in environmental monitoring through rapid recognition and response to environmental pollution.

Study of the mechanism of non-covalent interactions between chlorogenic acid and soy protein isolate: Multi-spectroscopic, in vitro, and computational docking analyses.

This study investigated the interaction mechanism between chlorogenic acid (CA) and soy protein isolate (SPI) through multi-spectroscopic and computational docking and analyzed the changes in its functional properties. The results showed that the interaction of CA with SPI changed its UV and fluorescence absorption, and the fluorescence quenching mechanism was static quenching. At the same time, the secondary structure of the protein was altered, with a reduction in α-helix, ß-sheet and ß-turn. Computer docking analysis showed that CA binds to SPI through hydrophobic interactions, van der Waals forces, and hydrogen bonding to form a more compact complex. In addition, the dose-dependent enhancement of CA improved the functional properties of the complexes, including foaming, emulsification, and antioxidant properties. This study systematically investigated the mechanism of interaction between CA and SPI, which supports further research on food complex systems containing CA and SPI, as well as the application of the complex.

Adding salt to foods and risk of psoriasis: A prospective cohort study.

BACKGROUND: High salt intake may play a critical role in the etiology of psoriasis. Yet, evidence on the association of high salt intake with risk of psoriasis is limited. OBJECTIVE: To estimate the association between frequency of adding salt to foods and risk of psoriasis. METHODS: We conducted a prospective cohort study of 433,788 participants from the UK Biobank. Hazard ratios (HRs) and their 95 % confidence intervals (CIs) for risk of psoriasis in relation to frequency of adding salt to foods were estimated using multivariable Cox proportional hazards models. We further evaluated the joint association of adding salt to foods and genetic susceptibility with risk of psoriasis. We conducted a mediation analysis to assess how much of the effect of adding salt to foods on risk of psoriasis was mediated through several selected mediators. RESULTS: During a median of 14.0 years of follow-up, 4279 incident cases of psoriasis were identified. In the multivariable-adjusted model, a higher frequency of adding salt to foods was significantly associated with an increased risk of psoriasis ("always" versus "never/rarely" adding salt to foods, HR = 1.25, 95 % CI: 1.10, 1.41). The observed positive association was generally similar across subgroups. In the joint association analysis, we observed that participants with a high genetic risk (above the second tertile) and the highest frequency of adding salt to foods experienced 149 % higher risk of psoriasis, when compared with participants with a low genetic risk (below the first tertile) and the lowest frequency of adding salt to foods (HR = 2.49, 95 % CI: 2.05, 3.02). Mediation analysis revealed that 1.8 %-3.2 % of the positive association between frequency of adding salt and risk of psoriasis was statistically significantly mediated by obesity and inflammatory biomarkers such as C-reactive protein and systemic immune-inflammation index (all P values < 0.004). CONCLUSIONS: Our study demonstrated a positive association between frequency of adding salt to foods and risk of psoriasis. The positive association was independent of multiple other risk factors, and may be partially mediated through obesity and inflammation.

Association between blood chromium and hepatic steatosis assessed by liver ultrasound transient elastography: National Health and Nutrition Examination Survey 2017-2020.

Background: Hepatic steatosis is a significant pathological feature of fatty liver disease (FLD) which is widely spread with no effective treatment available. Previous studies suggest that chromium (Cr) intake reduces lipid deposition in the liver in animals. However, the connection between blood Cr and hepatic steatosis among humans remains inconclusive. Methods: Using the data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020, we performed a cross-sectional analysis, including 4,926 participants. The controlled attenuation parameter (CAP) measured by the vibration controlled transient elastography (VCTE) was used to evaluate the degree of liver steatosis. Weighted univariate regression, multivariate linear regression, smooth fitting curves and subgroup analysis were used. In addition, we carried out trend tests, multiple interpolations, and interaction analyses to conduct sensitivity analyses. Results: After adjusting with various covariables, multivariate linear regression analysis demonstrated a significant negative correlation between blood Cr and CAP [ß (95% CI) = -5.62 (-11.02, -0.21)]. The negative correlation between blood Cr and CAP was more significant in the males, 50-59 years, overweight, hypercholesterolemia, HDL-C ≥ 65 mg/dL, HbA1c (5.70-6.10 %), HOMA-IR (0.12-2.76), total bilirubin (0.30-0.40 mg/dL), ever alcohol consumption subjects. Of note, the relationships between blood Cr and CAP followed a U-shaped curve in the smokers and non-smokers, with blood Cr thresholds of 0.48, 0.69 µg/L, respectively. Conclusions: There is an independently negative correlation between blood Cr and hepatic steatosis in American. Our study provides clinical researchers with a new insight into the prospective prevention of hepatic steatosis.

Rare Earth Single-Atom Catalysis for High-Performance Li-S Full Battery with Ultrahigh Capacity.

Lithium-sulfur (Li-S) batteries have many advantages but still face problems such as retarded polysulfides redox kinetics and Li dendrite growth. Most reported single atom catalysts (SACs) for Li-S batteries are based on d-band transition metals whose d orbital constitutes active valence band, which is inclined to occur catalyst passivation. SACs based on 4f inner valence orbital of rare earth metals are challenging for their great difficulty to be activated. In this work, we design and synthesize the first rare earth metal Sm SACs which has electron-rich 4f inner orbital to promote catalytic conversion of polysulfides and uniform deposition of Li. Sm SACs enhance the catalysis by the activated 4f orbital through an f-d-p orbital hybridization. Using Sm-N3C3 modified separators, the half cells deliver a high capacity over 600 mAh g-1 and a retention rate of 84.3 % after 2000 cycles. The fabricated Sm-N3C3-Li|Sm-N3C3@PP|S/CNTs full batteries can provide an ultra-stable cycling performance of a retention rate of 80.6 % at 0.2 C after 100 cycles, one of the best full Li-S batteries. This work provides a new perspective for the development of rare earth metal single atom catalysis in electrochemical reactions of Li-S batteries and other electrochemical systems for next-generation energy storage.

Floods and cause-specific mortality in the UK: a nested case-control study.

BACKGROUND: Floods are the most frequent weather-related disaster, causing significant health impacts worldwide. Limited studies have examined the long-term consequences of flooding exposure. METHODS: Flood data were retrieved from the Dartmouth Flood Observatory and linked with health data from 499,487 UK Biobank participants. To calculate the annual cumulative flooding exposure, we multiplied the duration and severity of each flood event and then summed these values for each year. We conducted a nested case-control analysis to evaluate the long-term effect of flooding exposure on all-cause and cause-specific mortality. Each case was matched with eight controls. Flooding exposure was modelled using a distributed lag non-linear model to capture its nonlinear and lagged effects. RESULTS: The risk of all-cause mortality increased by 6.7% (odds ratio (OR): 1.067, 95% confidence interval (CI): 1.063-1.071) for every unit increase in flood index after confounders had been controlled for. The mortality risk from neurological and mental diseases was negligible in the current year, but strongest in the lag years 3 and 4. By contrast, the risk of mortality from suicide was the strongest in the current year (OR: 1.018, 95% CI: 1.008-1.028), and attenuated to lag year 5. Participants with higher levels of education and household income had a higher estimated risk of death from most causes whereas the risk of suicide-related mortality was higher among participants who were obese, had lower household income, engaged in less physical activity, were non-moderate alcohol consumers, and those living in more deprived areas. CONCLUSIONS: Long-term exposure to floods is associated with an increased risk of mortality. The health consequences of flooding exposure would vary across different periods after the event, with different profiles of vulnerable populations identified for different causes of death. These findings contribute to a better understanding of the long-term impacts of flooding exposure.

Physiological versatility of ANME-1 and Bathyarchaeotoa-8 archaea evidenced by inverse stable isotope labeling.

BACKGROUND: The trophic strategy is one key principle to categorize microbial lifestyles, by broadly classifying microorganisms based on the combination of their preferred carbon sources, electron sources, and electron sinks. Recently, a novel trophic strategy, i.e., chemoorganoautotrophy-the utilization of organic carbon as energy source but inorganic carbon as sole carbon source-has been specifically proposed for anaerobic methane oxidizing archaea (ANME-1) and Bathyarchaeota subgroup 8 (Bathy-8). RESULTS: To further explore chemoorganoautotrophy, we employed stable isotope probing (SIP) of nucleic acids (rRNA or DNA) using unlabeled organic carbon and 13C-labeled dissolved inorganic carbon (DIC), i.e., inverse stable isotope labeling, in combination with metagenomics. We found that ANME-1 archaea actively incorporated 13C-DIC into RNA in the presence of methane and lepidocrocite when sulfate was absent, but assimilated organic carbon when cellulose was added to incubations without methane additions. Bathy-8 archaea assimilated 13C-DIC when lignin was amended; however, their DNA was derived from both inorganic and organic carbon sources rather than from inorganic carbon alone. Based on SIP results and supported by metagenomics, carbon transfer between catabolic and anabolic branches of metabolism is possible in these archaeal groups, indicating their anabolic versatility. CONCLUSION: We provide evidence for the incorporation of the mixed organic and inorganic carbon by ANME-1 and Bathy-8 archaea in the environment. Video Abstract.

Allergic Phenotypes and Sarcopenia: Evidence from Observational Studies and Mendelian Randomization Analysis.

Commonly affected in early-life population, the impact of allergic phenotypes on mid- or late-life health is less discussed. This study is to explore the association of allergic phenotypes including atopic dermatitis (AD), asthma, eosinophils count (EC), and sarcopenia. We conducted observational studies and mendelian randomization (MR) analysis based on UK Biobank (UKB), the China Health and Retirement Longitudinal Study (CHARLS) and data from genome-wide association study (GWAS). Based on the UKB data, AD, asthma and EC were positively correlated with pre-sarcopenia and decreased skeletal muscle mass index and hand grip in fully adjusted model. Asthma and EC were significantly associated with sarcopenia while AD was marginally associated (p = 0.095). Based on the CHARLS cohort, asthma significantly added 109.4% risk for pre-sarcopenia in adjusted model (relative risk = 2.094; p = 0.002), respectively. Both asthma (ß = 0.100, p = 0.006) and EC (ß = 0.023, p = 0.017) exerted significantly casual effects on pre-sarcopenia. However, as for sarcopenia, merely EC exhibited a significantly casual effect (ß = 0.005, p = 0.048). Significant casual effects of AD (ß = - 0.027, p = 0.003), asthma (ß = - 0.029, p = 0.027) and EC (ß = - 0.041, p < 0.001) on decreased appendicular lean mass (ALM) were observed using the inverse-variance weighted method and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method. Our results revealed a contributory role of AD, asthma and EC on sarcopenia, especially in terms of decreased ALM, an indicator for sarcopenia diagnosis. The findings of our study will raise the awareness of preventing aging-related disorders or geriatric syndromes among allergic populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00110-4.

One-Step Synthesis of Polyethyleneimine-Grafted Styrene-Maleic Anhydride Copolymer Adsorbents for Effective Adsorption of Anionic Dyes.

Wastewater containing organic dyes has become one of the important challenges in water treatment due to its high salt content and resistance to natural degradation. In this work, a novelty adsorbent, PEI-SMA, was prepared by grafting polyethyleneimine (PEI) onto styrene-maleic anhydride copolymer (SMA) through an amidation reaction. The various factors, such as pH, adsorbent dosage, contact time, dye concentration, and temperature, which may affect the adsorption of PEI-SMA for Reactive Black 5 (RB5), were systematically investigated by static adsorption experiments. The adsorption process of PEI-SMA for RB5 was more consistent with the Langmuir isotherm model and the pseudo-second-order model, suggesting a single-layer chemisorption. PEI-SMA exhibits excellent adsorption performance for RB5 dye, with a maximum adsorption capacity of 1749.19 mg g-1 at pH = 2. Additionally, PEI-SMA exhibited highly efficient RB5 competitive adsorption against coexisting Cl- and SO42- ions and cationic dyes. The adsorption mechanism was explored, and it can be explained as the synergistic effect of electrostatic interaction, hydrogen bonding and π-π interaction. This study demonstrates that PEI-SMA could act as a high performance and promising candidate for the effective adsorption of anionic dyes from aqueous solutions.

Multi-dimensional characterization of apoptosis in the tumor microenvironment and therapeutic relevance in melanoma.

PURPOSE: Melanoma is widely utilized as a prominent model for the development of immunotherapy, thought an inadequate immune response can occur. Moreover, the development of apoptosis-related therapies and combinations with other therapeutic strategies is impeded by the limited understanding of apoptosis's role within diverse tumor immune microenvironments (TMEs). METHODS: Here, we constructed an apoptosis-related tumor microenvironment signature (ATM) and employ multi-dimensional analysis to understand the roles of apoptosis in tumor microenvironment. We further assessed the clinical applications of ATM in nine independent cohorts, and anticipated the impact of ATM on cellular drug response in cultured cells. RESULTS: Our ATM model exhibits robust performance in survival prediction in multiple melanoma cohorts. Different ATM groups exhibited distinct molecular signatures and biological processes. The low ATM group exhibited significant enrichment in B cell activation-related pathways. What's more, plasma cells showed the lowest ATM score, highlighting their role as pivotal contributors in the ATM model. Mechanistically, the analysis of the interplay between plasma cells and other immune cells elucidated their crucial role in orchestrating an effective anti-tumor immune response. Significantly, the ATM signature exhibited associations with therapeutic efficacy of immune checkpoint blockade and the drug sensitivity of various agents, including FDA-approved and clinically utilized drugs targeting the VEGF signaling pathway. Finally, ATM was associated with tertiary lymphoid structures (TLS), exhibiting stronger patient stratification ability compared to classical "hot tumors". CONCLUSION: Our findings indicate that ATM is a prognostic factor and is associated with the immune response and drug sensitivity in melanoma.

Unexpected carbon utilization activity of sulfate-reducing microorganisms in temperate and permanently cold marine sediments.

Significant amounts of organic carbon in marine sediments are degraded, coupled with sulfate reduction. However, the actual carbon and energy sources used in situ have not been assigned to each group of diverse sulfate-reducing microorganisms (SRM) owing to the microbial and environmental complexity in sediments. Here, we probed microbial activity in temperate and permanently cold marine sediments by using potential SRM substrates, organic fermentation products at very low concentrations (15-30 µM), with RNA-based stable isotope probing. Unexpectedly, SRM were involved only to a minor degree in organic fermentation product mineralization, whereas metal-reducing microbes were dominant. Contrastingly, distinct SRM strongly assimilated 13C-DIC (dissolved inorganic carbon) with H2 as the electron donor. Our study suggests that canonical SRM prefer autotrophic lifestyle, with hydrogen as the electron donor, while metal-reducing microorganisms are involved in heterotrophic organic matter turnover, and thus regulate carbon fluxes in an unexpected way in marine sediments.

Highly efficient and fast modulation of magnetic coupling interaction in the SrCoO2.5/La0.7Ca0.3MnO3 heterostructure.

Effective manipulation of magnetic properties in transition-metal oxides is one of the crucial issues for the application of materials. Up to now, most investigations have focused on electrolyte-based ionic control, which is limited by the slow speed. In this work, the interfacial coupling of the SrCoO2.5/La0.7Ca0.3MnO3 (LCMO) bilayer is effectively modulated with fast response time. After being treated with diluted acetic acid, the bilayer changes from antiferromagnetic/ferromagnetic (AFM/FM) coupling to FM/FM coupling and the Curie temperature is also effectively increased. Meanwhile, the corresponding electric transport properties are modulated within a very short time. Combined with the structure characterization and X-ray absorption measurements, we find that the top SrCoO2.5 layer is changed from the antiferromagnetic insulator to the ferromagnetic metal phase, which is attributed to the formation of the active oxygen species due to the reaction between the protons in the acid and the SrCoO2.5 layer. The bottom LCMO layer remains unchanged during this process. The response time of the bilayer with the acid treatment method is more than an order of magnitude faster than other methods. It is expected that this acid treatment method may open more possibilities for manipulating the magnetic and electric properties in oxide-based devices.

Underlying Mechanism of Traditional Herbal Formula Chuang-Ling-Ye in the Treatment of Diabetic Foot Ulcer through Network Pharmacology and Molecular Docking.

BACKGROUND: Chuang-Ling-Ye (CLY) has been clinically proven to be an effective Chinese medicine for the treatment of diabetic foot ulcers (DFU). OBJECTIVES: This study aimed to investigate the possible mechanism of CLY in relation to DFU using network pharmacology and molecular docking. MATERIALS AND METHODS: Firstly, relevant targets of CLY against DFU were obtained from TCMSP, Swiss Target Prediction database and GEO database. Then, topological analysis was employed by Cytoscape to screen the top 6 core active ingredients and the top 8 hub targets. Furthermore, the OmicShare Tools were applied for gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the results of network pharmacology were verified by molecular docking method. RESULTS: CLY has 61 active compounds and 361 targets after de-duplication, and the top 8 hub targets were EGFR, TP53, CCND1, IL-1B, CREBBP, AR, PTGS2 and PGR. GO enrichment analysis is mainly related to signal transducer activity, receptor activity, and molecular transducer activity. KEGG pathway analysis indicated that these shared targets were primarily focused on AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, IL-17 signaling pathway, and JAK-STAT signaling pathway. Molecular docking results showed that physciondiglucoside, 2-cinnamoyl-glucose and kinobeon A were well bound with EGFR, IL-1B, AR and PTGS2. CONCLUSION: This study demonstrated that CLY has anti-oxidative stress and anti-inflammatory effects in the treatment of DFU through various constituents, multiple targets, and multiple pathways, which provides a valuable point of reference for future investigations on CLY.

Multiomics characterization of pyroptosis in the tumor microenvironment and therapeutic relevance in metastatic melanoma.

BACKGROUND: Pyroptosis, mediated by gasdermins with the release of multiple inflammatory cytokines, has emerged as playing an important role in targeted therapy and immunotherapy due to its effectiveness at inhibiting tumor growth. Melanoma is one of the most commonly used models for immunotherapy development, though an inadequate immune response can occur. Moreover, the development of pyroptosis-related therapy and combinations with other therapeutic strategies is limited due to insufficient understanding of the role of pyroptosis in the context of different tumor immune microenvironments (TMEs). METHODS: Here, we present a computational model (pyroptosis-related gene score, PScore) to assess the pyroptosis status. We applied PScore to 1388 melanoma samples in our in-house cohort and eight other publicly available independent cohorts and then calculated its prognostic power of and potential as a predictive marker of immunotherapy efficacy. Furthermore, we performed association analysis for PScore and the characteristics of the TME by using bulk, single-cell, and spatial transcriptomics and assessed the association of PScore with mutation status, which contributes to targeted therapy. RESULTS: Pyroptosis-related genes (PRGs) showed distinct expression patterns and prognostic predictive ability in melanoma. Most PRGs were associated with better survival in metastatic melanoma. Our PScore model based on genes associated with prognosis exhibits robust performance in survival prediction in multiple metastatic melanoma cohorts. We also found PScore to be associated with BRAF mutation and correlate positively with multiple molecular signatures, such as KRAS signaling and the IFN gamma response pathway. Based on our data, melanoma with an immune-enriched TME had a higher PScore than melanoma with an immune-depleted or fibrotic TME. Additionally, monocytes had the highest PScore and malignant cells and fibroblasts the lowest PScore based on single-cell and spatial transcriptome analyses. Finally, a higher PScore was associated with better therapeutic efficacy of immune checkpoint blockade, suggesting the potential of pyroptosis to serve as a marker of immunotherapy response. CONCLUSIONS: Collectively, our findings indicate that pyroptosis is a prognostic factor and is associated with the immune response in metastatic melanoma, as based on multiomics data. Our results provide a theoretical basis for drug combination and reveal potential immunotherapy response markers.

Association between the dietary inflammatory index and all-cause mortality in the U.S. cancer survivors: A prospective cohort study using the National Health and Nutrition Examination Survey database.

Background: Cancer remains one of the leading causes of mortality worldwide. Diet can impact inflammation and consequently affect cancer outcomes. The Dietary Inflammatory Index (DII) can serve as a tool to assess the inflammatory potential of cancer survivors' diets and further predict their survival. Objectives: To investigate the relationship between the DII and the survival of cancer survivors in National Health and Nutrition Examination Survey (NHANES). Methods: An overall sample of 2359 U.S. cancer survivors from the 2005-2014 cohorts of the NHANES were studied. The DII scores were calculated using 28 dietary components and the mortality status was ascertained until December 31, 2015. Based on the multiple analyses, the relationship between DII and all-cause mortality was examined. Results: The weighted mean age at baseline was 65.17 ± 14.46 years, 53.16 % were female and 71.30 % were non-Hispanic white. The average DII was 1.51 ± 1.97. After accounting for multiple covariates, positive associations were observed (P < 0.01). Based on Kaplan-Meier survival curves, their significant relationship remains same and the survival probability was decreased among the groups of anti-inflammatory diets (DII < 0) versus pro-inflammatory diets (DII ≥ 0) significantly (Log rank test; P = 0.03). Further analyses were conducted on subgroups and the results are still robust. Conclusions: An elevated DII was associated with a rising mortality rate among cancer survivors. DII might serve as a potential inflammatory predictor of cancer mortality prognosis, as well as guide nutritional care and even clinical treatment of cancer survivors.

The impacts of biologic treatment on metabolic profiling in psoriasis.

Psoriasis is an immune-mediated inflammatory disease commonly accompanied by various metabolic disorders. It is widely known that biologics could affect the metabolic status and comorbidities in psoriasis patients, however, the effects of biologics on metabolism in psoriasis patients remain poorly understood. The aim of this study was to elucidate the characteristic changes of metabolic profiling in psoriasis vulgaris (PsV) patients before and after applying biologics. Plasma samples were collected from a retrospective cohort of 43 PsV patients. Non-targeted metabolomics analyses were performed using liquid chromatography-mass spectrometry (LC-MS) to compare the metabolic profiles before and after applying adalimumab (ADA) or ixekizumab (IXE) for 4 weeks. Additionally, correlation analyses were conducted to investigate the associations between metabolite expression levels and clinical characteristics. The biologics significantly affected the metabolic profiles of PsV patients especially in glycerophospholipids (GPs). First, phosphatidylcholine (PC), unsaturated lysophosphatidylcholine (LPC), unsaturated lysophosphatidic acid (LPA) and unsaturated lysophosphatidylethanolamine (LPE) were significantly up-regulated, whereas phosphatidylethanolamine (PE), saturated LPC, saturated LPA and saturated LPE were predominantly down-regulated after biologic treatment. What is more, the changes in PE and LPA were mainly observed after applying IXE instead of ADA. Second, we also found GPs including PC, unsaturated LPC, unsaturated LPA and unsaturated LPE were primarily negatively correlated with disease severity, whereas, PE, saturated LPC, saturated LPA and saturated LPE displayed inverse correlations. Biologics could affect GP metabolism and facilitate the transition of metabolic status from a pro-inflammatory to an anti-inflammatory phenotype in PsV patients.