Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.

Preclinical and phase I studies of an antisense oligonucleotide drug targeting IGF-1R in liver cancer.

Aim: To evaluate a novel antisense oligonucleotide drug targeting human IGF-1R in preclinical and phase I studies of liver cancer. Materials & methods: The tolerability and safety of an investigational new drug were evaluated in a dose-escalation trial involving 17 patients with advanced liver cancer after preclinical assessment of pharmacokinetics and pharmacodynamics. Results: The drug exposure levels in the phase I trial were determined by the in vivo efficacy with pharmacokinetics evaluation in rats and rhesus monkeys. This clinical study showed that the maximum tolerated dose was 3.96 mg/kg, and the dose-limiting toxicity dose was 4.4 mg/kg. Conclusion: The drug was safe and tolerable in patients with advanced liver cancer.Clinical Trial Registration: ChiCTR2100044235 (www.chictr.org.cn).

CT102 is a potential new drug for liver cancer treatment. It belongs to a new form of medicine using gene therapy technology called antisense oligonucleotides. There are some antisense oligonucleotides approved for treating rare diseases. This study evaluated the antitumor effect, metabolism and safety of CT102 in preclinical and clinical trials. The results showed that CT102 could inhibit tumor growth in mice with liver cancer and maintain high levels in the liver. It was found that CT102 was safe and tolerable in patients with advanced liver cancer. This suggests that CT102 has therapeutic potential for liver cancer treatment. The good tolerability and safety of CT102 in patients supports further studies on liver cancer treatment.

Multi-Time-Scale Optimal Scheduling Strategy for Marine Renewable Energy Based on Deep Reinforcement Learning Algorithm.

Surrounded by the Shandong Peninsula, the Bohai Sea and Yellow Sea possess vast marine energy resources. An analysis of actual meteorological data from these regions indicates significant seasonality and intra-day uncertainty in wind and photovoltaic power generation. The challenge of scheduling to leverage the complementary characteristics of various renewable energy sources for maintaining grid stability is substantial. In response, we have integrated wave energy with offshore photovoltaic and wind power generation and propose a day-ahead and intra-day multi-time-scale rolling optimization scheduling strategy for the complementary dispatch of these three energy sources. Using real meteorological data from this maritime area, we employed a CNN-LSTM neural network to predict the power generation and load demand of the area on both day-ahead 24 h and intra-day 1 h time scales, with the DDPG algorithm applied for refined electricity management through rolling optimization scheduling of the forecast data. Simulation results demonstrate that the proposed strategy effectively meets load demands through complementary scheduling of wave power, wind power, and photovoltaic power generation based on the climatic characteristics of the Bohai and Yellow Sea regions, reducing the negative impacts of the seasonality and intra-day uncertainty of these three energy sources on the grid. Additionally, compared to the day-ahead scheduling strategy alone, the day-ahead and intra-day rolling optimization scheduling strategy achieved a reduction in system costs by 16.1% and 22% for a typical winter day and a typical summer day, respectively.

Predicting haemorrhagic transformation through serum biochemical indices for patients after endovascular treatment: a retrospective study.

INTRODUCTION: The aim of this study was to determine the serum biochemical markers that can predict the risk of haemorrhagic transformation (HT) before and after endovascular treatment (EVT). MATERIAL AND METHODS: This study included patients with anterior circulation large vessel occlusion (ACLVO) who underwent EVT within six hours of symptom onset between September 2017 and September 2022. These patients were retrospectively categorised into two groups: an HT group and a No-HT group. RESULTS: A total of 180 patients were included in the study, of whom 55 (30.6%) had HT. The monocyte count before EVT (p = = 0.005, OR = 0.694, 95% CI 0.536-0.898), the activated partial thromboplastin time before EVT (p = 0.009, OR = 0.186, 95% CI 0.699-0.952), and the eosinophil count after EVT (p = 0.038, OR = 0.001, 95% CI 0.000-0.018) were all found to be independent predictors of HT, with warning values of 6.65%, 22.95 seconds, and 0.035*10^9/L, respectively. When compared to prediction using only demographic data [AUC = 0.662,95% CI (0.545, 0.780)], adding biochemical indices before EVT [AUC = 0.719,95% CI (0.617, 0.821)], adding biochemical indices after EVT [AUC = 0.670,95% CI (0.566, 0.773)], and adding both [AUC = 0.778,95% CI (0.686, 0.870)], the prediction efficiency of HT was improved among all three combinations, with no statistical significance. CONCLUSIONS: The levels of serum biochemical markers were found to show significant changes before and after EVT in ACLVO patients. A combination of demographic data and serum biochemical markers proved to be effective in predicting the occurrence of HT in patients with ACLVO who underwent EVT.

Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients.

OBJECTIVE: A comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure. DESIGN: We 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. RESULTS: Both 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. CONCLUSION: Our 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.

Regulatory T cells differentiation in visceral adipose tissues contributes to insulin resistance by regulating JAZF-1/PPAR-γ pathway.

Regulatory T cell (Treg) activity and differentiation in visceral adipose tissue (VAT) play an important role in inhibiting chronic inflammation and insulin resistance. Whether JAZF-1 and PPAR-γ mediate VAT Treg differentiation to promote the inhibition of chronic inflammation and insulin resistance remains unclear. Here, we investigated the roles of JAZF-1 and PPAR-γ in VAT Treg differentiation, inflammation and insulin resistance using a transgenic mouse model. First, we determined that the levels of glucose and insulin biochemical markers in the JAZF-1 transgenic general feeding or high-fat groups were lower than those in the wild-type general feeding or high-fat groups. Second, the levels of CD4+ , CD25+ , and FOXP3+ differentiation markers in the JAZF-1 transgenic general feeding or high-fat groups were significantly higher than those in the wild-type groups. PPAR-γ inhibition was associated with low levels of CD4+ , CD25+ and FOXP3+ differentiation markers. Third, the levels of TNF-α, IL-1ß and IL-6 in the JAZF-1 transgenic groups were lower than those in the wild-type groups, whereas IL-10 and TGF-ß levels were higher in the JAZF-1 transgenic groups than in the wild-type groups. After using the PPAR-γ inhibitor, we observed that TNF-α, IL-1ß and IL-6 increased, while IL-10 and TGF-ß decreased. We found that JAZF-1 and PPAR-γ could promote Tregs differentiation and regulate insulin resistance by synergistically decreasing the expression levels of TNF-α, IL-1ß and IL-6 and increasing those of IL-10 and TGF-ß.

Ecological risk assessment for xylenes and propylbenzenes in aquatic environment using a species sensitivity distribution approach.

Xylenes and propylbenzenes (PBZs) are volatile aromatic hydrocarbons with high aquatic toxicity. Xylenes can be present in three isomers: o-xylene (OX), m-xylene (MX), and p-xylene (PX), while PBZs include two isomers: n-propylbenzene (n-PBZ) and isopropylbenzene (i-PBZ). Their accidental spills and improper discharges from petrochemical industries can cause severe contamination in water bodies posing potential ecological risks. In this study, the published acute toxicity data of these chemicals for aquatic species were collected to calculate hazardous concentrations protecting 95% species (HC5) using a species sensitivity distribution (SSD) approach. The acute HC5 values for OX, MX, PX, n-PBZ, and i-PBZ were estimated to be 1.73, 3.05, 1.23, 1.22, and 1.46 mg/L, respectively. The risk quotient (RQ) values calculated based on HC5 indicated their high risk (RQ: 1.23 ∼ 21.89) in groundwater, but low risk (RQ < 0.1) in natural seawater, river water, and lake water. When xylenes or PBZs leaked into the sea, they were expected to pose a high risk (RQ > 1) at the start and then a low risk (RQ < 0.1) after 10 days due to natural attenuation. These results may help to derive more reliable protection thresholds for xylenes and PBZs in aquatic environment and provide a basis for evaluating their ecological risks.

Intermediates formed during natural attenuation of C9 aromatics under simulated marine conditions: Identification, transformation pathway, and toxicity to microalgae.

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 EC50 values for P. tricornutum, the toxicity of the 12 intermediates, in descending order, was: 4-ethylphenol, 2-methylacetophenone, 2,3-dimethylbenzyl alcohol, 4-methylacetophenone, 3-methylacetophenone, 1-phenyl-1-propanol, 1-(2-methylphenyl) ethanol, 2-phenyl-2-propanol, 3,4-dimethylbenzoic acid, 2,4-dimethylbenzoic acid, 2,5-dimethylbenzoic acid, then 4-tolylacetic acid. The 96-h EC50 values of the intermediates of C9 aromatics to P. tricornutum ranged from 8.4 to 199.1 mg/L, which were lower than that of their corresponding parent compound. The findings provided essential fundamental insights for the assessment of marine environmental risk of C9 aromatics leakage accidents, and subsequent emergency disposal countermeasures.

Oxidative stress responses in two marine diatoms during acute n-butyl acrylate exposure and the toxicological evaluation with the IBRv2 index.

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-EC50 value of 2.23 mg/L for P. tricornutum and 8.19 mg/L for S. costatum, respectively. Although chlorophylls a and c exerted a hormesis effect in P. tricornutum, contents of pigments generally decreased at high concentrations. In P. tricornutum, all detected antioxidants (reduced glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) were stimulated at concentrations ranging from 1.50 to 3.82 mg/L. However, these elevations were not enough to reduce the oxidative damage caused by nBA, because the content of malondialdehyde (MDA) increased continuously during 96-h exposure. For S. costatum, the activities of only two antioxidants (GSH and CAT) were enhanced, which is enough to prevent the MDA content from rising, even at higher concentrations of nBA (5-10 mg/L). The Integrated Biomarker Response Version 2 (IBRv2) index that combines responses of the above five oxidative stress biomarkers, was not only correlated positively with nBA concentration but could also indicate the occurrence of oxidative stress caused by acute concentration of nBA. These findings showed that P. tricornutum was sensitive to nBA compared to S. costatum, and the IBRv2 index was an effective tool for evaluating ecotoxicological effects on marine microalgae due to nBA spills.

Acute kidney injury defined by cystatin C may be superior for predicting the outcomes of liver cirrhosis with acute gastrointestinal bleeding.

BACKGROUND & AIMS: Acute kidney injury (AKI) is conventionally evaluated by a dynamic change of serum creatinine (Scr). Cystatin C (CysC) seems to be a more accurate biomarker for assessing kidney function. This retrospective multicenter study aims to evaluate whether AKI re-defined by CysC can predict the in-hospital outcomes of patients with liver cirrhosis and acute gastrointestinal bleeding. METHODS: Overall, 677 cirrhotic patients with acute gastrointestinal bleeding, in whom both Scr and CysC levels were detected at admissions, were screened. eGFRScr, eGFRCysC, and eGFRScr-CysC were calculated. MELD-Na score and AKI were re-evaluated by CysC instead of Scr. Odds ratios (ORs) were calculated in the logistic regression analyses. The receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Univariate logistic regression analyses demonstrated that baseline Scr and CysC levels, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, MELD-Na score re-defined by CysC, and AKI re-defined by CysC, but not conventional AKI defined by Scr, were significantly associated with in-hospital death. ROC analyses showed that baseline CysC level, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, and MELD-Na score re-defined by CysC, but not baseline Scr level, could significantly predict the risk of in-hospital death. CONCLUSIONS: AKI re-defined by CysC may be superior for predicting the in-hospital mortality of cirrhotic patients with acute gastrointestinal bleeding.

Natural attenuation of sulfometuron-methyl in seawater: Kinetics, intermediates, toxicity change and ecological risk assessment.

This research aims to evaluate the environmental feasibility of sulfometuron-methyl (SM) as a growth inhibitor for restricting the growth of Spartina alterniflora. To achieve this purpose, the natural attenuation characteristics, ecological risk, degradation pathway, and comprehensive toxicity changes of SM in seawater were investigated under the simulated marine environmental conditions of Jiaozhou Bay, China. The natural attenuation of SM in seawater followed first-order reaction kinetics with a rate constant (K) of 0.0694 d-1 and a half-life of 9.99 days. When photolysis, hydrolysis, and biodegradation pathways act alone, the rate constants K of SM were 0.0167, 0.0143, and 0.0099 d-1 respectively, indicating that their contributions to the total removal of SM decreased in turn. The calculation results of risk quotient (RQ) showed that the seawater containing 10 mg/L of SM demonstrated a very high risk to marine diatom Skeletonema costatum before and after 21 days of attenuation with RQ values of 24.46 and 6.32, respectively, however, the risk to other marine organisms (fish, crustaceans, and bivalves) decreased from moderate (RQ < 1) to low (RQ < 0.01). Four attenuation products of SM were identified and two degradation pathways of SM in seawater were proposed. Based on the rate of inhibition of bioluminescence, SM in seawater was not harmful to Photobacterium phosphoreum T3, whereas the toxicity of seawater containing SM increased with the extension of attenuation time, suggesting the formation of intermediate products with high aquatic toxicity. According to the toxicity values predicted by ECOSAR, the toxicity of one identified attenuation product was higher than that of SM. To the best of our knowledge, this is the first report on the attenuation characteristics and toxicity changes of SM in seawater. The results indicated that the toxicity of both SM and its degradation products to non-target marine organisms should be considered in evaluating the feasibility of SM in controlling coastal Spartina alterniflora.

The breadth of concomitant virological features in a family cluster outbreak of COVID-19 pneumonia.

An outbreak of a novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had emerged in 2019 and rapidly posed a global epidemic. Here, we report the breadth of concomitant virological features of a family cluster with COVID-19. The period of virus shedding is significantly different between upper respiratory and feces samples. Even the SARS-CoV-2 virus titers were undetectable in feces, it could be positive again soon and likely related to fluctuated inflammation levels (interleukin-6, etc.) and lowered immune responses (CD4 + T lymphocyte, etc.). Our findings expand the novel understanding of the breadth of concomitant virological features during a non-severe family cluster of COVID-19.

Performance of different extraction methods for paralytic shellfish toxins and toxin stability in shellfish during storage.

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.

Attenuation pathways of erythromycin and biochemical responses related to algal growth and lipid synthesis in a microalga-effluent system.

Microalgal cultivation in municipal wastewater treatment plants (WWTPs) can realize the coupling of wastewater treatment and microalgae energy utilization, however, the residual antibiotics in effluents from WWTPs affect the growth of microalgae. In this study, green alga (Scenedesmus obliquus) cells were inoculated into the effluents to ascertain the attenuation pathways of erythromycin (ERY) and the biochemical responses of microalga in a microalga-effluent system. Results showed that hydrolysis, photolysis, and biodegradation (including bioadsorption) cause the attenuation of ERY in a microalga-effluent system, and the biodegradation (including bioadsorption) has the greatest removal rate (reaching a maximum of 57.87%), followed by hydrolysis (reaching a maximum of 34.13%), and photolysis (less than 5%) after five days. The photosynthetic pigment contents in cells of microalga decreased the most (by 35.66% for chlorophyll a), and the production of ROS was stimulated (by 33.75%) after five-day exposure to ERY at an initial concentration of 100 µg/L. Meanwhile, the activity of ribulose-1,5-biphosphate carboxylase (RuBPCase) decreased by 55.65%, and the activity of acetyl-CoA carboxylase (ACCase) increased by 55.65%. The ROS level, photosynthetic pigment content, and RuBPCase activity were extremely significantly correlated with each other (P < 0.01), indicating that exposure to ERY changed those biochemical responses related to the rate of photosynthesis of microalga, inhibiting the growth thereof. On the other hand, exposure to ERY increased lipid production by microalga through the induced ACCase activity.

Acclimation of Isochrysis galbana Parke (Isochrysidaceae) for enhancing its tolerance and biodegradation to high-level phenol in seawater.

Marine microalgae with high removal efficiency of phenol are needed for the remediation of polluted seawater in cases involving phenol spills. To achieve this purpose, adaptive laboratory evolution (ALE) was performed by a microalga Isochrysis galbana Parke MACC/H59, which is capable of degrading phenol at concentrations of less than 100 mg L-1 in 4 d. Two acclimation conditions were used: (i) 90 d at 100 mg L-1 phenol, and (ii) 90 d at 100 mg L-1 phenol followed by another 90 d at 200 mg L-1 phenol. By doing so, two strains (PAS-1 and PAS-2) could be obtained respectively. They grew rapidly at phenol concentrations up to 200 mg L-1 and 300 mg L-1, respectively, with a specific growth rate 2.52-3.40 times and 1.93-3.23 times that of the control (without phenol). Also, both strains had a higher removal capacity of phenol than the unacclimated alga. Phenol at an initial concentration of 200 mg L-1 was completely removed in 5 d thereby. For 300 mg L-1 phenol, a removal efficiency of 92% was achieved in 10 days by using PAS-2, with a removal rate constant of 30.01 d-1 (about twice that of PAS-1) and a half-life of 4.90 d (about half that of PAS-1), showing that a better strain may be obtained by extending the acclimation time. The enhancement of phenol biodegradation can be explained by the elevated activity of phenol hydroxylase (PH) in both strains. These results indicated that ALE could be an efficient tool used to enhance the tolerance and biodegradation of marine microalgae to phenol in seawater.

Natural attenuation characteristics and comprehensive toxicity changes of C9 aromatics under simulated marine conditions.

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 pathways by which the marine diatom Thalassiosira sp. OUC2 biodegrades p-xylene, combined with a mechanistic analysis at the proteomic level.

A marine diatom, Thalassiosira sp. OUC2, was isolated from natural seawater collected from Daya Bay, China. This diatom degraded 1.25-40 mg L-1p-xylene within five days, at a removal efficiency exceeding 98%. Gas chromatography-mass spectrometer (GC-MS) analysis indicated that p-xylene was converted into 4-methylbenzyl alcohol, p-toluic acid, and p-cresol in the presence of strain OUC2. Meanwhile, proteomic analysis showed that, after exposure to p-xylene, several algal enzymes were significantly upregulated: including monooxygenase, alcohol dehydrogenase, benzaldehyde dehydrogenase, benzoate 1,2-dioxygenase, and catechol 2,3-dioxygenase. Moreover, ecotoxicological tests suggested that the intermediate metabolites were less toxic than the parent compound (p-xylene). Thalassiosira sp. OUC2 may thus be suitable for the remediation of p-xylene-contaminated marine environments.

The long noncoding RNA HIF1A-AS2 facilitates cisplatin resistance in bladder cancer.

Chemotherapy drug resistance frequently happens in more than 50% of bladder cancer patients and is the major obstacle for the bladder cancer therapy. Recent studies have shown that long noncoding RNA (lncRNA) is involved in the development of chemoresistance. In this study, we reported hypoxia inducible factor 1α-antisense RNA 2 (HIF1A-AS2), as a subtype-specific hypoxia inducible lncRNA, is upregulated in bladder cancer cells and tissue after cisplatin (Cis) treatment. The induction of HIF1A-AS2 in bladder cancer cells rendered resistance to Cis-induced apoptosis. Silencing HIF1A-AS2 in Cis-resistant bladder cancer cells was re-sensitized to Cis-induced apoptosis. Mechanically, we found that HIF1A-AS2 suppressed the transcription activity of p53 family proteins by promoting the expression of high-mobility group A1 (HMGA1). The induction of HMGA1 physically interacts with p53, p63, and p73, and therefore constrains their transcriptional activity on Bax. Knockdown of HIF1A-AS2 or HMGA1 rescued the expression of Bax, which therefore enhanced the killing effect of Cis. Furthermore, we also found that the expression of HIF1A-AS2 was higher in the human bladder tumor tissues after Cis treatment, and was positive correlated to the expression of HIF1α and HMGA1. This study suggests that upregulated HIF1A-AS2 hampers the p53 family proteins dependent apoptotic pathway to promote Cis resistance in bladder cancer. Our data suggested that HIF1A-AS2 plays oncogenic roles and can be used as a therapeutic target for treating human bladder cancer.

Dysregulated Response of Follicular Helper T Cells to Hepatitis B Surface Antigen Promotes HBV Persistence in Mice and Associates With Outcomes of Patients.

BACKGROUND & AIMS: Production of neutralizing antibodies against hepatitis B surface antigen (HBsAg) is dysregulated in patients with persistent hepatitis B virus (HBV) infection. We investigated mechanisms by which this immune response to the virus is disrupted and whether it can be restored to promote clearance of HBV. METHODS: Immune-competent C57BL/6N and C57BL/6J, as well as mice deficient in follicular helper T cells (Tfh-cell-deficient), B cells, or Foxp3+ T-regulatory cells (Treg cell deficient), were given hydrodynamic injections of pAAV/HBV1.2 plasmids. Some mice were given injections of sorted Tfh cells, pan-B cells, Treg cells, or a blocking antibody against CTLA4. Production of antibodies against HBsAg and clearance of HBV were assessed by flow cytometry, enzyme-linked immunosorbent assay, polymerase chain reaction, and immunohistochemical analyses. We obtained blood samples from patients with HBV infection and isolated Treg cells. We measured the ability of Treg cells to suppress production of interleukin 21 (IL21) in CD4+ T cells. RESULTS: Immune-competent C57BL/6N and C57BL/6J mice transfected with the plasmid encoding HBV had features of viral clearance and viral persistence observed in humans. A Tfh-cell response to HBsAg was required for clearance of HBV and was suppressed by Treg cells in mice with persistent HBV infection. Depletion of Treg cells or inhibition of Treg-cell function (with blocking antibody against CTLA4) restored the Tfh-cell response against HBsAg and clearance of HBV in mice. Impaired Tfh-cell response to HBsAg was observed in blood from patients with chronic HBV infection, responsiveness was restored by depletion of Treg cells or blocking antibody against CTLA4. CONCLUSIONS: In studies of HBV-infected mice and blood from patients with chronic HBV infection, we found a Tfh-cell response to HBsAg of to be required for HBV clearance, and that this response was blocked by Treg cells. Inhibiting Treg-cell activity using neutralizing antibody against CTLA4 restored the ability of Tfh cells to clear HBV infection; this approach might be developed for treatment of patients with chronic HBV infection.

Biodegradation of phenol in saline or hypersaline environments by bacteria: A review.

With the continuous demand from industry for chemical raw materials, a large amount of high-salinity wastewater containing phenol is discharged into the aquatic environment, and the leakage of dangerous chemicals into the sea may lead to phenol pollution of the ocean. Phenol is a common chemical posing serious environmental hazard. Biodegradation is an effective, low-cost, environment-friendly method of removing phenol from water, but in hypersaline environments, traditional freshwater organisms are less efficacious. Here, at least 17 genera of bacteria from three phyla are found that can degrade phenol in different saline environments. The sources and taxonomy of halotolerant and halophilic bacteria are reviewed. Moreover, the pathway of phenol removal, kinetics of biodegradation, influencing factors, and recent treatment processes of wastewater are discussed.