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Background: Ubiquitin-specific protease 18 (USP18), is a member of the ubiquitin-specific protease family. Previous studies have shown that USP18 expression is upregulated in the patients with heart failure and USP18 is considered as a novel target for the treatment of heart failure. However, the role of USP18 in atherosclerosis remains unclear. In this study, we aimed to investigate the expression pattern of USP18 in atherosclerosis and its relationship between the extent of atherosclerotic and the cholesterol transporter protein ABCG1. Methods: GSE6054 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed by using the "limma" package in R (version 4.1.3). H-DOCK was applied to perform protein-protein docking for predicting the interaction between USP18 and ATP-binding cassette transporter protein G1 (ABCG1). Immunohistochemistry(IHC), immunofluorescence(IF), and Western blot were used to assess the protein expression of USP18 and ABCG1 in human coronary arteries. Dual immunofluorescencewas performed for co-localization analysis of USP18 and ABCG1 Results: Bioinformatics analysis identified 462 DEGs including 239 upregulated and 223 downregulated genes in familial hypercholesterolaemia (FH) patients, of which USP18 was upregulated in monocytes. Gene Ontology enrichment analysis indicated that the biological functions of USP18 were mainly enriched in endopeptidase activity and cytokine-mediated signaling. Protein-protein docking by H-DOCK showed that USP18 and ABCG1 interacted at a free energy of -20 kcal/mol (free energy < 0 was considered meaningful). USP18 expression is upregulated in patients with coronary artery disease and negatively correlates with the extent of atherosclerosis. At the same time, The expression of ABCG1 is downregulated in CHD and SCD patients and is more pronounced in SCD patients. In atherosclerotic tissues, USP18 and ABCG1 expression were positively correlated. In addition, double immunofluorescence assay showed co-localization of USP18 and ABCG1. Conclusions: USP18 is a differentially expressed gene of FH, and its expression in atherosclerosis is closely related to the extent of atherosclerosis.

The long-term survival of patients with advanced urothelial carcinoma (UCa) is limited because of innate resistance to treatment. We identified elevated expression of the histone methyltransferase EZH2 as a hallmark of aggressive UCa and hypothesized that EZH2 inhibition, via a small-molecule catalytic inhibitor, might have antitumor effects in UCa. Here, in a carcinogen-induced mouse bladder cancer model, a reduction in tumor progression and an increase in immune infiltration upon EZH2 inhibition were observed. Treatment of mice with EZH2i causes an increase in MHC class II expression in the urothelium and can activate infiltrating T cells. Unexpectedly, we found that the lack of an intact adaptive immune system completely abolishes the antitumor effects induced by EZH2 catalytic inhibition. These findings show that immune evasion is the only important determinant for the efficacy of EZH2 catalytic inhibition treatment in a UCa model.

Background Ubiquitin-specific protease 18 (USP18), also known as UBP43, is a member of the ubiquitin-specific protease family involved in suppressing viral activity and promoting tumor migration. Previous studies have shown that USP18 expression is upregulated in the patients with heart failure and USP18 is considered as a novel target for the treatment of heart failure. However, the role of USP18 in atherosclerosis remains unclear. In this study, we sought to explore the role of USP18 on ATP-binding cassette transporter protein G1 (ABCG1)-dependent cholesterol efflux. Methods GSE6054 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed by using the "limma" package in R (version 4.1.3). H-DOCK was applied to perform protein-protein docking for predicting the interaction between USP18 and ABCG1. Immunohistochemistry(IHC), immunofluorescence(IF), and Western blot were used to assess the protein expression of USP18 and ABCG1 in human coronary arteries. Dual immunofluorescence was performed for co-localization analysis of USP18 and ABCG1 Results Bioinformatics analysis identified 462 differentially expressed genes including 239 upregulated and 223 downregulated genes in familial hypercholesterolaemia (FH) patients, of which USP18 was upregulated in monocytes. Gene Ontology enrichment analysis indicated that the biological functions of USP18 were mainly enriched in endopeptidase activity and cytokine-mediated signaling. Protein-protein docking by H-DOCK showed that USP18 and ABCG1 interacted at a free energy of -20 kcal/mol (free energy < 0 was considered meaningful). IHC, IF and Western blot analyses revealed an increased expression level of USP18 in coronary arteries from patients with coronary atherosclerotic heart disease (CHD) , but Western blot analyses revealed a decreased expression level of USP18 in coronary arteries from patients with sudden cardiac death (SCD) compared with controls. At the same time, ABCG1 expression was decreased in coronary arteries from both CHD and SCD patients with a higher significance in SCD patients. In addition, double immunofluorescence assay showed no significant co-localization of USP18 and ABCG1. Conclusions USP18 may contribute to the development of atherogenesis through regulating ABCG1-dependent cholesterol efflux from macrophages.

Recently, microplastic pollution has become an environmental issue with widespread concern. As a bigger reservoir of microplastics than the ocean, microplastic pollution borne by soil has an impact on its structure and properties that cannot be ignored. Furthermore, with the help of plants, soil animals and microorganisms, this emerging pollutant will eventually threaten human health. Microplastics are difficult to recycle due to their small particle size, making it hard for traditional methods of plastic pollution management to work. In contrast, biodegradation methods are gaining attention because of its environmental sustainability and wide treatment range. This paper reviews the most popular microplastic biodegradation methods and their influencing factors, aiming to provide ideas and references for the biodegradation of microplastics.

The thriving nano-enabled agriculture facilitates the interaction of nanomaterials with plants. Recently, these interactions and their biological effects are receiving increasing attention. Upon entering plants via leaves, roots, stems, and other organs, nanoparticles adsorb numerous biomolecules inside plants and form bio-corona. In addition, nanoparticles that enter plants through roots may have formed eco-corona with root exudates in the rhizosphere environment before contacting with plant exogenous proteins. The most significant biological effects of plant protein corona include changes in protein structure and function, as well as changes in nanoparticle toxicity and targeting ability. However, the mechanisms, particularly how protein corona affects plant protein function, plant development and growth, and rhizosphere environment properties, require further investigation. Our review summarizes the current understanding of the formation and biological effects of nanoparticle-plant protein corona and provides an outlook on future research.

Nanoplastics, as an emerging pollutant in the environment, have the potential to adsorb various macromolecules onto the surface to form protein corona that may change the physicochemical properties and environmental fate of themselves, which deepens the uncertainty of their environmental hazards. Hence, in present study, we investigated the interaction between polystyrene nanoplastics and urease that forms protein corona over time in different conditions with atomic force microscopy, zeta potential, hydrodynamic diameter, and infrared spectroscopy. According to our results, polystyrene nanoplastics adsorbed urease and formed hard corona, changing the secondary structure of urease, and that the physicochemical properties of protein corona changed and stabilized over time. We concluded that even in a single-protein system, a dynamic process where protein molecules simultaneously adsorb onto and desorb from the surface of nanoplastics runs through the entire interaction. And we found that the formation and evolution of protein corona were governed by various interlinked factors (e.g., pH and nanoplastic surface modification types) instead of dominated by individual factor. This study aims to improve the knowledge about the formation of nanoplastic-protein corona and thus provide a reference for better evaluation of their environmental risk.

Objective This study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury. Methods Healthy Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the fluorosis group (F Group), the fluoride + blocker group (F + Cycl group: rats were treated with fluoride + cyclopamine), and the fluoride + blocker control group (F + DMSO group). After 6 months of intervention, the urinary fluoride content of rats in each group was detected. The primary osteoblasts of rats were selected for cell experiment, and the experiment was carried out after the cells were passaged from the second to the fourth generation. Results The proliferation rate of primary rat osteoblasts presented time-affected and dose-affected relationships in a short time under treatment with a low dose of sodium fluoride (NaF), but the proliferation of osteoblasts was inhibited by long-term and high-dose NaF exposure. In the F group, the alkaline phosphatase (ALP) activity of osteoblasts increased gradually. The ALP activity was lower in the F + Cycl group than in the F group, and there was no significant difference between the F + DMSO group and F group. With the increase in fluoride exposure, the expression of Hh signal factors and osteogenic-related factor proteins increased gradually. The expressions of Indian hedgehog (Ihh), smoothened (Smo), Glioma-associated oncogene homolog (Gli) 2, and Runt-related transcription factor 2 (Runx2)in the F + Cycl group increased with the dose of fluoride but they were significantly inhibited compared with the F group. Compared with the control group, the content of urinary fluoride in the F group was significantly higher (P < 0.05), but there was no significant change in urinary fluoride content in the F + Cycl group and the F + DMSO group. Compared with the control group, the serum bone alkaline phosphatase (BALP) contents of rats in the other groups increased after 6 months’ intake of fluoride water (P < 0.05). After drug blocking, the serum BALP content in the F + Cycl group was lower than that in the F + DMSO group (P < 0.05). The BALP content in the F + DMSO group was similar to that in the F group: it did not decrease. The mRNA expressions of Ihh, Smo, Gli2, and Runx2 in bone tissue of the F group were significantly higher than those in the control group (P < 0.05). After cyclopamine blocking, the expressions decreased (P < 0.05), but the differences between the F + DMSO group and F group were not statistically significant. Conclusion Hh signal plays an important role in fluoride-induced bone injury. The effective inhibition of cyclopamine is expected to be a new target for the treatment of skeletal damage caused by fluorosis.

Cancer cells accumulate somatic mutations as result of DNA damage, inaccurate repair and other mechanisms. Different genetic instability processes result in characteristic non-random patterns of DNA mutations, also known as mutational signatures. We developed mutSignatures, an integrated R-based computational framework aimed at deciphering DNA mutational signatures. Our software provides advanced functions for importing DNA variants, computing mutation types, and extracting mutational signatures via non-negative matrix factorization. Specifically, mutSignatures accepts multiple types of input data, is compatible with non-human genomes, and supports the analysis of non-standard mutation types, such as tetra-nucleotide mutation types. We applied mutSignatures to analyze somatic mutations found in smoking-related cancer datasets. We characterized mutational signatures that were consistent with those reported before in independent investigations. Our work demonstrates that selected mutational signatures correlated with specific clinical and molecular features across different cancer types, and revealed complementarity of specific mutational patterns that has not previously been identified. In conclusion, we propose mutSignatures as a powerful open-source tool for detecting the molecular determinants of cancer and gathering insights into cancer biology and treatment.

PurposeThis study aims to provide a literature review and bibliometric analysis of sustainable supply chain management using big data. We reviewed the literature on sustainable supply chain management under big data from 2012 to 2019 and extracted 777 articles.Design/methodology/approachWe conducted quantitative analysis and data network visualization of the chosen literature, including authors, journals, countries, research institutions and citations.FindingsWe discovered that the development of this interdisciplinary field has gained increasing popularity among researchers around the world, such as China and the US publishing the most articles and Western states having more cooperation, which indicates this research topic is growing in significance globally.Originality/valueScientific and technological revolutions such as big data have been incorporated in various industries. Modern supply chain management has also been combined with the advances in data science to achieve sustainability goals. No studies have reviewed the sustainable supply chain management based on big data. This study fills this gap.

To explore the relationship between total intelligence quotient (IQ), verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and fluoride exposure in children aged 8–12 years in coal-burning fluorosis area of Dafang County, Guizhou Province, China. The Wechsler Intelligence Scale for Children Revised in China (WISC-CR) was used to test the total IQ, VIQ, and PIQ in 99 children aged 8–12 years (55 in dental fluorosis group and 44 in control group). The differences in the intellectual levels between the two groups were compared, and the correlation between the intellectual level of children exposed to fluoride and the exposure dose of fluoride was analyzed. The VIQ, PIQ, and total IQ in the dental fluorosis group were 85.64 ± 16.53, 94.87 ± 12.73, and 88.51 ± 12.77, respectively, and these were lower than those in the control group (94.34 ± 16.04, 99.23 ± 12.44, and 96.64 ± 11.70, respectively). Significant difference was observed in VIQ and total IQ between the two groups (P = 0.002, P = 0.01), but not in the PIQ (P > 0.05). Each item of VIQ impairment (common sense, similar, arithmetic, vocabulary, and understanding) was significantly lower than those without VIQ impairment in the dental fluorosis group (P

Although the physical effects of air pollution on humans are well documented, there may be even greater impacts on the emotional state and health. Surveys have traditionally been used to explore the impact of air pollution on people’s subjective well-being (SWB). However, the survey techniques usually take long periods to properly match the air pollution characteristics from monitoring stations to each respondent’s SWB at both disaggregated spatial and temporal levels. Here, we used air pollution data to simulate fixed-scene images and psychophysical process to examine the impact from only air pollution on SWB. Findings suggest that under the atmospheric conditions in Beijing, negative emotions occur when PM2.5 (particulate matter with a diameter less than 2.5 µm) increases to approximately 150 AQI (air quality index). The British observers have a stronger negative response under severe air pollution compared with Chinese observers. People from different social groups appear to have different sensitivities to SWB when air quality index exceeds approximately 200 AQI., Air pollution can affect people’s emotional status and well-being. Here, the authors simulate fixed-scene images to show that under the atmospheric conditions in Beijing, negative emotions occur when air quality index of PM2.5 increases to approximately 150.

Nanoparticles interacting with proteins to form protein corona represent one of the most fundamental problems in the rapid development of nanotechnology. In the past decade, thousands of studies have pointed out this issue. Within multi-protein systems, the formation of protein corona is a homeostasis process in which proteins compete for the limited surface sites of nanoparticles. Besides, the formation of protein corona generally shows a tendency of evolving with time and involves many different driving forces controlled by properties of nanoparticles, proteins and environment. Therefore, recent research on the dynamic process and mechanisms of protein corona formation in both animals and plants are summarized in this review. The factors that affect the formation and the techniques that commonly used for protein corona analysis are proposed. Furthermore, in order to provide reference for the future research, the limitations and challenges in protein corona studies are assessed and the future perspectives are proposed.

INTRODUCTION AND OBJECTIVE:Men are three times more likely to develop bladder cancer (BC) than women. Mouse models have demonstrated that androgens are necessary for BC tumorigenesis. Herein, we as...

The chemical industry is a key energy-consuming sector in China. This paper aims to examine total-factor green growth performance, including energy efficiency and carbon shadow price of China's chemical sector from 1980 to 2013. On the basis of no-radial directional distance function, this paper takes into account both desirable and undesirable outputs. To investigate policy effects, we check the Granger causality test between shadow prices of emission and total-factor green energy efficiency. The results demonstrate that increased environmental regulation costs have substantial effect on total-factor green energy efficiency of the chemical industry in the last decade. The latter also causes significant improvement of the former.

As the world's second-largest economy, China plays a pivotal role in global CO2 emission abatement. In this study, we used an IPAT model to design 48 peak CO2 emission scenarios. We used a centralized DEA to evaluate the allocative efficiency of scenario-based CO2 emission paths by maximizing the aggregated potential GDP under fixed emission quantities. We found that maintaining relatively high GDP growth (around 6%), reducing energy intensity by about 75% of average annual decline rate of 2005–2015 (around 4%), and increasing non-fossil energy to 21% to meet the Innovation plan of energy technology revolution 2016–2030 requirements is the most efficient low-carbon behaviors towards 2030 peak CO2 emissions of 10.57 Gt. We also found that China can potentially reduce CO2 emission intensity (CEI) by up to 72.7% compared to the 2005 level in 2030, and therefore that official CEI reduction targets (60–65%) are well within reach. CEI will not readily converge in future years due to the large differences in energy-saving and emission abatement potential across different regions in China; the rank of convergence is CO2>CO2 per capita > CEI. Hebei, Shandong, Shanxi, Liaoning, Inner Mongolia, and Xinjiang are key areas in whether or not their respective regions complete the emission reduction task. To this effect, these provinces merit special attention.

China began a pilot carbon emissions trading scheme (ETS) in 2013. However, the real carbon mitigation effects of this policy are unclear. Moreover, the potential cost savings from internal or external trading among provinces are also uncertain. Based on panel data of 30 provincial industries from 2006 to 2015, this paper first employs a difference-in-differences model to explore the effects of the pilot ETS on industrial carbon emissions and carbon intensity. A Stochastic Frontier Analysis is then conducted to measure industrial energy efficiency and identify any carbon mitigation effects. We next use a parameterized directional output distance function to estimate the industrial carbon marginal abatement costs and analyze the potential cost savings/gains from internal trading among provinces within the same geographical regions and from external trading across regions. Results show that: (a) the pilot ETS has significant negative effects on industrial carbon emissions (10.1%) and carbon intensity (0.78%). (b) Energy efficiency plays an important role in the carbon mitigation effects. (c) the distribution of marginal abatement cost (MAC) shows significant geographical characteristics. (d) Provinces can realize greater potential cost saving/gains through regional external trading than internal trading.

e14552 Background: Recent advances in the field of cancer immunology have highlighted the importance of the immune system for eliminating tumors. Numerous studies have shown that tumor-infiltrating immune cells such as antigen-presenting cells (APCs), T cells, and natural killer (NK) cells play critical roles in tumor control. However, the inflammatory anti-tumor immune response is counteracted by the induction of immune regulatory mechanisms within the tumor microenvironment (TME). These findings have led to the development of immune-targeted therapies, which are aimed at activating anti-tumor immune signaling pathways and enhancing anti-tumor immune function. While immunotherapies, have revolutionized the treatment of several solid tumors and leukemias, at best response rates remain low at 25%-30%, and a portion of patients eventually develop resistance to therapy leading to disease progression and mortality. Methods: We have previously reported the potent effects of 3-4 daily intravenous infusions of immune modifying poly(lactic- co-glycolic acid) (PLGA) nanoparticles, ONP-302, free from drugs or other bioactive agents, for the amelioration of acute inflammatory diseases by targeting myeloid cells. The present studies describe a novel use for ONP-302 nanoparticles, employing an altered dosing scheme to reprogram myeloid cells resulting in significant enhancement of tumor immunity. The efficacy of ONP-302 nanoparticles at inducing an anti-tumor immune response was evaluated using syngeneic mouse tumor models. Results: ONP-302 infusion decreased tumor growth via the activation of the cGAS/STING pathway within myeloid cells, and subsequently increased NK cell activation via an IL-15-dependent mechanism. Additionally, ONP-302 treatment increased PD-1/PD-L1 expression in the tumor microenvironment, thereby allowing for functionality of anti-PD-1 for treatment in the B16.F10 melanoma tumor model which is normally unresponsive to monotherapy with anti-PD-1. Conclusions: These findings indicate that ONP-302 allows for tumor control via reprogramming myeloid cells via activation of the STING/IL-15/NK cell mechanism, as well as increasing anti-PD-1 response rates.

The present study investigated and evaluated the correlation between the expression of LACTB and LC3 and the clinical outcomes of patients with advanced gastric cancer treated with oxaliplatin plus S-1 neoadjuvant chemotherapy (NACT). A total of 51 patients with advanced gastric cancer underwent NACT treatment between June 2015 and June 2017. Pathomorphological changes in gastric cancer were analyzed by H&E staining. The expression level and subcellular localization of LACTB and LC3 in paraffin-embedded biopsies were detected by immunohistochemistry and immunofluorescence. The mRNA and protein expression of LACTB were investigated by reverse transcription quantitative polymerase chain reaction and Western blotting, respectively. Statistical analysis was performed to determine the association between the expression of LACTB and LC3 and clinical chemotherapy efficacy of NACT for gastric cancer. Among the 51 patients, 3 (5.88%), 27 (52.94%), 13 (25.49%) and 8 (15.69%) displayed complete remission, partial remission, stable disease and progressive disease, respectively. The rate of decreased LACTB expression was 68.6%, while the rate of increased LC3 expression was 60.8%. Furthermore, there was a significant negative correlation between the expression of LACTB and that of LC3 following NACT (P

This study was aimed at identifying molecular markers associated with the pathogenesis of sudden cardiac death (SCD). It provides a proteomic analysis of human left anterior descending coronary artery from subjects diagnosed with SCD through histological examination and cases of nondisease accidental deaths through autopsy. A total of 2784 proteins were obtained from label-free quantitative proteomic analysis. This included a total of 265 differential proteins which were involved in SCD-related processes, such as inflammation, muscle system process regulation, metal ion transport, and lysosomal pathway. Western blotting was carried out to measure the expressions of cathepsin C (CTSC), focal adhesion kinase (FAK), p-FAK, and proteins related to the p38/MAPK signaling pathway, whereas immunohistochemistry was performed to determine the localization and expression of CTSC, TNF-α, and CD206 in arterial tissues. It was found that CTSC were the most expressed proteins with a significant upward trend in SCD cases. Besides, CTSC regulated macrophage polarization to M1 through the FAK-induced p38/MAPK signaling pathway. This promoted the release of inflammatory factors and eventually increased the inflammatory response. In conclusion, this study implies that CTSC may be one of the key molecular targets for promoting macrophage M1 polarization in SCD, which may provide new therapeutic insights into the treatment of inflammatory diseases.

Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identify five distinctive genetic and transcriptomic programs and validate these in an independent neoadjuvant CPI trial to identify the features of response or resistance to CPI. By modeling the regulatory network, we identify the histone demethylase KDM5B as a repressor of tumor immune signaling pathways in one resistant subtype (S1, Luminal-excluded) and demonstrate that inhibition of KDM5B enhances immunogenicity in FGFR3-mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy.

Additional file of Significances of viable synergistic autophagy-associated cathepsin B and cathepsin D (CTSB/CTSD) as potential biomarkers for sudden cardiac death

Background The Cathepsins family, including cathepsin B and cathepsin D, potentially affects the entire processes involved in atherosclerosis. Although coronary heart disease (CHD) has been widely studied as the basis of Sudden Cardiac Death (SCD), the relationship between CHD and CTSB/D remains unclear. Methods We screened for differentially expressed proteins (DEPs) associated with autophagy by limma package in R. For the genes corresponding to the DEPs after screening, we used various databases to carry out functional enrichment of related DEGs to explore their possible influence on a specific aspect of the disease. Functional enrichment analysis of DEGs was performed by DAVID, Metascape and GSEA. STRING and Cytoscape were obtained the hub genes, the analysis of interaction networks through the GENMANIA and Networkanalyst. Western Blot was used to validate the protein expression level of target genes. TF and miRNA prediction were performed using Networkanalyst and visualized using Cytoscape. Results The expression levels of members of the cathepsin family were up regulated in CHD tissues compared with the control. GO and KEGG revealed that cathepsin was markedly enriched in endopeptidase activities, immune responses, lysosome pathways, et al. The correlation analysis showed that in patients with CHD, the CTSB/CTSD expression were negatively correlated with ATG4D and BNIP3, but positively with BCL2L1, CAPNS1, and TP53. In the TF-mRNA-miRNA network, has-miR-24-3p and has-miR-128-3p had higher degrees, CTSB/CTSD could be targeted by them. Conclusions Our findings elucidated the expression and regulatory role of cathepsins in coronary heart disease induced SCD and might further explore the potential mechanisms of autophagy in CHD.

Oxaliplatin (OXA), as a third-generation platinum anticancer drug, is a treatment drug for gastric cancer (GC). However, OXA resistance has become the main reason for OXA treatment failure. Serine beta-lactamase-like protein (LACTB), acts as a mitochondrial protein, can affect multiple cancer processes. Here, we aimed to investigate the function and mechanism of LACTB in OXA-resistant GC. After LACTB overexpression or autophagy activator (RAPA) treatment, cell proliferation, reactive oxygen species (ROS), apoptosis, mitochondrial dysfunction were evaluated through CCK-8 assay, Edu staining, flow cytometry and immunofluorescence assay. Moreover, DNA double-stranded damage and autophagy-related proteins were examined via western blot. We revealed that LACTB was downregulated in OXA-resistant MGC-803 cells, and overexpression of LACTB reduced the resistance of GC cells to OXA. Besides, our results uncovered that overexpression of LACTB induced apoptosis, reduced the mitochondrial membrane potential (MMP) and accelerated ROS accumulation in OXA-resistant MGC-803 (MGC-803/OXA) cells. Meanwhile, we verified that overexpression of LACTB decreased glucose uptake and ATP synthesis, induced mitochondria and DNA damages, and inhibited autophagy of MGC-803/OXA cells. Furthermore, our results certified that RAPA could weaken the function of LACTB on apoptosis and mitochondrial morphology and function in OXA-resistant MGC-803 cells with OXA treatment. Therefore, we demonstrated that LACTB could attenuate the resistance of MGC-803/OXA cells to OXA through autophagy-mediated mitochondrial morphological changes, mitochondrial dysfunction, and apoptosis, suggesting that LACTB, functions as a suppressor, is conducive to the therapy of OXA-resistant GC.

ObjectiveThis study aims to analyze the expressions of autophagy-related factors light chain 3 alpha (LC3A) and Beclin 1 and apoptosis-related factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (BAX) in primary osteoblasts treated with sodium fluoride (NaF).MethodsOsteoblasts were extracted from Sprague-Dawley rats and treated with 0, 2.5, 5, and 10 mg/L NaF solutions, followed by 10 mmol/L 3-methyladenine (3-MA) for 24 h. The apoptotic rate was determined by flow cytometry, and the expressions of the autophagy- and apoptosis-related factors were measured by western blotting and real-time quantitative polymerase chain reaction.ResultsThe mRNA expressions of LC3A, Beclin 1, and BAX in the NaF-treated osteoblast group were higher than those in the control group, while the protein expressions of these factors in the NaF-treated group were significantly higher than those in the control group. However, the Bcl-2 protein expression in the NaF-treated osteoblasts was significantly decreased compared to that in the control cells. After the 3-MA treatment, the protein expressions of LC3A, Beclin 1, and Bcl-2 were significantly decreased compared with those of the NaF-treated group, whereas the expression of BAX increased. Moreover, the apoptosis rate was increased after the addition of the 3-MA inhibitor.ConclusionNaF stimulation promoted autophagy and apoptosis of the osteoblasts, suggesting the involvement of fluoride damage in these processes.

Patients with locally advanced and metastatic urothelial carcinoma have a low survival rate (median 15.7 months, 13.1–17.8), with only a 23% response rate to monotherapy treatment with anti-PDL1 checkpoint immunotherapy. To identify new therapeutic targets, we profiled the immune regulatory signatures during murine cancer development using the BBN carcinogen and identified an increase in the expression of the T cell inhibitory protein B7-H4 (VTCN1, B7S1, B7X). B7-H4 expression temporally correlated with decreased lymphocyte infiltration. While the increase in B7-H4 expression within the bladder by CD11b+ monocytes is shared with human cancers, B7-H4 expression has not been previously identified in other murine cancer models. Higher expression of B7-H4 was associated with worse survival in muscle-invasive bladder cancer in humans, and increased B7-H4 expression was identified in luminal and luminal-papillary subtypes of bladder cancer. Evaluation of B7-H4 by single-cell RNA-Seq and immune mass cytometry of human bladder tumors found that B7-H4 is expressed in both the epithelium of urothelial carcinoma and CD68+ macrophages within the tumor. To investigate the function of B7-H4, treatment of human monocyte and T cell co-cultures with a B7-H4 blocking antibody resulted in enhanced IFN-γ secretion by CD4+ and CD8+ T cells. Additionally, anti-B7-H4 antibody treatment of BBN-carcinogen bladder cancers resulted in decreased tumor size, increased CD8+ T cell infiltration within the bladder, and a complimentary decrease in tumor-infiltrating T regulatory cells (Tregs). Furthermore, treatment with a combination of anti-PD-1 and anti-B7-H4 antibodies resulted in a significant reduction in tumor stage, a reduction in tumor size, and an increased level of tumor necrosis. These findings suggest that antibodies targeting B7-H4 may be a viable strategy for bladder cancers unresponsive to PD-1 checkpoint inhibitors.

Climate change and environmental management are issues of global concern. The advent of the era of Big Data has created a new research platform for the assessment of environmental governance and policies. However, little is known about Big Data application to climate change and environmental management research. This paper adopts bibliometric analysis in conjunction with network analysis to systematically evaluate the publications on carbon emissions and environmental management based on Big Data and Streaming Data using R package and VOSviewer software. The analysis involves 274 articles after rigorous screening and includes citation analysis, co-citation analysis, and co-word analysis. Main findings include (1) Carbon emissions and environmental management based on big data and streaming data is an emerging multidisciplinary research topic, which has been applied in the fields of computer science, supply chain design, transportation, carbon price assessment, environmental policy evaluation, and CO2 emissions reduction. (2) This field has attracted the attention of nations which are major contributors to the world economy. In particular, European and American scholars have made the main contributions to this topic, and Chinese researchers have also had great impact. (3) The research content of this topic is primarily divided into four categories, including empirical studies of specific industries, air pollution governance, technological innovation, and low-carbon transportation. Our findings suggest that future research should bring greater depth of practical and modeling analysis to environmental policy assessment based on Big Data.