Synergistic ferrate(VI) and chlorine for reclaimed water disinfection: Microbial control and chlorine decay mitigation.

Chlorination is the most widely used disinfection technology due to its simplicity and continuous disinfection ability. However, the drawbacks of disinfection by-products and chlorine-resistant bacteria have gained increasing attention. Nowadays, ferrate (Fe(VI)) is a multifunctional and environmentally friendly agent which has great potential in wastewater reclamation and reuse. This study investigated synergistic Fe(VI) and chlorine technology for reclaimed water disinfection in terms of microbial control and chlorine decay mitigation. Specifically, synergistic disinfection significantly improved the inactivation efficiency on total coliform, Escherichia coli and heterotrophic bacteria compared to sole chlorination. Synergistic disinfection also exhibited superior performance on controlling the relative abundance of chlorine-resistant bacteria and pathogenic bacteria. In addition, the decay rate of residual chlorine was relatively lower after Fe(VI) pretreatment, which was beneficial for microbial control during the reclaimed water distribution process. Technical and economic analyses revealed that synergistic Fe(VI) and chlorine disinfection was suitable and feasible. Results of this study are believed to provide useful information and alternative options on the optimization of reclaimed water disinfection.

Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in aging and obesity.

Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

Temporal Dynamics and Influential Factors of Taste and Odor Compounds in the Eastern Drinking Water Source of Chaohu Lake, China: A Comparative Analysis of Global Freshwaters.

The escalating proliferation of cyanobacteria poses significant taste and odor (T/O) challenges, impacting freshwater ecosystems, public health, and water treatment costs. We examined monthly variations in four T/O compounds from September 2011 to August 2012 in Chaohu Lake's eastern drinking water source (DECL). More importantly, we compared the reported T/O occurrence and the related factors in freshwater bodies worldwide. The assessment of T/O issues indicated a severe and widespread problem, with many cases surpassing odor threshold values. Remarkably, China reported the highest frequency and severity of odor-related problems. A temporal analysis revealed variations in odor occurrences within the same water body across different years, emphasizing the need to consider high values in all seasons for water safety. Globally, T/O issues were widespread, demanding attention to variations within the same water body and across different layers. Algae were crucial contributors to odor compounds, necessitating targeted interventions due to diverse odorant sources and properties. A correlation analysis alone lacked definitive answers, emphasizing the essential role of further validation, such as algae isolation. Nutrients are likely to have influenced the T/O, as GSM and MIB correlated positively with nitrate and ammonia nitrogen in DECL, resulting in proposed control recommendations. This study offers recommendations for freshwater ecosystem management and serves as a foundation for future research and management strategies to address T/O challenges.

Sophora flavescens-Astragalus mongholicus herb pair in the progression of hepatitis, cirrhosis, and hepatocellular carcinoma: a possible mechanisms and relevant therapeutic substances.

Background: Both Sophora flavescens (SF) and Astragalus mongholicus (AM) are known for their anti-inflammatory, antifibrotic, and anticancer activities. However, the efficacy, multi-target mechanisms, and therapeutic substances of SF-AM herb pair on the progression of hepatitis-cirrhosis-hepatocellular carcinoma hepatocellular carcinoma (HCC) remain unclear. Purpose: To investigate the efficacy, mechanisms, and potential therapeutic substances of SF-AM herb pair in the progression of hepatitis-cirrhosis-HCC. Methods: Firstly, diethylnitrosamine was used to establish the hepatitis-cirrhosis-HCC model. HE staining and non-targeted metabolomics were used to evaluate the efficacy of SF-AM herb pair. Subsequently, the absorbed components of SF-AM herb pair in the plasma of rats were determined through HPLC-Q-TOF-MS/MS analysis. Flow cytometry, Western blot, and qRT-PCR were then employed to assess CD4+ and CD8+ T lymphocytes, PI3K/Akt signaling pathway-related proteins, and their corresponding mRNAs. Simultaneously, the efficacy and mechanism of SF-AM herb pair on HCC were confirmed by in vitro experiments. Finally, Pearson correlation analysis was performed between pharmacodynamic indicators and in vivo components to identify the potential therapeutic substances of SF-AM herb pair. Results: SF-AM herb pair can alleviate the pathological damage and reverse metabolic abnormalities in hepatitis, cirrhosis, and HCC rats, particularly during the hepatitis and cirrhosis stages. Pharmacological researches have demonstrated that SF-AM herb pair can increase the proportion of CD8+ T lymphocytes, inhibit the expression of PI3K, Akt, p-Akt, NF-κB p65, NF-κB pp65, and Bcl-2, as well as increase the expression of IκBα, Bax, and cleaved caspase-3. These findings suggest that SF-AM herb pair has the ability to enhance immunity, anti-inflammation and promote apoptosis. Cell experiments have shown that SF-AM herb pair can inhibit the proliferation of HepG2 cell and regulate the PI3K/Akt signaling pathway. Moreover, 23 absorbed prototypical components and 53 metabolites of SF-AM herb pair were identified at different stages of HCC rats. Pearson correlation analysis revealed that matrine, cytisine, wogonoside, and isoastragaloside are potential therapeutic substances in SF-AM herb pair for the prevention and treatment of hepatitis, cirrhosis, and HCC. Conclusion: In summary, this study revealed the efficacy, mechanisms, and potential therapeutic substances of SF-AM herb pair in the hepatitis-cirrhosis-HCC axis and provided a reference for its clinical application.

Validation of Patient-Reported Outcome measure in pediatric chronic Kidney disease (PRO-Kid).

BACKGROUND: Measuring the burden of symptoms that matter most to children and adolescents with chronic kidney disease (CKD) is essential for optimizing patient-centered care. We developed a novel CKD-specific Patient-Reported Outcome measure (PRO-Kid) to assess both frequency and impact of symptoms in children. In the current study, we further assessed the validity and internal consistency of PRO-Kid. METHODS: In this multicenter study, children age 8 to 18 years with stages 3-5 CKD, including those on dialysis, were recruited from five pediatric centers. Children completed the 14-item PRO-Kid questionnaire and the validated Pediatric Quality of Life Inventory (PedsQL™ 4.0). We explored the dimensionality of the PRO-kid scale using exploratory and confirmatory factor analysis, to either establish that it is a unidimensional construct or identify evidence of subfactors. We then assessed internal consistency (Cronbach's alpha [Cα]) and construct validity (Pearson correlations). RESULTS: In total, 100 children were included. The median eGFR was 27.4 ml/min/1.73m2 [7.43, 63.4], and 26 children (26%) were on dialysis. Both the PRO-Kid frequency and the impact scales were unidimensional. Cα was high for both the PRO-Kid frequency and impact scales, 0.83 (95% CI = 0.78 to 0.88) and 0.84 (95% CI = 0.80 to 0.89) respectively, showing strong internal consistency. Pearson correlations between PRO-Kid and PedsQL™ scores were also strong: -0.78 (95% confidence interval [CI] = -0.85 to -0.70) for the frequency score and -0.69 (95% CI = -0.78 to -0.56) for the impact score, reflecting the association between poorer quality of life and higher symptom burden. CONCLUSIONS: PRO-Kid is a novel patient-reported symptom burden tool for children 8-18 years of age with CKD that correlates strongly in the expected direction with PedsQL™, supporting its validity. Future work will evaluate changes in PRO-Kid score with progression of CKD, and implementation of the tool into clinical care.

Exosomes regulate doxorubicin resistance in breast cancer via miR-34a-5p/NOTCH1.

Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA. In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance. Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function. In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.

Cu-Catalyzed Regioselective Silylation of Chloro-Substituted Allenyl-Bdan.

A copper-catalyzed efficient regioselective silylation reaction of chloro-substituted allenyl-Bdan was developed. Under mild reaction conditions, allenyl and propargyl silane compounds can be selectively obtained in moderate to high yields by adjusting the bases and solvents used in the reactions. This study offers direct and efficient methods for synthesizing multifunctionalized allenyl and propargyl silane compounds from the same initial material of chloro-substituted allenyl-Bdan.

Loss of LECT2 promotes ovarian cancer progression by inducing cancer invasiveness and facilitating an immunosuppressive environment.

Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that can bind to several receptors and mediate distinct molecular pathways in various cell settings. Changing levels of LECT2 have been implicated in multiple human disease states, including cancers. Here, we have demonstrated reduced serum levels of LECT2 in patients with epithelial ovarian cancer (EOC) and down-regulated circulating Lect2 as the disease progresses in a syngeneic mouse ID8 EOC model. Using the murine EOC model, we discovered that loss of Lect2 promotes EOC progression by modulating both tumor cells and the tumor microenvironment. Lect2 inhibited EOC cells' invasive phenotype and suppressed EOC's transcoelomic metastasis by targeting c-Met signaling. In addition, Lect2 downregulation induced the accumulation and activation of myeloid-derived suppressor cells (MDSCs). This fostered an immunosuppressive microenvironment in EOC by inhibiting T-cell activation and skewing macrophages toward an M2 phenotype. The therapeutic efficacy of programmed cell death-1 (PD-1)/PD-L1 pathway blockade for the ID8 model was significantly hindered. Overall, our data highlight multiple functions of Lect2 during EOC progression and reveal a rationale for synergistic immunotherapeutic strategies by targeting Lect2.

Effects of water quality on bacterial inactivation by ferrate(VI).

Ferrate (Fe(VI)) is an emerging green oxidant which has great potential and prospect in water disinfection. However, the effects of water quality on Fe(VI) disinfection remain unclear. This study systematically investigated the effects of pH, organic matters and inorganic ions on Fe(VI) inactivation of Escherichia coli (E. coli). Results showed that pH was the dominant influencing factor and the inactivation efficiency as well as inactivation rate constant was negatively correlated with pH (6.8-8.4). HFeO4- was found to be the critical Fe(VI) species contributing to the inactivation. As for organic matters (0-5 mg C/L), protein and humic acid significantly accelerated the decay of Fe(VI) and had negative effects on the inactivation efficiency, while polysaccharide slightly inhibited the inactivation due to the low reactivity with Fe(VI). As for inorganic ions, bicarbonate (0-2 mM) could stabilize Fe(VI) and decreased the inactivation rate constant, while ammonium (0-1 mM) had little effect on the inactivation of E. coli. In addition, the comprehensive effects of water quality on Fe(VI) disinfection in actual reclaimed water were also evaluated. The inactivation of E. coli in secondary effluent and denitrifying effluent was found to be inhibited compared to that in phosphate buffer. Overall, this study is believed to provide valuable information on Fe(VI) disinfection for water and wastewater treatment practices.

Intragraft regulatory T cells in the modern era: what can high-dimensional methods tell us about pathways to allograft acceptance?

Replacement of diseased organs with transplanted healthy donor ones remains the best and often only treatment option for end-stage organ disease. Immunosuppressants have decreased the incidence of acute rejection, but long-term survival remains limited. The broad action of current immunosuppressive drugs results in global immune impairment, increasing the risk of cancer and infections. Hence, achievement of allograft tolerance, in which graft function is maintained in the absence of global immunosuppression, has long been the aim of transplant clinicians and scientists. Regulatory T cells (Treg) are a specialized subset of immune cells that control a diverse array of immune responses, can prevent allograft rejection in animals, and have recently been explored in early phase clinical trials as an adoptive cellular therapy in transplant recipients. It has been established that allograft residency by Tregs can promote graft acceptance, but whether intragraft Treg functional diversification and spatial organization contribute to this process is largely unknown. In this review, we will explore what is known regarding the properties of intragraft Tregs during allograft acceptance and rejection. We will summarize recent advances in understanding Treg tissue residency through spatial, transcriptomic and high-dimensional cytometric methods in both animal and human studies. Our discussion will explore properties of intragraft Tregs in mediating operational tolerance to commonly transplanted solid organs. Finally, given recent developments in Treg cellular therapy, we will review emerging knowledge of whether and how these adoptively transferred cells enter allografts in humans. An understanding of the properties of intragraft Tregs will help lay the foundation for future therapies that will promote immune tolerance.

Inactivation of Bacteria in Water by Ferrate(VI): Efficiency and Mechanisms.

Ferrate (Fe(VI)) is an emerging green disinfectant and has received increasing attention nowadays. This study conducted systematic analyses of Fe(VI) disinfection on six typical bacteria in different water matrices. The results showed that Fe(VI) was more effective in inactivating Gram-negative (G-) bacteria than Gram-positive (G+) bacteria, and the disinfection performance of Fe(VI) was better in a phosphate buffer than that in a borate buffer and secondary effluent. The inactivation rate constants of G- bacteria were significantly higher than those of G+ bacteria. The cell membrane damage of G- bacteria was also more severe than that of G+ bacteria after Fe(VI) treatment. The cell wall structure, especially cell wall thickness, might account for the difference of the inactivation efficiency between G- bacteria and G+ bacteria. Moreover, it is revealed that Fe(VI) primarily reacted with proteins rather than other biological molecules (i.e., phospholipids, peptidoglycan, and lipopolysaccharide). This was further evidenced by the reduction of bacterial autofluorescence due to the destruction of bacterial proteins during Fe(VI) inactivation. Overall, this study advances the understanding of Fe(VI) disinfection mechanisms and provides valuable information for the Fe(VI) application in water disinfection.

Multiple impacts of Naa10p on cancer progression: Molecular functions and clinical prospects.

Nα-acetyltransferase 10 protein (Naa10p) is known as the catalytic subunit of N-terminal acetyltransferases A (NatA) complex, associating with Naa15p to acetylate N-termini of the human proteome. Recent investigations have unveiled additional functions for Naa10p, encompassing lysine ε-acetylation and acetyltransferase-independent activities. Its pleiotropic roles have been implicated in diverse physiological and pathological contexts. Emerging evidence has implicated Naa10p in cancer progression, demonstrating dual attributes as an oncogene or a tumor suppressor contingent on the cancer type and acetyltransferase activity context. In this comprehensive review, we present a pan-cancer analysis aimed at elucidating the intricacies underlying Naa10p dysregulation in cancer. Our findings propose the potential involvement of c-Myc as a modulatory factor influencing Naa10p expression. Moreover, we provide a consolidated summary of recent advancements in understanding the intricate molecular underpinnings through which Naa10p contributes to cancer cell proliferation and metastasis. Furthermore, we delve into the multifaceted nature of Naa10p's roles in regulating cancer behaviors, potentially attributed to its interactions with a repertoire of partner proteins. Through an exhaustive exploration of Naa10p's functions, spanning its acetylation activity and acetyltransferase-independent functionalities, this review offers novel insights with implications for targeted therapeutic strategies involving this pivotal protein in the realm of cancer therapeutics.

High-efficiency and low-carbon inactivation of UV resistant bacteria in reclaimed water by flow-through electrode system (FES).

With the increasingly serious shortage of water resources globally, it has been paid more attention on how to secure the biosafety of reclaimed water and other non-traditional water sources. However, the 3 most applied disinfection technics, which are chlorine, ultraviolet (UV), and ozone disinfection, all have their disadvantages of selecting undesired bacteria and low energy utilization efficiency. Electrode disinfection is a promising solution, but the current electrode disinfection process still needs to be optimized in terms of the use conditions of the configuration reactivation. In this paper, we built a flow electrode system (FES). To evaluate the disinfection techniques more precisely, we isolated ultraviolet-resistant bacteria (URB) bacteria from the water of the full-scale water plant and tested the disinfection performance of FES and UV. The inactivation rate, reactivation potential, and energy consumption were analyzed. FES could inactivate 99.99 % of the URB and cause irreversible damage to the residual bacteria. FES could make all bacteria strains apoptosis in the subsequent 24 h of storage after alternating pulse current (APC) treatment, 3 V, within 27.7 s. Besides, the energy consumption of FES is about 2 orders lower than that of UV disinfection under the same inactivation rate. In summary, APC-FES is an efficient and low-carbon alternative for future water disinfection, which could achieve the ideal disinfection effect of a high inactivation rate, no reactivation, and low energy consumption.

Diagnostic value of BinaxNOW antigen card for Severe Acute Respiratory Syndrome Coronavirus 2.

Rapid laboratory detection is remarkably crucial to diagnosing coronavirus disease 2019 (COVID-19) infection, due to whose outbreak causes to the world pandemic. The BinaxNOW antigen card (BinaxNOW) is a simple, effective, and cheap tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The meta-analysis in this study was conducted to evaluate the diagnostic performance of BinaxNOW for SARS-CoV-2. The researchers independently retrieved the related databases (PubMed, Embase, Web of Science, Cochrane Library) before May 1st, 2021, and extracted the relevant data based on the early inclusion/exclusion criterion. Quality Assessment of Diagnostic Accuracy Study-2 was used to evaluate the quality of the enrolled studies. Stata 16.0, Meta-DiSc 1.4, and Review Manager 5.3 were used to generate analytical data for the statistical analysis. 59 sets of data were identified from the seven studies included in this meta-analysis. The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their 95% confidence intervals were 0.77 (0.76 to 0.79), 0.99 (0.99 to 0.99), 65.72 (48.23 to 89.56), 0.23 (0.19 to 0.28), and 461.10 (281.55 to 755.13), respectively. The area under curve was 0.9910 in the summary receiver operating characteristic curve. BinaxNOW is beneficial for symptomatic patients' onset within 7 days. CT value and testing site may be the heterogeneity source of BinaxNOW accuracy. Moreover, this technology has an efficient performance for diagnosing COVID-19, especially in patients with heavy viral load. BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19 in the post-pandemic era.Highlights● Pooled sensitivity with 0.77 and specificity with 0.99 in the BinaxNOW assay.● CT value and testing site may be the heterogeneity source of BinaxNOW accuracy.● BinaxNOW is beneficial for symptomatic patients' onset within 7 days.● BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19.

Modeling and optimization of synergistic ozone-ultraviolet-chlorine process for reclaimed water disinfection: From laboratory tests to software simulation.

The ozone-ultraviolet (UV)-chlorine process is a highly effective method of disinfection in water reuse system, but currently still lacks precise quantification and accurate control. It is difficult to determine the dosage of each disinfectant because of the complex interactions that occur between disinfection units and the complicated mathematical calculation required. In this study, we proposed a dosage optimization model for ozone-UV-chlorine synergistic disinfection process. The model was able to identify the cost-effective doses of the disinfectants under the constraints of microbial inactivation, decolorization, and residual chlorine retention requirements. Specifically, the simulation of microbial inactivation rates during synergistic disinfection process was accomplished through quantification of the synergistic effects between disinfection units and the introduction of enhancement coefficients. In order to solve this optimization model rapidly and automatically, a MATLAB-based software program with graphical user interface was developed. This software consisted of calibration unit, prediction unit, assessment unit, and optimization unit, and was able to simulate synergistic ozone-UV-chlorine process and identify the optimal dose of ozone, UV, and chlorine. Validation experiments revealed good agreements between the experimental data and the results calculated by the developed software. The developed software is believed to help the water reclamation plants improve disinfection efficiency and reduce the operational costs of synergistic disinfection processes.

Identification of significant live bacterial community shifts in different reclaimed waters during ozone and chlorine disinfection.

Ozone and chlorine are the most widely used disinfectants for water and wastewater disinfection. They play important role in microbial inactivation but could also pose a considerable selection effect on the microbial community of reclaimed water. Classical culture-based methods that rely on the assessment of conventional bacterial indicators (e.g., coliform bacteria) could hardly reflect the survival of disinfection residual bacteria (DRB) and hidden microbial risks in disinfected effluents. Hence, this study investigated the shifts of live bacterial community during ozone and chlorine disinfection in three reclaimed waters (i.e., two secondary effluents and one tertiary effluent), adopting Illumina Miseq sequencing technology in combination with a viability assay, propidium monoazide (PMA) pretreatment. Notably, statistical analyses of Wilcoxon rank-sum test confirmed the existance of distinct differences in bacterial community structure between samples with or without PMA pretreatment. On the phylum level, Proteobacteria commonly dominated in three undisinfected reclaimed waters, while ozone and chlorine disinfection posed varied effects on its relative abundance among different influents. On the genus level, ozone and chlorine disinfection significantly changed the bacterial composition and dominant species in reclaimed waters. Specifically, the typical DRB identified in ozone disinfected effluents were Pseudomonas, Nitrospira and Dechloromonas, while for chlorine disinfected effluents, Pseudomonas, Legionella, Clostridium, Mycobacterium and Romboutsia were recognized as typical DRB, which call for much attention. The Alpha and Beta diversity analysis results also suggested that different influent compositions greatly affected the bacterial community structure during disinfection processes. Since the experiments in present study were conducted in a short period and the dataset was relatively limited, prolonged experiment under different operational conditions are needed in future to illustrate the potential long-term effects of disinfection on the microbial community structure. The findings of this study could provide insights into microbial safety concern and control after disinfection for sustainable water reclamation and reuse.

Tilianin alleviates lipid deposition and fibrosis in mice with nonalcoholic steatohepatitis by activating the PPARα/Nnat axis.

The understanding and treatment of nonalcoholic steatohepatitis (NASH) are still very limited. This study reports the therapeutic effect of tilianin on mice with NASH and further explores its possible molecular mechanisms. A mice model of NASH was established using low-dose streptozotocin combined with a high-fat diet and tilianin treatment. Liver function was assessed by determining serum aspartate aminotransferase and alanine aminotransferase in serum. Interleukin (IL)-1ß, IL-6, transforming growth factor ß1 (TGF-ß1), and tumor necrosis factor α (TNF-α) levels in serum were determined. Hepatocyte apoptosis was assessed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining. Oil Red O staining and boron dipyrrin staining were used to determine lipid deposition in liver tissues. Masson staining was used to evaluate liver fibrosis, and immunohistochemistry and western blot analysis were used to determine the expression of target proteins. Tilianin treatment significantly ameliorated liver function, inhibited hepatocyte apoptosis, and reduced lipid deposition and liver fibrosis in mice with NASH. The expression of neuronatin (Nnat) and peroxisome proliferator-activated receptor (PPAR) α was upregulated, whereas that of sterol regulatory element-binding protein 1 (SREBP-1), TGF-ß1, nuclear factor (NF)-κB p65, and phosphorylated p65 was downregulated in the liver tissues of mice with NASH after tilianin treatment. The above effects of tilianin were significantly reversed after Nnat knock-down, but its effect on PPARα expression was unaffected. Thus, the natural drug tilianin shows potential in treatig NASH. Its mechanism of action may be related to the targeted activation of PPARα/Nnat, thereby inhibiting the activation of the NF-κB signaling pathway.

A novel vaccine targeting ß1-adrenergic receptor.

Beta-blockers are widely used in the treatment of hypertension, heart failure and ischemic heart disease. However, unstandardized medication results in diverse clinical outcomes in patients. The main causes are unattained optimal doses, insufficient follow-up and patients' poor adherence. To improve the medication inadequacy, our team developed a novel therapeutic vaccine targeting ß1-adrenergic receptor (ß1-AR). The ß1-AR vaccine named ABRQß-006 was prepared by chemical conjugation of a screened ß1-AR peptide with Qß virus like particle (VLP). The antihypertensive, anti-remodeling and cardio-protective effects of ß1-AR vaccine were evaluated in different animal models. The ABRQß-006 vaccine was immunogenic that induced high titers of antibodies against ß1-AR epitope peptide. In the NG-nitro-L-arginine methyl ester (L-NAME) + Sprague Dawley (SD) hypertension model, ABRQß-006 lowered systolic blood pressure about 10 mmHg and attenuated vascular remodeling, myocardial hypertrophy and perivascular fibrosis. In the pressure-overload transverse aortic constriction (TAC) model, ABRQß-006 significantly improved cardiac function, decreased myocardial hypertrophy, perivascular fibrosis and vascular remodeling. In the myocardial infarction (MI) model, ABRQß-006 effectively improved cardiac remodeling, reduced cardiac fibrosis and inflammatory infiltration, which was superior to metoprolol. Moreover, no significant immune-mediated damage was observed in immunized animals. The ABRQß-006 vaccine targeting ß1-AR showed the effects on hypertension and heart rate control, myocardial remodeling inhibition and cardiac function protection. These effects could be differentiated in different types of diseases with diverse pathogenesis. ABRQß-006 could be a novel and promising method for the treatment of hypertension and heart failure with different etiologies.