Tumor-associated macrophages drive glycolysis through the IL-8/STAT3/GLUT3 signaling pathway in pancreatic cancer progression.

Glycolytic metabolism is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and tumor-associated stromal cells play important roles in tumor metabolism. We previously reported that tumor-associated macrophages (TAMs) facilitate PDAC progression. However, little is known about whether TAMs are involved in regulating glycolysis in PDAC. Here, we found a positive correlation between CD68+ TAM infiltration and FDG maximal standardized uptake (FDG SUVmax) on PET-CT images of PDAC. We discovered that the glycolytic gene set was prominently enriched in the high TAM infiltration group through Gene Set Enrichment Analysis using The Cancer Genome Atlas database. Mechanistically, TAMs secreted IL-8 to promote GLUT3 expression in PDAC cells, enhancing tumor glycolysis both in vitro and in vivo, whereas this effect could be blocked by the IL-8 receptor inhibitor reparixin. Furthermore, IL-8 promoted the translocation of phosphorylated STAT3 into the nucleus to activate the GLUT3 promoter. Overall, we demonstrated that TAMs boosted PDAC cell glycolysis through the IL-8/STAT3/GLUT3 signaling pathway. Our cumulative findings suggest that the abrogation of TAM-induced tumor glycolysis by reparixin might exhibit an antitumor impact and offer a potential therapeutic target for PDAC.

The dependence in microcystin removal with powdered activated carbon on variant properties, carbon properties, and dissolved organic matter.

Powdered activated carbon (PAC) is commonly used by water treatment plants to remove harmful cyanotoxins such as microcystins (MCs) produced during seasonal harmful algal blooms. MC removal by PAC depends upon the properties of the PAC, the properties of the MC variant, and the presence and properties of dissolved organic matter (DOM). To identify which of these factors has the greatest impact on the removal of MC by PAC, we evaluated the removal of four different MC variants (MC-LR, MC-LA, MC-RR and desmethylated MC-RR) by three different PAC types (wood-based, coal-blend and coal-based). The role of DOM properties was evaluated using DOM isolated from two different sources, a terrestrial source (Suwannee River Fulvic Acid, SRFA) and a microbial source (Grand Lake St Marys DOM, GLSM). The results of adsorption experiments conducted over a period of 72 h demonstrated the wood-based PAC, which had the highest surface area and mesopore volume of the PAC tested, had the highest adsorption rate and capacity for all four MC variants. Of the variants studied, neutrally charged MC-RR was adsorbed more rapidly and to a greater extent on all of the PAC types than were the other variants. Although MC-LA and MC-LR had the greatest hydrophobicity, their negative charges resulted in their being adsorbed the least. As expected, DOM inhibited microcystin adsorption to PAC. The degree of inhibition, however, did not significantly vary for the two DOM types evaluated, indicating the properties of the DOM on MC adsorption to PAC was less important than the PAC properties or MC variant properties. Overall, PAC properties were a more important factor in MC removal than were the MC properties or DOM conditions.

Pancancer analysis uncovers an immunological role and prognostic value of the m6A reader IGF2BP2 in pancreatic cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant gastrointestinal tumors worldwide with a dismal prognosis and high relapse rate. PDAC is considered a "cold cancer" for which immunotherapy is not effective. Therefore, to improve the prognosis for PDAC patients, it is urgent to explore the mechanism driving its insensitivity to immunotherapy. MATERIALS AND METHODS: We conducted pancancer analyses to test IGF2BP family expression and survival in patients with different cancers via TCGA and GETx databases. Then, we determined the immunological role and prognostic value of IGF2BP2 in vitro, in vivo and in clinical specimens. RESULTS: In the present study, we found that the m6A reader IGF2BP2 was the most clinically relevant member of the IGF2BP family for pancreatic cancer. High expression of IGF2BP2 was most associated with poor prognosis and an immunosuppressive microenvironment in PDAC. By IGF2BP2 knockdown, we found that tumor cell proliferation and invasive ability were significantly diminished. Importantly, we found that IGF2BP2 expression was closely associated with high expression of immunosuppressive molecules such as PD-L1. IGF2BP2 modulated downstream PD-L1 expression by regulating its mRNA stability via m6A methylation control, and we obtained the same verification in animal experiments and human tissue specimens. CONCLUSION: Our study contributes to existing knowledge regarding the IGF2BP2-regulated PD-L1 signaling pathway as a potential prognostic and immune biomarker in pancreatic cancer.

The Molecular Basis of Catalysis by SDR Family Members Ketoacyl-ACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis.

The short-chain dehydrogenase/reductase (SDR) superfamily members acyl-ACP reductases FabG and FabI are indispensable core enzymatic modules and catalytic orientation controllers in type-II fatty acid biosynthesis. Herein, we report their distinct substrate allosteric recognition and enantioselective reduction mechanisms. FabG achieves allosteric regulation of ACP and NADPH through ACP binding across two adjacent FabG monomers, while FabI follows an irreversible compulsory order of substrate binding in that NADH binding must precede that of ACP on a discrete FabI monomer. Moreover, FabG and FabI utilize a backdoor residue Phe187 or a "rheostat" α8 helix for acyl chain length selection, and their corresponding triad residues Ser142 or Tyr145 recognize the keto- or enoyl-acyl substrates, respectively, facilitating initiation of nucleophilic attack by NAD(P)H. The other two triad residues (Tyr and Lys) mediate subsequent proton transfer and (R)-3-hydroxyacyl- or saturated acyl-ACP production.

[Comparison of Cyclosporine A and Cyclosporine A Combined with Corticosteroid in the Treatment of Acquired Pure Red Cell Aplasia].

OBJECTIVE: To evaluate the efficacy, safety and relapse of cyclosporine A (CsA) and CsA combined with corticosteroid (CS) as the frontline therapy for patients with newly diagnosed acquired pure red cell aplasia (aPRCA). METHODS: The clinical features, treatment responses, relapses and clinical outcomes of patients with newly diagnosed aPRCA in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2020 were analyzed retrospectively. All the enrolled patients had been treated with either CsA or CsA+CS for at least 6 months and had been followed up for at least 12 months, with complete clinical data and consent forms. RESULTS: 96 patients including 72 treated with CsA and 24 treated with CsA+CS were enrolled. With comparable baseline characteristics and follow-up periods, patients treated with CsA or with CsA+CS had similar overall response rates (ORRs) and complete response rates (CRRs) at the 3rd, 6th and 12th month and at the end of follow-up (P>0.05). Meanwhile, no significant difference was found between the two groups in the optimal ORR, optimal CRR, time to response or time to complete response. CsA+CS and CsA groups had similar adverse event (AE) rates, but CsA+CS group had higher CS-related infection rate (P <0.05). One patient in CsA+CS group died of multiple infections. As for the relapse, the two groups had compatible relapse rates at different time points, time to relapse, overall relapse rate and relapse-free survival (P>0.05). CsA exposure time, rather than different therapy regimens, was the only influence factor for either ORR or relapse rate (P <0.05). CONCLUSION: CsA monotherapy has similar efficacy, AE rate and relapse rate as compared with CsA+CS for patients with newly diagnosed aPRCA, and shows less CS-related AEs such as infection.

Natural Algaecide Sphingosines Identified in Hybrid Straw Decomposition Driven by White-Rot Fungi.

Harmful algal blooms (HABs), which are promoted by eutrophication and intensified by global warming, occur worldwide. Allelochemicals, which are natural chemicals derived from plants or microbes, are emerging weapons to eliminate these blooms. However, the cost and technical challenges have limited the discovery of novel antialgal allelochemicals. Herein, the decomposition of agricultural straws is manipulated by white-rot fungi and achieved elevated antialgal efficiency. The transcriptomic analysis reveals that nutrient limitation activated fungal decomposition. By using a comparative nontarget metabolomics approach, a new type of allelochemical sphingosines (including sphinganine, phytosphingosine, sphingosine, and N-acetylsphingosine) is identified. These novel natural algaecides exhibit superior antialgal capability, with as high as an order of magnitude lower effective concentration on blooming species than other prevalent allelochemicals. The co-expression relationship between transcriptomic and metabolomic results indicate that sphinganine is strongly correlated with the differentially expressed lignocellulose degradation unigenes. The algal growth suppression is triggered by the activation of programmed cell death, malfunction of algal photosystem and antioxidant system, the disruption on CO2 assimilation and light absorption. The sphingosines reported here are a new category of allelochemicals in addition to the well-known antialgal natural chemicals, which are potential species-specific agents for HABs control identified by multi-omics methodology.

Development and validation of a radiomics model of magnetic resonance for predicting liver metastasis in resectable pancreatic ductal adenocarcinoma patients.

BACKGROUND: Nearly one fourth of patients with pancreatic ductal adenocarcinoma (PDAC) occur to liver metastasis after surgery, and liver metastasis is a risk factor for prognosis for those patients with surgery therapy. However, there is no effective way to predict liver metastasis post-operation. METHOD: Clinical data and preoperative magnetic resonance imaging (MRI) of PDAC patients diagnosed between July 2010 and July 2020 were retrospectively collected from three hospital centers in China. The significant MRI radiomics features or clinicopathological characteristics were used to establish a model to predict liver metastasis in the development and validation cohort. RESULTS: A total of 204 PDAC patients from three hospital centers were divided randomly (7:3) into development and validation cohort. Due to poor predictive value of clinical features, MRI radiomics model had similar receiver operating characteristics curve (ROC) value to clinical-radiomics combing model in development cohort (0.878 vs. 0.880, p = 0.897) but better ROC in validation dataset (0.815 vs. 0.732, p = 0.022). Radiomics model got a sensitivity of 0.872/0.750 and a specificity of 0.760/0.822 to predict liver metastasis in development and validation cohort, respectively. Among 54 patients randomly selected with post-operation specimens, fibrosis markers (α-smooth muscle actin) staining was shown to promote radiomics model with ROC value from 0.772 to 0.923 (p = 0.049) to predict liver metastasis. CONCLUSION: This study developed and validated an MRI-based radiomics model and showed a good performance in predicting liver metastasis in resectable PDAC patients.

Arsenic exposure and pruritus: Evidence from observational, interventional, and mendelian randomization studies.

BACKGROUND: Pruritus is identified as an adverse drug reaction to arsenic trioxide, but the association of arsenic exposure with pruritus has not been investigated. METHODS: A cross-sectional study was conducted in Shimen, China. A Mendelian randomization analysis was conducted to confirm the causal relationship between genetically predicted percentages of monomethylated arsenic (MMA%) and dimethylated arsenic (DMA%) in urine with chronic pruritus in UK Biobank. A case-control study was then conducted to determine the biomarker for pruritus. Arsenite-treated mice were used to confirm the biomarker, and von Frey test was used to induce scratching bouts. Last, a randomized, double-blind, placebo-controlled trial was conducted to test the efficacy of naloxone in arsenic-exposed patients with pruritus in Shimen. RESULTS: Hair arsenic (µg/g) showed a dose-response relationship with the intensity of itch in 1079 participants, with odds ratios (OR) of 1.11 for moderate-to-severe itch (p = 0.012). The Mendelian randomization analysis confirmed the causal relationship, with ORs of 1.043 for MMA% (p = 0.029) and 0.904 for DMA% (p = 0.077) above versus under median. Serum ß-endorphin was identified as a significant biomarker for the intensity of itch (p < 0.001). Consistently, treatment with arsenite upregulated the level of ß-endorphin (p = 0.002) and induced scratching bouts (p < 0.001) in mice. The randomized controlled trial in 126 participants showed that treatment with sublingual naloxone significantly relieved the intensity of itch in arsenic-exposed participants in 2 weeks (ß = -0.98, p = 0.04). CONCLUSION: Arsenic exposure is associated with pruritus, and ß-endorphin serves as a biomarker of pruritus. Naloxone relieves pruritus in patients with arseniasis.

Algal community structure prediction by machine learning.

The algal community structure is vital for aquatic management. However, the complicated environmental and biological processes make modeling challenging. To cope with this difficulty, we investigated using random forests (RF) to predict phytoplankton community shifting based on multi-source environmental factors (including physicochemical, hydrological, and meteorological variables). The RF models robustly predicted the algal communities composed by 13 major classes (Bray-Curtis dissimilarity = 9.2 ± 7.0%, validation NRMSE mostly <10%), with accurate simulations to the total biomass (validation R2 > 0.74) in Norway's largest lake, Lake Mjosa. The importance analysis showed that the hydro-meteorological variables (Standardized MSE and Node Purity mostly >0.5) were the most influential factors in regulating the phytoplankton. Furthermore, an in-depth ecological interpretation uncovered the interactive stress-response effect on the algal community learned by the RF models. The interpretation results disclosed that the environmental drivers (i.e., temperature, lake inflow, and nutrients) can jointly pose strong influence on the algal community shifts. This study highlighted the power of machine learning in predicting complex algal community structures and provided insights into the model interpretability.

CCL3 secreted by hepatocytes promotes the metastasis of intrahepatic cholangiocarcinoma by VIRMA-mediated N6-methyladenosine (m6A) modification.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a malignant disease characterized by onset occult, rapid progression, high relapse rate, and high mortality. However, data on how the tumor microenvironment (TME) regulates ICC metastasis at the transcriptomic level remains unclear. This study aimed to explore the mechanisms and interactions between hepatocytes and ICC cells. METHODS: We analyzed the interplay between ICC and liver microenvironment through cytokine antibody array analysis. Then we investigated the role of N6-methyladenosine (m6A) modification and the downstream target in vitro, in vivo experiments, and in clinical specimens. RESULTS: Our study demonstrated that cytokine CCL3, which is secreted by hepatocytes, promotes tumor metastasis by regulating m6A modification via vir-like m6A methyltransferase associated (VIRMA) in ICC cells. Moreover, immunohistochemical analyses showed that VIRMA correlated with poor outcomes in ICC patients. Finally, we confirmed both in vitro and in vivo that CCL3 could activate VIRMA and its critical downstream target SIRT1, which fuels tumor metastasis in ICC. CONCLUSIONS: In conclusion, our results enhanced our understanding of the interaction between hepatocytes and ICC cells, and revealed the molecular mechanism of the CCL3/VIRMA/SIRT1 pathway via m6A-mediated regulation in ICC metastasis. These studies highlight potential targets for the diagnosis, treatment, and prognosis of ICC.

Additional new species of the genus Hexarhopalus Fairmaire, 1891 (Coleoptera, Tenebrionidae: Cnodalonini) from China.

Three new species of the genus Hexarhopalus Fairmaire, 1891, all of the nominate subgenus, are described and figured from China: Hexarhopalus (Hexarhopalus) ferreri sp. nov. from Yunnan, H. (H.) tianbaoyanensis sp. nov. from Fujian, and H. (H.) yeziyangi sp. nov. from Jiangxi.

GLUT1 Regulates the Tumor Immune Microenvironment and Promotes Tumor Metastasis in Pancreatic Adenocarcinoma via ncRNA-mediated Network.

Pancreatic adenocarcinoma (PAAD) is a digestive tumor with extremely high malignancy. Previous studies have reported that Glucose transporter 1 (GLUT1) contributes to the aggressive tumor progression in various cancer types and indicates an unfavorable prognosis. However, the function of GLUT1 in PAAD remains largely unclear. Through pan-cancer analysis of GLUT1 expression, GLUT1 expression was significantly higher in several cancer types including PAAD. Survival analysis based on the GLUT1 expression showed that GLUT1 could serve as a predictor of poor prognosis. We further predicted and screened the candidate non-coding RNAs (ncRNAs) upstream of the GLUT1 mRNA through correlation analysis, and found that the CASC19/miR-140-5p axis contributing to the regulation of GLUT1 expression. Our study suggested a link exists between GLUT1 expression and selected immunity-related indicators. Subsequent analysis revealed overexpression of GLUT1 in pancreatic cancer specimens and patients with highly expressed GLUT1 expression had worse prognosis. Based on the significantly different expression of GLUT1, the possibility that GLUT1 participated in tumor progression was identified. Using online public databases, genes co-expressed with GLUT1 were screened and enriched to metastasis-related pathways by enrichment analysis. Additionally, functional assays verified that GLUT1 could function in the metastatic process of PAAD cancer cells. Therefore, we proposed that GLUT1 might serve as a role in tumor immunity and tumor metastasis, and was expected to be a prognostic factor in PAAD.

Kinesin family member 23, regulated by FOXM1, promotes triple negative breast cancer progression via activating Wnt/ß-catenin pathway.

BACKGROUND: Triple negative breast cancer (TNBC) is highly malignant and has a worse prognosis, compared with other subtypes of breast cancer due to the absence of therapeutic targets. KIF23 plays a crucial role in the tumorigenesis and cancer progression. However, the role of KIF23 in development of TNBC and the underlying mechanism remain unknown. The study aimed to elucidate the biological function and regulatory mechanism of KIF23 in TNBC. METHODS: Quantitative real-time PCR and Western blot were used to determine the KIF23 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of KIF23 on tumor growth and metastasis in TNBC. Chromatin immunoprecipitation assay was conducted to illustrate the potential regulatory mechanisms of KIF23 in TNBC. RESULTS: We found that KIF23 was significantly up-regulated and associated with poor prognosis in TNBC. KIF23 could promote TNBC proliferation, migration and invasion in vitro and in vivo. KIF23 could activate Wnt/ß-catenin pathway and promote EMT progression in TNBC. In addition, FOXM1, upregulated by WDR5 via H3K4me3 modification, directly bound to the promoter of KIF23 gene to promote its transcription and accelerated TNBC progression via Wnt/ß-catenin pathway. Both of small inhibitor of FOXM1 and WDR5 could inhibit TNBC progression. CONCLUSIONS: Our findings elucidate WDR5/FOXM1/KIF23/Wnt/ß-catenin axis is associated with TNBC progression and may provide a novel and promising therapeutic target for TNBC treatment.

Algal bloom forecasting with time-frequency analysis: A hybrid deep learning approach.

The rapid emergence of deep learning long-short-term-memory (LSTM) technique presents a promising solution to algal bloom forecasting. However, the discontinuous and non-stationary processes within algal dynamics still largely limit the functions of LSTMs. To overcome this challenge, an advanced time-frequency wavelet analysis (WA) technique was introduced to enhance the prediction accuracy of LSTMs. Herein, the novel hybrid approach (named WLSTM) successfully decreased the algal forecasting inaccuracy of classic LSTMs by 41% ± 8% in Lake Mendota (Wisconsin, USA), with powerful one-step-ahead predictions at hourly, daily, and monthly time resolutions (R2 = 0.976, 0.878, and 0.814, respectively). In addition, the WLSTM outperformed the other two widely used algal forecasting approaches - deep neural network (DNN), and autoregressive-integrated-moving-average (ARIMA) model, represented by average 72% and 85% decrease in root-mean-square-error, respectively. Furthermore, the WLSTM was implemented in an experimentally fertilized lake (Lake Tuesday, Michigan) for a multi-step forecasting examination. It satisfactorily forecasted the algal fluctuations involving substantial peak and extreme values (average R2 > 0.900) and presented accurate judgment outcomes to their bloom levels with high accuracy > 95% on average. This work highlighted the utility of deep learning approaches in effective early-warning for algal blooms, and demonstrated an important direction for improving the adaptability of conventional deep learning approaches to the aquatic problems.

3-Indoleacrylic acid from canola straw as a promising antialgal agent - Inhibition effect and mechanism on bloom-forming Prorocentrum donghaiense.

Harmful algal blooms (HABs) have induced severe damage worldwide. A novel high-efficient antialgal natural chemical, 3-indoleacrylic acid (3-IDC) with a 5-day half-maximal inhibitory concentration (IC50, 5d), was discovered from canola straw, and its algal inhibition mechanism was investigated. Adverse effects were observed on the growth of P. donghaiense with 3-IDC addition, following an increase in reactive oxygen species (ROS) production. 3-IDC also hindered the photosynthetic mechanism of P. donghaiense cells. Transcriptional results showed 3-IDC inhibiting the functions of all the nutrient assimilating genes, down-regulated ribulose-1,5-bisphosphate carboxylase/oxygenase II, and cytochrome f genes. The expression of heat shock protein (HSP) 70 and 90 and rhodopsin genes were also suppressed. The binding affinity of investigated receptors was observed. The conformational changes induced by the spatial microstructural alteration through 3-IDC may further contribute to the perturbation of those enzyme catalytic activities. The present results provide new insights on controlling HABs using 3-IDC.

RBMS2 Chemosensitizes Breast Cancer Cells to Doxorubicin by Regulating BMF Expression.

Chemoresistance is closely related to the therapeutic effect and prognosis in breast cancer patients. Increasing evidences demonstrated that RNA binding proteins (RBPs) have notable roles in regulating cancer cell proliferation, metastasis and chemotherapeutic sensitivity. RNA binding motif single stranded interacting protein 2 (RBMS2), an RBP, has been considered to be a tumor suppressor in several cancers. However, its role of doxorubicin sensitivity in breast cancer patients has not yet been fully revealed. Here, we performed doxorubicin cytotoxicity assay, flow cytometry and mouse xenograft model to examine the influence of RBMS2 on doxorubicin sensitization in vitro and in vivo. RIP assay and dual-luciferase reporter assay were performed to explore the relationship between RBMS2 and BMF. Our data demonstrated that upregulation of RBMS2 in breast cancer cells could enhance sensitivity to doxorubicin and promote apoptosis in the presence of doxorubicin, while inhibition of RBMS2 showed an opposite trend. Moreover, this chemosensitizing effect of RBMS2 could be reversed by the inhibition of Bcl-2 modifying factor (BMF). RBMS2 positively regulated BMF expression and increased BMF-induced expression of (cleaved) caspase 3, (cleaved) caspase 9 and poly (ADP-Ribose) polymerase (PARP). These results uncovered a novel mechanism for RBMS2 in the sensibilization of doxorubicin, suggesting that RBMS2 may act as a potential therapeutic target for drug-resistant breast cancer.

Sirolimus is effective for refractory/relapsed/intolerant acquired pure red cell aplasia: results of a prospective single-institutional trial.

Some patients with acquired pure red cell aplasia (aPRCA) have no response or are intolerant to cyclosporine A. From April 2017 to August 2020, patients diagnosed with aPRCA at Peking Union Medical College Hospital who were refractory/recurrent/intolerant to at least 6 months of full-dose cyclosporin A (CsA) with/without steroids were recruited and treated with sirolimus for at least 6 months. Finally, a total of 64 patients were enrolled. The overall response rate and complete response rate after 3, 6 and 12 months of sirolimus were 60.9%, 84.4%, and 73.5% and 50.0%, 65.6%, and 66.0%, respectively. At a median of 14.5 (6-47) months of follow-up, 14.8% (8/54) of the patients relapsed. Apart from haemoglobin improvement, patients had decreased creatine levels and serum ferritin levels at the end of the follow-up compared with the baseline (169.3 µmol/L vs. 146.4 µmol/L, p = 0.041; 2121.5 ng/mL vs. 1018.3 ng/mL, p = 0.013). Adverse events were recorded in 19 patients, including infections and increase of creatine. Secondary aPRCA with stable underlying diseases had similar results as those with primary aPRCA. In summary, sirolimus is effective for patients with refractory/recurrent/intolerant aRPCA with a low recurrence rate and toxicities.

Perfluoroalkyl substances are linked to incident chronic spontaneous urticaria: A nested case-control study.

Previous studies suggested immunotoxicity of perfluoroalkyl substances (PFASs), but contradictory findings were reported for the associations of PFASs with allergies. The current study aimed to investigate the association of serum PFASs with incident chronic spontaneous urticaria (CSU) in adults. A nested case-control study within a longitudinal cohort of 7051 government employees in China was conducted. Participants with urticaria at the baseline were excluded. During the first follow-up, 70 incident CSU cases were included, and 70 matched healthy controls were randomly selected. In serum samples collected at the baseline, eight PFASs were determined using the UHPLC-MS/MS approach. The median serum concentrations of perfluorobutanoic acid (PFBA) and perfluoroheptanoic acid (PFHpA) were significantly higher in participants with incident CSU. The area under the receiver operating characteristic curve was 0.714 (95% CI: 0.60-0.83) based on the joint prediction by PFBA and PFHpA. The Bayesian kernel machine regression showed a nonlinear positive overall effect of the mixture of PFASs, and identified significant single effects of PFBA and PFHpA. Serum interleukin-4 was significantly higher in the case group at baseline, and was positively associated with PFHpA (r = 0.24). Causal mediation analysis indicated interleukin-4 as a partial mediator (14.8%) in the association of PFHpA with CSU. In conclusion, serum PFASs are associated with an increased risk of incident CSU, and PFBA and PFHpA might be the effective compounds.

Impact of financial inclusion and green bond financing for renewable energy mix: implications for financial development in OECD economies.

The study aims to empirically estimate the nexus of green bond financing with renewable energy index OECD countries. Using the OECD countries data over the period of the 2011-2019, the study estimated the nexus between constructs. To justify the study findings and present widespread policy implications on recent topicality Padroni unit root test, FMOLS and DOLS technique is applied. For robustness analysis, long-run sensitivity analysis using FMOLS extension is used, and a comparative picture of green bond financing nexus with renewable energy index is presented. The study presented the consistent effects of green bond financing on renewable energy index indicators. This asymmetrical role of green bonds is confirmed on renewable energy indicators over the sample period. OECD countries injected 31% role of green bond financing on renewable energy index constructs, and it raised 9.4% of per unit energy efficiency in renewable energy systems; by this, the study findings warrant maximum support through public office, energy ministries, and departments for energy efficiency optimization. The study presents multiple policy implications to enhance renewable energy generation for energy efficiency through different alternative sources. Despite growing literature, the empirical discussion on this topicality is still shattered and less studied, which is extended and contributed by recent research. Furthermore, efficient regulation in the renewable energy sector may convert financial uncertainty into a huge opportunity. Investing in renewable energy stocks might help investors diversify their portfolios.