Vitamin D3 exacerbates steatosis while calcipotriol inhibits inflammation in non-alcoholic fatty liver disease in Sod1 knockout mice: a comparative study of two forms of vitamin D.

The role of vitamin D (VD) in non-alcoholic fatty liver disease (NAFLD) remains controversial, possibly due to the differential effects of various forms of VD. In our study, Sod1 gene knockout (SKO) mice were utilized as lean NAFLD models, which were administered 15 000 IU VD3 per kg diet, or intraperitoneally injected with the active VD analog calcipotriol for 12 weeks. We found that VD3 exacerbated hepatic steatosis in SKO mice, with an increase in the levels of Cd36, Fatp2, Dgat2, and CEBPA. However, calcipotriol exerted no significant effect on hepatic steatosis. Calcipotriol inhibited the expression of Il-1a, Il-1b, Il-6, Adgre1, and TNF, with a reduction of NFκB phosphorylation in SKO mice. No effect was observed by either VD3 or calcipotriol on hepatocyte injury and hepatic fibrosis. Co-immunofluorescence stains of CD68, a liver macrophage marker, and VDR showed that calcipotriol reduced CD68 positive cells, and increased the colocalization of VDR with CD68. However, VD3 elevated hepatocyte VDR expression, with no substantial effect on the colocalization of VDR with CD68. Finally, we found that VD3 increased the levels of serum 25(OH)D3 and 24,25(OH)2D3, whereas calcipotriol decreased both. Both VD3 and calcipotriol did not disturb serum calcium and phosphate levels. In summary, our study found that VD3 accentuated hepatic steatosis, while calcipotriol diminished inflammation levels in SKO mice, and the difference might stem from their distinct cellular selectivity in activating VDR. This study provides a reference for the application of VD in the treatment of lean NAFLD.

Outbreak of NDM-5-producing Klebsiella pneumoniae ST307: an emerging high-risk antimicrobial resistance clone in Shanghai, China.

The high-risk clone Klebsiella pneumoniae ST307, associated with various carbapenem resistance genes, exhibits a global distribution and prevalence. However, in China, it has remained sporadic and has rarely been detected. In this study, we reported an outbreak caused by nine ST307 CRKP isolates harboring blaNDM-5 in Shanghai, China, in 2022. We employed antimicrobial susceptibility testing, conjugation assay, whole-genome sequencing (WGS) and comparative genomics, phylogenetic analysis, and fitness and virulence comparison to further characterize the isolates causing the outbreak. Besides blaNDM-5, these nine isolates co-carried blaCTX-M-15 and blaDHA-1, exhibiting nearly identical resistance profiles with high-level resistance to carbapenems and ceftazidime/avibactam, while showing susceptibility to colistin and tigecycline. blaNDM-5 was located on an IncX3 plasmid of 45,403 bp with a high frequency of conjugative ability. Phylogenetic and single-nucleotide polymorphism (SNP) analysis indicated the nature of clonal transmission with a maximum of five SNPs between these nine isolates, and they were closely related to strains obtained from the United States. ST307 isolates in our study showed a relatively lower virulence but higher growth rates and certain adaptability compared with ST11 isolates. Clinical investigation revealed that shared nursing staff in a mixed emergency intensive care unit ward and doctors' movement between wards might be responsible for the outbreak. The nonexistence before and sudden emergence of ST307 suggested that the currently circulating ST307 clone was a newly introduced superbug in our hospital. In conclusion, we revealed that blaNDM-5-producing ST307 CRKP isolates, a globally significant high-risk clone, are spreading in China, posing a substantial threat to public health.IMPORTANCEThe high-risk clone ST307, associated with various carbapenemases, including KPC, NDM, and OXA, has a global distribution. However, it is rarely reported in China, let alone causing outbreaks. Here, we found an outbreak caused by the clonal transmission of nine ST307 CRKP isolates. Clinical investigation revealed that shared nurses in a mixed emergency intensive care unit ward and doctors' movement between wards might be responsible for the outbreak. In our study, the nine NDM-5-producing ST307 isolates exhibited high-level resistance to carbapenems and ceftazidime-avibactam, high conjugative ability to Escherichia coli J53, and certain adaptability to environment, phylogenetically closet to the United States. All these features make ST307 clone the next successful clone comparable to ST11 clone in China. Therefore, it is imperative for us to vigilantly monitor the prevalence of carbapenem-resistant Klebsiella pneumoniae and promptly implement measures to control the spread of K. pneumoniae ST307 in China.

Diagnostic CT of colorectal cancer with artificial intelligence iterative reconstruction: A clinical evaluation.

OBJECTIVES: To investigate the clinical value of a novel deep-learning based CT reconstruction algorithm, artificial intelligence iterative reconstruction (AIIR), in diagnostic imaging of colorectal cancer (CRC). METHODS: This study retrospectively enrolled 217 patients with pathologically confirmed CRC. CT images were reconstructed with the AIIR algorithm and compared with those originally obtained with hybrid iterative reconstruction (HIR). Objective image quality was evaluated in terms of the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality was graded on the conspicuity of tumor margin and enhancement pattern as well as the certainty in diagnosing organ invasion and regional lymphadenopathy. In patients with surgical pathology (n = 116), the performance of diagnosing visceral peritoneum invasion was characterized using receiver operating characteristic (ROC) analysis. Changes of diagnostic thinking in diagnosing hepatic metastases were assessed through lesion classification confidence. RESULTS: The SNRs and CNRs on AIIR images were significantly higher than those on HIR images (all p < 0.001). The AIIR was scored higher for all subjective metrics (all p < 0.001) except for the certainty of diagnosing regional lymphadenopathy (p = 0.467). In diagnosing visceral peritoneum invasion, higher area under curve (AUC) of the ROC was found for AIIR than HIR (0.87 vs 0.77, p = 0.001). In assessing hepatic metastases, AIIR was found capable of correcting the misdiagnosis and improving the diagnostic confidence provided by HIR (p = 0.01). CONCLUSIONS: Compared to HIR, AIIR offers better image quality, improves the diagnostic performance regarding CRC, and thus has the potential for application in routine abdominal CT.

Spatiotemporal variations and impact factors of nutrients in the Sanya Bay, northern South China Sea.

Nutrients play a fundamental role in maintaining coastal ecosystem stability. Based on two cruise observations in the winter of 2020 and the summer of 2021, the spatiotemporal variations of dissolved inorganic nitrogen (DIN) and orthophosphate (PO43-) and their influencing factors in Sanya Bay were analyzed. Results show that the mean DIN concentrations in the bay are 2.36 µmol/L in winter and 1.73 µmol/L in summer, and the mean PO43- concentrations are 0.08 µmol/L in winter and 0.04 µmol/L in summer. The nutrient concentrations and composition are significantly affected by the Sanya River. The surface DIN concentrations at the Sanya River estuary are 15.80 and 5.25 times than those inside the bay in winter and summer, respectively. Meanwhile, a high proportion of NO3- (74%) and a low proportion of NH4+ (20%) in DIN appear near the river estuary, while a low proportion of NO3- (37%) and a high proportion of NH4+ (53%) occur away from the estuary. In addition, the thermocline promotes the accumulation of NH4+ at the bottom layer in summer. The high proportion of NO3- is likely not favorable for the survival of coral reefs in eastern bay. Compared with the previous nutrient concentrations, the DIN concentration in the bay has a decrease after 2014, which might benefit from the implementation of the environmental protection policy by government.

Prognostic value of the ratio of pretreatment carcinoembryonic antigen to tumor volume in rectal cancer.

Background: As a commonly used biomarker in rectal cancer (RC), the prognostic value of carcinoembryonic antigen (CEA) remains underexplored. This study aims to evaluate the prognostic value of pretreatment CEA/tumor volume in RC. Methods: This retrospective study included patients who underwent pretreatment magnetic resonance imaging (MRI) with histologically confirmed primary rectal adenocarcinoma from November 2012 to April 2018. Patients were divided into high-risk and low-risk groups according to the median values of CEA/Diapath (CEA to pathological diameter), CEA/DiaMRI (CEA to MRI tumor diameter), and CEA/VolMRI (CEA to MRI tumor volume). Cox regression analysis was utilized to determine the prognostic value of CEA, CEA/Diapath, CEA/DiaMRI, and CEA/VolMRI. Stepwise regression was used to establish nomograms for predicting disease-free survival (DFS) and overall survival (OS). Predictive performance was estimated by using the concordance index (C-index) and area under curve receiver operating characteristic (AUC). Results: A total of 343 patients [median age 58.99 years, 206 (60.06%) males] were included. After adjusting for patient-related and tumor-related factors, CEA/VolMRI was superior to CEA, CEA/Diapath, and CEA/DiaMRI in distinguishing high-risk from low-risk patients in terms of DFS [hazard ratio (HR) =1.83; P=0.010] and OS (HR =1.67; P=0.048). Subanalysis revealed that CEA/VolMRI stratified high death risk in CEA-negative individuals (HR =2.50; P=0.038), and also stratified low recurrence risk in CEA-positive individuals (HR =2.06; P=0.024). In the subanalysis of stage II or III cases, the highest HRs and the smallest P values were observed in distinguishing high-risk from low-risk patients according to CEA/VolMRI in terms of DFS (HR =2.44; P=0.046 or HR =2.41; P=0.001) and OS (HR =1.96; P=0.130 or HR =2.22; P=0.008). The nomograms incorporating CEA/VolMRI showed good performance, with a C-index of 0.72 [95% confidence interval (CI): 0.68-0.79] for DFS and 0.73 (95% CI: 0.68-0.80) for OS. Conclusions: Higher CEA/VolMRI was associated with worse DFS and OS. CEA/VolMRI was superior to CEA, CEA/Diapath, and CEA/DiaMRI in predicting DFS and OS. Pretreatment CEA/VolMRI may facilitate risk stratification and treatment decision-making.

Emergence of a Hypermucoviscous Klebsiella pneumoniae Strain Coproducing K. pneumoniae Carbapenemase-2 and New Delhi Metallo-ß-Lactamase-5 Carbapenemases in Shanghai, China.

Background: Recently, the emergence of carbapenem-resistant hypermucoviscous Klebsiella pneumoniae has aroused increasing attention in China. We investigated the characteristics of a Klebsiella pneumoniae carbapenemase-2 (KPC-2) and New Delhi metallo-ß-lactamase-5 (NDM-5) coproducing hypermucoviscous K. pneumoniae strain, named RJ-8061, which was isolated from the urine of an 86-year-old female patient with pneumonia. Methods: The RJ-8061 strain was investigated by string test, antimicrobial susceptibility testing, polymerase chain reaction for carbapenemase genes detection, capsular genotyping, multilocus sequence typing, whole-genome sequencing, and phylogenetics. A serum killing assay and a Galleria mellonella infection model were used to evaluate the virulence of RJ-8061 in vitro and in vivo. Results: RJ-8061 belonged to the sequence type 11 K64 serotype and showed high-level resistance to almost all frequently used antibiotics, only remaining susceptible to amikacin, colistin, and tigecycline. The complete genome size of RJ-8061 was 6,106,028 bp, including a 5,394,921 bp chromosome and seven circular plasmids. Plasmid pRJ-8061-hybrid is a 294,249 bp hybrid plasmid that co-harbored resistance genes [blaTEM-1B, mph(A), aac(3)-IId] and virulence genes (iucABCDiutA, rmpA2), whereas rmpA2 is a truncated version. In addition, blaKPC-2 and blaNDM-5 were located on plasmids 171,321 bp pRJ-8061-KPC-2 (IncFII/IncR) and 46,161 bp pRJ-8061-NDM-5 (IncX3), respectively. K-mer-based phylogenetic analysis grouped RJ-8061 into a carbapenem-resistant Klebsiella pneumoniae cluster. The G. mellonella infection model revealed that RJ-8061 showed relatively low virulence, with a 50% lethal dose of 106 cfu. Conclusions: To the best of our knowledge, this is the first report of a hypermucoviscous K. pneumoniae coproducing KPC-2 and NDM-5 carbapenemases.

Molecular Epidemiology of Antimicrobial Resistance, Virulence and Capsular Serotypes of Carbapenemase-Carrying Klebsiella pneumoniae in China.

This study analyzed genomic data of 4643 strains of carbapenemase-carrying Klebsiella pneumoniae (KPN) in China by using the Kleborate software package. The data showed rich diversity in carbapenemase-carrying KPN genomes, which contain not only 152 sequence types but also 90 capsular serotypes. In 2013, the transfer of carbapenemase to hypervirulent Klebsiella pneumoniae (HvKP) of KL1 and KL2 occurred, and since 2014, the propagation of carbapenemase into mammals, poultry, and insects has been detected. The ST11 capsular serotype had a reversal of the prevalence of KL47 and KL64 in 2016, with KL64 replacing KL47 as the dominant serotype. Colibactin is a very suitable indicator to differentiate KL1-type HvKP and classic Klebsiella pneumoniae. The most prevalent yersiniabactin of KL1 is ybt1 ICEKp10, and that of ST11 carbapenem-resistant KPN(ST11-CRKP) is ybt9 ICEKp3. The virulence genes of KL1 carbapenem-resistant hypervirulent KPN (KL1-CRHvKP), as well as ST65- and ST86-type KL2-CRHvKP, were not lost after carbapenemase was obtained.

An Outbreak of ST859-K19 Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae in a Chinese Teaching Hospital.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has been increasingly reported worldwide. Here, we report an outbreak caused by sequence type 859-K19 (ST859-K19) CR-hvKP isolates in a teaching hospital in China. Interestingly, K. pneumoniae ST859 was a single-locus variant of ST11 but has never been reported before. A total of 11 nonrepetitive ST859 CR-hvKP isolates were collected from 11 patients, 3 of which died of severe CR-hvKP infection. Antimicrobial susceptibility assay results showed that all the 11 CR-hvKP isolates exhibited high-level resistance to commonly used antibiotics, only remaining susceptible to colistin, tigecycline, and ceftazidime/avibactam. Whole-genome sequencing (WGS) was performed using the Illumina platform for the 11 CR-hvKP isolates, and RJ9299 was further sequenced using the PacBio platform. A phylogram tree using WGS data revealed that all the 11 CR-hvKP isolates were clustered in 1 clade, which probably indicated clone transmission. Determinants of resistance and virulence gene analysis using WGS data confirmed the 11 isolates had almost identical resistance gene profiles (blaKPC-2, blaTEM-1B, blaSHV-187, rmtB, fosA6) and virulence gene (rmpA, rmpA2, iucABCDiutA) profiles, which hint at clone spread again. The complete genome size of RJ9299 was 5,875 kb, including a 5,445-kb chromosome, a 215-kb virulence plasmid (pVir-CR-hvKP-RJ9299), a 109-kb blaKPC-2-harboring plasmid (pKPC-2-RJ9299), and three circular plasmids. Comparative genomics showed pVir-RJ9299 (IncHI1B type) and pKPC-2-RJ9299 (IncFII-IncR) possessed over 99% similarity to pLVPK and pKPC-CR-hvKP-C789, respectively. Serum resistance assays and a Galleria mellonella infection model showed the 11 isolates exhibited different levels of virulence. This is the first report of an outbreak caused by ST859 CR-hvKP isolates. IMPORTANCE The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) in China has posed a great threat to public health, especially in the highly transmissible ST11 clone. With the transmission of virulence and resistance determinants, CR-hvKP isolates have been reported in an increasing number of sequence types (STs), including ST23, ST65, ST1797, ST43, ST231, ST147, ST15, ST383, ST268, ST595, ST375, ST48, and ST307. Here, we report an outbreak caused by ST859-K19 CR-hvKP isolates in a teaching hospital in China. ST859 is a single-locus variant of ST11. There is no literature on ST859 K. pneumoniae in public databases, let alone ST859 CR-hvKP isolates. To our knowledge, this is the first report to depict the molecular and genomic characteristics of ST859 CR-hvKP isolates. Active surveillance approaches should be implemented to promptly find the spread of CR-hvKP isolates in health care settings.

Ultrahigh recovery rate of nitrate from synthetic wastewater by Chlorella-based photo-fermentation with optimal light-emitting diode illumination: From laboratory to pilot plant.

To achieve ultrahigh recovery rate of nitrate from synthetic wastewater by Chlorella pyrenoidosa-based photo-fermentation, light-emitting diode (LED) spectrum was firstly evaluated in 5-L glass photo-fermenter with surrounding LED panels. Results showed that warm white LED was favorable to improve biomass yield and recovery rate of nutrients than mixed white LED. When scaling up from laboratory (50-L, 500-L) to pilot scale photo-fermenter with inner LED panels, the maximum recovery rates of NO3- (5.77 g L-1 d-1) and PO43- (0.44 g L-1 d-1) were achieved in 10,000-L photo-fermenter, along with high productivity of biomass (11.06 g L-1 d-1), protein (3.95 g L-1 d-1) and lipids (3.79 g L-1 d-1), respectively. This study demonstrated that photo-fermenter with inner warm white LED illumination is a superhigh-efficient system for nitrate and phosphate recovery with algal biomass coproduction, providing a promising application in pilot demonstration of wastewater bioremediation and facilitating novel facility development for green manufacturing.

The Effects of Interval Training and Continuous Training on Cardiopulmonary Fitness and Exercise Tolerance of Patients with Heart Failure-A Systematic Review and Meta-Analysis.

PURPOSE: To investigate the effects of interval training (IT) as compared with continuous training (CT) on cardiorespiratory fitness and exercise tolerance of patients with heart failure (HF), with the aim to provide reasonable exercise prescriptions for patients with HF. METHODS: Through searching electronic databases, randomized controlled studies were collected. The included studies were evaluated for methodological quality using the Cochrane risk of bias assessment tool, and statistical analyses were carried out using Review Manager 5.3 and Stata MP 15.1 software. RESULTS: A total of seventeen randomized controlled trials (i.e., studies) with 617 patients were included. The meta-analysis showed that IT can improve a patient's peak oxygen uptake (VO2peak) (MD = 2.08, 95% CI 1.16 to 2.99, p < 0.00001), left ventricular ejection fraction (LVEF) (MD =1.32, 95% CI 0.60 to 2.03, p = 0.0003), and 6-minute walk distance (6MWD) (MD = 25.67, 95% CI 12.87 to 38.47, p < 0.0001) as compared with CT. However, for respiratory exchange ratio (RER) (MD = 0.00, 95% CI -0.02 to 0.03, p = 0.81), CO2 ventilation equivalent slope (VE/VCO2 slope) (SMD = 0.04, 95% CI -0.23 to 0.31, p = 0.75), and resting heart rate (HRrest) (MD = 0.15, 95% CI -3.00 to 3.29, p = 0.93) there were no statistical significance. CONCLUSIONS: The evidence shows that IT is better than CT for improving the cardiorespiratory fitness and exercise tolerance of patients with HF. Moreover, an intensity of 60-80% peak heart rate of IT is the optimal choice for patients. It is hoped that, in the future, more well-designed studies would further expand the meta-analysis results.

Combined Effects of Allelopathic Polyphenols on Microcystis aeruginosa and Response of Different Chlorophyll Fluorescence Parameters.

Polyphenols are allelochemicals secreted by aquatic plants that effectively control cyanobacteria blooms. In this study, sensitive response parameters (including CFPs) of Microcystis aeruginosa were explored under the stress of different polyphenols individually and their combination. The combined effects on M. aeruginosa were investigated based on the most sensitive parameter and cell densities. For pyrogallic acid (PA) and gallic acid (GA), the sensitivity order of parameters based on the EC50 values (from 0.73 to 3.40 mg L-1 for PA and from 1.05 to 2.68 mg L-1 for GA) and the results of the hierarchical cluster analysis showed that non-photochemical quenching parameters [NPQ, q N, q N(rel) and q CN] > photochemical quenching parameters [YII, q P, q P(rel) and q L] or others [F v/F m, F' v /F' m, q TQ and UQF(rel)] > cell densities. CFPs were not sensitive to ellagic acid (EA) and (+)-catechin (CA). The sensitivity order of parameters for M. aeruginosa with PA-GA mixture was similar to that under PA and GA stress. The quantitative (Toxicity Index, TI) and qualitative (Isobologram representation) methods were employed to evaluate the combined effects of PA, GA, and CA on M. aeruginosa based on cell densities and NPQ. TI values based on the EC50 cells suggested the additive effects of binary and multiple polyphenols, but synergistic and additive effects according to the EC50 NPQ (varied from 0.16 to 1.94). In terms of NPQ of M. aeruginosa, the binary polyphenols exhibited synergistic effects when the proportion of high toxic polyphenols PA or GA was lower than 40%, and the three polyphenols showed a synergistic effect only at the ratio of 1:1:1. Similar results were also found by isobologram representation. The results showed that increasing the ratio of high toxic polyphenols would not enhance the allelopathic effects, and the property, proportion and concentrations of polyphenols played an important role in the combined effects. Compared with cell densities, NPQ was a more suitable parameter as evaluating indicators in the combined effects of polyphenols on M. aeruginosa. These results could provide a method to screen the allelochemicals of polyphenols inhibiting cyanobacteria and improve the inhibitory effects by different polyphenols combined modes.

Increased Plasmid Copy Number Contributes to the Elevated Carbapenem Resistance in OXA-232-Producing Klebsiella pneumoniae.

A total of 345 unique (one isolate per patient) clinical carbapenem-resistant Klebsiella pneumoniae isolates were recovered in our hospital over the past 3 years (2016-2018), with 325, 14, and 6 isolates carried blaKPC-2, blaNDM-1, and blaOXA-232, respectively. The six OXA-232-Kp isolates were recovered in neurosurgery intensive care unit in 2018. All OXA-232-Kp belonged to ST15, differed by one or two pulsed-field gel electrophoresis (PFGE) bands, and belonged to the same clone. However, three isolates (RJ18-04-6) displayed elevated carbapenem resistance, with imipenem minimum inhibitory concentration (MIC) of 16-32 µg/mL. In contrast, other three isolates (RJ18-01-3) had imipenem MIC of 0.5-1 µg/mL. S1-PFGE revealed two different plasmid profiles and all strains had at least four plasmids. Strain RJ18-01 and RJ18-06 were selected for whole-genome sequencing, and a ColE2-type 6,141 bp blaOXA-232-carrying plasmid was identified. No blaOXA-232 gene was located on chromosome or other plasmids. Furthermore, no ß-lactamase resistance gene other than blaCTX-M-15 was identified. Polymerase chain reaction-based sequencing of blaOXA-232-carrying plasmid was performed, and all OXA-232-Kp shared identical blaOXA-232-carrying plasmid sequences. The expression and copy number of blaOXA-232 in RJ18-04-6 were significantly higher than those of other isolates. The hydrolysis activity of nitrocefin and carbapenems were about six-fold higher in RJ18-04-6. Since only one copy of blaOXA-232 gene was spotted on the plasmid, the elevated carbapenem resistance could be attributed to the increased copy number of blaOXA-232-carrying plasmids. OmpK35 porin deficiency was observed in one isolate with decreased carbapenem susceptibility and two isolates with elevated carbapenem resistance, suggesting that OmpK35 deficiency did not significantly alter carbapenem MICs in OXA-232-Kp.

Biological removal of nitrogen oxides by microalgae, a promising strategy from nitrogen oxides to protein production.

Nitrogen oxides (NOx) are the components of fossil flue gases that give rise to serious environmental and health hazards. Among the available techniques for NOx removal, microalgae-based biological removal of NOx (BioDeNOx) is a promising and competent technology with eco-friendly path of low energy and low-cost solution for the pollution. In this review article, current biological technologies including bacteria-based and microalgae-related BioDeNOx are discussed. Comparing to direct BioDeNOx approach, indirect BioDeNOx by microalgae is more promising since it is more stable, reliable and efficient. By transforming inorganic nitrogen nutrients to organic nitrogen, microalgae can potentially play an important role in converting NOx into high-value added products. The microalgae-based BioDeNOx process displays an attractive prospect for flue gas treatment to reduce environmental NOx pollution and potentially supply protein products, establishing an efficient circular-economy strategy.

Dilution characteristics of riverine input contaminants in the Seto Inland Sea.

Riverine input is an important source of contaminants in the marine environments. Based on a hydrodynamic model, the dilution characteristics of riverine contaminants in the Seto Inland Sea and their controlling factors were studied. Results showed that contaminant concentration was high in summer and low in winter. Contaminant concentration decreased with the reduction of its half-life period, and the relationship between them followed power functions. Sensitivity experiments suggested that the horizontal current and vertical stratification associated with air-sea heat flux controlled the seasonal cycle of contaminant concentration in the water column; however, surface wind velocity was the dominant factor affecting the surface contaminant concentration. In addition, contaminant concentration in a sub-region was likely controlled by the variations in river discharges close to the sub-region. These results are helpful for predicting contaminant concentrations in the sea and are expected to contribute to assessing the potential ecological risks to aquatic organisms.

E2-Induced Activation of the NLRP3 Inflammasome Triggers Pyroptosis and Inhibits Autophagy in HCC Cells.

Emerging evidence suggests that 17ß-estradiol (E2) and estrogen receptor (ER) signaling are protective against hepatocellular carcinoma (HCC). In our previous study, we showed that E2 suppressed the carcinogenesis and progression of HCC by targeting NLRP3 inflammasome activation, whereas the molecular mechanism by which the NLRP3 inflammasome initiated cancer cell death was not elucidated. The present study aimed to investigate the effect of NLRP3 inflammasome activation on cell death pathways and autophagy of HCC cells. First, we observed an increasing mortality in E2-treated HCC cells, and then apoptotic and pyroptotic cell death were both detected. The mortality of HCC cells was largely reversed by the caspase 1 antagonist, YVAD-cmk, suggesting that E2-induced cell death was associated with caspase 1-dependent pyroptosis. Second, the key role of the NLRP3 inflammasome in autophagy of HCC cells was assessed by E2-induced activation of the NLRP3 inflammasome, and we demonstrated that autophagy was inhibited by the NLRP3 inflammasome via the E2/ERß/AMPK/mTOR pathway. Last, the interaction of pyroptosis and autophagy was confirmed by flow cytometry methods. We observed that E2-induced pyroptosis was dramatically increased by 3-methyladenine (3-MA) treatment, which was abolished by YVAD-cmk treatment, suggesting that caspase 1-dependent pyroptosis was negatively regulated by autophagy. In conclusion, E2-induced activation of the NLRP3 inflammasome may serve as a suppressor in HCC progression, as it triggers pyroptotic cell death and inhibits protective autophagy.

Combination of EZH2 inhibitor and BET inhibitor for treatment of diffuse intrinsic pontine glioma.

BACKGROUND: Diffuse intrinsic pontine glioma is an infiltrative, often high-grade glioma of the brainstem that is not amenable to surgical resection. The current treatment of DIPG by radiation therapy showed dramatically improvement of patient's condition, however, the tumor recurs rapidly. More and more studies are focused on the genetic and epigenetic drivers of DIPGs, which may provide more and more novel therapy target for DIPG. EZH2 has been proved to be a potential therapeutic target for H3K27M-mutant pediatric gliomas recently. Meanwhile, BET family protein is a hot target in many different types of cancers, including DIPG. In this study, we performed the treatment of both EZH2 and BET inhibitor for DIPG cells. RESULTS: The combination of these two inhibitors exhibited better inhibition of the tumor growth both in vitro and in vivo compared to use the inhibitor individually. This inhibition was performed by blocking the proliferation and promoting the cell apoptosis. Meanwhile, combination treatment of these two inhibitors would also affect the epigenetic markers which were abnormal in the tumors of the certain set of genes. CONCLUSION: Thus we provided a novel therapy strategy for clinical treatment of DIPG.

Surfactants assist in lipid extraction from wet Nannochloropsis sp.

An efficient approach involving surfactant treatment, or the modification and utilization of surfactants that naturally occur in algae (algal-based surfactants), was developed to assist in the extraction of lipids from wet algae. Surfactants were found to be able to completely replace polar organic solvents in the extraction process. The highest yield of algal lipids extracted by hexane and algal-based surfactants was 78.8%, followed by 78.2% for hexane and oligomeric surfactant extraction, whereas the lipid yield extracted by hexane and ethanol was only 60.5%. In addition, the saponifiable lipids extracted by exploiting algal-based surfactants and hexane, or adding oligomeric surfactant and hexane, accounted for 78.6% and 75.4% of total algal lipids, respectively, which was more than 10% higher than the lipids extracted by hexane and ethanol. This work presents a method to extract lipids from algae using only nonpolar organic solvents, while obtaining high lipid yields and high selectivity to saponifiables.

Aqueous enzymatic process for cell wall degradation and lipid extraction from Nannochloropsis sp.

An effective cell disruption method, including alkaline pretreatment and subsequent enzymatic treatment, was established to break cell walls and extract lipid from Nannochloropsis sp. A synergistic effect was found between alkaline pretreatment and enzymatic treatment. The combination of commercialize enzymes (cellulase, protease, lysozyme, and pectinase) achieved higher lipid yield compared with a single enzyme application. With the compromise between economic feasibility and lipid yield, the optimum reaction conditions were obtained with alkaline pretreatment at pH 10.5 at 110°C for 4h, and subsequent enzymatic treatment at pH 4 at 50°C for 30min with the dosage of each enzyme at 200IU/g. As high as 90.0% of lipid was extracted under optimal conditions from Nannochloropsis sp.

The Acceptor Side of Photosystem II Is the Initial Target of Nitrite Stress in Synechocystis sp. Strain PCC 6803.

Nitrite, a common form of inorganic nitrogen (N), can be used as a nitrogen source through N assimilation. However, high levels of nitrite depress photosynthesis in various organisms. In this study, we investigated which components of the photosynthetic electron transfer chain are targeted by nitrite stress in Synechocystis sp. strain PCC 6803 cells. Measurements of whole-chain and photosystem II (PSII)-mediated electron transport activities revealed that high levels of nitrite primarily impair electron flow in PSII. Changes in PSII activity in response to nitrite stress occurred in two distinct phases. During the first phase, which occurred in the first 3 h of nitrite treatment, electron transfer from the primary quinone acceptor (QA) to the secondary quinone acceptor (QB) was retarded, as indicated by chlorophyll (Chl) a fluorescence induction, S-state distribution, and QA- reoxidation tests. In the second phase, which occurred after 6 h of nitrite exposure, the reaction center was inactivated and the donor side of photosystem II was inhibited, as revealed by changes in Chl fluorescence parameters and thermoluminescence and by immunoblot analysis. Our data suggest that nitrite stress is highly damaging to PSII and disrupts PSII activity by a stepwise mechanism in which the acceptor side is the initial target. IMPORTANCE In our previous studies, an alga-based technology was proposed to fix the large amounts of nitrite that are released from NOX-rich flue gases and proved to be a promising industrial strategy for flue gas NOX bioremediation (W. Chen et al., Environ Sci Technol 50:1620-1627, 2016, https://doi.org/10.1021/acs.est.5b04696; X. Zhang et al., Environ Sci Technol 48:10497-10504, 2014, https://doi.org/10.1021/es5013824). However, the toxic effects of high concentrations of nitrite on algal cells remain obscure. The analysis of growth rates, photochemistry, and protein profiles in our study provides important evidence that the inhibition by nitrite occurs in two phases: in the first phase, electron transfer between QA- and QB is retarded, whereas in the second, the donor side of PSII is affected. This is an excellent example of investigating the "early" inhibitory effects (i.e., within the first 6 h) on the PSII electron transfer chain in vivo This paper provides novel insights into the mechanisms of nitrite inhibition of photosynthesis in an oxygenic phototrophic cyanobacterium.