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Neuroinflammation is closely related to the pathogenesis of neurodegenerative diseases. Activation of microglia, the resident immune cells in CNS, induces inflammatory responses, resulting in the release of neurotoxic molecules, which favors neuronal death and neurodegeneration. Nuclear receptor-related 1 (Nurr1) protein, one of the orphan nuclear receptor superfamilies, is an emerging target for neuroprotective therapy. In addition, the anti-inflammatory function of cannabinoid (CB) receptors has attracted increasing interest. As both CB receptors (especially CB2 receptor) and Nurr1 exist in microglia, and regulate a number of same molecular points such as NF-κB, we herein explored the interplay between the CB2 receptor and Nurr1 as well as the regulatory mechanisms in microglial cells. We showed that the application of CB2 receptor agonists JWH015 (1, 10 μM) significantly increased the nuclear Nurr1 protein in BV-2 cells and primary midbrain microglia. Overexpression of Nurr1 or application of Nurr1 agonist C-DIM12 (10 μM) significantly increased the mRNA level of CB2 receptor in BV-2 cells, suggesting that positive expression feedback existing between the CB2 receptor and Nurr1. After 2-AG and JWH015 activated the CB2 receptors, the levels of p-ERK, p-AKT, p-GSK-3β in BV-2 cells were significantly increased. Using ERK1/2 inhibitor U0126 and PI3K/AKT inhibitor LY294002, we revealed that the amount of Nurr1 in the nucleus was upregulated through β-arrestin2/ERK1/2 and PI3K/AKT/GSK-3β signaling pathways. With these inhibitors, we found a cross-talk interaction between the two pathways, and the ERK1/2 signaling pathway played a more dominant regulatory role. Furthermore, we demonstrated that when the CB2 receptor was activated, the phagocytic function of BV-2 cells was significantly weakened; the activation of Nurr1 also inhibited the phagocytic function of BV-2 cells. Pretreatment with the signaling pathway inhibitors, especially U0126, reversed the inhibitory effect of 2-AG on phagocytosis, suggesting that CB2 receptor may regulate the phagocytic function of microglia by activating Nurr1. In conclusion, CB2 receptor or/and Nurr1-mediated signal pathways play instrumental roles in the progress of phagocytosis, which are expected to open up new treatment strategies for neurodegenerative diseases.

Metal-containing covalent organic frameworks (MCOFs), as a class of crystalline organic polymers with abundant single-atom metal sites, can respond effectively to various vital reactions, including hydrogen evolution reaction (HER), CO2 reduction reaction (CO2RR), oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The advent of MCOFs provides a platform for the establishment of model catalysts with highly repetitive structure to facilitate theoretical calculations and high-throughput screening while designing flexibility in monomer construction to lay the foundation for the development of highly selective and active photo/electrocatalysts. In this review, we summarize the recent progress in this field and highlight several important MCOFs photo/electrocatalysts for OER, ORR, HER, and CO2RR. Moreover, various approaches are also mentioned to improve or optimize the catalysts and indicate the future research direction on enhancing the performance of MCOFs catalysts based on the current existing challenges.

OBJECTIVES Our aim is to investigate the associations of sleep disorders with cerebrospinal fluid (CSF) α-synuclein (α-syn) in healthy controls (HCs), and patients with prodromal and early Parkinson's disease (PD). METHODS We included a total of 575 individuals, consisting of 360 PD individuals, 46 prodromal PD individuals, and 169 HCs. Multiple linear regression models and linear mixed-effects models were used to investigate the associations of sleep disorders with baseline and longitudinal CSF α-syn. Associations between the change rates of sleep disorders and CSF α-syn were further investigated via multiple linear regression models. RESULTS In PD, probable Rapid-eye-movement sleep Behavior Disorder (pRBD) (β = - 0.1199; P = 0.0444) and RBD sub-items, such as aggressive dreams (β = - 0.1652; P = 0.0072) and hurting bed partner (β = - 0.2468; P = 0.0010), contributed to lower CSF α-syn. The association between aggressive dreams and lower CSF α-syn further survived Bonferroni correction (P

Flexible power sources featuring high-performance, prominent flexibility and raised safety have received mounting attention in the area of wearable electronic devices. However, many great challenges remain to be overcome, notably the design and fabrication of flexible electrodes with excellent electrochemical performance and matching them with safe and reliable electrolytes. Herein, a facile approach for preparing flexible electrodes, which employs carbon cloth derived from commercial cotton cloth as the substrate of cathode and a flexible anode, is proposed and investigated. The promising cathode (NVPOF@FCC) with high conductivity and outstanding flexibility is prepared by efficiently coating Na3V2(PO4)2O2F (NVPOF) on flexible carbon cloth (FCC), which exhibits remarkable electrochemical performance and the significantly improved reaction kinetics. More importantly, a novel flexible quasi-solid-state sodium-ion full battery (QSFB) is feasibly assembled by sandwiching a P(VDF-HFP)-NaClO4 gel-polymer electrolyte film between the advanced NVPOF@FCC cathode and FCC anode. And the QSFBs are further evaluated in flexible pouch cells, which not only demonstrates excellent energy-storage performance in aspect of great cycling stability and high-rate capability, but also impressive flexibility and safety. This work offers a feasible and effective strategy for the design of flexible electrodes, paving the way for the progression of practical and sustainable flexible batteries.

SIVA-1 plays a critical role in the induction of apoptosis in a number of different cell lines and participates in the mechanism of cisplatin (DDP)-mediated antitumor effects. However, the involvement of SIVA-1 in cisplatin resistance in gastric carcinoma has not been revealed. To explore the effect of SIVA-1 on DDP resistance, a recombinant pGV358-GFP-SIVA-1 lentiviral vector was constructed and transfected into human cisplatin-resistant MKN45/DDP gastric cancer cells. Subsequently, stable SIVA-1 overexpression was established in MKN45/DDP cells, which resulted in increased DDP sensitivity in MKN45/DDP cells in vitro. Flow cytometry demonstrated that SIVA-1 overexpression increased the percentage of apoptotic cells compared to that in the control. The colony formation assay clearly revealed that cell growth and proliferation were significantly suppressed following SIVA-1 overexpression. In addition, overexpression of SIVA-1 inhibited the migratory and invasive potential of MKN45/DDP cells in vitro. Western blot analysis indicated that SIVA-1 increased the expression levels of p53, p73, and p14ARF, whereas it reduced Bcl-2, MDM2, and Bcl-xL expression. In short, SIVA-1 upregulated the protein expression of p53, p73, and p14ARF and decreased that of Bcl-2, MDM2, and Bcl-xL in vitro and subsequently reversed cisplatin resistance in gastric cancer cells, suggesting that SIVA-1 serves as a valuable potential target for attenuating chemotherapy resistance.

Acute appendicitis is one of the most common surgical conditions that are diagnosed with acute abdominal pain in the emergency department. Atypical location of the appendix as in left-sided appendicitis has an increased risk of delayed diagnosis and mortality. The appendix varies in its location according to the position of the cecum. We reported a case of a 75-year-old previously healthy man with left-sided acute appendicitis (LSAA) to increase the awareness in the management of this atypical and variant condition. In addition to detail descriptions of the case report, we reviewed the current literature for LSAA provided in this article.

Adaptation of insects to different altitudes remain largely unknown, especially those endemic to the Tibetan Plateau (TP). Here, we generated the transcriptomes of Gynaephora menyuanensis and G. alpherakii, inhabiting different high altitudes on the TP, and used these and the previously available transcriptomic and genomic sequences from low-altitude insects to explore potential genetic basis for divergent high-altitude adaptation in Gynaephora. An analysis of 5,869 orthologous genes among Gynaephora and other three low-altitude insects uncovered that fast-evolving genes and positively selected genes (PSGs) in the two Gynaephora species were enriched in energy metabolism and hypoxia response categories (e.g. mitochondrion, oxidation-reduction process, and response to oxidative stress). Particularly, mTOR signaling pathway involving hypoxia was enriched by PSGs, indicating this well-known pathway in mammal hypoxia adaptation may be an important signaling system in Gynaephora. Furthermore, some PSGs were associated with response to hypoxia (e.g. cytochrome proteins), cold (e.g. dehydrogenase) and DNA repair (e.g. DNA repair proteins). Interestingly, several insect-specific genes that were associated with exoskeleton and cuticle development (e.g. chitinase and ecdysteroids) had experienced positive selection, suggesting the specific adaptive mechanisms in insects. This study is favourable for understanding the adaptive evolution of Gynaephora and even TP insects to divergent altitudes.

An algorithm using fixed-lag smooth filtering to improve the precision of EIS algorithm is presented in this paper. Firstly, gray projection algorithm (GPA) is used to calculate the interframe global motion vectors. Secondly, the fixed-lag smooth filter is used to smoothen the motion track of the original video sequence, according to different motion models. At last, the original sequence is compensated by using the compensation vectors calculated from filtering. This algorithm has been proved superior in filtering precision by experiments of video sequences in different motion scenes. This algorithm also satisfies the real-time request.