Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data ...analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.
Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative ...diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L.
The development of an intelligent biomaterial system that can efficiently accumulate at the tumor site and release a drug in a controlled way is very important for cancer chemotherapy. PEG is widely ...selected as a hydrophilic shell to acquire prolonged circulation time and enhanced accumulation at the tumor site, but it also restrains the cellular transport and uptake and leads to insufficient therapeutic efficacy. In this work, a PEG-detachable pH-responsive polymer that forms micelles from copolymer cholesterol grafted poly(ethylene glycol) methyl ether-Dlabile -poly(β-amino ester)-Dlabile -poly(ethylene glycol) methyl ether (MPEG-Dlabile -PAE-g-Chol) is developed to overcome the aforementioned challenges based on pH value changes among normal physiological, extracellular (pHe), and intracellular (pHi) environments. PEGylated doxorubicin (DOX)-loaded polymeric micelles (DOX-PMs) can accumulate at the tumor site via an enhanced permeability and retention effect, and the PEG shell is detachable induced by cleavage of the pHe-labile linker between the PEG segment and the main chain. Meanwhile, the pHi-sensitive poly(β-amino ester) segment is protonated and has a high positive charge. The detachment of PEG and protonation of PAE facilitate cellular uptake of DOX-PMs by negatively charged tumor cells, along with the escape from endo-/lysosome due to the “proton-sponge” effect. The DOX molecules are controlled release from the carriers at specific pH values. The results demonstrate that DOX-PMs have the capability of showing high therapeutic efficacy and negligible cytotoxicity compared with free DOX in vitro and in vivo. Overall, we anticipate that this PEG-detachable and tumor-acidity-responsive polymeric micelle can mediate effective and biocompatible drug delivery “on demand” with clinical application potential.
Traditionally, the factorization method is applied to reconstruct the 3D geometry of a target from its sequential inverse synthetic aperture radar images. However, this method requires performing ...cross-range scaling to all the sub-images and thus has a large computational burden. To tackle this problem, this paper proposes a novel method for joint cross-range scaling and 3D geometry reconstruction of steadily moving targets. In this method, we model the equivalent rotational angular velocity (RAV) by a linear polynomial with time, and set its coefficients randomly to perform sub-image cross-range scaling. Then, we generate the initial trajectory matrix of the scattering centers, and solve the 3D geometry and projection vectors by the factorization method with relaxed constraints. After that, the coefficients of the polynomial are estimated from the projection vectors to obtain the RAV. Finally, the trajectory matrix is re-scaled using the estimated rotational angle, and accurate 3D geometry is reconstructed. The two major steps, i.e., the cross-range scaling and the factorization, are performed repeatedly to achieve precise 3D geometry reconstruction. Simulation results have proved the effectiveness and robustness of the proposed method.
Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China’s most populous ...province, during early 2020 resulted in 1,388 reported RNA-positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China, we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain because of low virus genetic variation early in the pandemic. Our results illustrate how the timing, size, and duration of putative local transmission chains were constrained by national travel restrictions and by the province’s large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required, because the number of cases imported from other countries has increased.
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•1.6 million tests identified 1,388 SARS-CoV-2 infections in Guangdong by 19 March•Virus genomes can be recovered using a variety of sequencing approaches•Analyses reveal multiple viral importations with limited local transmission•Effective control measures helped reduce and eliminate chains of viral transmission
Genomic and epidemiological analyses provide insights into how COVID-19 was contained in China’s most populous province using a combination of surveillance and travel restriction measures.
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•The damage degree of engineered cementitious composites after freeze–thaw was successfully evaluated by the electrochemical impedance spectroscopy method.•After the application of ...300 freeze–thaw cycles, the volume resistance of engineered cementitious composites decreased by approximately 64 %.•The evolution of the conductive path reasonably reflected the freeze–thaw damage mechanism of engineered cementitious composites.
The mechanical properties of engineered cementitious composites (ECC) in service in cold regions can be significantly degraded by periodic freezing and thawing. In this work, the damage degree of freeze–thaw of ECC was systematically assessed by using the electrochemical impedance spectroscopy (EIS) technique. In addition, Nuclear Magnetic Resonance (NMR) Relaxometry measurements were also performed to obtain pore structure parameters, and the uniaxial tensile tests were also carried out to analyse the tensile performance after freeze–thaw cycles. From the acquired results, it was demonstrated that the EIS behaviour of ECC varied with the freeze–thaw cycles. The diameter of the Nyquist curve in high-frequency was gradually reduced by increasing the freeze–thaw cycles. Furthermore, the volume resistance of ECC after freeze–thaw gradually decreased with the increase in the number of freeze–thaw cycles. The simplified microstructure and conductive paths were used to describe the freeze–thaw damage mechanism of ECC. An equivalent circuit model of ECC exposed to freeze–thaw cycles was proposed, and the parameters of the equivalent circuit model were thoroughly analysed. The experimental findings clearly indicate that the EIS method is an appropriate technique for evaluating the damage degree of freeze–thaw of ECC.
The purpose of this research was to extract and separate the compounds from frankincense, and then evaluate their anti-inflammatory effects. The isolated compound was a representative tetracyclic ...triterpenes of glycine structure according to ¹H-NMR and
C-NMR spectra, which is β-elemonic acid (β-EA). We determined the content of six different localities of frankincense; the average content of β-EA was 41.96 mg/g. The toxic effects of β-EA administration (400, 200, 100 mg/kg) for four weeks in Kunming (KM) mice were observed. Compared with the control group, the body weight of mice, the visceral coefficients and serum indicators in the β-EA groups showed no systematic variations. The anti-inflammatory effects of β-EA were evaluated in LPS-induced RAW264.7 cells, xylene-induced induced ear inflammation in mice, carrageenin-induced paw edema in mice, and cotton pellet induced granuloma formation in rats. β-EA inhibited overproduction of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), soluble TNF receptor 1 (sTNF R1), Eotaxin-2, Interleukin 10 (IL-10) and granulocyte colony-stimulating factor (GCSF) in the RAW264.7 cells. Intragastric administration with β-EA (300, 200, and 100 mg/kg in mice, and 210, 140, and 70 mg/kg in rats) all produced distinct anti-inflammatory effects in vivo in a dose-dependent manner. Following treatment with β-EA (300 mg/kg, i.g.), the NO level in mice ears and PGE2 in mice paws both decreased (
0.01). In conclusion, our study indicates that β-EA could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.
The aim was to understand persistence of the virus in body fluids the and immune response of an infected host to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an agent of coronavirus ...disease 2019 (COVID-19).
We determined the kinetics of viral load in several body fluids through real time reverse transcription polymerase chain reaction, serum antibodies of IgA, IgG and IgM by enzyme-linked immunosorbent assay and neutralizing antibodies by microneutralization assay in 35 COVID-19 cases from two hospitals in Guangdong, China.
We found higher viral loads and prolonged shedding of virus RNA in severe cases of COVID-19 in nasopharyngeal (1.3 × 106 vs 6.4 × 104, p < 0.05; 7∼8 weeks) and throat (6.9 × 106 vs 2.9 × 105, p < 0.05; 4∼5 weeks), but similar in sputum samples (5.5 × 106 vs 0.9 × 106, p < 0.05; 4∼5 weeks). Viraemia was rarely detected (2.8%, n = 1/35). We detected early seroconversion of IgA and IgG at the first week after illness onset (day 5, 5.7%, n = 2/35). Neutralizing antibodies were produced in the second week, and observed in all 35 included cases after the third week illness onset. The levels of neutralizing antibodies correlated with IgG (rs = 0.85, p < 0.05; kappa = 0.85) and IgA (rs = 0.64, p < 0.05; kappa = 0.61) in severe, but not mild cases (IgG, rs = 0.42, kappa = 0.33; IgA, rs = 0.32, kappa = 0.22). No correlation with IgM in either severe (rs = 0.17, kappa = 0.06) or mild cases (rs = 0.27, kappa = 0.15) was found.
We revealed a prolonged shedding of virus RNA in the upper respiratory tract, and evaluated the consistency of production of IgG, IgA, IgM and neutralizing antibodies in COVID-19 cases.
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Magnesium oxide-based magnetic heterostructures with perpendicular magnetic anisotropy are receiving increasing attention for their applications in building high-density magnetic random memories. To ...obtain high thermal stability and flexible data writability, a large and tunable magnetic anisotropy constant (
K
i
) is required. In this paper,
K
i
is calculated for MgO/PtMnAs heterostructures with two different interfacial configurations using first-principles calculations. The MgO/AsMn_Pt heterostructure with interfacial atoms of Mn/As has a larger
K
i
of 4.74 mJ/m
2
. It is further found that a unilateral voltage-controlled magnetic anisotropy coefficient (VCMA) of 616 fJ/Vm is produced when the electric field is below − 0.2 V/nm for the MgO/AsMn_Pt heterostructure. The most significant contribution of the VCMA results from the Pt layers. The origin of these behaviors is analyzed by orbital-resolved magnetic anisotropy energy. The spin–orbit coupling of the
d
z
2
/
d
yz
orbitals of Pt atoms is responsible for the
K
i
variation with voltage. This study offers a useful guide to designing magnesium oxide-based magnetic heterostructures with high and tunable magnetic anisotropy.
Background
KIT is frequently mutated in gastrointestinal stromal tumors (GISTs), and the treatment of GISTs largely relies on targeting KIT currently. In this study, we aimed to investigate the role ...of sprouty RTK signaling antagonist 4 (SPRY4) in GISTs and related mechanisms.
Methods
Ba/F3 cells and GIST-T1 cell were used as cell models, and mice carrying germline KIT/V558A mutation were used as animal model. Gene expression was examined by qRT-PCR and western blot. Protein association was examined by immunoprecipitation.
Results
Our study revealed that KIT increased the expression of SPRY4 in GISTs. SPRY4 was found to bind to both wild-type KIT and primary KIT mutants in GISTs, and inhibited KIT expression and activation, leading to decreased cell survival and proliferation mediated by KIT. We also observed that inhibition of SPRY4 expression in KIT
V558A/WT
mice led to increased tumorigenesis of GISTs in vivo. Moreover, our results demonstrated that SPRY4 enhanced the inhibitory effect of imatinib on the activation of primary KIT mutants, as well as on cell proliferation and survival mediated by the primary KIT mutants. However, in contrast to this, SPRY4 did not affect the expression and activation of drug-resistant secondary KIT mutants, nor did it affect the sensitivity of secondary KIT mutants to imatinib. These findings suggested that secondary KIT mutants regulate a different downstream signaling cascade than primary KIT mutants
.
Conclusions
Our results suggested that SPRY4 acts as negative feedback of primary KIT mutants in GISTs by inhibiting KIT expression and activation. It can increase the sensitivity of primary KIT mutants to imatinib. In contrast, secondary KIT mutants are resistant to the inhibition of SPRY4.
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