Sja-let-7 suppresses the development of liver fibrosis via Schistosoma japonicum extracellular vesicles.

Schistosomiasis is a fatal zoonotic parasitic disease that also threatens human health. The main pathological features of schistosomiasis are granulomatous inflammation and subsequent liver fibrosis, which is a complex, chronic, and progressive disease. Extracellular vesicles (EVs) derived from schistosome eggs are broadly involved in host-parasite communication and act as important contributors to schistosome-induced liver fibrosis. However, it remains unclear whether substances secreted by the EVs of Schistosoma japonicum, a long-term parasitic "partner" in the hepatic portal vein of the host, also participate in liver fibrosis. Here, we report that EVs derived from S. japonicum worms attenuated liver fibrosis by delivering sja-let-7 into hepatic stellate cells (HSCs). Mechanistically, activation of HSCs was reduced by targeting collagen type I alpha 2 chain (Col1α2) and downregulation of the TGF-ß/Smad signaling pathway both in vivo and in vitro. Overall, these results contribute to further understanding of the molecular mechanisms underlying host-parasite interactions and identified the sja-let-7/Col1α2/TGF-ß/Smad axis as a potential target for treatment of schistosomiasis-related liver fibrosis.

Ultrafast Imaging of Jahn-Teller Distortion and the Correlated Proton Migration in Photoionized Cyclopropane.

The Jahn-Teller (JT) distortion is one of the fundamental processes in molecules and condensed phase matters. For photoionized organic molecules with high symmetry, the JT effect leads to geometric instability in certain electron configurations and thus has a significant effect on the subsequent isomerization and proton migration processes. Utilizing the femtosecond pump-probe Coulomb explosion method, we probe the isomerization dynamics process of a monovalent cyclopropane cation (C3H6+) caused by proton migration and reveal the relationship between proton migration and JT distortion. We found that the C3H6+ cation evolves from the D3h symmetric equilateral triangle geometry either to the acute triangle via two elongated C-C bonds (JT1) or to the obtuse triangle via a single elongated C-C bond (JT2). The JT1 pathway does not involve proton migration, while the JT2 pathway drives proton migration and can be mapped into the indirect dissociation channel of Coulomb explosion. The time-resolved experiment indicates that the delay time between those two JT pathways can be as large as ∼600 fs. After the JT distortion, the cyclopropane cation undergoes a subsequent structural evolution, which brings a greater variety of dissociation channels.

The scaffold of neutrophil extracellular traps promotes CCA progression and modulates angiogenesis via ITGAV/NFκB.

Neutrophil extracellular traps (NETs) have garnered attention for their dual role in host defense and tumor promotion. With their involvement documented across a spectrum of tumors, their influence on the progression of cholangiocarcinoma (CCA) is of paramount interest. We employed immunohistochemistry and immunofluorescence to detect NET deposition in CCA tissues. Through in vitro and in vivo investigation, including CCA organoid and transposon-based models in PAD4 KO mice, we explored the effects of NETs on cell proliferation and metastasis. Molecular insights were gained through RNA sequencing, enzyme linked immunosorbent assay, and chromatin immunoprecipitation. Elevated intratumoral NET deposition within CCA tissues was associated with poor survival. The influence of NETs on CCA proliferation, migration and invasion was primarily mediated by NET-DNA. RNA sequencing unveiled the activation of the NFκB signaling pathway due to NET-DNA stimulation. NET-DNA pull-down assay coupled with mass spectrometry revealed the interaction between NET-DNA and αV integrin (ITGAV), culmination in the activation of the NFκB pathway. Furthermore, NET-DNA directly upregulated the expression of VEGF-A in cancer cells. The study unequivocally establishes NETs as facilitators of CCA progression, orchestrating proliferation, metastasis, and angiogenesis through ITGAV/NFκB pathway activation. This novel insight positions NETs as prospective therapeutic targets for managing CCA patients. By implementing a variety of methodologies and drawing intricate connections between NETs, DNA interactions, and signaling pathways, this research expands our comprehension of the complex interplay between the immune system and cancer progression, offering promising avenues for intervention.

Molecular and functional characterization of Schistosoma japonicum annexin A13.

Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host-parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host-parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host-parasite interactions as a potential vaccine candidate.

Melatonin inhibits atherosclerosis progression via galectin-3 downregulation to enhance autophagy and inhibit inflammation.

Autophagy deficiency in macrophages exacerbates inflammation in atherosclerosis (AS), and recently, galectin-3 (Gal-3) has been implicated as a critical promoter of inflammation in AS. Further, melatonin (Mel) exerts an autophagy-promoting effect in many chronic inflammatory diseases. In this study, we aimed to investigate whether Mel inhibits AS progression by downregulating Gal-3 to enhance autophagy and inhibit inflammation. Thus, we performed in vivo and in vitro experiments using high-fat diet (HFD)-fed ApoE-/-  mice and THP-1 macrophages, respectively. Smart-seq of AS plaque macrophages revealed that the differentially expressed genes (DEGs) downregulated by Mel were enriched in immune-related processes, and changes in inflammation status were confirmed based on lower levels of proinflammatory factors in Mel-treated HFD-fed ApoE-/-  mice and THP-1 macrophages. Further, via transcriptome-based multiscale network pharmacology platform (TMNP), the upstream target genes of the smart-seq DEGs were identified, and Gal-3 showed a high score. Gal-3 was downregulated both in vivo and in vitro by Mel treatment. Besides, the enrichment of the target genes predicted via the TMNP method indicated that autophagy considerably affected the DEGs. Mel treatment as well as Gal-3 knockdown downregulated most inflammatory response-related proteins could attribute to enhancing autophagy. Mechanistically, Mel treatment inhibited Gal-3 leading to lowering the activity of the nuclear transcription factor-kappa B (NF-κB) pathway, and promoting the nuclear localization of transcription factor EB (TFEB). However, increased secretion of Gal-3 activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway and impaired autophagy via binding to CD98. Thus, Mel promoted autophagy and restrained inflammation by downregulating Gal-3, implying that it holds promise as a treatment for AS.

SeNPs alleviates BDE-209-induced intestinal damage by affecting necroptosis, inflammation, intestinal barrier and intestinal flora in layer chickens.

As environmental pollutants, polybrominated diphenyl ethers (PBDEs) can have toxic effects on living organisms and has a bioaccumulative effect. Low doses of selenium nanoparticles (SeNPs) can exert antioxidant, anti-inflammatory and anti-toxin functions on the organism. This experiment evaluated SeNPs' ability to prevent chicken's intestinal damage from decabromodiphenyl ether (BDE-209) exposure. Sixty layer chickens were separated into four groups at randomly and equally: Control group, SeNPs group (1 mg/kg SeNPs), BDE-209 group (400 mg/kg BDE-209), and BDE-209 +SeNPs group (400 mg/kg BDE-209 and 1 mg/kg SeNPs), for 42 days. The results showed that BDE-209 increased MDA content, decreased the activities of T-SOD, T-AOC, GSH and iNOS, up-regulated the expression of TNF-α, RIPK1, RIPK3 and MLKL, promoted the production of inflammatory factors, reduced the levels of tight junction proteins (Claudin-1, Occludin, ZO-1). SeNPs attenuated intestinal oxidative stress, necroptosis, inflammation and intestinal barrier damage caused by BDE-209. This protective effect is associated with the MAPK/NF-κB signaling pathway. Moreover, SeNPs restores flora alpha and beta diversity, improves intestinal flora composition and its abundance. It shifts the dysbiosis of intestinal flora caused by BDE-209 to normal. Overall, SeNPs can alleviate BDE-209-induced intestinal barrier damage and intestinal flora disorders, which are associated with intestinal oxidative stress, necroptosis and inflammation.

Metabolic Dysregulation Explains the Diverse Impacts of Obesity in Males and Females with Gastrointestinal Cancers.

The prevalence of obesity, defined as the body mass index (BMI) ≥ 30 kg/m2, has reached epidemic levels. Obesity is associated with an increased risk of various cancers, including gastrointestinal ones. Recent evidence has suggested that obesity disproportionately impacts males and females with cancer, resulting in varied transcriptional and metabolic dysregulation. This study aimed to elucidate the differences in the metabolic milieu of adenocarcinomas of the gastrointestinal (GI) tract both related and unrelated to sex in obesity. To demonstrate these obesity and sex-related effects, we utilized three primary data sources: serum metabolomics from obese and non-obese patients assessed via the Biocrates MxP Quant 500 mass spectrometry-based kit, the ORIEN tumor RNA-sequencing data for all adenocarcinoma cases to assess the impacts of obesity, and publicly available TCGA transcriptional analysis to assess GI cancers and sex-related differences in GI cancers specifically. We applied and integrated our unique transcriptional metabolic pipeline in combination with our metabolomics data to reveal how obesity and sex can dictate differential metabolism in patients. Differentially expressed genes (DEG) analysis of ORIEN obese adenocarcinoma as compared to normal-weight adenocarcinoma patients resulted in large-scale transcriptional reprogramming (4029 DEGs, adj. p < 0.05 and |logFC| > 0.58). Gene Set Enrichment and metabolic pipeline analysis showed genes enriched for pathways relating to immunity (inflammation, and CD40 signaling, among others) and metabolism. Specifically, we found alterations to steroid metabolism and tryptophan/kynurenine metabolism in obese patients, both of which are highly associated with disease severity and immune cell dysfunction. These findings were further confirmed using the TCGA colorectal adenocarcinoma (CRC) and esophageal adenocarcinoma (ESCA) data, which showed similar patterns of increased tryptophan catabolism for kynurenine production in obese patients. These patients further showed disparate alterations between males and females when comparing obese to non-obese patient populations. Alterations to immune and metabolic pathways were validated in six patients (two obese and four normal weight) via CD8+/CD4+ peripheral blood mononuclear cell RNA-sequencing and paired serum metabolomics, which showed differential kynurenine and lipid metabolism, which corresponded with altered T-cell transcriptome in obese populations. Overall, obesity is associated with differential transcriptional and metabolic programs in various disease sites. Further, these alterations, such as kynurenine and tryptophan metabolism, which impact both metabolism and immune phenotype, vary with sex and obesity together. This study warrants further in-depth investigation into obesity and sex-related alterations in cancers that may better define biomarkers of response to immunotherapy.

Cost-Optimization-Based Quantum Key Distribution over Quantum Key Pool Optical Networks.

The Measurement-Device-Independent-Quantum Key Distribution (MDI-QKD) has the advantage of extending the secure transmission distances. The MDI-QKD combined with the Hybrid-Trusted and Untrusted Relay (HTUR) is used to deploy large-scale QKD networks, which effectively saves deployment cost. We propose an improved scheme for the QKD network architecture and cost analysis, which simplifies the number of QKD transmitters and incorporates the quantum key pool (QKP) in the QKD network. We developed a novel Hybrid-QKD-Network-Cost (HQNC) heuristic algorithm to solve the cost optimization problem. Simulations verified that the scheme in this paper could save the cost by over 50 percent and 90 percent, respectively.

A Resource-Adaptive Routing Scheme with Wavelength Conflicts in Quantum Key Distribution Optical Networks.

Quantum key distribution (QKD) has great potential in ensuring data security. Deploying QKD-related devices in existing optical fiber networks is a cost-effective way to practically implement QKD. However, QKD optical networks (QKDON) have a low quantum key generation rate and limited wavelength channels for data transmission. The simultaneous arrival of multiple QKD services may also lead to wavelength conflicts in QKDON. Therefore, we propose a resource-adaptive routing scheme (RAWC) with wavelength conflicts to achieve load balancing and efficient utilization of network resources. Focusing on the impact of link load and resource competition, this scheme dynamically adjusts the link weights and introduces the wavelength conflict degree. Simulation results indicate that the RAWC algorithm is an effective approach to solving the wavelength conflict problem. Compared with the benchmark algorithms, the RAWC algorithm can improve service request success rate (SR) by up to 30%.

Terahertz switchable VO2-Au hybrid active metasurface holographic encryption.

The combination of metasurface and holographic technology is the most cutting-edge development, but most of the proposed designs are static and do not allow active changes through external stimulation after fabrication, which takes only a limited part of the advantage provided by metasurface. Here, we propose and demonstrate a switchable hybrid active metasurface hologram in the terahertz (THz) regime composed of dynamic pixels (VO2-CSRR) and static pixels (Au-CSRR) based on an intelligent algorithm, which can display some/all information in different temperature ranges. In particular, such performance shows excellent potential in the field of optical communication security, making it a promising candidate. To prove this possibility, we propose a scheme for optical information encryption/decryption and transmission, which takes metasurfaces as carriers of encrypted information and state/polarization/positions as the secret key components. Only when the two matches correctly can we get the hidden real information. The security of our proposed scheme has reached an unprecedented level, providing a new road for communication security.

Hong-Ou-Mandel Interference between Two Hyperentangled Photons Enables Observation of Symmetric and Antisymmetric Particle Exchange Phases.

Two-photon Hong-Ou-Mandel (HOM) interference is a fundamental quantum effect with no classical counterpart. The existing research on two-photon interference was mainly limited in one degree of freedom (DOF); hence, it is still a challenge to realize quantum interference in multiple DOFs. Here, we demonstrate HOM interference between two hyperentangled photons in two DOFs of polarization and orbital angular momentum (OAM) for all 16 hyperentangled Bell states. We observe hyperentangled two-photon interference with a bunching effect for ten symmetric states (nine boson-boson states and one fermion-fermion state) and an antibunching effect for six antisymmetric states (three boson-fermion states and three fermion-boson states). More interestingly, expanding the Hilbert space by introducing an extra DOF for two photons enables one to transfer the unmeasurable external phase in the initial DOF to a measurable internal phase in the expanded two DOFs. We directly measured the symmetric exchange phases being 0.012±0.002, 0.025±0.002, and 0.027±0.002 in radian for the three boson states in OAM and the antisymmetric exchange phase being 0.991π±0.002 in radian for the other fermion state, as theoretical predictions. Our Letter may not only pave the way for more wide applications of quantum interference, but also develop new technologies by expanding Hilbert space in more DOFs.

Targeting uridine-cytidine kinase 2 induced cell cycle arrest through dual mechanism and could improve the immune response of hepatocellular carcinoma.

BACKGROUND: Pyrimidine metabolism is critical for tumour progression. Uridine-cytidine kinase 2 (UCK2), a key regulator of pyrimidine metabolism, is elevated during hepatocellular carcinoma (HCC) development and exhibits carcinogenic effects. However, the key mechanism of UCK2 promoting HCC and the therapeutic value of UCK2 are still undefined. The aim of this study is to investigate the potential of UCK2 as a therapeutic target for HCC. METHODS: Gene expression matrices were obtained from public databases. RNA-seq, co-immunoprecipitation and RNA-binding protein immunoprecipitation were used to determine the mechanism of UCK2 promoting HCC. Immune cell infiltration level and immune-related functional scores were evaluated to assess the link between tumour microenvironment and UCK2. RESULTS: In HCC, the expression of UCK2 was upregulated in part by TGFß1 stimulation. UCK2 promoted cell cycle progression of HCC by preventing the degradation of mTOR protein and maintaining the stability of PDPK1 mRNA. We also identified UCK2 as a novel RNA-binding protein. Downregulation of UCK2 induced cell cycle arrest and activated the TNFα/NFκB signalling pathway-related senescence-associated secretory phenotype to modify the tumour microenvironment. Additionally, UCK2 was a biomarker of the immunosuppressive microenvironment. Downregulated UCK2 induced a secretory phenotype, which could improve the microenvironment, and decreased UCK2 remodelling metabolism could lower the resistance of tumour cells to T-cell-mediated killing. CONCLUSIONS: Targeting UCK2 inhibits HCC progression and could improve the response to immunotherapy in patients with HCC. Our study suggests that UCK2 could be an ideal target for HCC.

The Ferroptosis Molecular Subtype Reveals Characteristics of the Tumor Microenvironment, Immunotherapeutic Response, and Prognosis in Gastric Cancer.

Ferroptosis is a relatively new form of programmed cell death, which can enhance the efficacy of tumor immunotherapy by regulating the tumor microenvironment (TME). In the face of the dilemma of a great difference in the efficacy of immunotherapy for gastric cancer (GC) patients, the exploration of ferroptosis may assist us in predicting immunotherapy efficacy prior to treatment. The potential role of ferroptosis in TME still needs further elucidation. Based on ferroptosis-related genes (FRGs), we systematically evaluated ferroptosis molecular subtypes in gastric cancer. Additionally, the association between these molecular subtypes and the characteristics of TME was examined. A ferroptosis score was constructed to further explore the predictive efficacy of ferroptosis on the immunotherapy response in gastric cancer. There were also 32 other cancers that were evaluated. Three molecular subtypes of ferroptosis in gastric cancer were identified. The three immunophenotypes of tumor immune inflamed, immune excluded, as well as immune desert were mostly in agreement with the TME features of these three subtypes. The individual tumor genetic variation, TME characteristics, immunotherapy response, and prognosis could be assessed by a ferroptosis score. High ferroptosis scores in gastric cancer suggest stromal activation and immunosuppression. It is noted that tumors with a low ferroptosis score are characterized by extensive tumor mutations as well as an immune activation, which are associated with an enhanced immunotherapy response and an improved prognosis. This study reveals that ferroptosis plays an integral role in the regulation of the tumor immune microenvironment. The ferroptosis score may serve as an independent prognostic factor for GC and will deepen our understanding of the TME infiltration mechanisms as well as lead to more rational immunotherapy regimens.

Metals compositions of indoor PM2.5, health risk assessment, and birth outcomes in Lanzhou, China.

The study aimed to investigate the metal compositions in indoor PM2.5 and the potential health risks they pose to residents of an urban area in China. A total of 41 and 54 households were surveyed in February and September 2013, respectively. The results showed that the indoor concentrations of metals varied depending on the types of cooking fuels used. All measured concentrations of metals were highest among households using coal for cooking. In the majority of households, non-carcinogenic risks were posed by the use of coal. The carcinogenic risks posed by chromium (VI) and arsenic were generally higher among households using coal for cooking than among those using gas or electricity. The multivariate linear regression model suggested a potential adverse effect from arsenic and cadmium on birth weight and gestational weeks. This study also found that cooking fuel was the most significant factor that contributed to the differences in concentrations of metals in indoor PM2.5 and highlighted the importance of using clean energy for cooking and heating.

[Condition optimization for bio-oxidation of high-S and high-As gold concentrate].

OBJECTIVE: To study the effects of temperature and lixivium return on the concentrate bio-oxidation and rate of gold cyanide leaching. METHODS: The bioleaching of a high-sulphur (S) and high-arsenic (As) refractory gold concentrate was conducted, and we studied the effects of different temperature (40 ° and 45 °C) and lixivium return (0 and 600 mL) on the bio-oxidation efficiency. The bacterial community structure also was investigated by 16S rRNA gene clone library. RESULTS: The results showed that both the temperature and lixivium return significantly influenced the oxidation system. The temperature rising elevated the oxidation level, while the addition of lixivium depressed the oxidation. Dissimilarity and DCA (detrended correspondence analysis) indicated the effect of temperature on oxidation system was much greater than lixivium. The bacterial community was comprised by Acidithiocacillus caldu (71%) Leptospirillum ferriphilum (23%) and Sulfobacillus thermosulfidooxidans (6%) indicated by the clone library, and the OTU coverage based on 97% sequence similarity was as high as 93.67%. CONCLUSION: Temperature rising to 45 T would improve the oxidation efficiency while lixivium return would decrease it. This study is helpful to provide an important guiding value for the industry cost optimization of mesophile bacterial oxidation and reduction process.

Selenomethionine alleviates decabromodiphenyl ether-induced oxidative stress and ferroptosis via the NRF2/GPX4 pathway in the chicken brain.

Decabromodiphenyl ether (BDE209) is a toxic environmental pollutant that can cause neurotoxicity, behavioral abnormalities, and cognitive impairment in animals. However, the specific mechanisms of BDE209-induced neurological injury and effective preventative and therapeutic interventions are lacking. Even though selenomethionine (Se-Met) has a significant detoxification effect and protects the nervous system, it remains unclear whether Se-Met can counteract the toxic effects of BDE209. For the in vivo test, we randomly divided 60 1-week-old hy-line white variety chicks into the Con, BDE209, Se-Met, and BDE209 +Se-Met groups. In vitro experiments were performed, exposing chick embryo brain neurons to BDE209, Se-Met, N-Acetylcysteine (NAC, a ROS inhibitor), and RSL3 (a GPX4 inhibitor). We demonstrated that BDE209 induced oxidative stress and ferroptosis in the chicken brain, which mainly manifested as mitochondrial atrophy, cristae breakage, increased Fe2+ and MDA content, decreased antioxidant enzyme activity, and the inhibition of the NRF2/GPX4 signaling pathway in the brain neurons. However, Se-Met supplementation reversed these changes by activating the NRF2/GPX4 pathway, reducing mitochondrial damage, enhancing antioxidant enzyme activity, and alleviating ferroptosis. This study provides insight into the mechanism of BDE209-related neurotoxicity and suggests Se-Met as an effective preventative and control measure against BDE209 poisoning.

CO2 emission prediction based on carbon verification data of 17 thermal power enterprises in Gansu Province.

The energy and power industry is an important field for CO2 emission reduction. The CO2 emitted by thermal power enterprises is a major cause of global climate change, and also a key challenge for China to achieve the goals of "carbon peaking and carbon neutrality." Therefore, it is essential to scientifically and accurately predict the CO2 emissions of key thermal power enterprises in the region. This will guide carbon reduction strategies and policy recommendations for leaders, and also provide a valuable reference for similar regions globally. This study utilizes the factor analysis method to extract the common factors influencing CO2 emissions based on the carbon verification data of 17 thermal power enterprises in Gansu Province. Additionally, the DISO (distance between indices of simulation and observation) index is employed to comprehensively evaluate three prediction models, namely multiple linear regression, support vector regression, and GA-BP neural network. Ultimately, this study provides a reasonable prediction of CO2 emissions for the aforementioned enterprises in Gansu Province. The results show that the three common factors obtained by factor analysis, namely energy consumption and output factor, energy quality factor, and energy efficiency factor, can effectively predict the CO2 emissions from thermal power enterprises. In the three prediction models, GA-BP neural network has the best overall performance with DISO value of 0.95, RMSE value of 11848.236, and MAE value of 7880.543. Over the period 2022-2030, CO2 emissions from 17 thermal power enterprises in Gansu Province are predicted to increase. Under the low-carbon, scenario baseline, and high-carbon scenarios, the CO2 emissions will reach 71.58 Mt, 79.25 Mt, and 87.97 Mt, respectively, by 2030.

Analysis of the seasonal water quality variation at the hydraulic junction of a dual-source water distribution system.

The implementation of a dual-source water supply system offers an increased level of reliability in water provision; however, intricate hydraulic dynamics introduce apprehensions regarding water safety at the hydraulic junction. In this study, we gathered data of the water quality at the hydraulic junction of a dual-source water supply system (plant A and plant B, sampling site A10 was near plant A, and sampling site A12 was near plant B) for one year in Suzhou Industrial Park. Our findings indicated that seasonal variations and water temperature exerted significant influence on the composition and formation of disinfection byproducts (DBPs). Notably, during the warmer months spanning from June to September, the concentration of trihalomethanes was the highest at the hydraulic junction, whereas the concentration of residual chloride was the lowest. The analysis on DBPs revealed that more Br-containing precursors in water in plant A resulted in the accumulation of more Br-containing DBPs at A10, whereas the highest concentration of Cl-containing DBPs accumulated at A12. The analysis of the dissolved organic matter (DOM) composition indicated an increase in concentration at A10 and A12 compared with that in plant A and plant B. The highest concentration of humic acids was observed at A10, whereas A12 accumulated the highest concentration of aromatic proteins and microbial metabolites. Owing to the fluctuations in water consumption patterns at the hydraulic junction, the water quality was susceptible to variability, thereby posing an elevated risk. Consequently, extensive efforts are warranted to ensure the maintenance of water safety and quality at this critical interface.

Nano­selenium alleviates the pyroptosis of cardiovascular endothelial cells in chicken induced by decabromodiphenyl ether through ERS-TXNIP-NLRP3 pathway.

Decabromodiphenyl ether (BDE-209) is one of the most widely used flame retardants that can infect domestic and wildlife through contaminated feed. Nano­selenium (Nano-Se) has the advantage of enhancing the anti-oxidation of cells. Nonetheless, it remains uncertain whether Nano-Se can alleviate vascular Endothelial cells damage caused by BDE-209 exposure in chickens. Therefore, we established a model with 60 1-day-old chickens, and administered BDE-209 intragastric at a ratio of 400 mg/kg bw/d, and mixed Nano-Se intervention at a ratio of 1 mg/kg in the feed. The results showed that BDE-209 could induce histopathological and ultrastructural changes. Additionally, exposure to BDE-209 led to cardiovascular endoplasmic reticulum stress (ERS), oxidative stress and thioredoxin-interacting protein (TXNIP)-pyrin domain-containing protein 3 (NLRP3) pathway activation, ultimately resulting in pyroptosis. Using the ERS inhibitor 4-PBA in Chicken arterial endothelial cells (PAECs) can significantly reverse these changes. The addition of Nano-Se can enhance the body's antioxidant capacity, inhibit the activation of NLRP3 inflammasome, and reduce cellular pyroptosis. These results suggest that Nano-Se can alleviate the pyroptosis of cardiovascular endothelial cells induced by BDE-209 through ERS-TXNIP-NLRP3 pathway. This study provides new insights into the toxicity of BDE-209 in the cardiovascular system and the therapeutic effects of Nano-Se.

Neutrophil extracellular traps promote immune escape in hepatocellular carcinoma by up-regulating CD73 through Notch2.

Immune escape is the main reason that immunotherapy is ineffective in hepatocellular carcinoma (HCC). Here, this study illustrates a pathway mediated by neutrophil extracellular traps (NETs) that can promote immune escape of HCC. Mechanistically, we demonstrated that NETs up-regulated CD73 expression through activating Notch2 mediated nuclear factor kappa B (NF-κB) pathway, promoting regulatory T cells (Tregs) infiltration to mediate immune escape of HCC. In addition, we found the similar results in mouse HCC models by hydrodynamic plasmid transfection. The treatment of deoxyribonuclease I (DNase I) could inhibit the action of NETs and improve the therapeutic effect of anti-programmed cell death protein 1 (PD-1). In summary, our results revealed that targeting of NETs was a promising treatment to improve the therapeutic effect of anti-PD-1.