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This study investigated the degradation characteristics of propylbenzenes (PBZs, including isopropylbenzene and n-propylbenzene), with high leakage risks and ecological hazards, by a newly isolated marine microalga named Rhinomonas reticulata S6A which is a promising candidate for eco-friendly bioremediation from marine. About 72% and 56% of n-PBZ and i-PBZ can be degraded after 7 days in culture. The acute toxicity of n-PBZ (96h - EC50 = 2.38 mg/L) was higher than that of i-PBZ (96h - EC50 = 3.65 mg/L). The growth inhibition kinetics of this strain were consistent with the Edwards model (R2 = 0.998) and Aiba model (R2 = 0.999). The optimal concentrations for the degradation of n-PBZ and i-PBZ were calculated to be 2.42 mg/L and 2.78 mg/L, respectively. The degradation trends of PBZs conformed to the zero-order kinetic model, and k increased with initial concentrations. The moderate increase in inoculation density could accelerate the degradation of PBZs, with the maximum specific growth rates (r) of 1.116/d (n-PBZ) and 1.230/d (i-PBZ) at the initial inoculation density of 104 cells/mL, while over-inoculation (initial microalgae density more than 105 cells/mL) was not conducive to the degradation of the pollutants. There is not much data on the biodegradation of PBZs in the aquatic environment, so it would be worthwhile to try to apply the new microalgae to explore the fate of PBZs.

ObjectiveA comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure.DesignWe performed single-cell RNA sequencing of 2 43 000 cells from 46 paired liver and blood samples of 23 individuals, including six immune tolerant, 5 immune active (IA), 3 acute recovery (AR), 3 chronic resolved and 6 HBV-free healthy controls (HCs). Flow cytometry and histological assays were applied in a second HBV cohort for validation.ResultsBoth IA and AR were characterised by high levels of intrahepatic exhausted CD8+ T (Tex) cells. In IA, Tex cells were mainly derived from liver-resident GZMK+ effector memory T cells and self-expansion. By contrast, peripheral CX3CR1+ effector T cells and GZMK+ effector memory T cells were the main source of Tex cells in AR. In IA but not AR, significant cell–cell interactions were observed between Tex cells and regulatory CD4+ T cells, as well as between Tex and FCGR3A+ macrophages. Such interactions were potentially mediated through human leukocyte antigen class I molecules together with their receptors CANX and LILRBs, respectively, contributing to the dysfunction of antiviral immune responses. By contrast, CX3CR1+GNLY+ central memory CD8+ T cells were concurrently expanded in both liver and blood of AR, providing a potential surrogate marker for viral resolution. In clinic, intrahepatic Tex cells were positively correlated with serum alanine aminotransferase levels and histological grading scores.ConclusionOur study dissects the coordinated immune responses for different HBV infection phases and provides a rich resource for fully understanding immunopathogenesis and developing effective therapeutic strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient's immunological status and found dramatic changes in the IGH within the patient's immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion, and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones 2-3 weeks after the onset of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34, and IGHV4-39 in COVID-19 patients were more abundant than those of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

Background & aims Immunotherapy with hepatitis B virus (HBV)-specific TCR redirected T (HBV-TCR-T) cells in HBV-related hepatocellular carcinoma (HBV-HCC) patients after liver transplantation was reported to be safe and had potential therapeutic efficacy. We aim to investigate the safety of HBV-TCR-T-cell immunotherapy in advanced HBV-HCC patients who had not met the criteria for liver transplantation. Methods We enrolled eight patients with advanced HBV-HCC and adoptively transferred short-lived autologous T cells expressing HBV-specific TCR to perform an open-label, phase 1 dose-escalation study (NCT03899415). The primary endpoint was to evaluate the safety of HBV-TCR-T-cell therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03) during the dose-escalation process. The secondary endpoint was to assess the efficacy of HBV-TCR-T-cell therapy by evaluating the anti-tumor responses using RECIST criteria (version 1.1) and the overall survival. Results Adverse events were observed in two participants among the 8 patients enrolled. Only one patient experienced a Grade 3 liver-related adverse event after receiving a dose of 1 × 105 HBV-TCR-T cells/kg, then normalized without interventions with immunosuppressive agents. Among the patients, one achieved a partial response lasting for 27.7 months. Importantly, most of the patients exhibited a reduction or stabilization of circulating HBsAg and HBV DNA levels after HBV-TCR-T-cell infusion, indicating the on-target effects. Conclusions The adoptive transfer of HBV-TCR-T cells into advanced HBV-HCC patients were generally safe and well-tolerated. Observations of clinical efficacy support the continued development and eventual application of this treatment strategy in patients with advanced HBV-related HCC. Clinical trials registration This study was registered at ClinicalTrials.gov (NCT03899415).

Microcosmic experiments were performed under a simulated marine environment to investigate the natural attenuation of C9 aromatics using nine components (propylbenzene, isopropylbenzene, 2-ethyltoluene, 3-ethyltoluene, 4-ethyltoluene, 1,2,3-trimethylbenzene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene, and indene). This research aims to assess the contribution of biodegradation and abiotic activity to total attenuation of C9 aromatics and ascertain the changes in the comprehensive toxicity of seawater in the natural environment. The process of natural attenuation indicates the agreement with pseudo-first-order kinetics for all nine components in microcosmic experiments. The half-lives of the nine main compounds in C9 aromatics ranged between 0.34 day and 0.44 day under optimal conditions. The experiments showed that the natural attenuation of nine aromatic hydrocarbons mainly occurred via abiotic processes. Seawater samples significantly inhibited the luminescence of P. phosphoreum (the luminescence inhibition ratio reached 100%) at the beginning of the experiment. In addition, the toxicity declined slowly and continued for 25 days. The attenuation kinetics and changes in toxicity could be applied to explore the natural attenuation of C9 aromatics in the marine environment.

The increases in chemical shipping volumes increase the risk of hazardous noxious substances (HNSs) spills at sea. As one of the most frequently transported HNSs, acrylonitrile (ACN) spill incidents occur from time to time. The spilled ACN will have a wide range of short-term and long-term impacts on the marine environment. To reasonably standardise and optimise the emergency response countermeasures for ACN spill and maintain marine ecological health, the marine ecological hazards and physico-chemical behaviours of ACN were summarised. Based on this, the emergency response countermeasures for ACN spill at sea were studied and summarised in five aspects: spill source control, rapid prediction, emergency monitoring, numerical simulation and impact assessment, and elimination of ACN. This review forms a set of systematic emergency response countermeasures for deployment in ACN maritime spill incidents.

Exosomes represent a subtype of extracellular vesicle that is released through retrograde transport and fusion of multivesicular bodies with the plasma membrane1. Although no perfect methodologies currently exist for the high-throughput, unbiased isolation of pure plasma exosomes2,3, investigation of exosome-enriched plasma fractions of extracellular vesicles can confer a glimpse into the endocytic pathway on a systems level. Here we conduct high-coverage lipidomics with an emphasis on sterols and oxysterols, and proteomic analyses of exosome-enriched extracellular vesicles (EVs hereafter) from patients at different temporal stages of COVID-19, including the presymptomatic, hyperinflammatory, resolution and convalescent phases. Our study highlights dysregulated raft lipid metabolism that underlies changes in EV lipid membrane anisotropy that alter the exosomal localization of presenilin-1 (PS-1) in the hyperinflammatory phase. We also show in vitro that EVs from different temporal phases trigger distinct metabolic and transcriptional responses in recipient cells, including in alveolar epithelial cells, which denote the primary site of infection, and liver hepatocytes, which represent a distal secondary site. In comparison to the hyperinflammatory phase, EVs from the resolution phase induce opposing effects on eukaryotic translation and Notch signalling. Our results provide insights into cellular lipid metabolism and inter-tissue crosstalk at different stages of COVID-19 and are a resource to increase our understanding of metabolic dysregulation in COVID-19.

In order to investigate the effect of cooling time on the properties of crystal formed directly on cooling the melt, we have prepared the KCl1−xBrx crystals [with x = 0.0 (pure KCl), 0.2, 0.4, 0.5, 0.6, 0.8 and 1.0 (pure KBr)] by cooling their melts directly with different cooling times (0, 2, 4, 6, 8, 10, 12 and 14 h) in each case. The prepared crystals have been characterized structurally, optically, mechanically, thermally and electrically by carrying out X-ray diffraction (XRD), atomic force microscopic (AFM), optical absorption, micro-hardness, specific heat capacity and electrical conductivity measurements. XRD analysis indicates halite structure for all the crystals formed. AFM results show an increase of grain size with the cooling time. Optical absorption spectra obtained have illustrated the presence of peak at 229 nm for the KCl crystal and 342.2 nm for the mixed crystals, the peak gradually shifts to shorter wavelengths with the increase of cooling time. Hardness analysis shows nonlinear variation with the cooling time, KCl0.5Br0.5 crystal having the maximum value when the cooling time is 4 h. Temperature and composition have influences on the thermal conductivity, specific heat capacity and thermal diffusivity, while the cooling time has a little influence on the thermal performance. Electrical conductivity measurement indicates a little influence of cooling time and strong influences of temperature and composition on the electrical conductivity and activation energy.

The traditional research method of fault diagnosis mechanism has poor stability, which leads to the difference of fault diagnosis and location results. Therefore, under the complex geological environment, a new research method of fault diagnosis mechanism of gear and bearing for coal mining equipment is proposed. This method calculates gears and bearings’ yield strength by analyzing coal mining equipment’s bearing capacity elasticity. According to the fitting degree, the equipment sample’s projection space is confirmed, the fault features of gear and bearing are extracted by segmentation algorithm, the optimal fitness is set by positioning algorithm, the location of fault center is obtained, and the fault mechanism diagnosis is studied. Experimental results show that compared with the traditional method, the proposed method is more stable, and the difference in fault diagnosis results is minimal. It can be seen that this method is more suitable for fault diagnosis of coal mining equipment.

Background: The development of severe coronavirus disease 2019 (COVID-19) is associated with systemic hyperinflammation, which drives multi-organ failure and death. Disease deterioration tends to occur when the virus is receding; however, whether other factors besides viral products are involved in the inflammatory cascade remains unclear. Methods: Twenty-eight COVID-19 patients with laboratory-confirmed SARS-CoV-2 infection hospitalized at the Fifth Medical Center of Chinese PLA General Hospital from January 23 to February 20, 2020 and nine healthy donors during the same period were recruited in the study. COVID-19 patients were grouped as mild, moderate, severe based on disease severity. Plasma damage-associated molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), calprotectin (S100A8/A9), surfactant protein A (SP-A), cold-inducible RNA-binding protein (CIRBP), and Histone H4 were detected by ELISA assay, and analyzed in combination with clinical data. Plasma cytokines, chemokines and lymphocytes were determined by flow cytometry. Results: Plasma levels of HMGB1 (38292.3 ± 4564.4 vs. 32686.3 ± 3678.1, P = 0.002), S100A8/A9 (1490.8 ± 819.3 vs. 742.2 ± 300.8, P = 0.015), and SP-A (6713.6 ± 1708.7 vs. 5296.3 ± 1240.4, P = 0.048) were increased in COVID-19 patients compared to healthy donors, while CIRBP (57.4 ± 30.7 vs. 111.9 ± 55.2, P = 0.004) levels decreased. Five DAMPs did not vary among mild, moderate, and severe patients. Moreover, SP-A levels correlated positively with inflammatory cytokines and negatively with time elapsed after symptom onset, whereas CIRBP showed an opposite pattern. Conclusions: These findings suggest SP-A may involve in the inflammation of COVID-19, while CIRBP likely plays a protective role. Therefore, DAMPs represent a potential target in the prevention or treatment of COVID-19.

SARS-CoV-2 is the cause of the current global pandemic of COVID-19; this virus infects multiple organs, such as the lungs and gastrointestinal tract. The microbiome in these organs, including the bacteriome and virome, responds to infection and might also influence disease progression and treatment outcome. In a cohort of 13 COVID-19 patients in Beijing, China, we observed that the gut virome and bacteriome in the COVID-19 patients were notably different from those of five healthy controls. We identified a bacterial dysbiosis signature by observing reduced diversity and viral shifts in patients, and among the patients, the bacterial/viral compositions were different between patients of different severities, although these differences are not entirely distinguishable from the effect of antibiotics. Severe cases of COVID-19 exhibited a greater abundance of opportunistic pathogens but were depleted for butyrate-producing groups of bacteria compared with mild to moderate cases. We replicated our findings in a mouse COVID-19 model, confirmed virome differences and bacteriome dysbiosis due to SARS-CoV-2 infection, and observed that immune/infection-related genes were differentially expressed in gut epithelial cells during infection, possibly explaining the virome and bacteriome dynamics. Our results suggest that the components of the microbiome, including the bacteriome and virome, are affected by SARS-CoV-2 infections, while their compositional signatures could reflect or even contribute to disease severity and recovery processes.

BackgroundProgrammed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immune-related adverse events (irAEs) are inevitable in patients with liver cancer. Although the incidence of severe irAEs is low, but can result in fatal consequences. To date, only a few commonly used clinical biomarkers have been reported.AimTo assess commonly used clinical biomarkers associated with the occurrence of irAEs to enable better management of irAEs by clinicians.MethodsWe retrospectively reviewed patients with liver cancer treated with at least one cycle of PD-1 immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs). IrAEs were documented according to the common terminology criteria for adverse events version 5. Clinical and laboratory parameters were also evaluated.ResultsA total of 67 patients were included, 36 with irAEs and 31 without irAEs. A total of 104 adverse events occurred; 83 of these events were grade 1/2 (G1/G2), 21 were grade 3/4 (G3/G4), and one died of G4 hepatitis. Patients with irAEs had higher levels of C-reactive protein (CRP) and interleukin-6 (IL-6) and lower levels of lymphocyte subsets, except natural killer (NK) cell counts, than those without irAEs (P <0.05). Patients who experienced G3/G4 irAEs had higher levels of CRP and IL-6 and lower levels of CD4+ T lymphocytes and B lymphocytes than those who experienced G1/G2 irAEs (P ). Of note, impairments in liver function and routine blood tests were also observed (P . The results of univariate and multivariate analyses for any grade of irAEs revealed that the combination of sintilimab and lenvatinib (P= 0.004, odds ratio [OR]: 7.414, 95% confidence interval [95% CI]: 1.925–28.560) and CRP ≥8.2 mg/L (P= 0.024, OR: 3.727, CI: 1.185–11.726) were independent risk factors. Univariate and multivariate analyses of the risk factors of G3/G4 irAEs suggested that the combination of sintilimab and lenvatinib was a potential risk factor (P = 0.049, OR: 8.242, CI: 1.006–67.532).ConclusionChanges in patient CRP, IL-6, and lymphocyte subsets were associated with irAE onset and may act as potential biomarkers of irAEs. Impairments in liver function and routine blood tests owing to the occurrence of irAEs may become new concerns for clinicians.

BackgroundThus far, few studies have investigated the safety and efficacy of programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) antibodies in patients with hepatitis B virus (HBV)-related liver cancer.ObjectiveTo investigate the effect of combination therapy with programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) on HBV-related liver cancer.MethodsUntil January 31, 2022, liver cancer patients with hepatitis B surface antigen (HBsAg) or HBV DNA positivity, treated with PD-1 ICIs and TKIs combined with nucleoside analogs (NAs), were retrospectively reviewed. The correlation between the change in HBV DNA and HBsAg levels and tumor response was analyzed using the χ2 test. Cox univariate and multivariate survival analyses and Kaplan–Meier curves were used to identify and compare risk factors and overall survival (OS).ResultsA total of 48 patients were enrolled in the study, with an objective response rate (ORR) of 31.3%, a disease control rate (DCR) of 66.7%; the incidence of adverse events was mostly mild. A significant decrease in HBV DNA and HBsAg levels was observed at 12 and 24 weeks compared with the baseline (p < 0.05). Compared to patients with progressive disease (PD), patients with disease control showed a more significant decrease in HBV DNA and HBsAg levels at 12 and 24 weeks (p < 0.001). Eleven patients showed elevations in HBV DNA level and one of them showed HBV reactivation; however, the reactivation was not associated hepatitis. Moreover, eight patients showed elevation in HBsAg. Elevation in HBV DNA level was associated with poor tumor response (P=0.001, OR=18.643 [95% CI: 3.271–106.253]). Cox survival analysis suggested that HBV DNA increase (P=0.011, HR=4.816, 95% CI: 1.439–16.117) and HBsAg increase (P=0.022, HR=4.161, 95% CI: 1.224–16.144) were independent risk factors associated with survival time. Kaplan–Meier curves suggested that patients who exhibited an increase in HBV DNA (6.87 months vs undefined, log-rank test: p= 0.004) and HBsAg (8.07 months vs undefined, log-rank test: p= 0.004) levels had a shorter median survival time (MST). Patients without increased HBsAg showed better baseline liver function and routine blood tests (pConclusionHBV-related liver cancer patients treated with combination therapy showed improved efficacy and safety profiles. Combination therapy has some effect on HBV infection, and a correlation between tumor response and antiviral efficacy was found. Elevation of HBV DNA and HBsAg levels may indicate poorer tumor response and survival time. Better baseline liver function and early immune activation may be associated with decline in HBsAg levels.

The growth performance, nutrient removal, lipid accumulation and morphological changes of Cyanobacterium aponinum OUC1 and Scenedesmus obliquus which were cultured in secondary effluents from two wastewater treatment plants: Tuandao Wastewater Treatment Plant (ETD) and Licun River Wastewater Treatment Plant (ELR) were investigated. The results showed that both C. aponinum OUC1 and S. obliquus have superior growth performances in both undiluted effluents, while the better of them was that in ETD effluent, with cell densities of C. aponinum OUC1 and S. obliquus increased by 159% and 66% over that of BG11 (control), respectively. Regarding nutrient removal, S. obliquus could completely remove inorganic phosphorus, and decrease ammonia nitrogen in ETD effluent by 81%. In addition, both C. aponinum OUC1 and S. obliquus cultivated in ETD exhibited extraordinary potential for biofuel production, increasing lipid productivities by 133% and 89% of that cultivated in ELR, respectively. As to ultrastructural changes, the differences in the lipoidal globules and glycogen granules of S. obliquus and C. aponinum OUC1 among the ETD and ELR treatments were mostly related to phosphorus limitations. The findings from this research reveal the probability using the secondary effluents as cultivation media to enhance algal biomass, nutrient removal and lipid productivity.

Perovskite solar cell (PSC) is a promising candidate of tandem solar cells (TSCs), especially as the top cell in perovskite/Si TSCs due to the easily tunable energy bandgap. However, the deposition...

This study determined growth and lipid accumulation in Nannochloropsis sp. MASCC 11 cultivated at different pH, temperatures, and CO2 concentrations in 10-day period. The suitability for biodiesel production was also evaluated based on the fatty acid profiles of microalgae lipid. Nannochloropsis sp. MASCC 11 showed an excellent tolerance to acidic pH (as low as 4.0), high temperatures (at least 40°C), and high CO2 concentrations (5%–15%), which are major stressed conditions in flue gas. The highest algal biomass was acquired at pH of 9.0 (0.44 gL−1), a temperature of 35C (0.63 g L−1), and a CO2 concentration of 5% (2.27gL−1). Maximum lipid production was obtained at pH of 6.0 (108.2 mg L−1), a temperature of 35°C (134.6mgL−1), and a CO2 concentration of 5% (782.7mg L−1). Synthesis of polyunsaturated fatty acids (PUFAs) in biomass was stimulated under high CO2 concentrations, remaining above 80% of total fatty acids, mainly composed of C16:3, C18:2, and C18:3. This led to the algae-based biodiesel having a lower oxidation stability, better cold flow properties, and other parameters such as its kinematic viscosity, cetane number, and specific gravity complied with ASTM or EN 14214 biodiesel specifications. Therefore, the improvement of oxidative stability needs to be considered before Nannochloropsis sp. MASCC 11 lipid can be used for biodiesel production, even if this species can grow well under stressful conditions.

Background: Terlipressin can effectively control acute gastrointestinal bleeding (GIB) in cirrhotic patients by acting on the V1 receptors, but may lead to the development of dilutional hyponatremi...

Background: Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis–related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis–related complications. Methods: Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts’ clinical experiences. Results: Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. Conclusion: The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis–related complications.

A framework of the plastic-damage model with double scalar variables is established in nominal stress space under the small deformation assumption. In the damaged part, a damage tensor comp...

n-Butyl acrylate (nBA), a typical hazardous and noxious substance (HNS), is the largest-volume acrylate ester used to produce various types of polymers. With the increasing volume of nBA subject to maritime transportation, its accidental leakage poses a great risk to the marine organisms. Therefore, it is necessary to evaluate the ecological risk of nBA in marine environments. In this study, two species of marine microalgae, Skeletonema costatum and Phaeodactylum tricornutum, were used to explore the toxic effects of nBA based on their growth, pigment content, and oxidative stress. The growth of each species was significantly inhibited by nBA, showing a 96 h-EC

In this work, the insertion of AlScN ferroelectric gate dielectric on the performance of the AlGaN/GaN HEMT device is investigated. With negative pre-poling on AlScN, the threshold voltage (V th) of the device shifts positively with a swing range of 3.26 V. The influence of polarization modulation is also reflected by the suppression of gate leakage and the reduction of the subthreshold swing of the device. The AlScN-integrated GaN HEMT exhibits an on/off ratio of 106 and a subthreshold swing of 80 mV dec−1. The depletion mechanism of 2DEG at the AlGaN/GaN interface was well described by a TCAD model.

The neurotoxin β-N-methylamino-L-alanine (BMAA) has been presumed as an environmental cause of human neurodegenerative disorders, such as Alzheimer's disease. Marine diatoms Thalassiosira minima are demonstrated here to produce BMAA-containing proteins in axenic culture while the isomer diaminobutyric acid was bacterially produced. In the co-culture with Cyanobacterium aponinum, diatom growth was inhibited but the biosynthesis of BMAA-containing proteins was stimulated up to seven times higher than that of the control group by cell-cell interactions. The stimulation effect was not caused by the cyanobacterial filtrate. Nitrogen deprivation also doubled the BMAA content of T. minima cells. Transcriptome analysis of the diatom in mixed culture revealed that pathways involved in T. minima metabolism and cellular functions were mainly influenced, including KEGG pathways valine and leucine/isoleucine degradation, endocytosis, pantothenate and CoA biosynthesis, and SNARE interactions in vesicular transport. Based on the expression changes of genes related to protein biosynthesis, it was hypothesized that ubiquitination and autophagy suppression, and limited COPII vesicles transport accuracy and efficiency were responsible for biosynthesis of BMAA-containing proteins in T. minima. This study represents a first application of transcriptomics to investigate the biological processes associated with BMAA biosynthesis in diatoms.

The application of hepatitis B virus (HBV)-T-cell receptor (TCR) T-cell immunotherapy in patients with HBV-related hepatocellular carcinoma (HBV-HCC) has been apathetic, as the expression of HBV antigens by both normal HBV-infected hepatocytes and HCC cells with HBV-DNA integration increases the risk of on-target off-tumor severe liver inflammatory events. To increase the safety of this immunotherapeutic approach, we developed messenger RNA (mRNA) HBV-TCR-redirected T cells that-due to the transient nature of mRNA-are functionally short lived and can be infused in escalating doses. The safety of this approach and its clinical potential against primary HBV-HCC have never been analyzed in human trials; thus, we studied the clinical and immunological parameters of 8 patients with chronic HBV infection and diffuse nonoperable HBV-HCC treated at weekly intervals with escalating doses (1 × 10

Objective: At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis.Methods: In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI 2), normal weight (18.5 ≤ BMI < 23.0 kg/m2), and overweight/obese (BMI ≥ 23.0 kg/m2).Results: In the first part, Kaplan–Meier curve analyses demonstrated a significantly higher cumulative survival rate in the overweight/obese group than the normal weight group (p = 0.047). Cox regression analyses demonstrated that overweight/obesity was significantly associated with decreased long-term mortality compared with the normal weight group [hazard ratio (HR) = 0.635; 95% CI: 0.405–0.998; p = 0.049] but not an independent predictor after adjusting for age, gender, and Child–Pugh score (HR = 0.758; 95%CI: 0.479–1.199; p = 0.236). In the second part, Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between the overweight/obese and the normal weight groups (p = 0.094). Cox regression analyses also demonstrated that overweight/obesity was not significantly associated with in-hospital mortality compared with normal weight group (HR = 0.349; 95%CI: 0.096-1.269; p = 0.110). In both of the two parts, the Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between underweight and normal weight groups.Conclusion: Overweight/obesity is modestly associated with long-term survival in patients with cirrhosis but not an independent prognostic predictor. There is little effect of overweight/obesity on the short-term survival of patients with cirrhosis and with AGIB.

C9 aromatics - benzene hydrocarbon containing nine carbon atoms among - leakage accident has caused serious damage to the marine ecology near Quangang District, Fujian Province, China. The ecological restoration of the accident sea area is basically realized through natural attenuation. To determine whether the natural attenuation of C9 aromatics in the marine environment will generate highly toxic intermediates, and thus cause more serious harm to marine ecology, the intermediates of C9 aromatics (n-propylbenzene, isopropylbenzene, 2-ethyltoluene, 3-ethyltoluene, 4-ethyltoluene, 1,2,3-trimethylbenzene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene, and indene) in the process of natural attenuation were studied under the marine conditions simulated by a microcosm. The acute toxic effects of 12 intermediates with longer residual time on Phaeodactylum tricornutum were also ascertained. Twenty natural attenuation intermediates of C9 aromatics were identified. These products primarily include the derivatives of phenols, aromatic alcohols, aromatic aldehydes, aromatic ketones, and aromatic acids, as well as an aromatic lactone compound. No intermediates of 1,3,5-trimethylbenzene and indene during the attenuation process were determined. The indirect photooxidation initiated by hydroxyl radical might play an essential role in the formation of intermediates of C9 aromatic. Based on the 96-h EC

Adaptive laboratory evolution (ALE) experiments are a serviceable method for the industrial utilization of the microalgae, which can improve the phenotype, performance, and stability of microalgae to obtain strains containing beneficial mutations. In this article, we reviewed the research into the microalgae ALE test and assessed the improvement of microalgae growth, tolerance, metabolism, and substrate utilization by ALE. In addition, the principles of ALE and the key factors of experimental design, as well as the issues and drawbacks of the microalgae ALE method were discussed. In general, improving the efficiency of ALE and verifying the stability of ALE resulting strains are the primary problems that need to be solved in future research, making it a promising method for the application of microalgae biotechnology.

Background: Psoriasis is a T help 17 (Th17) cell-mediated chronic inflammatory skin disease. Recent studies have shown that dihydroartemisinin (DHA) can significantly reduce experimental autoimmune encephalomyelitis and rheumatoid arthritis by regulating Th17 cells.Objective: To verify whether DHA can improve the symptoms of psoriasis and to further explore the possible mechanism.Methods: The efficiency of DHA was preliminary detected on human keratinocytes (HaCaT) cells in psoriatic condition. Then, imiquimod-induced psoriasis-like model in BALB/c mice was established to evaluate the effects of DHA in vivo.Results: Under the stimulation of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), DHA inhibited the proliferation of HaCaT cells and significantly affected the mRNA expression levels of IFN-γ, interleukin (IL), IL-17A and IL-23. DHA treatment reduced the severity of psoriasis-like skin and resulted in less infiltration of immune cells in skin lesions. DHA restored the expression of IFN-γ, IL-17A, and IL-23 in skins, as well as a decrease of cytokines and chemokines in skin supernatant. DHA also altered the cellular composition in the spleen, which is the makeup of the T cells, dendritic cells (DCs), and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17+CD4+T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and the expression of Th17 cell-related transcription factors retinoid-related orphan receptor-gamma t (ROR-γt) in vitro. In addition, phosphorylation of signal transducer and activator of transcription-3 (STAT3) was significantly reduced in DHA treatment mice, suggesting that the IL-23/Th17 axis plays a pivotal role.Conclusion: DHA inhibits the progression of psoriasis by regulating IL-23/Th17 axis and is expected to be an effective drug for the treatment of psoriasis.

Sponge-like lithium (Li) deposition results in high-surface-area morphology that harmfully accelerates the side reactions between Li and electrolyte, arousing serious safety issues of next high energy density Li metal batteries (LMBs). Herein, we propose a strategy to suppress the sponge-like Li deposition by plating Li metal on aluminum nitride (AlN)-modified substrates. For a practical Li deposition of 4 mAh cm

Using the effluent of municipal wastewater treatment plant (WWTP) to cultivate lipid-producing microalgae is likely to reduce the production cost of algae-derived biodiesel. However, the toxicity of antibiotics present in the effluent may affect the growth of microalgae and lipid production. This study investigated the effects of erythromycin (ERY) and tetracycline (TC) on the growth and lipid production of Tetradesmus (Scenedesmus) obliquus cultivated in the effluent of municipal WWTP. The results indicated that ERY was more toxic to T. obliquus compared to TC. The critical concentrations of ERY resulting in S. obliquus algae growth inhibition and increased lipid accumulation were 100 and 10 μg L−1, respectively. Maximum lipid accumulation was observed at an ERY concentration of 50 μg L−1, while lipid accumulation was significantly decreased at ERY concentrations greater than 250 μg L−1. Interestingly, the contents of polyunsaturated fatty acids in T. obliquus exposed to ERY were significantly increased, while the contents of total saturated fatty acids and monounsaturated fatty acids were significantly decreased. TC had no effect on the growth or lipid production when the concentration reached 500 μg L−1. Overall, the presence of ERY and TC in the municipal WWTP effluent does not largely affect the growth or lipid production of T. obliquus.

Phenol is a common industrial chemical produced and transported worldwide largely. Therefore, accidental spillage of phenol in the ocean causes an increasing concern. Microalgae are promising to remove phenol from marine waters. However, temperature and light intensity are two main factors that markedly influence biodegradation in marine environments. In this study, a marine golden alga Isochrysis galbana is selected to research the removal of phenol under different temperatures (10–30°C) and light intensities (0–240 µmol/(m2·s)). The results show that the most suitable temperature and light intensity for phenol removal are 20°C and 180 µmol/(m2·s), respectively, and 100 mg/L of phenol can be completely removed by microalga in 24 h at these conditions. I. galbana can also remove phenol under dark and low-temperature conditions. The removal of phenol by I. galbana at diverse temperatures and light intensities conform to first-order kinetics, and the process under dark conditions conform to zero-order kinetics. Thus, I. galbana can be used in the in-situ bioremediation of polluted seawater by phenol.

Introduction Acute gastrointestinal bleeding (GIB) is a major cause of death in liver cirrhosis. This multicenter study aims to develop and validate a novel and easy-to-access model for predicting the prognosis of patients with cirrhosis and acute GIB. Methods Patients with cirrhosis and acute GIB were enrolled and randomly divided into the training (n = 865) and validation (n = 817) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses, and then a new prognostic model (i.e., CAGIB score) was established. Area under curve (AUC) of CAGIB score was calculated by receiver operating characteristic curve analysis and compared with Child–Pugh, model for end-stage liver disease (MELD), MELD-Na, and neutrophil–lymphocyte ratio (NLR) scores. Results In the training cohort, hepatocellular carcinoma (HCC), diabetes, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), and serum creatinine (Scr) were independent predictors of in-hospital death. CAGIB score = diabetes (yes = 1, no = 0) × 1.040 + HCC (yes = 1, no = 0) × 0.974 + TBIL (μmol/L) × 0.005 − ALB (g/L) × 0.091 + ALT (U/L) × 0.001 + Scr (μmol/L) × 0.012 − 3.964. In the training cohort, the AUC of CAGIB score for predicting in-hospital death was 0.829 (95% CI 0.801–0.854, P

The toxic effects of p-xylene, 4-methylbenzyl alcohol, p-methyl benzaldehyde, and p-toluic acid on two marine microalgae (Phaeodactylum tricornutum Bohlin, and Skeletonema costatum) were investigated. p-Xylene was the most toxic to Pha. tricornutum with a 96 h EC50 value of 6.76 mg L−1. Based on the 96 h EC50 values for two microalgae, the toxicity of the four chemicals, in descending order, was: p-xylene, p-methyl benzaldehyde, 4-methylbenzyl alcohol, then p-toluic acid. The results showed that the toxicity of the transformed products of p-xylene was lower than that of p-xylene.

Negative oxygen (O−) ions in the sputter deposition of oxides play a non-negligible role in determining their structures as well as physical properties. Knowledge of bombardment by O− ions induced local disorder in magnetron sputtered ZnO: Al (AZO) films is of fundamental interesting whereas that is currently limited. Here we report our initial results of the local structural changes characterized by a combination of Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and X-ray absorption spectroscopy (XAS). The bombardment conditions during the film deposition was varied through changing the discharge voltage (i.e., |Vd| = 80–220 V) and the substrate positions (i.e., center or erosion region of the target). We found that highly-energetic O− ions bombardment induced a coexistence of various point defects such as oxygen vacancies (VO), oxygen interstitials (Oi), and zinc interstitials (Zni). The concentration of these defects and thus the local disorder can be noticeably reduced through decreasing the |Vd| down to a sufficient low level. These results can be used to further optimize the growth processes to achieve the ZnO-based and related thin films with a high structural order.

As interest in new generations of nuclear reactors is increasing worldwide, development of accident tolerant fuel (ATF) cladding materials is crucial but suffers from large amounts of time and experimental efforts. Here, we present a strategy of the theory-guided bottom-up design of ATF cladding materials using ab initio calculations and the CALPHAD (CALculation of PHAse Diagrams) approach in combination with key experiments, which has been utilized to investigate the Fe Cr Al system. The thermochemical, physical and elastic mechanical properties, as well as the phase diagrams of the FeCrAl alloys, are well described using both modeling and experiment. Apart from the reported high-temperature steam oxidation resistance as the initial criterion, the present selection and optimization of the FeCrAl alloys as accident tolerant fuel cladding materials is based on three constraints: (i) single phase at 320 °C, a service temperature in a light water reactor; (ii) high melting point; (iii) good elastic mechanical property. Further optimization takes into account of alloy performance in literature. Consequently, a compositional range has been proposed as a guidance for the fabrication of new FeCrAl alloys, i.e., 0 at.%

1-phenylethanol (1-PEA) is a flavor extensively used in the production of cosmetics, beverages, and food. The release of 1-PEA into coastal environments has aroused great concern. However, its potential effects on marine organisms are still unknown. In order to provide a better understanding of the ecological risks of 1-PEA in marine environments, this study determined the toxic effects of 1-PEA on two marine diatoms (Phaeodactylum tricornutum and Skeletonema costatum). The diatoms were grown in culture medium containing different concentrations of 1-PEA for 96 h. The contents of chlorophyll a, chlorophyll c, glutathione (GSH), malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were measured at the end of the exposure period. 1-PEA was shown to significantly inhibit the growth of diatoms, with 96-h EC50 values of 257.14 mg/L and 126.46 mg/L in P. tricornutum and S. costatum, respectively. In P. tricornutum, the levels of SOD, CAT, GPx, GSH, and MDA were stimulated only when 1-PEA concentrations were close to or greater than the 96 h EC50 value. However, in S. costatum, the activities of SOD and CAT, and the syntheses of two chlorophylls were inhibited even at an exposure concentration below the 96 h EC50 value. Taken together, these findings indicate a potential ecological risk by discharging 1-PEA into coastal areas and its species-specific toxic effects on marine organisms.

Accurate analysis of paralytic shellfish toxins (PSTs) in shellfish is important to protect seafood safety and human health. In this study, the performance of different extraction protocols for PSTs from scallop tissues is compared and discussed, including regular extraction solvents hydrochloric acid (HCl) and acetic acid (AcOH) followed by heating and solid-phase extraction (SPE) purification, and a novel technique of matrix solid-phase dispersion (MSPD) without heating. The possible conversion of C1/2 and GTX2/3 standards after heating, and the stability of PSTs in wet scallop tissues stored at −20 °C for a 6-month period are also explored. Results showed that the MSPD technique could effectively mitigate matrix interference, but its recoveries of PSTs were significantly lower than those of the HCl and AcOH extraction methods followed by carbon SPE purification. The molar concentrations of M-toxins obtained by the MSPD method were generally lower than those analyzed by the HCl and AcOH extraction methods, which demonstrated a weak chemical conversion of C1/2 and GTX2/3 due to the heating process. Most of the PSTs were relatively stable in scallop tissues during 1-month storage at −20 °C, while the concentrations of PSTs in scallop tissues obviously changed after 6 months due to the degradation and transformation of PSTs during long-term storage at −20 °C. This work helps improve our understanding of the performance of different extraction methods and the stability of PSTs in scallop tissues stored at −20 °C.

Microplastics (MP) widely distributed in aquatic environments have adverse effects on aquatic organisms. Currently, the impact of MP on toxigenic red tide microalgae is poorly understood. In this study, the strain of Alexandriumpacificum ATHK, typically producing paralytic shellfish toxins (PST), was selected as the target. Effects of 1 and 0.1 μm polystyrene MP with three concentration gradients (5 mg L−1, 25 mg L−1 and 100 mg L−1) on the growth, chlorophyll a (Chl a), photosynthetic activity (Fv/Fm) and PST production of ATHK were explored. Results showed that the high concentration (100 mg L−1) of 1 μm and 0.1 μm MP significantly inhibited the growth of ATHK, and the inhibition depended on the size and concentration of MP. Contents of Chl a showed an increase with various degrees after MP exposure in all cases. The photosynthesis indicator Fv/Fm of ATHK was significantly inhibited in the first 11 days, then gradually returned to the level of control group at day 13, and finally was gradually inhibited in the 1 μm MP treatments, and promotion or inhibition to some degree also occurred at different periods after exposure to 0.1 μm MP. Overall, both particle sizes of MP at 5 and 25 mg L−1 had no significant effect on cell toxin quota, and the high concentration 100 mg L−1 significantly promoted the PST biosynthesis on the day 7, 11 and 15. No significant difference occurred in the cell toxin quota and the total toxin content in all treatments at the end of the experiment (day 21). All MP treatments did not change the toxin profiles of ATHK, nor did the relative molar percentage of main PST components. The growth of ATHK, Chl a content, Fv/Fm and toxin production were not affected by MP shading. This is the first report on the effects of MP on the PST-producing microalgae, which will improve the understanding of the adverse impact of MP on the growth and toxin production of A. pacificum.