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Acetaminophen (APAP) is one of the most widely used drugs in the world. The literature shows that excessive or long-term use of APAP can lead to increased cardiovascular dysfunction. An acute increase in angiotensin Ⅱ (Ang Ⅱ) caused by APAP use in fatty liver disease may increase the risk and severity of vascular injury. However, the underlying mechanism remains unclear. Caveolin-1 (CAV1) is a broad-spectrum kinase inhibitor that significantly determines endothelial function. This study aimed to observe the effects of APAP on the vasculature in non-alcoholic fatty liver disease (NAFLD) and to determine whether CAV1 could alleviate vascular oxidative stress and inflammation by targeting Ang Ⅱ or its downstream pathways. In this study, 7-week-old C57BL/6 male mice (18-20 g) were administered APAP by gavage after eight weeks of a high-fat diet. Any resulting vascular oxidative stress and inflammation were assessed. Levels of Ang Ⅱ, CAV1, and other related proteins were measured using ELISA and western blotting. In APAP-treated NAFLD mice, CAV1 expression was downregulated and Ang Ⅱ expression was upregulated compared to normal APAP-treated mice. In vitro, HUVECs were incubated with Ang Ⅱ (300 nM) for 48 h. Overexpression of CAV1 in HUVECs attenuated Ang Ⅱ-induced oxidative stress and inflammation and downregulated the expression of Protein kinase C (PKC) and p-P38/P38. After intervention with CAV1-siRNA, immunofluorescence results showed that the fluorescence intensity of PKC on mitochondria was further increased, and flow cytometry results showed that the mitochondrial membrane potential increased. PKC inhibitors alleviated Ang Ⅱ-induced endothelial injury. In conclusion, our findings confirmed that CAV1 exerts a protective effect against vascular injury by inhibiting oxidative stress and inflammation through the PKC/MAPK pathway. Therefore, restoration of CAV1 may have clinical benefits in reducing APAP-induced vascular damage in NAFLD patients.

Acetaminophen (APAP) is a widely used antipyretic analgesic which can lead to acute liver failure after overdoses. Chronic alcoholic fatty liver disease (AFLD) appears to enhance the risk and severity of APAP-induced liver injury, and the level of angiotensin II (Ang II) increased sharply at the same time. However, the underlying mechanisms remain unclear. Caveolin-1 (CAV1) has been proven to have a protective effect on AFLD. This study aimed to examine whether CAV1 can protect the APAP-induced hepatotoxicity of AFLD by affecting Ang II or its related targets. In vivo, the AFLD model was established according to the chronic-plus-binge ethanol model. Liver injury and hepatic lipid accumulation level were determined. The levels of Angiotensin converting enzyme 2 (ACE2), Ang II, CAV1, and other relevant proteins were evaluated by western blotting. In vitro, L02 cells were treated with alcohol and oleic acid mixture and APAP. CAV1 and ACE2 expression was downregulated in APAP-treated AFLD mice compared to APAP-treated mice. The overexpression of CAV1 in mice and L02 cells alleviated APAP-induced hepatotoxicity in AFLD and downregulated Ang II, p-EGFR/EGFR and P-ERK/ERK expression. Immunofluorescence experiments revealed interactions between CAV1, Ang II, and EGFR. The application of losartan (an Ang II receptor antagonist) and PD98059 (an ERK1/2 inhibitor) alleviated APAP-induced hepatotoxicity in AFLD. In conclusion, our findings verified that CAV1 alleviates APAP-aggravated hepatotoxicity in AFLD by downregulating the Ang II /EGFR/ERK axis, which could be a novel therapeutic target for its prevention or treatment.

SummaryThe capacity to generate functional hepatocytes from renewable human pluripotent stem cells (hPSCs) could address limited supplies of primary human hepatocytes. However, hepatocytes differentiated from hPSCs in vitro are functionally immature. To understand mechanisms regulating maturation of in vitro derived hepatocytes, we developed a 3D spheroid differentiation system and compared gene regulatory elements in uncultured human primary hepatocytes with those in hepatocytes that were differentiated in 2D or 3D conditions from human PSCs by RNA-seq, ATAC-seq, and H3K27Ac ChIP-seq. Three-dimensional differentiation improved enhancer activity and expression of transcription factor ONECUT1, but was insufficient to upregulate human-specific mature hepatocytes marker gene CYP3A4 or super-enhancer regulated transcription factor gene NFIC. Regulome comparisons showed reduced enrichment of thyroid receptor THRB motifs in accessible chromatin and in active enhancers without reduced transcription of THRB, suggesting the regulation at the level of THRB ligands in PSC-differentiated hepatocytes. Addition of thyroid hormone T3 to the PSC-differentiated hepatocytes increased CYP3A4 expression. T3 increased binding of THRB to the CYP3A4 proximal enhancer and restored the super-enhancer status and gene expression of NFIC and reduced expression of AFP. The resultant hPSC-hepatocytes showed gene expression, epigenetic status and super-enhancer landscape closer to primary hepatocytes and activated regulatory regions including non-coding SNPs associated with liver-related diseases. Transplanting the 3D PSC-hepatocytes into immunocompromised mice resulted in engraftment of human hepatocytes in the mouse liver parenchyma without disrupting normal liver histology at 6 months after transplantation. This work provides insights into the functions of nuclear receptor THRB and highlights the importance of the environmental factors-nuclear receptors axis in regulating maturation of human PSC-differentiated cell types.

Objectives : Studies have demonstrated that CK2 is engaged in CD4+ T cell proliferation and activation. We investigated the potential involvement of CK2 in the pathogenesis of rheumatoid arthritis (RA). Methods Peripheral blood and synovial fluid mononuclear cells (PBMC and SFMC) of RA patients, as well as splenocytes of collagen-induced arthritis (CIA) mice were treated with different doses of CK2 inhibitor CX4945 in vitro. Then, the Th1, Th2, Th17, and Treg cell responses were analyzed. In addition, CIA mice were administrated with CX4945 via oral gavage. Accordingly, the arthritis scores, bone destruction, tissue damage, and the CD4+ T cell subsets were assessed. Results The expression of CK2 was upregulated in CD4+ T cells under RA circumstance. In vitro CX4945 treatment significantly inhibited the Th1 and Th17 cell responses, while promoted the Th2 cell responses in RA patient PBMC, SFMC and CIA mouse splenocytes, dampening IFN-γ and IL-17A production. Moreover, administration of CX4945 ameliorated the severity of arthritis in CIA mice, along with decreased Th1 and Th17 cells. However, CX4945 seemed to have minimal effect on RA Treg cells. Conclusion CK2 serves as an important regulator of the Th1 and Th17 cell axes in RA, thus contributing to the disease aggravation.

Advances in urban infrastructure, a flourishing polymer sector, and more traffic have all contributed to a rise in micro(nano)plastics in the environment. Researchers are exploring the production, fate, toxicity threshold, and severity of micro(nano)plastic exposure. Albeit, understanding sampling protocols, preservation of samples, and characterization of micro(nano)plastics obtained from the different mediums (e.g., soil, water, air, and living bodies) is still challenging. Particularly identification of micro(nano)plastics, on the other hand, is restricted and limited to the typical generic definition of contaminating sources. In addition, before micro(nano)plastics degrade naturally, many challenges must be overcome, enhancing the need for research on assisted degradation. Thus, a systematic review is presented, which begins by discussing micro(nano)plastic identification, sampling, and handling; then showcases the environmental and health consequences and how to control them; finally, it discusses environmental micro(nano)plastics management options. According to studies, biological and chemical methods to break down micro(nano)plastics have risen in popularity. However, these methods often only cover one type of plastic. Furthermore, these solutions can transform polymers into micro(nano)plastics and may also produce byproducts, increasing environmental contamination risk. Therefore, control, prevention, and management strategies are all investigated to generate more realistic and long-term solutions. The literature suggests a combination of different microorganisms (e.g., different bacterial species) and different approaches (e.g., filtration with degradation) could be more effective in the treatment of micro(nano)plastics. Furthermore, according to the literature, relevant health risks associated with micro(nano)plastics to humans from various exposure routes are currently unclear. Likewise, standardization of methods supported with sophisticated state-of-the-art apparatus for detecting micro(nano)plastics is required. Overall, precision in micro(nano)plastic identification and treatment strategy selection is critical, and their usage should be regulated if their environmental behavior is not properly addressed.

Fragile X syndrome (FXS) is characterized by physical abnormalities, anxiety, intellectual disability, hyperactivity, autistic behaviors, and seizures. Abnormal neuronal development in FXS is poorly understood. Data on patients with FXS remain scarce, and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons.To mimic human neuron development in vivo, we coinjected neural precursor cells derived from FXS patient-derived induced pluripotent stem cells and neural precursor cells derived from corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice.The transplanted cells populated the brain and a proportion differentiated into neurons and glial cells. Immunofluorescence and single and bulk RNA sequencing analyses showed accelerated maturation of FXS neurons after an initial delay. Additionally, we found increased percentages of Arc- and Egr-1-positive FXS neurons and wider dendritic protrusions of mature FXS striatal medium spiny neurons.This transplantation approach provides new insights into the alterations of neuronal development in FXS by facilitating physiological development of cells in a 3-dimensional context.

Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The transplanted cells populated the brain and a proportion differentiated into neurons and glial cells. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons after an initial delay. Additionally, increased percentages of Arc- and Egr1-positive FXS neurons and wider dendritic protrusions of mature FXS striatal medium spiny neurons pointed to an increase in synaptic activity and synaptic strength as compared to control. This transplantation approach provides new insights into the alterations of neuronal development in FXS by facilitating physiological development of cells in a 3D context, and could be used to test new therapeutic compounds correcting neuronal development defects in FXS.

The shortage of fossil fuels is actually a major economic issue in the context of increasing energy demand. Renewable energies are thus gaining in importance. For instance, microalgae-based fuels are viewed as an alternative. Microalgae are microscopic unicellular plants, which typically grow in marine and freshwater environments. They are fast growing, have high photosynthetic efficiency, and have relatively small land requirement and water consumption in comparison with conventional land crops biofuels. Nonetheless, selling biofuels is still limited by high cost. Here, we review biofuel production from microalgae, including cultivation, harvesting, drying, extraction and conversion of microalgal lipids. Cost issues may be solved by upstream and downstream measures: (1) upstream measures, in which highly productive strains are obtained by strain selection, genetic engineering and metabolic engineering, and (2) downstream measures, in which high biofuels yields are obtained by enhancing the cellular lipid content and by advanced conversion of microalgal biomass to biofuels. Maximum biomass and high biofuels production can be achieved by two-stage culture strategies, which is a win–win approach because it solves the conflicts between cell growth and biomass accumulation.

Background Lupus nephritis (LN) is an inflammation of the kidneys and is a major cause of mortality in systemic lupus erythaematosus (SLE) patients. In addition, Th17/Treg balance is one of the most important factors that can promote the development of LN. It has been reported that vasoactive intestinal peptide (VIP) is associated with the downregulation of both inflammatory and autoimmune diseases through regulating T lymphocyte balance. Therefore, the aim of this study was to determine the role of VIP in modulating Th17/Treg balance in LN. Methods LN was induced in BALB/c female mice by injection pristane. After 3 months, mice were randomly divided into four groups: control, VIP + control, LN and VIP + LN. Autoantibody levels were tested by ELISA. The distribution of Th17/Treg cells in vivo and in vitro was detected by FC. Renal tissues were examined by PASM and DIF for pathology and Foxp3+CD3+. The mRNA and protein expression levels of pro- and anti-inflammatory cytokines were detected by qRT-PCR and western blotting. Results VIP can improve renal injury by regulating Th17/Treg imbalance in LN mice. Proteinuria, renal function defects and autoantibodies were significantly decreased, and Th17/Treg cell balance was restored in VIP compared with LN mice. In addition, VIP improved renal lesions by promoting the expression of Foxp3+CD3+ in renal tissue. Furthermore, VIP downregulated the mRNA and protein expression of IL-17, IL-6 and upregulated Foxp3, IL-10 expression. Conclusions VIP reduced LN proteinuria and renal function defects and restored the Th17/Treg cell balance. Furthermore, VIP also downregulated autoantibody and inflammatory cytokine expression and upregulated Foxp3 and IL-10 expression.

Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases as well as being associated with the progression of kidney disease. Activation of the Wnt/β-catenin pathway is associated with the pathogenesis of podocyte dysfunction and can play a role in renal injury. Furthermore, the expression of fractalkine (FKN) induced by lipopolysaccharides (LPS) is also one of crucial inflammation factors closely related to renal tissue damage. The aim of this study is to explore the mechanism of LPS-induced FKN expression leading to podocyte injury and contribute to acute kidney injury (AKI) through regulation of Wnt/β-catenin pathway. An AKI model was established for in vivo experiments and blood was collected for serum BUN and Cr measurement, and histopathological features of the kidneys were studied by PASM and IHC staining. For in vitro experiments, a mouse podocyte cell line was stimulated with different concentrations of LPS for 24 and 48 h after which podocyte viability and apoptosis of cells were evaluated. The expression of podocyte-specific markers, FKN and Wnt/β-catenin pathway mRNA and protein was detected in mice and cells by using qRT-PCR and western blotting. LPS induced the expression of FKN and activation of the Wnt/β-catenin pathway, leading to a decrease of podocyte-specific proteins which resulted in poor renal pathology and dysfunction in the AKI mouse model. Moreover, LPS treatment significantly decreased cell viability and induced podocyte apoptosis in a dose-dependent manner that causes changes in the expression of podocyte-specific proteins through activation of FKN and the Wnt/β-catenin pathway. Thus, the expression of FKN and Wnt/β-catenin pathway by LPS is closely associated with podocyte damage or loss and could therefore account for progressive AKI. Our findings indicate that LPS induce podocyte injury and contribute to the pathogenesis of AKI by upregulating the expression of FKN and Wnt/β-catenin pathway.

Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The cells populated the brain and differentiated into neurons and astrocytes. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons, an increased proportion of Arc-positive FXS neurons and increased dendritic protrusion width of FXS striatal medium spiny neurons. Our data show faster maturation and suggest increased synaptic activity and synaptic strength of FXS transplanted neurons. This model provides new insights into the alterations in FXS neuronal development.

Doped semiconductors supporting localized surface plasmon resonances, such as nonstoichiometric copper chalcogenides Cu2–xSe, have been intensively researched for their potential applications in photoacoustic imaging and photothermal therapy. For these self-doped nanoparticles, their physicochemical attributes such as size and surface chemistry will not only affect their cellular uptake and biodistribution but also influence their own optical properties. Thus, optimization of the physicochemical properties is crucial for their nanobio-applications. Through a seeded growth approach, aqueous phase synthesis of monodisperse Cu2–xSe with various sizes has been developed for the first time. Taking three different sized Cu2–xSe NPs (35, 65, and 105 nm in diameter) as examples, their size-dependent optical cross-section, photothermal property, and cellular cytotoxicity have been investigated, and the 65 nm one displays the largest optical cross-section at 21.57 L g–1 cm–1 and best photothermal property per unit ...

Active control of nanocrystal optical and electrical properties is crucial for many of their applications. By electrochemical (de)lithiation of Cu2-xSe, a highly doped semiconductor, dynamic and reversible manipulation of its NIR plasmonics has been achieved. Spectroelectrochemistry results show that NIR plasmon red-shifted and reduced in intensity during lithiation, which can be reversed with perfect on-off switching over 100 cycles. Electrochemical impedance spectroscopy reveals that a Faradaic redox process during Cu2-xSe (de)lithiation is responsible for the optical modulation, rather than simple capacitive charging. XPS analysis identifies a reversible change in the redox state of selenide anion but not copper cation, consistent with DFT calculations. Our findings open up new possibilities for dynamical manipulation of vacancy-induced surface plasmon resonances and have important implications for their use in NIR optical switching and functional circuits.

To date, the degradation of microplastics (MPs;5 mm) in different environments, particularly their adsorption characteristics for coexisted metal pollutants remains to be elucidated. Thus, this study investigated the effects of aging MPs, including polyamide (mPA), polyethylene terephthalate (mPET), polystyrene (mPS), and polyvinyl chloride (mPVC) for 3 months under UVA irradiation in four environmental media (air, seawater, sand, and soil) and adsorption of heavy metals (Cu, Cd) onto seawater-aged mPS and mPVC. The results showed that surface morphological changes, including cracks, oxidized particles, and wrinkles, appeared on aged MPs. The heavy metal adsorption capacity decreased in the order aged mPVCaged mPS unaged mPS unaged mPVC, and the Cu

Theranostic nanomedicine, which uses both imaging and therapeutic components for simultaneous disease diagnosis and treatment, is expected to improve patient treatment safety and outcomes by offering a more personalized approach to medicine. However, the poor reproducibilities of nanomedicines synthesized for optimized bioavailability and their potential toxicity are impeding clinical development. Moreover, milligram-scale synthetic methods are often inconsistent when transferred to mass production. To address these challenges, a facile, room temperature, aqueous phase synthesis of nanotheranostic agents using clinically validated mesoporous silica and naturally derived polydopamine has been developed. Since the synthetic procedure is simple and robust, and requires only simple mixing under ambient conditions, excellent batch-to-batch consistency has been achieved. As a result, this process can be easily scaled-up to produce gram-scale batches with physicochemical parameters similar to those of materials synthesized in smaller batches. The resulting nanotheranostic agents exhibit efficient X-ray tomography and T1-weighted magnetic resonance image contrast enhancing abilities due to their chemically ligated, benign Bi3+ and Fe3+ ions. Furthermore, the inclusion of a polydopamine shell makes the nanoparticle surface easy to functionalize and renders these materials highly efficient as photothermal agents. These nanotheranostic agents are suitable for mass production and for potential applications in multimodal imaging-guided therapy in clinical settings.

Microglia are essential for maintenance of normal brain function, with dysregulation contributing to numerous neurological diseases. Protocols have been developed to derive microglia-like cells from human induced pluripotent stem cells (hiPSCs). However, primary microglia display major differences in morphology and gene expression when grown in culture, including down-regulation of signature microglial genes. Thus, in vitro differentiated microglia may not accurately represent resting primary microglia. To address this issue, we transplanted microglial precursors derived in vitro from hiPSCs into neonatal mouse brains and found that the cells acquired characteristic microglial morphology and gene expression signatures that closely resembled primary human microglia. Single-cell RNA-sequencing analysis of transplanted microglia showed similar cellular heterogeneity as primary human cells. Thus, hiPSCs-derived microglia transplanted into the neonatal mouse brain assume a phenotype and gene expression signature resembling that of resting microglia residing in the human brain, making chimeras a superior tool to study microglia in human disease.

The rapidly growing demands for powerful AI algorithms in many application domains have motivated massive investment in both high-quality deep neural network (DNN) models and high-efficiency implementations. In this position paper, we argue that a simultaneous DNN/implementation co-design methodology, named Neural Architecture and Implementation Search (NAIS), deserves more research attention to boost the development productivity and efficiency of both DNN models and implementation optimization. We propose a stylized design methodology that can drastically cut down the search cost while preserving the quality of the end solution.As an illustration, we discuss this DNN/implementation methodology in the context of both FPGAs and GPUs. We take autonomous driving as a key use case as it is one of the most demanding areas for high quality AI algorithms and accelerators. We discuss how such a co-design methodology can impact the autonomous driving industry significantly. We identify several research opportunities in this exciting domain., 8 pages, ICCAD 2019

Microplastics (MPs) pollution has been increasingly investigated in marine and freshwater environments, even in atmosphere in China. Current literatures show that MPs contamination is highly related to human activities and geomorphology. Higher MPs occurrences were detected in freshwaters than those in seawaters in China. Furthermore, the abundance of MPs was influenced by many factors, including sampling method, unit of measurement, characteristics of sampling area, and others. Currently, investigating the condition of MPs occurrences and distribution on a broader scale and developing standardized protocol, along with basic toxicological research, will help to address crucial knowledge gaps regarding MPs pollution, their interaction with other pollutants and ecological consequences on individual, population or ecosystem levels in the environment. Meanwhile, this review calls for more efforts to be made for better and scientifically sound risk management for mitigation of MPs pollution in China.

Autonomous driving cars need highly complex hardware and software systems, which require high performance computing platforms in order to enable a real time AI-based perception and decision making pipeline. The industry has been exploring various in-vehicle accelerators such as GPUs, ASICs and FPGAs. Yet the autonomous driving platform design is far from mature when taking into account of system reliability, redundancy and higher level of autonomy. In this work, we propose a hybrid computing system design, which integrates a GPU as the primary computing system and a FPGA as a secondary system. This hybrid system architecture has multiple advantages: 1) The FPGA can be constantly running as a complementary system with very short latency, helping to detect main system failure and anomalous behavior, contributing to system functionality verification and reliability. 2) If the primary system fails (mostly from sensor or interconnection error), the FPGA will quickly detect the failure and run a safe-mode task with a subset of sensors. 3) The FPGA can be used as an independent computing system to run extra algorithm components to improve the overall system autonomy. For example, FPGA can handle driver monitoring tasks while GPU focuses on driving functions. Together they can boost the driving function from L2 (constantly requires driver’s attention) to L3 (allows driver to mind off for 10 seconds). This paper defines how such a system works, discusses various use cases and potential design challenges, and shares some initial results and insights about how to make such a system deliver the maximum value for autonomous driving.

Plastic litters have become the predominant components of marine debris due to extensive consumption plastics and mismanagement of plastic wastes. As part of the problem, microplastics (MPs) and nanoplastics (NPs) have generated special concerns due to their unique features that make them easy to transfer among oceans in the marine ecosystem, across different trophic levels inside the food web, and even across different tissues inside contaminated animals. Studies have demonstrated the almost omnipresence of MPs in the marine ecosystem, which present serious threats to the health of marine animals, causing symptoms such as malnutrition, inflammation, chemical poisoning, growth thwarting, decrease of fecundity, and death due to damages at individual, organ, tissue, cell, and molecule levels. The information on NPs in the marine ecosystem has been scarce due to the challenges in sampling and detecting these nano-scaled entities. In vitro and in vivo experiments have demonstrated that NPs have the potential to penetrate different biological barriers including the gastrointestinal barrier and the brain blood barrier and have been detected in many important organs such as brains, the circulation system and livers of sampled animals.

Fractalkine (FKN), also known as chemokine (C-X3-C motif) ligand 1, constitutes an intriguing chemokine with a documented role in the development of numerous inflammatory diseases including autoimmune disease. Specifically, it has been reported that FKN is involved in the disease progression of lupus nephritis (LN). The epithelial-mesenchymal transition (EMT) plays a significant role in the formation of tubulointerstitial lesions (TIL), which are increasingly recognized as a hallmark of tissue fibrogenesis after injury. However, the correlation between FKN and EMT or TIL in LN has not been determined. To investigate the potential role of FKN in EMT and TIL, MRL lymphoproliferation (MRL/lpr) strain mice were treated with an anti-FKN antibody, recombinant-FKN chemokine domain, or isotype antibody. Our results revealed that treatment with the anti-FKN antibody improved EMT, TIL, and renal function in MRL/lpr mice, along with inhibiting activation of the Wnt/β-catenin signaling pathway. In contrast, administration of the recombinant-FKN chemokine domain had the opposite effect. Furthermore, to further explore the roles of FKN in EMT, we assessed the levels of EMT markers in FKN-depleted or overexpressing human proximal tubule epithelial HK-2 cells. Our results provide the first evidence that the E-cadherin level was upregulated, whereas α-SMA and vimentin expression was downregulated in FKN-depleted HK-2 cells. In contrast, overexpression of FKN in HK-2 cells enhanced EMT. In addition, inhibition of the Wnt/β-catenin pathway by XAV939 negated the effect of FKN overexpression, whereas activation of the Wnt/β-catenin pathway by Ang II impaired the effect of the FKN knockout on EMT in HK-2 cells. Together, our data indicate that FKN plays essential roles in the EMT progression and development of TIL in MRL/lpr mice, most likely through activation of the Wnt/β-catenin signaling pathway.

This study investigated microplastics (MPs) pollution in Haikou Bay in the northern South China Sea (SCS). Eight sampling sites were selected on the basis of their functions as hotel-intensive areas, public beaches, harbors, municipal discharge sites, and public waters. A total of 1053 putative plastic particles of which 1019 were from seawater and 34 from sediment were collected using 333 μm nylon Neuston nets and a bottom collector, respectively. The results showed that the abundance of MPs ranged from 0.26 to 0.84 items/m3 (hereafter defined as n/m3) in the surface water and 0.66 ± 0.58 n/50 g (d.w.)–17.00 ± 6.56 n/50 g (d.w.) in the sediment of Haikou Bay. For the surface seawater samples, the predominant MPs were fibers (83.12%) in rayon (52.73%). For the sediment samples, MPs were predominantly in fibers (67.65%), while PE (28.41%), polyolefin (25.50%), rayon (23.53%) were frequently detected. MPs are widely found in coastal seawater and sediment, but with different abundance in different functional areas. A higher abundance of MPs was found in the seawaters of public beaches and sediments of sewage discharge ditches. Our results highlight the occurrence of MPs in Haikou Bay, and we also offer field study results for the evaluation of environmental risks posed by MPs in the northern SCS.

Numerous studies have reported that angiotensin (Ang) II, nephrin, and podocin serve pivotal roles in podocyte injury, and thus can lead to the occurrence of proteinuria and the progression of kidney diseases. This study aimed to investigate the effects of Ang II on the production of nephrin and podocin, and their relationship with podocyte injury. We also aimed to determine whether nephrin, podocin and caspase-9 production depends on the PI3K/Akt/nuclear factor (NF)-κB signaling pathway in cultured mouse podocytes. We treated mouse podocytes with different doses of Ang II (10−9, 10−8, 10−7 and 10−6 mol/l) for 12, 24, and 48 h to analyse cell viability, and at 10−6 mol/l Ang II for 12, 24, and 48 h to evaluate cell apoptosis. Cells were treated with 10−6 mol/l of Ang II and/or LY294002 (inhibitor of Akt) or 740Y-P (activator of PI3K) for 48 h to detect Akt, phosphorylated (phospho)-Akt, p65 NF-κB, and phospho-p65 NF-κB, nephrin, podocin and caspase-9 expression, and podocyte apoptosis. Treatment with Ang II suppressed the viability and promoted the apoptosis of podocytes in a dose- and time-dependent manner. Ang II decreased phospho-Akt, phospho-p65 NF-κB, nephrin, and podocin and increased caspase-9 expression, while podocyte apoptosis was promoted. LY294002 further enhanced Ang II-induced downregulation of Akt and p65 NF-κB activation, as well as upregulation of caspase-9 mRNA and protein, and promoted the apoptosis of podocytes. Of note, 740Y-P restored Ang II-induced downregulation of Akt and p65 NF-κB activation, and upregulation of caspase-9, and decreased podocyte apoptosis. Interestingly, LY294002 and 740Y-P were determined to have no notable effects on the expression of nephrin and podocin. The data suggested that Ang II could regulate the expression of nephrin, podocin and caspase-9. Collectively, our findings suggested that the PI3K/Akt/NF-κB survival axis may serve a pivotal role in podocyte injury.

Background. The transcriptional networks of Cyr61 and its function in cell injury are poorly understood. The present study depicted the lncRNA and mRNA profiles and the involvement in angiotensin II-induced injury after Cyr61 knockdown mediated by CRISPR/Cas9 in HEK293T cells. Methods. HEK293T cells were cultured, and Cyr61 knockdown was achieved by transfection of the CRISPR/Cas9 KO plasmid. lncRNA and mRNA microarrays were used to identify differentially expressed genes (DEGs). Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine biofunctions and signaling pathways. RT-PCR was used to validate the microarray results. Cells were divided into four groups: control, Cyr61 knockdown, angiotensin II (Ang II) without Cyr61 knockdown, and Ang II with Cyr61 knockdown. CCK8, western blotting, and flow cytometry analysis were carried out to dissect cellular function. Results. A total of 23184 lncRNAs and 28264 mRNAs were normalized. 26 lncRNAs and 212 mRNAs were upregulated, and 74 lncRNAs and 233 mRNAs were downregulated after Cyr61 knockdown. Analysis of cellular components, molecular functions, biological processes, and regulatory pathways associated with the differentially expressed mRNAs revealed downstream mechanisms of the Cyr61 gene. The differentially expressed genes were affected for small cell lung cancer, axon guidance, Fc gamma R-mediated phagocytosis, MAPK signaling pathway, focal adhesion, insulin resistance, and metabolic pathways. In addition, Cyr61 expression was increased in accordance with induction of cell cycle arrest and apoptosis and inhibition of cell proliferation induced by Ang II. Knockdown of Cyr61 in HEK293T cells promoted cell cycle procession, decreased apoptosis, and promoted cell proliferation. Conclusions. The Cyr61 gene is involved in Ang II-induced injury in HEK293T cells. Functional mechanisms of the differentially expressed lncRNAs and mRNAs as well as identification of metabolic pathways will provide new therapeutic targets for Cyr61-realated diseases.

Active control of nanocrystal optical and electrical properties is crucial for many of their applications. By electrochemical (de)lithiation of Cu

This study investigated the effect of selenate and selenite application on the distribution, transformation of selenium (Se) fractions in soil, as well as the accumulation and availability of Se in each part of wheat plants. A pot experiment was conducted using different concentrations of exogenous selenite or selenate (0.5, 1, 2.5, 5, and 10 mg Se kg−1 soil). Sequential extraction was used to determine the Se fractions in soil, and different models were used to study the behavior of Se in soil and its availability to wheat. Results showed that the distribution and availability of Se in soil and its accumulation in wheat affected both by Se concentrations and forms of exogenous Se. In selenite-treated soil, the proportion of exchangeable and carbonate-bound Se (EXC–Se) (21–42%) fraction increased compared to that in control (12%), while organic matter-bound Se (OM–Se) (23–33%) and Fe–Mn oxide-bound Se (FMO–Se) (11–15%) fractions decreased compare with those in control (37 and 32%, respectively). In selenate-treated soil, soluble-Se (SOL–Se) fraction (30–54%) increased and the OM–Se (9.8–20%) and FMO–Se (4.7–14.2%) fractions decreased compared with those in control. Residual Se (RES–Se) fraction was increased for selenite (7.4–13.4%) and selenate (12–20%) treatments compared with that in control (6.5%). In comparison with control, the available Se (SOL−Se + EXC−Se) fraction increased for both selenite (32–47%) or selenate (54–72%) treatments. Moreover, at the same rate of Se application, Se availability was higher in wheat grown in selenate-treated soils than that in selenite-treated soils. The redistribution index (U ts) of Se increased from 1 (in control) to 1.2–1.9 and 1.5–2 for selenite and selenate treatments, respectively; additionally, the mobility factor (MF) in selenate-treated soil was 40–90% higher than that in selenite-treated soil. Furthermore, relative bonding intensity (I R ) for both selenite (0.38–0.45) and selenate treatment (0.33–0.41) decreased compared with that in control (0.55). These differences indicated that selenite and selenate varied in terms of fixation capacities in soil, in transformation and distribution of Se in soil fractions, and in their availability to plants. The results of Michaelis–Menten equation demonstrated the high affinity of leaf to selenate, and the high affinity of roots and grains to selenite. Selenate was dominant in nearly all parts of wheat plants and in each application level. However, the affinity of selenite to wheat grains suggests that selenite is a useful Se fertilizer that must be considered in biofortification programs. In-depth studies at the pot and field scales by using different wheat varieties and application methods of Se in different ecological zones must be conducted to elucidate the mechanism and biochemical properties of Se in soil-plant system and ultimately produce Se-rich staple foods.

SummarySertoli cells are considered the “supporting cells” of the testis that play an essential role in sex determination during embryogenesis and in spermatogenesis during adulthood. Their essential roles in male fertility along with their immunosuppressive and neurotrophic properties make them an attractive cell type for therapeutic applications. Here we demonstrate the generation of induced embryonic Sertoli-like cells (ieSCs) by ectopic expression of five transcription factors. We characterize the role of specific transcription factor combinations in the transition from fibroblasts to ieSCs and identify key steps in the process. Initially, transduced fibroblasts underwent a mesenchymal to epithelial transition and then acquired the ability to aggregate, formed tubular-like structures, and expressed embryonic Sertoli-specific markers. These Sertoli-like cells facilitated neuronal differentiation and self-renewal of neural progenitor cells (NPCs), supported the survival of germ cells in culture, and cooperated with endogenous embryonic Sertoli and primordial germ cells in the generation of testicular cords in the fetal gonad.

Upland and paddy soils, as well as corn samples, were collected in the selenosis area of Naore Village, Ziyang County, Shaanxi Province, China. A five-step sequential extraction procedure was used for selenium (Se) fractionation, including soluble Se, exchangeable Se and carbonate-bound Se, iron and manganese oxide-bound Se, organic matter-bound Se, and the residual Se fraction. Species of soluble Se in upland soils included Se(-2), Se(4+), and Se(6+). The results showed that soluble Se and exchangeable Se fractions accounted for less than 1% of the total Se in the upland soil, but approximately 16.1% in the paddy soil. Concentrations of residual Se were lower than those of iron and manganese oxide-bound Se and organic matter-bound Se in both upland and paddy soils. Iron- and manganese oxide-bound Se was the dominant fractions in upland soil, whereas organic matter-bound Se abounded in paddy soil. Concentrations (mg kg(-1)) of Se in the corn samples ranged from 0.05 to 14.5 in seed, 0.31 to 12.3in root, 0.09 to 9.15 in stalk, and 0.16 to 36.15 in leaf. Path analysis indicated that soluble Se(6+) significantly (P

Mir-290 through mir-295 ( mir-290–295 ) is a mammalian-specific microRNA (miRNA) cluster that, in mice, is expressed specifically in early embryos and embryonic germ cells. Here, we show that mir-290–295 plays important roles in embryonic development as indicated by the partially penetrant lethality of mutant embryos. In addition, we show that in surviving mir-290–295 -deficient embryos, female but not male fertility is compromised. This impairment in fertility arises from a defect in migrating primordial germ cells and occurs equally in male and female mutant animals. Male mir-290–295 −/− mice, due to the extended proliferative lifespan of their germ cells, are able to recover from this initial germ cell loss and are fertile. Female mir-290–295 −/− mice are unable to recover and are sterile, due to premature ovarian failure.