Exosomal microRNAs (miRNAs) have been suggested to participate in the pathogenesis of neuropsychiatric diseases, but their role in major depressive disorder (MDD) is unknown. We performed a ...genome-wide miRNA expression profiling of blood-derived exosomes from MDD patients and control subjects and revealed the top differentially expressed exosomal miRNA, i.e. hsa-miR-139-5p (upregulation), had good performance to differentiate between MDD patients and controls. Tail vein injection of blood exosomes isolated from MDD patients into normal mice caused their depressive-like behaviors as determined by the forced swimming, tail suspension, and novelty suppressed feeding tests, and injection of blood exosomes isolated from healthy volunteers into unpredictable mild stress (CUMS)-treated mice alleviated their depressive-like behaviors. CUMS mice also showed significantly increased blood and brain levels of exosomal miR-139-5p. Furthermore, the depressive-like behaviors in CUMS-treated mice were rescued by intranasal injection of miR-139-5p antagomir, suggesting that increased exosomal miR-139-5p levels may mediate stress-induced depression-like behavior in mice. Both exosome treatment and miR-139-5p antagomir treatment increased hippocampal neurogenesis in the CUMS-treated mice, and treatment of exosome from MDD patients decreased hippocampal neurogenesis in the normal mice. The role of miR-139-5p in neurogenesis was validated by in vitro experiments, demonstrating that miR-139-5p is a negative regulator for neural stem cell proliferation and neuronal differentiation. Our findings together suggest that exosomes from patients with major depression caused depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis. Therefore, exosomal miRNAs are promising targets for the diagnosis and treatment of MDD.
Aims
To characterize the peripheral inflammatory cytokine profile in people with substance use disorders (SUDs).
Design
Systematic review and meta‐analysis.
Setting
Clinical studies that evaluated ...peripheral blood inflammatory cytokine levels in patients with SUDs and healthy controls
Participants
SUD patients and healthy controls.
Measurements
PubMed and Web of Science were systematically searched for relevant studies. Two investigators independently selected studies and extracted data. A total of 77 articles were included in the meta‐analysis, containing 5649 patients with SUDs and 4643 healthy controls. Data were pooled using a random‐effects model by the Comprehensive Meta‐Analysis version 2 software.
Findings
Concentrations of interleukin (IL)‐6) in 32 studies, tumor necrosis factor (TNF)‐α in 28 studies, IL‐10 in 20 studies, IL‐8 in 17 studies, C‐reactive protein in 14 studies, IL‐4 in 10 studies, IL‐12 in seven studies, monocyte chemoattractant protein (MCP)‐1 in 6 studies, TNF‐receptor 2 (TNF‐R2) in four studies and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) in three studies were significantly higher in patients with SUDs compared with healthy controls, while concentrations of leptin in 14 studies were significantly lower in patients with SUDs compared with healthy controls. The findings were inconclusive for the associations between interferon‐γ, IL‐1β, IL‐2, IL‐1 receptor antagonist (IL‐1RA), transforming growth factor (TGF)‐β1, G‐CSF, C‐C motif chemokine 11, TGF‐α and SUDs.
Conclusions
People with substance use disorders (SUDs) appear to have higher peripheral concentrations of IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, TNF‐α, C‐reactive protein, MCP‐1, TNF‐R2 and GM‐CSF and lower peripheral concentrations of leptin than people without SUDs. This strengthens the view that SUD is accompanied by an inflammatory response.
Fast radio bursts (FRBs) are a mysterious astrophysical phenomenon of bright pulses emitted at radio frequencies, and they are expected to be frequently detected in the future. The dispersion ...measures of FRBs are related to cosmological parameters, thus FRBs have the potential to be developed into a new cosmological probe if their data can be largely accumulated in the future. In this work, we study the capability of future FRB data to improve cosmological parameter estimation in two dynamical dark energy models. We find that the simulated FRB data can break the parameter degeneracies inherent in the current cosmic microwave background (CMB) data. Therefore, the combination of CMB and FRB data can significantly improve the constraints on the Hubble constant and dark energy parameters, compared to those using CMB or FRB alone. If 10,000 FRB events with known redshifts are detected in the future, they would perform better than the baryon acoustic oscillation (BAO) data in breaking the parameter degeneracies inherent in the CMB data. We also find that the combination of FRB and gravitational-wave (GW) standard siren data provides an independent low-redshift probe to verify the results from the CMB and BAO data. For the data combination of CMB, GW, and FRB, it is found that the main contribution to the constraints comes from the CMB and GW data, but the inclusion of the FRB data still can evidently improve the constraint on the baryon density.
Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in ...China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest
National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV
(the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children’s Regional Medical Center, Children’s Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.
Halide perovskite single-crystals have recently been widely highlighted to possess high light harvesting capability and superior charge transport behaviour, which further enable their attractive ...performance in photovoltaics. However, their application in photoelectrochemical cells has not yet been reported. Here, a methylammonium lead bromide MAPbBr
single-crystal thin film is reported as a photoanode with potential application in photoelectrochemical organic synthesis, 2,5-dimethoxy-2,5-dihydrofuran. Depositing an ultrathin Al
O
layer is found to effectively passivate perovskite surface defects. Thus, the nearly 5-fold increase in photoelectrochemical performance with the saturated current being increased from 1.2 to 5.5 mA cm
is mainly attributed to suppressed trap-assisted recombination for MAPbBr
single-crystal thin film/Al
O
. In addition, Ti
-species-rich titanium deposition has been introduced not only as a protective film but also as a catalytic layer to further advance performance and stability. As an encouraging result, the photoelectrochemical performance and stability of MAPbBr
single-crystal thin film/Al
O
/Ti-based photoanode have been significantly improved for 6 h continuous dimethoxydihydrofuran evolution test with a high Faraday efficiency of 93%.
The inference of gene regulatory networks (GRNs) from expression data can mine the direct regulations among genes and gain deep insights into biological processes at a network level. During past ...decades, numerous computational approaches have been introduced for inferring the GRNs. However, many of them still suffer from various problems, e.g., Bayesian network (BN) methods cannot handle large-scale networks due to their high computational complexity, while information theory-based methods cannot identify the directions of regulatory interactions and also suffer from false positive/negative problems. To overcome the limitations, in this work we present a novel algorithm, namely local Bayesian network (LBN), to infer GRNs from gene expression data by using the network decomposition strategy and false-positive edge elimination scheme. Specifically, LBN algorithm first uses conditional mutual information (CMI) to construct an initial network or GRN, which is decomposed into a number of local networks or GRNs. Then, BN method is employed to generate a series of local BNs by selecting the k-nearest neighbors of each gene as its candidate regulatory genes, which significantly reduces the exponential search space from all possible GRN structures. Integrating these local BNs forms a tentative network or GRN by performing CMI, which reduces redundant regulations in the GRN and thus alleviates the false positive problem. The final network or GRN can be obtained by iteratively performing CMI and local BN on the tentative network. In the iterative process, the false or redundant regulations are gradually removed. When tested on the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in E.coli, our results suggest that LBN outperforms other state-of-the-art methods (ARACNE, GENIE3 and NARROMI) significantly, with more accurate and robust performance. In particular, the decomposition strategy with local Bayesian networks not only effectively reduce the computational cost of BN due to much smaller sizes of local GRNs, but also identify the directions of the regulations.
To meet more application requirements, improving mechanical properties and self-healing efficiency has become the focus of current research on self-healing PU. The competitive relationship between ...self-healing ability and mechanical properties cannot be avoided by a single self-healing method. To address this problem, a growing number of studies have combined dynamic covalent bonding with other self-healing methods to construct the PU structure. This review summarizes recent studies on PU materials that combine typical dynamic covalent bonds with other self-healing methods. It mainly includes four parts: hydrogen bonding, metal coordination bonding, nanofillers combined with dynamic covalent bonding and multiple dynamic covalent bond bonding. The advantages and disadvantages of different self-healing methods and their significant role in improving self-healing ability and mechanical properties in PU networks are analyzed. At the same time, the possible challenges and research directions of self-healing PU materials in the future are discussed.
This review summarizes recent advances in self-healing PU by the "dynamic covalent bonding + X" method, where X represents dynamic covalent bonds, hydrogen bonding, metal coordination bonding, nanofillers and others.
Display omitted
•U accumulation damaged the root microstructure and inhibited root growth.•Root cell wall and intercellular spaces were the main sites of U accumulation.•U significantly interfered ...with the mineral nutrition metabolism of plants.•Uranium (U) phytotoxicity had an adverse effect on the metabolome and transcriptome.•Uranium (U) phytotoxicity caused abnormal regulation of the auxin signal transduction pathway.
Uranium (U) is a nonessential element that is readily adsorbed and retained in plant roots, causing root damage plants, rather than being translocated to other parts of the plant. The phytotoxicity mechanism of U is poorly understood. In this study, Vicia faba, a model plant for toxicological research, was selected as experimental material to investigate the phytotoxicity mechanism of U. In this study, the effects of U on the growth and development, methonome, transcriptome and mineral nutrient metabolism of V. faba were studied under different U treatments (0–25 μM) by integrating metabolomics, transcriptomic, and mineral nutrient metabolism analysis techniques. The results showed that U accumulation in roots and aboveground parts reached 164.34–927.90 μg/pot, and 0.028–0.119 μg/pot, respectively. U was mainly accumulated in the cell wall of roots, which damaged the root microstructure and inhibited root growth and development. In terms of mineral nutrient metabolism, U treatment (0–25 μM) led to changes in mineral metabolic profiles of seedlings. In total, 612 different metabolites were identified in nontargeted metabolomics, including 309 significantly upregulated metabolites and 303 significantly downregulated metabolites. Using RNA-seq, 4974 differentially expressed genes (DEGs) were identified under the high-concentration U treatment (25 μM), including 1654 genes significantly upregulated genes and 3320 genes significantly downregulated genes. Metabolic pathway analysis showed that a high concentration of U led to an imbalance of mineral nutrient metabolism in plants and changes in the metabolism and transcriptome pathway of plants, including alterations in the function of plasmodesmata and auxin signal transduction pathway. The latter finding may potentially explain the toxic effect of U on plant roots.
TGFβ contributes to chemoresistance in advanced colorectal cancer (CRC) via diverse immune-microenvironment mechanisms. Here, we found that cancer cell autonomous TGFβ directly triggered tumor ...programmed cell death 1 ligand 1 (PD-L1) upregulation, resulting in resistance to chemotherapy. Inhibition of tumor PD-L1 expression sensitized cancer cells to chemotherapy, reduced lung metastasis and increased the influx of CD8+ T cells. However, chemorefractory cancer cell-derived CSF1 recruited TAMs for TGFβ-mediated PD-L1 upregulation via a vicious cycle. High infiltration of macrophages was clinically correlated with the status of tumor PD-L1 after chemotherapy treatment in CRC patients. We found that depletion of immunosuppressive CSF1R+ TAM infiltration and blockade of the TGFβ receptor resulted in an increased influx of cytotoxic CD8+ T and effector memory CD8+ cells, a reduction in regulatory T cells, and a synergistic inhibition of tumor growth when combined with chemotherapy. These findings show that CSF1R+ TAMs and TGFβ are the dominant components that regulate PD-L1 expression within the immunosuppressive tumor microenvironment, providing a therapeutic strategy for advanced CRC patients.
The purpose of this study was to reveal the accumulation and phytotoxicity mechanism of sweet potato (Ipomoea batatas L.) roots following exposure to toxic levels of uranium (U) and cadmium (Cd). We ...selected two accumulation-type sweet potato cultivars as experimental material. The varietal differences in U and Cd accumulation and physiological metabolism were analyzed by a hydroponic experiment. High concentrations of U and Cd inhibited the growth and development of sweet potato and damaged the microstructure of root. The roots were the main accumulating organs of U and Cd in both sweet potato. Root cell walls and vacuoles (soluble components) were the main distribution sites of U and Cd. The chemical forms of U in the two sweet potato varieties were insoluble and oxalate compounds, while Cd mainly combined with pectin and protein. U and Cd changed the normal mineral nutrition metabolism in the roots, and also significantly inhibited the photosynthetic metabolism of sweet potatoes. RNA-seq showed that the cell wall and plant hormone signal transduction pathways responded to either U or Cd toxicity in both varieties. The inorganic ion transporter and organic compound transporter in roots of both sweet potato varieties are sensitive to U and Cd toxicity.
Display omitted
•U or Cd significantly damaged the root edge cell layer and cell wall of sweet potato.•Root cell walls and soluble components are the main distribution sites of U and Cd.•U is difficult to transfer because it exists in the root in the form of insoluble state.•U and Cd inhibited the expression genes of cell wall structure proteins, pectate lyases and cellular synthesis.
PDF
