Time-dependent hormesis transfer from five high-frequency personal care product components to mixtures.

There is potential for personal care products (PCPs) components and mixtures to induce hormesis. How hormesis is related to time and transmitted from components to mixtures are not clear. In this paper, we conducted determination of components in 16 PCP products and then ran frequent itemset mining on the component data. Five high-frequency components (HFCs), betaine (BET), 1,3-butanediol (BUT), ethylenediaminetetraacetic acid disodium salt (EDTA), glycerol (GLO), and phenoxyethanol (POE), and 14 mixtures were identified. For each mixture system, one mixture ray with the actual mixture ratios in the products was selected. Time-dependent microplate toxicity analysis was used to test the luminescence inhibition toxicity of five HFCs and 14 mixture rays to Vibrio qinghaiensis sp.-Q67 at 12 concentration gradients and eight exposure times. It is showed that BET, EDTA, POE, and 13 mixture rays containing at least one J-type component showed time-dependent hormesis. Characteristic parameters used to describe hormesis revealed that the absolute value of the maximum stimulatory effect (|Emin|) generally increased with time. Notably, mixtures composed of POE and S-type components showed greater |Emin| than POE alone at the same time. Importantly, the maximum stimulatory effective concentration, NOEC/the zero effective concentration point, and EC50 remained relatively stable. Nine hormesis transmission phenomena were observed in different mixture rays. While all mixtures primarily exhibited additive action, varying degrees of synergism and antagonism were noted in binary mixtures, with no strong synergism or antagonism observed in ternary and quaternary mixtures. These findings offer valuable insights for the screening of HFCs and their mixtures, as well as the study of hormesis transmission in personal care products.

Optimal ultrasonic treatment frequency and duration parameters were used to detect the pathogenic bacteria of orthopedic implant-associated infection by ultrasonic oscillation.

INTRUDUCTON: The most accurate method for detecting the pathogen of orthopedic implant-associated infections (OIAIs) is sonication fluid (SF). However, the frequency and duration of ultrasound significantly influence the number and activity of microorganisms. Currently, there is no consensus on the selection of these two parameters. Through this study, the choice of these two parameters is clarified. METHODS: We established five ultrasonic groups (40kHz/10min, 40kHz/5min, 40 kHz/1min, 20kHz/5min, and 10kHz/5min) based on previous literature. OIAIs models were then developed and applied to ultrasound group treatment. Subsequently, we evaluated the efficiency of bacteria removal by conducting SEM and crystal violet staining. The number of live bacteria in the SF was determined using plate colony count and live/dead bacteria staining. RESULTS: The results of crystal violet staining revealed that both the 40kHz/5min group and the 40kHz/10min group exhibited a significantly higher bacterial clearance rate compared to the other groups. However, there was no significant difference between the two groups. Additionally, the results of plate colony count and fluorescence staining of live and dead bacteria indicated that the number of live bacteria in the 40kHz/5min SF group was significantly higher than in the other groups. CONCLUSION: 40kHz/5min ultrasound is the most beneficial for the detection of pathogenic bacteria on the surface of orthopedic implants.

Screening for frequently detected quaternary ammonium mixture systems in waters based on frequent itemset mining and prediction of their toxicity.

Screening and prioritizing research on frequently detected mixture systems in the environment is of great significance, as conducting toxicity testing on all mixtures is impractical. Therefore, the frequent itemset mining (FIM) was introduced and applied in this paper to identify variables that commonly co-occur in a dataset. Based on the dataset of the quaternary ammonium compounds (QACs) in the water environment, the four frequent QAC mixture systems with detection rate ≥ 35 % were found, including [BDMM]+Cl--[BTMM]+Cl- (M1), [BDMM]+Cl--[BHMM]+Cl- (M2), [BTMM]+Cl- -[BHMM]+Cl- (M3), and [BDMM]+Cl--[BTMM]+Cl--[BHMM]+Cl- (M4). [BDMM]+Cl-, [BTMM]+Cl-, and [BHMM]+Cl- are benzyl dodecyl dimethyl ammonium chloride, benzyl tetradecyl dimethyl ammonium chloride, and benzyl hexadecyl dimethyl ammonium chloride, respectively. Then, the toxicity of the representative mixture rays and components for the four frequently detected mixture systems was tested using Vibrio qinghaiensis sp.-Q67 (Q67) as a luminescent indicator organism at 0.25 and 12 h. The toxicity of the mixtures was predicted using concentration addition (CA) and independent action (IA) models. It was shown that both the components and the representative mixture rays for the four frequently detected mixture systems exhibited obvious acute and chronic toxicity to Q67, and their median effective concentrations (EC50) were below 7 mg/L. Both CA and IA models predicted the toxicity of the four mixture systems well. However, the CA model had a better predictive ability for the toxicity of the M3 and M4 mixtures than IA at 12 h.

Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKß/AMPK pathway.

OBJECTIVE: Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism of liraglutide against obesity-related kidney disease. METHODS: Thirty-six C57BL/6J male mice were randomly divided into six groups (n = 6 per group). Obesity-related nephropathy was induced in mice by continuous feeding of high-fat diet (HFD) for 12 weeks. After 12 weeks, liraglutide (0.6 mg/kg) and AMP-activated protein kinase (AMPK) agonists bortezomib (200 µg/kg) were injected for 12 weeks, respectively. Enzyme-linked immunosorbent assay was employed to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine in serum, as well as urinary protein in urine. Besides, hematoxylin-eosin staining and periodic acid-Schiff staining were used to observe the pathological changes of kidney tissue; immunohistochemistry, western blot, and real-time quantitative PCR to assess the calmodulin-dependent protein kinase kinase beta (CaMKKß)/AMPK signaling pathway activation. RESULTS: Liraglutide significantly reduced serum lipid loading, improved kidney function, and relieved kidney histopathological damage and glycogen deposition in the mouse model of obesity-related kidney disease induced by HFD. In addition, liraglutide also significantly inhibited the CaMKKß/AMPK signaling pathway in kidney tissue of HFD-induced mice. However, bortezomib partially reversed the therapeutic effect of liraglutide on HDF-induced nephropathy in mice. CONCLUSIONS: Liraglutide has a therapeutic effect on obesity-related kidney disease, and such an effect may be achieved by inhibiting the CaMKKß/AMPK signaling pathway in kidney tissue.

Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive deposition of fatty acids in the liver. Further deterioration leads to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, creating a heavy burden on human health and the social economy. Currently, there are no effective and specific drugs for the treatment of NAFLD. Therefore, it is important to further investigate the pathogenesis of NAFLD and explore effective therapeutic targets for the prevention and treatment of the disease. Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a STEAP family protein, is a metalloreductase. Studies have shown that it can participate in the regulation of liver ischemia-reperfusion injury, hepatocellular carcinoma, myocardial hypertrophy, and other diseases. In this study, we found that the expression of STEAP3 is upregulated in NAFLD. Deletion of STEAP3 inhibits the development of NAFLD in vivo and in vitro, whereas its overexpression promotes palmitic acid/oleic acid stimulation-induced lipid deposition in hepatocytes. Mechanistically, it interacts with transforming growth factor beta-activated kinase 1 (TAK1) to regulate the progression of NAFLD by promoting TAK1 phosphorylation and activating the TAK1-c-Jun N-terminal kinase/p38 signaling pathway. Taken together, our results provide further insight into the involvement of STEAP3 in liver pathology.

Identification of signalling downstream of the transcription factor forkhead box protein M1 that protects against endoplasmic reticulum stress in a diabetic foot ulcer model.

AIMS: Diabetic foot ulcer (DFU) has a significant impact on the quality of life of diabetic mellitus (DM) patients. Here, we aimed to explore the molecules with aberrant expression and their regulatory mechanisms in DFU. METHODS: The expression of gene and protein was examined using quantitative polymerase chain reaction (qPCR) and western blot. Pearson's correlation analysis was used to analyse interactions among FOXM1, GAS5 and SDF4. Immunofluorescence was used to detect PDI and GRP78 expression. Flow cytometry was used to assess cell apoptosis. Tube formation assay was used to determine angiogenic capacity. Fluorescence in situ hybridization (FISH) assay was employed to determine the cellular localization of GAS5 and SDF4 in human umbilical vein endothelial cells (HUVECs). The interactions among FOXM1, GAS5 and SDF4 were validated by chromatin immunoprecipitation (ChIP), luciferase, RNA pull-down and RNA immunoprecipitation (RIP) assays. RESULTS: FOXM1, GAS5 and SDF4 were decreased in the skin tissues of DFU patients. High glucose (HG) stimulation induced endoplasmic reticulum (ER) stress and cell apoptosis but suppressed angiogenesis in HUVECs, which were abolished by FOXM1 overexpression. FOXM1 promoted GAS5 transcriptional activity, resulting in increased GAS5 expression, and GAS5 knockdown reversed the effects of FOXM1 overexpression in HG-treated HUVECs. Moreover, GAS5 recruited TAF15 to promote SDF4 expression in HUVECs. GAS5 overexpression inhibited ER stress, cell apoptosis and induced angiogenesis in HG-treated HUVECs which could be reversed by silencing SDF4. CONCLUSION: Our results revealed that FOXM1 suppressed ER stress, cell apoptosis and promoted angiogenesis in HG-induced HUVECs via mediating GAS5/TAF15/SDF4 axis, providing a novel therapeutic molecule mechanism for DFU.

Effect of a carbohydrate-rich beverage on rate of cesarean delivery in primigravidae with epidural labor analgesia: a multicenter randomized trial.

BACKGROUND: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. METHODS: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. RESULTS: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. CONCLUSIONS: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. TRIAL REGISTRATION: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.

Errate: Efficacy and Toxicity of Adjuvant Therapies for High-Risk Endometrial Cancer in Stage I-III: A Systematic Review and Network Meta-Analysis.

Source of support: This study was supported by grants from the Key Research and Development projects of Sichuan Province (No.2020YFS0129) and the Natural Science Foundation of China (No.61875249). Reference: Mengyin Ao, Ting Ding, Dan Tang, Mingrong Xi: Efficacy and Toxicity of Adjuvant Therapies for High-Risk Endometrial Cancer in Stage I-III: A Systematic Review and Network Meta-Analysis. Med Sci Monit, 2020; 26: e925595. DOI: 10.12659/MSM.925595.

Dynamic changes of bacteria and screening of potential spoilage markers of lamb in aerobic and vacuum packaging.

Microorganisms proliferate, consume nutrients, and produce many undesired metabolites, which are the main reason for the spoilage of fresh meat. Screening spoilage markers is of great significance for characterizing the freshness of fresh meat. At present, there are few studies on the volatile spoilage markers (VSMs) of lamb and their relationship with bacteria. In this study, the spoilage evolution of lamb was evaluated by multiple indicators. The changes of bacteria and volatile organic compounds (VOCs) in aerobic-packaged (AP) and vacuum-packaged (VP) lamb were measured by 16S next-generation sequencing (NGS) and headspace solid-phase microextraction (HS-SPME)-gas chromatography-mass spectrometry (GC-MS) respectively. The potential VSMs were also screened. Results showed that the shelf life of AP lamb at 4 °C was less than 10 d and VP lamb was less than 28 d. Pseudomonas was the dominant bacteria in AP lamb, while Latilactobacillus and Lactococcus were the dominant bacteria in VP lamb. Several VOCs could be recommended as potential spoilage markers, including 1-octen-3-ol, 1-hexanol, nonanal, methoxy-phenyloxime, 2,3-octanedione, acetoin and 1-pentanol for AP lamb; acetoin, 1-hexanol, 2,3-octanedione, hexanoic acid, 1-octen-3-ol, nonanal, hexanal and 2,3-octanediol for VP lamb. This study can provide information for characterizing and predicting the freshness of fresh lamb.

Targeted delivery of inhalable drug particles in a patient-specific tracheobronchial tree with moderate COVID-19: A numerical study.

The coronavirus disease 2019 (COVID-19) pandemic has led to severe social and economic disruption worldwide. Although currently no consent has been reached on a specific therapy that can treat COVID-19 effectively, several inhalation therapy strategies have been proposed to inhibit SARS-CoV-2 infection. These strategies include inhalations of antiviral drugs, anti-inflammatory drugs, and vaccines. To investigate how to enhance the therapeutic effect by increasing the delivery efficiency (DE) of the inhaled aerosolized drug particles, a patient-specific tracheobronchial (TB) tree from the trachea up to generation 6 (G6) with moderate COVID-19 symptoms was selected as a testbed for the in silico trials of targeted drug delivery to the lung regions with pneumonia alba, i.e., the severely affected lung segments (SALS). The 3D TB tree geometry was reconstructed from spiral computed tomography (CT) scanned images. The airflow field and particle trajectories were solved using a computational fluid dynamics (CFD) based Euler-Lagrange model at an inhalation flow rate of 15 L/min. Particle release maps, which record the deposition locations of the released particles, were obtained at the inlet according to the particle trajectories. Simulation results show that particles with different diameters have similar release maps for targeted delivery to SALS. Point-source aerosol release (PSAR) method can significantly enhance the DE into the SALS. A C++ program has been developed to optimize the location of the PSAR tube. The optimized simulations indicate that the PSAR approach can at least increase the DE of the SALS by a factor of 3.2× higher than conventional random-release drug-aerosol inhalation. The presence of the PSAR tube only leads to a 7.12% change in DE of the SALS. This enables the fast design of a patient-specific treatment for reginal lung diseases.

ZmGLP1, a Germin-like Protein from Maize, Plays an Important Role in the Regulation of Pathogen Resistance.

A gene encoding a protein similar to germin-like proteins (GLPs) was obtained from maize (Zea mays) and designated as ZmGLP1. Based on the ZmGLP1 conserved domain and phylogenetic status, ZmGLP1 was grouped into GLP subfamily b and has high similarity to OsGLP8-14 from Oryza sativa. ZmGLP1 is expressed in different maize tissues during different growth stages and is mainly expressed in the stems and leaves. The induced expression patterns confirmed that ZmGLP1 is differentially expressed under abiotic and hormone stress; it had an early response to jasmonic acid (JA) and ethephon (ET) but a late response to salicylic acid (SA) and was significantly upregulated under Bipolaris maydis infection. The overexpression of ZmGLP1 in Arabidopsis improved the resistance to biotrophic Pseudomonas syringae pv. tomato DC3000 (PstDC3000) and necrotrophic Sclerotinia sclerotiorum by inducing the expression of JA signaling-related genes. Moreover, the hydrogen peroxide (H2O2) content increased due to the overexpression of ZmGLP1 in Arabidopsis after pathogen infection. Compared to the wild-type control, the H2O2 content of ZmGLP1-overexpressing Arabidopsis infected by PstDC3000 increased significantly but was lower in transgenic plants infected with S. sclerotiorum. Furthermore, high-performance liquid chromatography-tandem mass (HPLC-MS/MS) spectrometry showed that the JA contents of ZmGLP1-overexpressing Arabidopsis markedly increased after pathogen infection. However, the improved resistance of ZmGLP1-overexpressing Arabidopsis pretreated with the JA biosynthetic inhibitor, sodium diethyldithiocarbamate trihydrate (DIECA), was suppressed. Based on these findings, we speculate that ZmGLP1 plays an important role in the regulation of Arabidopsis resistance to biotrophic PstDC3000 and necrotrophic S. sclerotiorum; the regulatory effects are achieved by inducing plant oxidative burst activity and activation of the JA signaling pathway.

Potential Influence of Menstrual Status and Sex Hormones on Female Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Cross-sectional Multicenter Study in Wuhan, China.

BACKGROUND: Recent studies have indicated that females with coronavirus disease 2019 (COVID-19) have a lower morbidity, severe case rate, and mortality and better outcome than those of male individuals. However, the reasons remained to be addressed. METHODS: To find the factors that potentially protect females from COVID-19, we recruited all confirmed patients hospitalized at 3 branches of Tongji Hospital (N = 1902), and analyzed the correlation between menstrual status (n = 509, including 68 from Mobile Cabin Hospital), female hormones (n = 78), and cytokines related to immunity and inflammation (n = 263), and the severity/clinical outcomes in female patients <60 years of age. RESULTS: Nonmenopausal female patients had milder severity and better outcome compared with age-matched men (P < .01 for both). Menopausal patients had longer hospitalization times than nonmenopausal patients (hazard ratio [HR], 1.91 [95% confidence interval {CI}, 1.06-3.46]; P = .033). Both anti-Müllerian hormone (AMH) and estradiol (E2) showed a negative correlation with severity of infection (adjusted HR, 0.146 [95% CI, .026-.824], P = .029 and 0.304 [95% CI, .092-1.001], P = .05, respectively). E2 levels were negatively correlated with interleukin (IL) 2R, IL-6, IL-8, and tumor necrosis factor alpha in the luteal phase (P = .033, P = .048, P = .054, and P = .023) and C3 in the follicular phase (P = .030). CONCLUSIONS: Menopause is an independent risk factor for female COVID-19 patients. AMH and E2 are potential protective factors, negatively correlated with COVID-19 severity, among which E2 is attributed to its regulation of cytokines related to immunity and inflammation.

Design, synthesis, biological evaluation and molecular dynamics simulation studies of imidazolidine-2,4-dione derivatives as novel PTP1B inhibitors.

Protein tyrosine phosphatase 1B (PTP1B) is a member of the phosphotyrosine phosphatase family and plays an important role in the signal transduction of diabetes. Inhibition of PTP1B activity can increase insulin sensitivity and reduce blood sugar levels. Therefore, it is urgent to find compounds with novel structures that can inhibit PTP1B. This study designed imidazolidine-2,4-dione derivatives through the computer-aided drug design (CADD) strategy, and the Comp#10 showed outstanding inhibitory ability. (IC50 = 2.07 µM) and selectivity. The inhibitory mechanism at molecular level of Comp#10 on PTP1B was studied by molecular dynamics simulation. The results show that the catalytic region of PTP1B protein is more stable, which makes the catalytic sites unsuitable for exposure. Interestingly, the most obvious changes in the interaction between residues in the P-loop region (such as: His214, Cys215, and Ser216). In short, this study reported for the first time that imidazolidine-2,4-dione derivatives as novel PTP1B inhibitors had good inhibitory activity and selectivity, providing new ideas for the development of small molecule PTP1B inhibitors.

The amino acid variants in HLA II molecules explain the major association with adult-onset Still's disease in the Han Chinese population.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10-14) and Asn in HLA-DRß1 position 37 (p = 5.12 × 10-11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10-14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10-13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10-9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.

Passive anti-sunlight glare traffic signs with non-axisymmetric freeform lens design.

This paper proposes a passive optical brightening element design, a non-axisymmetric freeform lens (NAFL), arranged and assembled on a traditional traffic sign. NAFL is the first optical design which can effectively solve the traffic problem that direct sunlight affects the driver's inability to look directly at the traffic sign. The NAFL can converge the sunlight behind the traffic sign and diverge forward to 150 meters away. In this way, the NAFL array combinations on the traffic sign can directly rely on sunlight as image information pixels. According to the simulation, the optical efficiency of the NAFL can be as high as 81.5%. Besides, the angular tolerance is also analyzed to evaluate the working hours of the NAFL. Finally, we made the prototype and proved that such passive brightening components could effectively improve the traffic sign's visibility in harsh sunlight.

Sphingomyelin synthase 2 facilitates M2-like macrophage polarization and tumor progression in a mouse model of triple-negative breast cancer.

High infiltration of M2-polarized macrophages in the primary tumor indicates unfavorable prognosis and poor overall survival in the patients with triple-negative breast cancer (TNBC). Thus, reversing M2-polarized tumor-associated macrophages in the tumors has been considered as a potential therapeutic strategy for TNBC. Sphingomyelin synthase 2 (SMS2) is the key enzyme for sphingomyelin production, which plays an important role in plasma membrane integrity and function. In this study we investigated whether SMS2 inhibitor or SMS2 gene knockout could reduce macrophages M2 polarization and tumor progression in a mouse model of TNBC. We showed that SMS2 mRNA expression was linked to immunosuppressive tumor microenvironment and poor prognosis in TNBC patients. The knockout of SMS2 or application of 15w (a specific SMS2 inhibitor) markedly decreased the generation of M2-type macrophages in vitro, and reduced the tumor weight and lung metastatic niche formation in a 4T1-TNBC mouse model. We further demonstrated that the in vivo antitumor efficacy of 15w was accompanied by a multifaceted remodeling of tumor immune environment reflecting not only the suppression of M2-type macrophages but also diminished levels of regulatory T cells and myeloid-derived suppressor cells leading to a dramatically improved infiltration of antitumor CD8+ T lymphocytes. Collectively, our results reveal a novel and important role of SMS2 in the protumorigenic function and may offer a new strategy for macrophage-targeted anticancer therapy.

Water quality criteria and ecological risk assessment for ammonia in the Shaying River Basin, China.

Current Chinese surface water environmental quality standard GB3838-2002 for ammonia fails to take water quality factors and native organism distributions in different basins into consideration. In this study, ammonia toxicity tests were performed using three aquatic organisms native to the Shaying River Basin (China). Published ammonia toxicity data with pH and temperature, and toxicity data acquired in this study were used to establish water quality criteria. The final criterion maximum concentration (CMC) and criterion continuous concentration (CCC) for the Shaying River Basin were 5.09 and 1.36 (mg total ammonia nitrogen (TAN))/L (pH 7 and 20 °C), respectively. In addition, based on the corresponding relationship between ammonia toxicity and temperature and pH, the ecological risk assessment of ammonia was conducted in different seasons for the Shaying River using a tiered approach of both hazard quotient (HQ) and the joint probability (JPC) methods. Two methods gave consistent results: the ecological risks of ammonia to aquatic species in the Shaying River Basin were severe and the risk could be ranked as wet season > flat season > dry season. It is therefore indicating that monitoring, evaluation, and early warning of ammonia pollution need to be taken to prevent and control the risks posed by ammonia pollution, especially for wet season (because of high temperatures and pH) or flat season (because of high pH values). We hope the present work could provide valuable information to manage and control ammonia pollution in the Shaying River Basin.

Two rapid and sensitive methods based on TaqMan qPCR and droplet digital PCR assay for quantitative detection of Bacillus subtilis in rhizosphere.

AIMS: Bacillus subtilis, a typical plant growth-promoting rhizobacteria, can benefit plant through promoting growth and reducing disease. The colonization intensity of B. subtilis in rhizosphere is a key factor for improving their effectiveness of field application. In this study, we developed a rapid and sensitive method for detecting B. subtilis in rhizosphere via TaqMan qPCR and droplet digital PCR (ddPCR) methods. METHODS AND RESULTS: The primers/probe set targeting gyrB gene could successfully distinguish B. subtilis from its close-related species. Both the TaqMan qPCR and ddPCR methods exhibited a good linear relationship in the sensitivity assay, suggesting the developed method was specific, effective and reliable. Finally, the two methods were used to detect the colonization dynamic of B. subtilis within Arabidopsis rhizosphere. Both of them showed a consistent trend compared with the traditional cultivation-based and microscopy-based methods. CONCLUSIONS: The TaqMan qPCR and droplet digital PCR (ddPCR) methods we developed could be used to rapidly detect B. subtilis in rhizosphere. SIGNIFICANCE AND IMPACT OF THE STUDY: The TaqMan qPCR and ddPCR methods developed in this study can be applied to rapid quantitative detection of B. subtilis populations, and will be helpful to evaluate their effectiveness of field application.

Efficacy and Toxicity of Adjuvant Therapies for High-Risk Endometrial Cancer in Stage I-III: A Systematic Review and Network Meta-Analysis.

BACKGROUND The use of adjuvant therapy for high-risk endometrial cancer patients (HREC) in International Federation of Gynecology and Obstetrics (FIGO) stage I-III remains debatable. This network meta-analysis was conducted to compare and rank adjuvant therapies based on efficacies and toxicities to facilitate clinical decision-making and further research. MATERIAL AND METHODS We searched 3 databases - PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials - from inception to December 9, 2019. Only randomized controlled trials that compared any of these adjuvant therapies (pelvic radiotherapy, vaginal brachytherapy, chemotherapy, and chemoradiotherapy) with each other or surgery alone were included. The network meta-analysis was performed in a frequentist framework using Stata software 15.0. RESULTS Fourteen RCTs with 5872 participants were eligible. No significant difference between treatments was observed in 5-year overall survival (OS) or distant metastasis. Compared with surgery alone, adjuvant pelvic radiotherapy plus chemotherapy (pelvic RT-CT) prolonged 5-year progression-free survival (PFS) and pelvic radiotherapy (pelvic RT) (RR=0.61, 95% CI 0.39-0.96; RR=0.779, 95% CI 0.63-0.95). Compared with surgery alone, pelvic RT, the combination of pelvic RT and vaginal brachytherapy (pelvic RT-VBT), chemotherapy (CT), and pelvic RT-CT led to fewer local recurrences (RR=0.33, 95% CI 0.21-0.50; RR=0.15, 95% CI 0.03-0.74; RR=0.39, 95% CI 0.21-0.73; RR=0.17, 95% CI 0.06-0.46). Adjuvant CT was found to result in more grade III/IV late toxicities than surgery alone (RR=11.8, 95% CI 1.02-137.14). Pelvic RT-CT ranked first for OS, PFS, distant metastasis, and local recurrence. CONCLUSIONS Pelvic RT-CT is superior to other treatments for PFS and local recurrence rate, and associated related toxicities are tolerable, suggesting it may be an ideal adjuvant therapy for HREC patients.

IDH2 protects against nonalcoholic steatohepatitis by alleviating dyslipidemia regulated by oxidative stress.

Nonalcoholic fatty liver disease (NAFLD) has become an epidemic across the world. A large and growing unmet therapeutic requirement has inspired plenty exploration in the field. Isocitrate dehydrogenase 2 (IDH2), localized in mitochondria, decreases NADP+ to NADPH during the decarboxylation of isocitrate to α-ketoglutarate. Although the NADPH producing system is closely related to oxidative stress and lipid accumulation, the effects of IDH2 on hepatic steatosis and the associated metabolic disorders remain elusive. In our study, we found that IDH2 expression was markedly reduced by palmitate stimulation in primary hepatocytes, accompanied with increased lipid accumulation. In response to high fat diet (HFD) administration, IDH2 knockout (KO) further contributed to the pathological progression of insulin resistance and hepatic steatosis. In addition, HFD treatment-induced mitochondrial oxidative injury and dyslipidemia were markedly elevated in liver of mice with IDH2 knockout. The expression of mitochondrial fission and fusion mediators, including dynamin-related protein 1 (DRP1), mitofusin 1 (MFN1) and fission protein 1 (FIS1), induced by HFD was further exacerbated in liver of IDH2 knockout mice. Furthermore, the over-expression of IDH2 in hepatocytes led to the suppression of ROS production and DRP1 expression, but the alleviation of dyslipidemia. Taken together, these results established IDH2 as a critical suppressor of steatohepatitis, which might be a promising therapeutic target for developing effective treatment to prevent nonalcoholic steatohepatitis progression.