Persulfate activation with biochar supported nanoscale zero- valent iron: Engineering application for effective degradation of NCB in soil.

Nitrochlorobenzene (NCB) is very common in pesticide and chemical industries, which has become a major problem in soil environment. However, the remediation of NCB contaminated soil is received finite concern. Using biochar as a substrate for nanoscale-zero valent iron (nZVI/p-BC) to activate peroxodisulfate (PDS), a novel heterogeneous oxidative system had been applied in the current study to remediate NCB contaminants in soil. The degradation efficiencies and kinetics of m-NCB, p-NCB, and o-NCB by various systems were contrasted in soil slurry. Key factors including the dosage of nZVI/p-BC, the molar ratio of nZVI/PDS, initial pH and temperature on degradation of NCB were further examined. The results confirmed that the nZVI/p-BC/PDS displayed the remarkable performance for removing NCB compared with other systems. Higher temperature with nZVI/PDS molar ratio of 2:1 under the acidic condition favored the reduction of NCB. The treatment for NCB with optimal conditions were evaluated for the engineering application. The mechanism of nZVI/p-BC/PDS indicated that electron transfer between p-BC and nZVI was responsible for activation of PDS, generating active species (SO4•-, •OH and 1O2) via both the free and non-free radical pathways. Experimental results revealed prominent availability of nZVI/p-BC/PDS system in remediation of actual contaminated field by NCB.

Cryopreserved leukapheresis material can be transferred from controlled rate freezers to ultracold storage at warmer temperatures without affecting downstream CAR-T cell culture performance and in-vitro functionality.

Chimeric antigen receptor (CAR) T-cell therapies are increasingly adopted as a commercially available treatment for hematologic and solid tumor cancers. As CAR-T therapies reach more patients globally, the cryopreservation and banking of patients' leukapheresis materials is becoming imperative to accommodate intra/inter-national shipping logistical delays and provide greater manufacturing flexibility. This study aims to determine the optimal temperature range for transferring cryopreserved leukapheresis materials from two distinct types of controlled rate freezing systems, Liquid Nitrogen (LN2)-based and LN2-free Conduction Cooling-based, to the ultracold LN2 storage freezer (≤-135 °C), and its impact on CAR T-cell production and functionality. Presented findings demonstrate that there is no significant influence on CAR T-cell expansion, differentiation, or downstream in-vitro function when employing a transfer temperature range spanning from -30 °C to -80 °C for the LN2-based controlled rate freezers as well as for conduction cooling controlled rate freezers. Notably, CAR T-cells generated from cryopreserved leukapheresis materials using the conduction cooling controlled rate freezer exhibited suboptimal performance in certain donors at transfer temperatures lower than -60 °C, possibly due to the reduced cooling rate of lower than 1 °C/min and extended dwelling time needed to reach the final temperatures within these systems. This cohort of data suggests that there is a low risk to transfer cryopreserved leukapheresis materials at higher temperatures (between -30 °C and -60 °C) with good functional recovery using either controlled cooling system, and the cryopreserved materials are suitable to use as the starting material for autologous CAR T-cell therapies.

Bioaccumulation of Microcystin-LR and Induced Physio-Biochemical Changes in Rice (Oryza sativa L.) at Vegetative Stage under Hydroponic Culture Conditions.

Irrigation with water containing a variety of microcystins (MCs) may pose a potential threat to the normal growth of agricultural plants. To investigate the phytotoxicity of MC-LR at environmental concentrations on rice (Oryza sativa L.), the characteristics of uptake and accumulation in plant tissues, as well as a series of key physio-biochemical process changes in leaves of rice seedlings, were measured at concentrations of 0.10, 1.0, 10.0, and 50.0 µg·L-1 in hydroponic nutrient solutions for 7, 15, 20, and 34 days. Results showed that MC-LR could be detected in rice leaves and roots in exposure groups; however, a significant accumulation trend of MC-LR in plants (BCF > 1) was only found in the 0.10 µg·L-1 group. The time-course study revealed a biphasic response of O2•- levels in rice leaves to the exposure of MC-LR, which could be attributed to the combined effects of the antioxidant system and detoxification reaction in rice. Exposure to 1.0-50.0 µg·L-1 MC-LR resulted in significant depletion of GSH and MDA contents in rice leaves at later exposure times (15-34 days). Low MC-LR concentrations promoted nitric oxide synthase (NOS) activity, whereas high concentrations inhibited NOS activity during the later exposure times. The reduced sucrose synthase (SS) activities in rice exposed to MC-LR for 34 days indicated a decrease in the carbon accumulation ability of plants, and therefore may be directly related to the inhibition of plant growth under MC exposure. These findings indicate that the normal physiological status would be disrupted in terrestrial plants, even under exposure to low concentrations of MC-LR.

How Fe-bearing materials affect soil arsenic bioavailability to rice: A meta-analysis.

Arsenic (As) contamination is widespread in soil and poses a threat to agricultural products and human health due to its high susceptibility to absorption by rice. Fe-bearing materials (Fe-Mat) display significant potential for reducing As bioavailability in soil and bioaccumulation in rice. However, the remediation effect of various Fe-Mat is often inconsistent, and the response to diverse environmental factors is ambiguous. Here, we conducted a meta-analysis to quantitatively assess the effects of As in soils, rice roots, and grains based on 673, 321, and 305 individual observations from 67 peer-reviewed articles, respectively. On average, Fe-Mat reduced As bioavailability in soils, rice roots, and grains by 28.74 %, 33.48 %, and 44.61 %, respectively. According to the analysis of influencing factors, the remediation efficiency of Fe-Mat on As-contaminated soil was significantly enhanced with increasing Fe content in the material, in which the industry byproduct was the most effective in soils (-42.31 %) and rice roots (-44.57 %), while Fe-biochar was superior in rice grains (-54.62 %). The efficiency of Fe-Mat in minimizing soil As mobility was negatively correlated with soil Fe content, CEC, and pH. In addition, applying Fe-Mat in alkaline soils with higher silt, lower clay and available P was more effective in reducing As in rice grains. A higher efficiency of applying Fe-Mat under continuous flooding conditions (27.39 %) compared with alternate wetting and drying conditions (23.66 %) was also identified. Our results offer an important reference for the development of remediation strategies and methods for various As-contaminated paddy soils.

The Developmental Toxicity and Endocrine-Disrupting Effects of Fenpropathrin on Gobiocypris rarus during the Early Life Stage.

In the present study, the developmental toxicity and endocrine-disrupting effects of fenpropathrin on Gobiocypris rarus during the early life stage were studied using a semi-static water exposure method. The results showed that the LOEC (lowest observed effect concentration) of fenpropathrin on the incubation of rare minnow embryos was above 2.5 µg·L-1. The LOEC and NOEC (no observed effect concentration) of fenpropathrin on the developmental malformations and death indicators were 2.0 and 1.5 µg·L-1, respectively. After exposure to 1.5 µg·L-1 of fenpropathrin for 31 days, the expressions of androgen receptor genes (AR) and sex hormone-synthesis-related genes (CYP17 and CYP19a) were significantly decreased and the expressions of thyroid hormone receptor genes (TRß) and aryl hydrocarbon receptor genes (AhR1a and AhR2) were significantly increased in juvenile Gobiocypris rarus. The expression levels of the androgen receptor gene (AR), estrogen receptor gene (ER1), and the sex hormone-synthesis-related genes (HMGR, CYP17, and CYP19a) were significantly decreased, while the estrogen receptor gene (ER2a), thyroid hormone receptor gene (TRß), and aromatic hydrocarbon receptor genes (AhR1a and AhR2) were upregulated in juvenile Gobiocypris rarus under exposure to 2.0 µg·L-1 of fenpropathrin. Relatively low concentrations of fenpropathrin can affect the expression of sex hormone receptor genes, genes related to sex hormone synthesis, thyroid hormone receptor genes, and aromatic hydrocarbon receptor genes, thus interfering with the reproductive system, thyroid system, and metabolic level in Gobiocypris rarus. Therefore, more attention should be paid to the endocrine-disrupting effect caused by the pyrethroid insecticides in the water environment. Furthermore, studies on the internal mechanism of the endocrine-disrupting effect of pyrethroid insecticides on fish is needed in the future.

Protective effects of Zishen Huoxue recipe against neuronal injury in the neurovascular unit of rats with vascular dementia by interfering with inflammatory cascade-induced pyroptosis.

OBJECTIVE: Chinese herbal formulas show considerable therapeutic benefits in dementia. This study specifically explored the protective action of Zishen Huoxue recipe on the neurovascular unit (NVU) of rats with vascular dementia (VD). METHODS: VD rat models were established by permanent bilateral common carotid artery occlusion and treated with Zishen Huoxue recipe. In vitro glucose­oxygen deprivation (OGD)-injured NVU models were established and treated with miR-124-3p agomir or rat medicated serum. The neurological damage, histopathological changes, and neuronal injury in the rat hippocampus were assessed using Morris water maze test and histological stainings. Expression of miR-124-3p was determined using RT-qPCR. The blood-brain barrier/NVU injury, cell pyroptosis, NLRP3 inflammasome activation, and release of inflammatory factors were analyzed mainly by immunofluorescence analysis, TUNEL staining, Western blot, and ELISA. QS-21 (an NLRP3 activator) was used to verify the role of miR-124-3p/NLRP3. RESULTS: Zishen Huoxue recipe ameliorated the learning/memory deficits, neuronal injury, NVU insults, cell pyroptosis, activation of NLRP3 inflammasome, and extensive secretion of lactate dehydrogenase/IL-1ß/IL-18 in VD rats. miR-124-3p was downregulated in VD rats but upregulated after treatment of this recipe. miR-124-3p overexpression ameliorated NVU insults, reduced cell pyroptosis, lowered NLRP3 inflammasome activation, and suppressed inflammatory responses in OGD-injured NVU models. NLRP3 inflammasome activation partly counteracted the amelioration effect of miR-124-3p on pyroptosis. Zishen Huoxue recipe could upregulate miR-124-3p to suppress pyroptosis and protect NVU function. CONCLUSION: Zishen Huoxue recipe can upregulate miR-124-3p expression to repress the inflammatory cascade-evoked pyroptosis, thereby protecting against neuronal injury in the NVU of VD rats.

Remediation technologies for neonicotinoids in contaminated environments: Current state and future prospects.

Neonicotinoids (NEOs) are synthetic insecticides with broad-spectrum insecticidal activity and outstanding efficacy. However, their extensive use and persistence in the environment have resulted in the accumulation and biomagnification of NEOs, posing significant risks to non-target organisms and humans. This review provides a summary of research history, advancements, and highlighted topics in NEOs remediation technologies and mechanisms. Various remediation approaches have been developed, including physiochemical, microbial, and phytoremediation, with microbial and physicochemical remediation being the most extensively studied. Recent advances in physiochemical remediation have led to the development of innovative adsorbents, photocatalysts, and optimized treatment processes. High-efficiency degrading strains with well-characterized metabolic pathways have been successfully isolated and cultured for microbial remediation, while many plant species have shown great potential for phytoremediation. However, significant challenges and gaps remain in this field. Future research should prioritize isolating, domesticating or engineering high efficiency, broad-spectrum microbial strains for NEO degradation, as well as developing synergistic remediation techniques to enhance removal efficiency on multiple NEOs with varying concentrations in different environmental media. Furthermore, a shift from pipe-end treatment to pollution prevention strategies is needed, including the development of green and economically efficient alternatives such as biological insecticides. Integrated remediation technologies and case-specific strategies that can be applied to practical remediation projects need to be developed, along with clarifying NEO degradation mechanisms to improve remediation efficiency. The successful implementation of these strategies will help reduce the negative impact of NEOs on the environment and human health.

Contaminant characterization at pesticide production sites in the Yangtze River Delta: Residue, distribution, and environmental risk.

The Yangtze River Delta (YRD) is the largest pesticide-producing region in the world. Contamination of pesticide production sites has always been a focus of public attention. Twenty pesticide production sites in YRD were selected to analyze the residue, distribution, and environmental risk of organic contaminants in soil and groundwater. A total of 194 organic chemicals were detected in all soil and groundwater samples from the 20 sites. Eighty-eight constituents of concern (COCs) exceeded the comparison values of Regional Screening Levels (RSLs), and 80 % exceeded the RSLs by more than five times. The toxic effects of COCs in soil and groundwater were dominated by the carcinogenic risk, referred as "non-threshold". Benzene toluene ethylbenzene & xylene (BTEX) and chloroaliphatic hydrocarbons (CAHs) were the most prevalent at pesticide sites in YRD rather than pesticides, followed by chlorobenzene, chlorophenols, and polycyclic aromatic hydrocarbons (PAHs). CAHs and BTEX could penetrate up to 24 m, while the others were primarily limited to 12 m. Most pesticide production sites showed a great contamination depth of >8 m, some even deeper than 20 m, posing a great risk of contamination to the confined aquifer. Due to the close interconnection of soil with water bodies, the shallow groundwater and adjacent surface water resources are also susceptible to suffering from environmental risk. More than half of the pesticide production sites in the YRD consist primarily of low-permeable clay layers, making in-situ contamination remediation difficult. This study provides a basis for developing remediation technology for pesticide sites in YRD and an ecological reference for further cleaning production and green manufacturing in the pesticide industry.

miR-486-5p and miR-22-3p Enable Megakaryocytic Differentiation of Hematopoietic Stem and Progenitor Cells without Thrombopoietin.

Megakaryocytes release submicron size microparticles (MkMPs) in circulation. We have shown that MkMPs target CD34+ hematopoietic stem/progenitor cells (HSPCs) to induce megakaryocytic differentiation, and that small RNAs in MkMPs play an important role in the development of this phenotype. Here, using single-molecule real-time (SMRT) RNA sequencing (RNAseq), we identify the synergetic effect of two microRNAs (miRs), miR-486-5p and miR-22-3p (highly enriched in MkMPs), in driving the Mk differentiation of HSPCs in the absence of thrombopoietin (TPO). Separately, our data suggest that the MkMP-induced Mk differentiation of HSPCs is enabled through JNK and PI3K/Akt/mTOR signaling. The interaction between the two signaling pathways is likely mediated by a direct target of miR-486-5p and a negative regulator of PI3K/Akt signaling, the phosphatase and tensin homologue (PTEN) protein. Our data provide a possible mechanistic explanation of the biological effect of MkMPs in inducing megakaryocytic differentiation of HSPCs, a phenotype of potential physiological significance in stress megakaryopoiesis.

Manufacturing a chimpanzee adenovirus-vectored SARS-CoV-2 vaccine to meet global needs.

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production. We discuss the process economics and the "distributed manufacturing" approach we have taken to provide the vaccine at globally-relevant scale and with international security of supply. Together, these approaches have enabled the largest viral vector manufacturing campaign to date, providing a substantial proportion of global COVID-19 vaccine supply at low cost.

Oxidative stress induced in rice suspension cells exposed to microcystin-LR at environmentally relevant concentrations.

Microcystins (MCs) are cyclic heptapeptide hepatotoxins that are highly soluble in water and can be transferred to farmland through irrigation with potentially substantial effects on crops, especially rice. In order to investigate the possible negative effects of microcystin-LR (MC-LR) on rice, the oxidative stress induced in rice suspension cells exposed to MC-LR at environmentally relevant concentrations (0.05, 0.5, 5.0, and 50.0 µg·L-1) was investigated. Results showed that the exposure to MC-LR at 0.5-50.0 µg·L-1 resulted in a significant decline in viability of rice suspension cells and an increase in malondialdehyde (MDA) contents. In the 50.0-µg·L-1 MC-LR treatment group, the content of MDA was as much as 5.39 times that of the control group after 6 days of exposure. The excess MDA production indicated that MC-LR exposure has caused lipid peroxidation damage in rice cells, whereas these negative effects could be recovered over time when suspension cells were exposed to low concentration of MC-LR (0.05 µg·L-1). When exposed to MC-LR for 3 days, the O2- content in all treatment groups increased significantly compared with the control group. Additionally, the antioxidant system of rice suspension cells initiated a positive stress response to MC-LR exposure. Indeed, peroxidase (POD) played an active role in the removal of reactive oxygen species (ROS) in rice suspension cells during the early period of exposure, while total superoxide dismutase (T-SOD) was induced after 6 days. Similarly, after 6 days of exposure, the anti-superoxide anion free radical activity (ASAFR), glutathione (GSH), and glutathione-S transferase (GST) in rice suspension cells were higher than that in the control group. These results provided a comprehensive understanding of the exposure time- and dose-dependent oxidative stress induced by the environmentally relevant concentrations of MC-LR in rice suspension cells.

Addressing Patient to Patient Variability for Autologous CAR T Therapies.

Chimeric Antigen Receptor (CAR) T cell therapy clinical trials have had unprecedented success in the endeavors to cure cancer patients, particularly those having hematological cancers. As researchers learn more about the ways to make CAR T cells more effective to kill tumor cells, equally important will be understanding the differences between T cells from healthy donors and cancer patients and how these differences could affect ex vivo expansion of T cells during CAR T production. This undoubtedly could be a crucial factor in treating solid tumors, where CAR T cells are needed in significantly higher numbers. As the evidence for significant differences between the patients and healthy donors is compelling, an adaptable and robust production process should be designed to allow manufacture of the required CAR T cells for all cancer patients. Improving the fundamental understanding of the cellular metabolism and accompanying epigenetic and phenotypic changes during in vivo and ex vivo expansion of T cells will be just as important. Such discoveries will provide an invaluable tool box from which actionable knowledge could be drawn for designing an adaptable CAR T production process that is able to absorb the patient-to-patient variation.

Comparison of Four Amendments for Arsenic and Cadmium Combined Contaminated Soil.

Arsenic (As) and cadmium (Cd) are common soil pollutants whose opposing geochemical behaviors must be taken into account in the development of cost-effective, environmentally friendly remediation strategies. In this study, a pot experiment with lettuce and a field experiment with wheat were performed to examine the impacts of zeolite, biochar, MnO2, zero-valent iron (ZVI) individually and in binary combinations thereof on As-Cd pollution. The results of the pot experiment showed that biochar, MnO2 and ZVI had good passivation effects on As and Cd when provided individually, but the effects of a combination of 0.2% ZVI/0.5% biochar or 0.2% MnO2/0.5% ZVI were even better. These amendments were further investigated in a field experiment, which confirmed the positive effect of 0.2% MnO2/0.5% ZVI. Therefore, ZVI/biochar and MnO2/ZVI mixtures may offer effective solutions to the remediation of farmland soil contaminated with both As and Cd.

Ecotoxicity of the nonsteroidal ecdysone mimic RH-5849 to Daphnia magna.

The nonsteroidal ecdysone mimic 1,2-dibenzoyl-1-tert-butylhydrazine (RH-5849), a novel insect growth regulator, is mainly registered for use in rice fields. So far, its toxicity and ecological risks towards aquatic cladoceran invertebrates remain unclear. In this study, RH-5849 was evaluated for its acute and 21-day chronic toxicity towards Daphnia magna. The viability, morphology, growth, and reproduction of D. magna were observed to establish a concentration-toxicity relationship associated with the RH-5849 exposure. In addition, the relationship between the changes of physiological and biochemical indices and the chronic indices was analyzed in order to find potential early warning indicators in D. magna to the chronic risk of RH-5849 exposure. The results showed that the 48-h EC50 of acute immobilization and EC50 of 21-day survival of RH-5849 on D. magna were 45.3 and 1.34 mg/L, respectively. Chronic exposure to RH-5849 mainly affected the reproductive parameters of D. magna and the no observed effect concentration (NOEC) and the EC50 were 0.050 and 0.5423 mg/L, respectively. The number of offspring per female reduced significantly after 21-day exposure to 0.10 mg/L of RH-5849. The morphological changes, manifested in head width and body length, the length of the helmet or apical spine, and the curvature and transparency of the body, were observed in RH-5849-treated groups. Moreover, it was found that the alkaline phosphatase activity in D. magna after 5-7-day exposure was positively correlated with the number of offspring per female after 21 days. These results indicate the potential risk of RH-5849 towards aquatic crustaceans should be taken into consideration when applied to rice fields.

How do megakaryocytic microparticles target and deliver cargo to alter the fate of hematopoietic stem cells?

Megakaryocytic microparticles (MkMPs), the most abundant MPs in circulation, can induce the differentiation of hematopoietic stem and progenitor cells (HSPCs) into functional megakaryocytes. This MkMP capability could be explored for applications in transfusion medicine but also for delivery of nucleic acids and other molecules to HSPCs for targeted molecular therapy. Understanding how MkMPs target, deliver cargo and alter the fate of HSPCs is important for exploring such applications. We show that MkMPs, which are distinct from Mk exosomes (MkExos), target HSPCs with high specificity since they have no effect on other ontologically or physiologically related cells, namely mesenchymal stem cells, endothelial cells or granulocytes. The outcome is also specific: only cells of the megakaryocytic lineage are generated. Observation of intact fluorescently-tagged MkMPs inside HSPCs demonstrates endocytosis as one mechanism of cargo delivery. Fluorescent labeling and scanning electron microscopy (SEM) imaging show that direct fusion of MkMPs into HSPCs is also engaged in cargo delivery. SEM imaging detailed the membrane-fusion process in four stages leading to full adsorption of MkMPs into HSPCs. Furthermore, macropinocytosis and lipid raft-mediated were shown here as mechanisms of MkMP uptake by HSPC. In contrast, the ontologically related platelet-derived MPs (PMPs) cannot be taken up by HSPCs although they bind to and induce HSPC aggregation. We show that platelet-like thrombin activation is apparently responsible for the different biological effects of MkMPs versus PMPs on HSPCs. We show that HSPC uropods are the preferential site for MkMP binding, and that CD54 (ICAM-1), CD11b, CD18 and CD43, localized on HSPC uropods, are involved in MkMP binding to HSPCs. Finally, we show that MkMP RNA is largely responsible for HSPC programming into Mk differentiation.

Oxidative stress and histopathological alterations in liver of Cyprinus carpio L. induced by intraperitoneal injection of microcystin-LR.

Microcystins (MCs) are a group of cyclic heptapeptide hepatotoxic peptides produced by cyanobacteria. Microcystins-LR (MC-LR) can inhibit the activities of protein phosphatase type 1 and type 2A (PP1 and PP2A) and induce excessive production of reactive oxygen species (ROS). However, the detailed toxicological mechanism involving oxidative stress in carp (Cyprinus carpio L.) remains largely unclear. In our present study, the effects of sublethal intraperitoneal doses of MC-LR on the oxidative stress and pathological changes in carp liver were investigated. No significant changes of xanthine oxidase were observed, suggesting it might not contribute to over-production of ROS in the liver of fish during 48 h exposure to sublethal intraperitoneal doses of MC-LR. Superoxide dismutase activity in the 50 µg kg(-1) group was significantly induced at 1-24 h. The strongest inhibition of the catalase activity was shown at 48 h after 120 µg kg(-1) MC-LR exposure, with an inhibition rate of 33.7% compared to the control group. In general, a significant depletion of intracellular reduced glutathione was found at 5-12 h after 50 and 120 µg kg(-1) MC-LR exposure, which was mainly due to the conjugation reaction to MC-LR catalyzed by glutathione-S-transferase and its subsequent excretion. Oxidative damages induced by MC-LR were evidenced by the significant elevation in malondialdehyde levels. In addition, a series of histopathological alterations in fish livers were observed, and the most severe hepatic injuries were found at 5-12 h, which could contribute to the efflux of intracellular GSH. Our study further supports the important role of oxidative stress involved in MC-LR induced liver injury in aquatic organisms.

Shear enhances thrombopoiesis and formation of microparticles that induce megakaryocytic differentiation of stem cells.

In vivo visualization of thrombopoiesis suggests an important role for shear flow in platelet biogenesis. In vitro, shear stress was shown to accelerate proplatelet formation from mature megakaryocytes (Mks). Yet, the role of biomechanical forces on Mk biology and platelet biogenesis remains largely unexplored. In this study, we investigated the impact of shear stress on Mk maturation and formation of platelet-like particles (PLPs), pro/preplatelets (PPTs), and Mk microparticles (MkMPs), and furthermore, we explored a physiological role for MkMPs. We found that shear accelerated DNA synthesis of immature Mks in an exposure time- and shear stress level-dependent manner. Both phosphatidylserine exposure and caspase-3 activation were enhanced by shear stress. Exposure to physiological shear dramatically increased generation of PLPs/PPTs and MkMPs by up to 10.8 and 47-fold, respectively. Caspase-3 inhibition reduced shear-induced PLP/PPT and MkMP formation. PLPs generated under shear flow displayed improved functionality as assessed by CD62P exposure and fibrinogen binding. Significantly, coculture of MkMPs with hematopoietic stem and progenitor cells promoted hematopoietic stem and progenitor cell differentiation to mature Mks synthesizing α- and dense-granules, and forming PPTs without exogenous thrombopoietin, thus identifying a novel and unexplored potential physiological role for MkMPs.

Proteomic analysis of hepatic tissue of Cyprinus carpio L. exposed to cyanobacterial blooms in Lake Taihu, China.

With the rapid development of industry and agriculture and associated pollution, the cyanobacterial blooms in Lake Taihu have become a major threat to aquatic wildlife and human health. In this study, the ecotoxicological effects of cyanobacterial blooms on cage-cultured carp (Cyprinus carpio L.) in Meiliang Bay of Lake Taihu were investigated. Microcystins (MCs), major cyanobacterial toxins, have been detected in carp cultured at different experimental sites of Meiliang Bay. We observed that the accumulation of MCs in carp was closely associated with several environmental factors, including temperature, pH value, and density of cyanobacterial blooms. The proteomic profile of carp liver exposed to cyanobacterial blooms was analyzed using two-dimensional difference in-gel electrophoresis (2D-DIGE) and mass spectrometry. The toxic effects of cyanobacterial blooms on carp liver were similar to changes caused by MCs. MCs were transported into liver cells and induced the excessive production of reactive oxygen species (ROS). MCs and ROS inhibited protein phosphatase and aldehyde dehydrogenase (ALDH), directly or indirectly resulting in oxidative stress and disruption of the cytoskeleton. These effects further interfered with metabolic pathways in the liver through the regulation of series of related proteins. The results of this study indicated that cyanobacterial blooms pose a major threat to aquatic wildlife in Meiliang Bay in Lake Taihu. These results provided evidence of the molecular mechanisms underlying liver damage in carp exposed to cyanobacterial blooms.

Microcystin-LR induced reactive oxygen species mediate cytoskeletal disruption and apoptosis of hepatocytes in Cyprinus carpio L.

Microcystins (MCs) are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR) contains Leucine (L) and Arginine (R) in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A) activities and induce excessive production of reactive oxygen species (ROS). The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L.) remains largely unclear. In our present study, the hydroxyl radical (•OH) was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS) production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC) provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO) exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12-48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity.

Stem-cell niche based comparative analysis of chemical and nano-mechanical material properties impacting ex vivo expansion and differentiation of hematopoietic and mesenchymal stem cells.

The ability of stem cells to self-renew with minimal or no differentiation and, when appropriately cued, to give rise to many types of progenitor and mature cells, is the basis for applications in regenerative and transfusion medicine, but also in drug discovery and in vitro toxicology. Inspired by the complex interactions between stem cells and their microenvironment, the so-called stem-cell niche, the properties of supporting biomaterials, including surface biochemistry, topography (type, size, organization, and geometry of nanostructures), and mechanical properties, have been identified as important determinants of stem-cell fate in vitro. 3D culture environments that could recapitulate the complexity of the in vivo stem-cell microenvironment could further expand the complexity and repertoire of engineered environments with exciting translational applications. Herein, the material aspects that affect the expansion and differentiation fate of adult hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stem cells (MSCs), two powerful cell types that co-reside in the bone-marrow niche, but with distinct, sometime complementary, differentiation fates, properties, and translational applications, are examined. Although MSCs are adherent cells and, in contrast, HSPCs are non- or weakly adherent cells, both can sense and respond to material properties, including surface (bio)chemistry, ECM composition, topography, and matrix elasticity, possibly through similar molecular mechanisms.