As a measure to enhance drying kinetics, efficiency, and quality of the whole American ginseng root, step-down relative humidity (RH) convective hot air drying strategy was experimentally ...investigated. The effects of drying temperature (45, 50, 55, and 60 °C), RH (20, 30, and 40%), step-down RH, and continuous dehumidification, on hot air drying characteristics and quality attributes were examined. Results showed that the effective moisture diffusion coefficient varied from 1.155 × 10
−10
to 2.885 × 10
−10
m
2
/s while the activation energy was found to be 51.14 kJ/mol. Quality evaluation revealed that drying temperature, RH, and step-down RH had significant effect on color change. Additionally, the energy consumption was related to the drying time. The total ginsenosides content decreased with increasing drying temperature and decreasing RH. Microstructure comparison showed that a gel layer was formed on the sample surface when dried at temperature of 60 °C, which impeded internal moisture diffusion. Based on evaluation of the drying time and quality, air temperature of 55 °C and RH of 40% holding 5 h and then dropping it to 20% were proposed as the best drying conditions for whole root.
Although the anterior cingulate cortex (ACC) plays a vital role in neuropathic pain-related aversion, the underlying mechanisms haven't been fully studied. The mesolimbic dopamine system encodes ...reward and aversion, and participates in the exacerbation of chronic pain. Therefore, we investigated whether the ACC modulates aversion to neuropathic pain via control of the mesolimbic dopamine system, in a rat model of chronic constriction injury (CCI) to the sciatic nerve. Using anterograde and retrograde tracings, we confirmed that a subgroup of ACC neurons projected to the nucleus accumbens (NAc) and ventral tegmental area (VTA), which are two crucial nodes of the mesolimbic dopamine system. Combining electrophysiology in juvenile rats 7 days post-CCI, we found that the NAc/VTA-projecting neurons were hyperexcitable after CCI. Chemogenetic inhibition of these projections induced conditioned place preference in young adult rats 10–14 days post-CCI, without modulating the evoked pain threshold, whereas activation of these projections in sham rats mimicked aversive behavior. Furthermore, the function of the ACC projections was probably mediated by NAc D2-type medium spiny neurons and VTA GABAergic neurons. Taken together, our findings suggest that projections from the ACC to the NAc and VTA mediate neuropathic pain-related aversive behavior.
•ACC output neurons project directly to NAc and VTA.•The ACC-NAc/VTA projection mediates aversion of chronic pain.•ACC activates NAc D2-type medium spiny neurons during chronic pain.•ACC inhibits the VTA by activating GABAergic neurons after CCI.
•Actinidia chinensis Planch(ACP) suppresses proliferation and migration of gastric cancer cells.•ACP treatment elevated the apoptosis and ferroptosis but suppressed mesenchymal phenotype in HGC-27 ...cells.•ACP suppressed tumor growth in the zebrafish xenograft model.
Actinidia chinensis Planch (ACP) was the kiwifruit plant Chinese kiwifruit Actinidia chinensis Planch Root, which had been approved to be an anti-tumor drug widespread in clinical. However, the specific mechanism of ACP in resistance to gastric cancer remained unclear. Therefore, our study was dedicated to investigate the anti-proliferation and anti-migration effects of ACP on gastric cancer cells and its molecular mechanisms. Firstly, we utilized HPLC-MS to analyze the composition of ACP decoction, the results showed that ACP contained two main anti-tumor components, Ursolic acid and Oleanolic acid. The proliferation and migration ability of HGC-27 were examined by CCK-8 and cell scratch tests respectively. In addition, we also investigated HGC-27 cells apoptosis, mesenchymal phenotype and ferroptosis after ACP rat drug-containing serum (ACPs) treatment. EGFP-expressing lentiviral vectors were utilized to construct HGC-27 cells which containing green fluorescence. Then we take advantages of containing green fluorescence cells to establish a zebrafish xenograft model in vivo. The CCK-8 and cell scratch experiments verified that ACPs significantly inhibited proliferation and migration of HGC-27 in vitro. ACPs increased cells apoptosis rate, while were rescued by apoptosis inhibitor Z-VAD-FMK. Furthermore, ACPs downregulated the expression levels of Vimentin protein and Snail protein markedly. Intriguingly, ACPs increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. Furthermore, the zebrafish xenograft study further confirmed that administration of ACP suppressed the xenograft growth and metastasis of transplanted HGC-27 cells in vivo. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype.
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•Shedding of soluble extracellular domain of p75NTR (p75ECD) is reduced in SD.•Intraperitoneal injection of p75ECD-Fc (10 mg/kg) rescues cognitive decline of SD mice.•p75ECD-Fc ...alleviates SD-induced hippocampal neuronal apoptosis, synaptic plasticity impairment, and neuroinflammation.
The neurotrophin receptor p75 (p75NTR) is a circadian rhythm regulator and mediates cognitive deficits induced by sleep deprivation (SD). The soluble extracellular domain of p75NTR (p75ECD) has been shown to exert a neuroprotective function in Alzheimer’s disease (AD) and depression animal models. Nevertheless, the role of p75ECD in SD-induced cognitive dysfunction is unclear. In the present study we administrated p75ECD-Fc (10, 3 mg/kg), a recombinant fusion protein of human p75ECD and fragment C of immunoglobulin IgG1, to treat mice via intraperitoneal injection. The results revealed that peripheral supplementation of high-dose p75ECD-Fc (10 mg/kg) recovered the balance between Aβ and p75ECD in the hippocampus and rescued the cognitive deficits in SD mice. We also found that p75ECD-Fc ameliorated other pathologies induced by SD, including neuronal apoptosis, synaptic plasticity impairment and neuroinflammation. The current study suggests that p75ECD-Fc is a potential candidate for SD and peripheral supplementation of p75ECD-Fc may be a prospective preventive measure for cognitive decline in SD.
β‐arrestin2, a member of the arrestin family, mediates the desensitization and internalization of most G protein‐coupled receptors (GPCRs) and functions as a scaffold protein in signalling pathways. ...Previous studies have demonstrated that β‐arrestin2 expression is dysregulated in malignant tumours, fibrotic diseases, cardiovascular diseases and metabolic diseases, suggesting its pathological roles. Transcription and post‐transcriptional modifications can affect the expression of β‐arrestin2. Furthermore, post‐translational modifications, such as phosphorylation, ubiquitination, SUMOylation and S‐nitrosylation affect the cellular localization of β‐arrestin2 and its interaction with downstream signalling molecules, which further regulate the activity of β‐arrestin2. This review summarizes the structure and function of β‐arrestin2 and reveals the mechanisms involved in the regulation of β‐arrestin2 at multiple levels. Additionally, recent studies on the role of β‐arrestin2 in some major diseases and its therapeutic prospects have been discussed to provide a reference for the development of drugs targeting β‐arrestin2.
Torreya grandis cv. Merrillii is an important economic tree widely cultivated in hilly subtropical areas in China and some parts of Japan and Korea. Crown and root rot was found on T. grandis in ...Zhejiang Province of China. Three isolates with similar morphology were isolated from diseased samples, and used for identification and pathogenicity tests. The pathogenicity of the isolates was confirmed by fulfilling Koch's postulates. The pathogen was identified as Fusarium commune based on morphological characteristics and phylogenetic tree constructed by combining ITS and TEF‐1α gene sequences. This is the first report of F. commune causing crown and root rot on T. grandis in China.
Highlights • miR-379-5p is significantly down-regulated in HCC. • miR-379-5p can inhibit HCC invasion and metastasis. • FAK is a direct target of miR-379-5p. • miR-379-5p exerts its functions through ...inhibiting FAK/AKT signaling. • miR-379-5p might be a potential therapeutic target and prognostic marker for HCC.
Entrainment at the top of the planetary boundary layer (PBL) is of significant importance because it controls the upward growth of the PBL height. An option called ysu_topdown_pblmix, which provides ...a parameterization of fog-top entrainment, has been proposed for valley fog modeling and introduced into the YSU (Yonsei University) PBL scheme in the Weather Research and Forecasting (WRF) model. However, enabling this option in simulations of sea fog over the Yellow Sea typically results in unrealistic dissipation near the fog bottom and even within the entire fog layer. In this study, we theoretically examine the composition of the option ysu_topdown_pblmix, and then argue that one term in this option might be redundant for sea-fog modeling. The fog-top variables are employed in this term to determine the basic entrainment in the dry PBL, which is already parameterized by the surface variables in the original YSU PBL scheme. This term likely leads to an overestimation of the fog-top entrainment rate, so we refer to it as redundant. To explore the connection between the redundant term and unrealistic dissipation, a widespread sea-fog episode over the Yellow Sea is employed as a case study based on the WRF model. The simulation results clearly attribute the unrealistic dissipation to the extra entrainment rate that the redundant term induces. Fog-top entrainment is unexpectedly overestimated due to this extra entrainment rate, resulting in a significantly drier and warmer bias within the interior of sea fog. When sea fog develops and reaches a temperature lower than the sea surface, the sea surface functions as a warming source to heat the fog bottom jointly with the downward heat flux brought by the fog-top entrainment, leading the dissipation to initially occur near the fog bottom and then gradually expand upwards. We suggest a straightforward method to modify the option ysu_topdown_pblmix for sea-fog modeling that eliminates the redundant term. The improvement effect of this method was supported by the results of sensitivity tests. However, more sea-fog cases are required to validate the modification method.
Stroke survivors with impaired balance and motor function tend to have relatively poor functional outcomes. The cerebellum and primary motor cortex (M1) have been suggested as targets for ...neuromodulation of balance and motor recovery after stroke. This study aimed to compare the efficacy and safety of intermittent theta-burst stimulation (iTBS) to the cerebellum or M1 on balance and motor recovery in patients with stroke.
In this randomized, double-blind, sham-controlled clinical trial, patients with subacute stroke were randomly divided into 3 groups: M1-, cerebellar-, and sham-iTBS (n=12 per group; 15 sessions, 3 weeks). All outcomes were evaluated before intervention (T0), after 1 week of intervention (T1), after 3 weeks of intervention (T2), and at follow-up (T3). The primary outcome was the Berg balance scale score at T2. Secondary outcomes include the Fugl-Meyer assessment scale for lower extremities, the trunk impairment scale, the Barthel index, the modified Rankin Scale, the functional ambulation categories, and cortical excitability.
A total of 167 inpatients were screened, 36 patients (age, 57.50±2.41 years; 10 women, 12 ischemic) were enrolled between December 2020 and January 2023. At T2, M1- or cerebellar-iTBS significantly improved Berg balance scale scores by 10.7 points (95% CI, 2.7-18.6,
=0.009) and 14.2 points (95% CI, 1.2-27.2,
=0.032) compared with the sham-iTBS group. Moreover, the cerebellar-iTBS group showed a significantly greater improvement in Fugl-Meyer assessment scale for lower extremities scores by 5.6 points than the M1-iTBS (95% CI, 0.3-10.9,
=0.037) and by 7.8 points than the sham-iTBS (95% CI, 1.1-14.5,
=0.021) groups at T2. The motor-evoked potential amplitudes of the M1- and cerebellar-iTBS groups were higher than those of the sham-iTBS group (
<0.001).
Both M1- and cerebellar-iTBS could improve balance function. Moreover, cerebellar-iTBS, but not M1-iTBS, induced significant effects on motor recovery. Thus, cerebellar-iTBS may be a valuable new therapeutic option in stroke rehabilitation programs.
URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2100047002.
Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aβ) ...accumulation. However, the mechanism by which Aβ induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aβ and mediates Aβ neurotoxicity, implying that p75NTR may mediate Aβ-induced tau phosphorylation in AD. Here, we showed that Aβ-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3β (GSK3β) significantly changed Aβ/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aβ to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aβ-induced tau pathology and is a potential druggable target for AD and other tauopathies.
•p75NTR mediates Aβ-induced neuronal tau hyperphosphorylation.•The calpain/CDK5 and AKT/GSK3β pathways are involved in Aβ/p75NTR-induced tau hyperphosphorylation.•Modulation of p75NTR is a potential therapeutic approach to rescue brain tau pathology in AD.
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