This article takes an "abnormal petition" incident as a case study to explore the changes in the responsibility boundary of grassroots governments and the emergence of relevant action strategies. The ...research finds that grassroots governments have a dual role orientation of "business department" and "political unit", and their respective behavioral logics are also different. The former suits for a rational bureaucracy, and its design of clear task boundaries causes the ambiguity of the responsibility boundaries of grassroots governments in practice, leaving institutional space for their risk avoidance strategies. The latter applies to the political integration, and its blurred task boundary design in fact forces grassroots governments to re-clarify their responsibility boundaries and enforce their sense of responsibility. Affected by the logic of the two systems, the responsibility boundary of grassroots governments exhibits the characteristic of "fluidity", and governments' behaviors have also shifted from "
The special historical background of modern China made the modern construction of traditional art embark on a different path from that of the West. Through a careful examination of the preparatory ...process of Mei Lanfang's performance tour to the United States in 1930,this paper concluded that,unlike modern Western art,which had to confront the impact of rationalization and marketization after breaking away from religious and political dependence,Peking Opera,as traditional leisure entertainment,is influenced by Western artistic trends and thus shows the development orientation of actively pursuing"instrumentalization"and"de-cmmodification". At the same time, as an unintended consequence of the "National Opera Movement",Peking Opera became China's "National Opera",shouldering the historical mission of carrying forward traditional culture,a mission that was accomplished by adapting Western modern artistic concepts to traditional Peking Opera. Through examples of modern intellectual such as Qi Rushan and his tra
Cognitive function is an important ability of the brain, but cognitive dysfunction can easily develop once the brain is injured in various neuropathological conditions or diseases. Photobiomodulation ...therapy is a type of noninvasive physical therapy that is gradually emerging in the field of neuroscience. Transcranial photobiomodulation has been commonly used to regulate neural activity in the superficial cortex. To stimulate deeper brain activity, advanced photobiomodulation techniques in conjunction with photosensitive nanoparticles have been developed. This review addresses the mechanisms of photobiomodulation on neurons and neural networks and discusses the advantages, disadvantages and potential applications of photobiomodulation alone or in combination with photosensitive nanoparticles. Photobiomodulation and its associated strategies may provide new breakthrough treatments for cognitive improvement.
Auditory-cued goal-oriented behaviors requires the participation of cortical and subcortical brain areas, but how neural circuits associate sensory-based decisions with goal locations through ...learning remains poorly understood. The hippocampus is critical for spatial coding, suggesting its possible involvement in transforming sensory inputs to the goal-oriented decisions. Here, we developed an auditory discrimination task in which rats learned to navigate to goal locations based on the frequencies of auditory stimuli. Using in vivo calcium imaging in freely behaving rats over the course of learning, we found that dentate granule cells became more active, spatially tuned, and responsive to task-related variables as learning progressed. Furthermore, only after task learning, the activity of dentate granule cell ensembles represented the navigation path and predicts auditory decisions as early as when rats began to approach the goals. Finally, chemogenetic silencing of dentate gyrus suppressed task learning. Our results demonstrate that dentate granule cells gain task-relevant firing pattern through reinforcement learning and could be a potential link of sensory decisions to spatial navigation.
The East Kunlun Orogen (EKO) is located in the western part of the Central Asian Orogenic Belt, and it records the Neoproterozoic-Early Devonian tectonic evolution involving the subduction and ...extinction of the Proto-Tethys Ocean. The Heihaibei granite is located in the South Kunlun belt within EKO. In this study, geochronology, geochemistry, and Hf isotope analysis of Heihaibei monzogranite and granodiorite were carried out. Their LA-ICP-MS zircon U-Pb results yielded ages of 414.1 ± 2.0 and 417.8 ± 2.0 Ma. The Heihaibei granite is peraluminous (A/CNK = 0.99-1.30), with high alkali contents (7.76-9.14 wt.%) and 10 000 Ga/Al (2.60-3.38), FeOT/MgO (27.6-49.5), and Y/Nb ratios (1.93-2.93), suggesting that the Heihaibei granite is an A2-type granite. The Heihaibei granite samples have zircon εHf(t) values ranging from -6.3 to -0.3, which suggests that the Early Devonian granite was derived from partial melting of Mesoproterozoic (TDM2 = 1797-1415 Ma) crust. When considering data on contemporaneous granites, geochronological and geochemical data for the Heihaibei granite indicate that it was emplaced in a post-collisional extension environment following the closure of the Proto-Tethys Ocean. The Heihaibei granite was formed by extension of the southern subduction accretionary complex as part of the post-collisional setting during the closure of the Proto-Tethys Ocean.
Tourists are often exposed to imagery of a destination through advertisement modalities such as texts and pictures before they visit the place. This research used an eye-tracking technique to examine ...the effect of spatial and modality configurations on tourist destination advertisement attention and travel intention. Drawing on multiple resource theory and based on two 4 (spatial displacement) × 3 (modality) experiments, results reveal that spatial location and modality have an impact on tourist attention with respect to their dwell time and fixation counts, which lead to greater propensity to visit a place. In addition, tourists paid more attention to advertisements that occupy congruent attentional resources than to those using interference resources.
Gut microbial disturbance affects allergic diseases including asthma, atopic dermatitis (AD) via the aberrant immune response. Some Bifidobacterial species and strains have been reported to improve ...AD via modulating immune-microbe interactions in patients. However, the effective metabolites and mechanism of alleviating AD in bifidobacteria remain to be elucidated. This study aimed to explore the microbial metabolite and mechanism of Bifidobacterium longum to improve AD. Based on shotgun metagenomic sequencing and UHPLC Q-Exactive-MS targeted metabolic experiments in vitro and in vivo, we focused on tryptophan metabolism and indole derivatives, which are endogenous ligands for aryl hydrocarbon receptor (AHR). Indole-3-carbaldehyde (I3C), a tryptophan metabolite of B. longum CCFM1029 activated AHR-mediated immune signaling pathway to improve AD symptoms in animal and clinical experiments. B. longum CCFM1029 upregulated tryptophan metabolism and increased I3C to suppress aberrant T helper 2 type immune responses, but these benefits were eliminated by AHR antagonist CH223191. Furthermore, B. longum CCFM1029 reshaped gut microbial composition in AD patients, increased fecal and serum I3C, and maintained the abundance of Lachnospiraceae related to tryptophan metabolism of gut microbiota. The results suggested that based on the interactions of the gut-skin axis, B. longum CCFM1029 upregulated tryptophan metabolism and produced I3C to activate AHR-mediated immune response, alleviating AD symptoms. Indole derivates, microbial metabolites of tryptophan, may be the potential metabolites of bifidobacteria to alleviate AD via the AHR signaling pathway.
Inflammatory depression is closely related to neuroinflammation. However, current anti-inflammatory drugs have low permeability to cross blood-brain barrier with difficulties reaching the central ...nervous system to provide therapeutic effectiveness. To overcome this limitation, the nano-based drug delivery technology was used to synthesize melanin-like polydopamine nanoparticles (PDA NPs) (~ 250 nm) which can cross the blood-brain barrier. Importantly, PDA NPs with abundant phenolic hydroxyl groups function as excellent free radical scavengers to attenuate cell damage caused by reactive oxygen species or acute inflammation. In vitro experiments revealed that PDA NPs exhibited excellent antioxidative properties. Next, we aimed to investigate the therapeutic effect of PDA NPs on inflammatory depression through intraperitoneal injection to the lipopolysaccharide-induced inflammatory depression model in mice. PDA NPs significantly reversed the depression-like behavior. PDA NPs was also found to reduce the peripheral and central inflammation induced by LPS, showing that alleviated splenomegaly, reduced serum inflammatory cytokines, inhibited microglial activation and restored synaptic loss. Various experiments also showed that PDA NPs had good biocompatibility both in vivo and in vitro. Our work suggested that PDA NPs may be biocompatible nano-drugs in treating inflammatory depression but their clinical application requires further study.
We previously demonstrated the association between epithelial-to-mesenchymal transition (EMT) and drug response in lung cancer using an EMT signature derived in cancer cell lines. Given the ...contribution of tumor microenvironments to EMT, we extended our investigation of EMT to patient tumors from 11 cancer types to develop a pan-cancer EMT signature.
Using the pan-cancer EMT signature, we conducted an integrated, global analysis of genomic and proteomic profiles associated with EMT across 1,934 tumors including breast, lung, colon, ovarian, and bladder cancers. Differences in outcome and in vitro drug response corresponding to expression of the pan-cancer EMT signature were also investigated.
Compared with the lung cancer EMT signature, the patient-derived, pan-cancer EMT signature encompasses a set of core EMT genes that correlate even more strongly with known EMT markers across diverse tumor types and identifies differences in drug sensitivity and global molecular alterations at the DNA, RNA, and protein levels. Among those changes associated with EMT, pathway analysis revealed a strong correlation between EMT and immune activation. Further supervised analysis demonstrated high expression of immune checkpoints and other druggable immune targets, such as PD1, PD-L1, CTLA4, OX40L, and PD-L2, in tumors with the most mesenchymal EMT scores. Elevated PD-L1 protein expression in mesenchymal tumors was confirmed by IHC in an independent lung cancer cohort.
This new signature provides a novel, patient-based, histology-independent tool for the investigation of EMT and offers insights into potential novel therapeutic targets for mesenchymal tumors, independent of cancer type, including immune checkpoints.
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