Improving people's well-being is a key way to meet people’s needs for a better life, and is of great importance in resolving the major contradictions in Chinese society. In this study, we evaluated ...peer relationships and self-actualization as potential mediators between physical exercise and subjective well-being in a sample of Chinese middle school students. A total of 1056 middle school students from six middle schools in Sichuan, China volunteered to complete questionnaires comprising the Physical Activity Rating Scale, Student Peer Relationship Scale, Short Index of Self-Actualization, Positive and Negative Affect Scale, and Satisfaction with Life Scale. Descriptive statistics, Pearson’s product-moment correlation, and structural equation modeling were conducted using SPSS statistics 19.0. and AMOS 21.0 statistical software. The results showed that peer relationships and self-actualization partially mediate between physical exercise and subjective well-being. The mediation analysis revealed two paths: first, the single mediating path via peer relationships indirect effect = 0.091, 95% CI: (0.053, 0.132) and second, the serial mediating path via peer relationships and self-actualization indirect effect = 0.015, 95% CI: (0.008, 0.024). The study confirmed for the first time the serial mediating role of peer relationships and self-actualization between physical exercise and subjective well-being of middle school students. It was suggested that middle school students could improve their peer relationships during physical exercise, thereby increasing the level of self-actualization, which results in better subjective well-being.
•The fatigue behavior of the BFRP/concrete interface under wet–dry cycles was investigated.•The fatigue mode would change from debonding to BFRP rupture with increasing exposure.•A modified method ...was presented to capture the fatigue life of the BFRP/concrete interface.•The fatigue strength of the BFRP/concrete interface is approximately 60%.
Basalt fiber-reinforced polymer (BFRP) retrofitted concrete structures are often exposed to harsh marine environments, such as temperature variations and wet-dry cycles. The fatigue performance of the BFRP/concrete interface is vital to the durability these structures. To evaluate the fatigue behavior of the bond interface under wet-dry cycles in ocean environment, 26 specimens were manufactured and tested, including 11 control specimens that were placed in an ambient environment. The remaining specimens were subjected to fatigue loading after exposure to wet-dry cycles in salt water with concentration of 3.5%. This exposure has a great influence on the fatigue properties of the BFRP/concrete interface. With increasing exposure, the failure mode changed from adhesive debonding to BFRP rupture with partial adhesive debonding, the active bond length shortened and the fatigue life decreased. A modified method was also presented to capture the fatigue life of the BFRP/concrete interface exposed to a chloride-containing environment. It was shown that the fatigue strength of the BFRP/concrete interface under similar conditions to the present study was approximately 60% of the ultimate load capacity.
Cell transplantation therapy provides a regenerative strategy for neural repair. We tested the hypothesis that selective excitation of transplanted induced pluripotent stem cell-derived neural ...progenitor cells (iPS-NPCs) could recapitulate an activity-enriched microenvironment that confers regenerative benefits for the treatment of stroke. Mouse iPS-NPCs were transduced with a novel optochemogenetics fusion protein, luminopsin 3 (LMO3), which consisted of a bioluminescent luciferase,
luciferase, and an opsin,
Channelrhodopsin 1. These LMO3-iPS-NPCs can be activated by either photostimulation using light or by the luciferase substrate coelenterazine (CTZ).
stimulations of LMO3-iPS-NPCs increased expression of synapsin-1, postsynaptic density 95, brain derived neurotrophic factor (BDNF), and stromal cell-derived factor 1 and promoted neurite outgrowth. After transplantation into the ischemic cortex of mice, LMO3-iPS-NPCs differentiated into mature neurons. Synapse formation between implanted and host neurons was identified using immunogold electron microscopy and patch-clamp recordings. Stimulation of transplanted cells with daily intranasal administration of CTZ enhanced axonal myelination, synaptic transmission, improved thalamocortical connectivity, and functional recovery. Patch-clamp and multielectrode array recordings in brain slices showed that CTZ or light stimulation facilitated synaptic transmission and induced neuroplasticity mimicking the LTP of EPSPs. Stroke mice received the combined LMO3-iPS-NPC/CTZ treatment, but not cell or CTZ alone, showed enhanced neural network connections in the peri-infarct region, promoted optimal functional recoveries after stroke in male and female, young and aged mice. Thus, excitation of transplanted cells via the noninvasive optochemogenetics treatment provides a novel integrative cell therapy with comprehensive regenerative benefits after stroke.
Neural network reconnection is critical for repairing damaged brain. Strategies that promote this repair are expected to improve functional outcomes. This study pioneers the generation and application of an optochemogenetics approach in stem cell transplantation therapy after stroke for optimal neural repair and functional recovery. Using induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) expressing the novel optochemogenetic probe luminopsin (LMO3), and intranasally delivered luciferase substrate coelenterazine, we show enhanced regenerative properties of LMO3-iPS-NPCs
and after transplantation into the ischemic brain of different genders and ages. The noninvasive repeated coelenterazine stimulation of transplanted cells is feasible for clinical applications. The synergetic effects of the combinatorial cell therapy may have significant impacts on regenerative approach for treatments of CNS injuries.
Dry eye syndrome (DES) is a common ocular disease worldwide. Currently, anti-inflammatory agents and immunosuppressive drugs, such as cyclosporine A, have been widely used to treat this chronic ...condition. However, the multifactorial etiology of DES, poor tolerance, low bioavailability, and prolonged treatment to response time have limited their usage. In this study, nimesulide, a cyclooxygenase (COX)-2 selective inhibitor, was conjugated with hyaluronic acid (HA), and the HA-nimesulide conjugates were expected to increase the solubility and biocompatibility for alleviating the DES in the benzalkonium chloride (BAC)-induced goblet cell-loss dry eye model. The therapeutic efficacy of HA-nimesulide was assessed using fluorescein staining, goblet cell density by conjunctival impression cytology, and histology and immunohistochemistry of corneal tissues. Compared to commercial artificial tears and Restasis
, the HA-nimesulide conjugates could promote goblet cell recovery and enhance the regeneration of the corneal epithelium. Importantly, immunofluorescent staining studies demonstrated that the HA-nimesulide conjugates could decrease the number of infiltrating CD11b-positive cells after two weeks of topical application. In the anti-inflammatory test, the HA-nimesulide conjugates could inhibit the production of pro-inflammatory cytokines and prostaglandin E
(PGE2) in the lipopolysaccharide (LPS)-stimulated Raw 264.7 cell model. In conclusion, we demonstrated that HA-nimesulide conjugates had anti-inflammatory activity, and promoted goblet cell recovery and corneal epithelium regeneration when used as topical eye drops; accordingly, the HA-nimesulide conjugates could potentially be effective for the treatment of DES.
Sports anomie behavior hurts the fairness of sports and the physical and mental health of sports participants. Previous studies have not focused on the psychological mechanisms of youth sports anomie ...behavior. This study explores the influence of intrinsic and extrinsic sports motivation on students’ sports anomie behavior and provides theoretical references for reducing students’ sports anomie behavior. A total of 2340 college students from twenty universities in China voluntarily participated in the survey. The results showed that (1) both intrinsic sports motivation (τ = -0.11, 95% CI = (-0.14, -0.08)) and extrinsic sports motivation (τ = -0.07, 95% CI = (-0.10, -0.03)) were significantly and negatively related to sports anomie behavior, and (2) intrinsic and extrinsic sports motivation was significantly and positively related (τ = 0.56, 95% CI = (0.54, 0.59) ), and (3) in the structural equation model, intrinsic sports motivation could negatively predict sports anomie behavior (β = -0.28,
p
< 0.001) and extrinsic sports motivation could negatively influence sports anomie behavior through the mediating role of intrinsic sports motivation (β = -0.25, 95% CI = (-0.428, -0.089)). The study concluded that the stronger the students’ intrinsic sports motivation, the fewer sports anomie behavior occurred, and if extrinsic sports motivation can be better transformed into intrinsic sports motivation, it also has a suppressive effect on sports anomie behavior.
Nanocarrier-based delivery systems are promising strategies for enhanced therapeutic efficacy and safety of toxic drugs. Photodynamic therapy (PDT)-a light-triggered chemical reaction that generates ...localized tissue damage for disease treatments-usually has side effects, and thus patients receiving photosensitizers should be kept away from direct light to avoid skin phototoxicity. In this study, a clinically therapeutic antibody cetuximab (C225) was conjugated to the surface of methoxy poly(ethylene glycol)-
-poly(lactide) (mPEG-
-PLA) micelles via thiol-maleimide coupling to allow tumor-targetable chlorin e6 (Ce6) delivery. Our results demonstrate that more C225-conjugated Ce6-loaded polymeric micelles (C225-Ce6/PM) were selectively taken up than Ce6/PM or IgG conjugated Ce6/PM by epidermal growth factor receptor (EGFR)-overexpressing A431 cells observed by confocal laser scanning microscopy (CLSM), thereby decreasing the IC
value of Ce6-mediated PDT from 0.42 to 0.173 μM. No significant differences were observed in cellular uptake study or IC
value between C225-Ce6/PM and Ce6/PM groups in lower EGFR expression HT-29 cells. For antitumor study, the tumor volumes in the C225-Ce6/PM-PDT group (percentage of tumor growth inhibition, TGI% = 84.8) were significantly smaller than those in the Ce6-PDT (TGI% = 38.4) and Ce6/PM-PDT groups (TGI% = 53.3) (
< 0.05) at day 21 through reduced cell proliferation in A431 xenografted mice. These results indicated that active EGFR targeting of photosensitizer-loaded micelles provides a possible way to resolve the dose-limiting toxicity of conventional photosensitizers and represents a potential delivery system for PDT in a clinical setting.
The central nervous system has evolved to coordinate the regulation of both the behavior response to the external environment and homeostasis of energy expenditure. Recent studies have indicated the ...dorsomedial ventromedial hypothalamus (dmVMH) as an important hub that regulates both innate behavior and energy homeostasis for coping stress. However, how dmVMH neurons control neuronal firing pattern to regulate chronic stress-induced anxiety and energy expenditure remains poorly understood. Here, we found enhanced neuronal activity in VMH after chronic stress, which is mainly induced by increased proportion of burst firing neurons. This enhancement of VMH burst firing is predominantly mediated by Cav3.1 expression. Optogenetically evoked burst firing of dmVMH neurons induced anxiety-like behavior, shifted the respiratory exchange ratio toward fat oxidation, and decreased food intake, while knockdown of Cav3.1 in the dmVMH had the opposite effects, suggested that Cav 3.1 as a crucial regulator. Interestingly, we found that fluoxetine (anxiolytics) could block the increase of Cav3.1 expression to inhibit the burst firing, and then rescued the anxiety-like behaviors and energy expenditure changes. Collectively, our study first revealed an important role of Cav3.1-driven bursting firing of dmVMH neurons in the control of anxiety-like behavior and energy expenditure, and provided potential therapeutic targets for treating the chronic stress-induced emotional malfunction and metabolism disorders.
The spin effect of bound magnetopolaron in a triangular quantum well is investigated within Pekar variational method. The expression of the bound magnetopolaron ground-state energy is obtained ...through theoretical calculation. The relationship between the ground-state energy of the polaron and the wave vector, the electron areal density, the magnetic field cyclotron resonance frequency and the Coulomb bound potential is discussed, respectively. Due to the crystal structural inversion asymmetry and the time inversion asymmetry, the polaron energy experiences Rashba spin–orbit splitting and Zeeman splitting. We discussed the dominant position of Rashba effect and Zeeman effect in strong and weak magnetic fields, respectively. Due to the presence of impurities, the polaron is more stable than the bare electron state, and the energy splitting of polaron is more stable.
Previous investigations suggest that DL-3-n-butylphthalide (NBP) is a promising multifaceted drug for the treatment of stroke. It is not clear whether NBP can treat traumatic brain injury (TBI) and ...what could be the mechanisms of therapeutic benefits. To address these issues, TBI was induced by a controlled cortical impact in adult male mice. NBP (100 mg/kg) or saline was intraperitoneally administered within 5 min after TBI. One day after TBI, apoptotic events including caspase-3/9 activation, cytochrome c release from the mitochondria, and apoptosis-inducing factor (AIF) translocation into the nucleus in the pericontusion region were attenuated in NBP-treated mice compared to TBI-saline controls. In the assessment of the nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway, NBP ameliorated the p65 expression and the p-IκB-α/IκB-α ratio, indicating reduced NF-κB activation. Consistently, NBP reduced the upregulation of proinflammatory cytokines such as tumor necrotizing factor-alpha (TNF-α) and interleukin-1beta (IL-1β) after TBI. In sub-acute treatment experiments, NBP was intranasally delivered once daily for 3 days. At 3 days after TBI, this repeated NBP treatment significantly reduced the contusion volume and cell death in the pericontusion region. In chronic experiments up to 21 days after TBI, continues daily intranasal NBP treatment increased neurogenesis, angiogenesis, and arteriogenesis in the post-TBI brain, accompanied with upregulations of regenerative genes including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), endothelial-derived nitric oxide synthase (eNOS), and matrix metallopeptidase 9 (MMP-9). The NBP treatment significantly improved sensorimotor functional recovery and reduced post-TBP depressive behavior. These new findings demonstrate that NBP shows multiple therapeutic benefits after TBI.
•DL-3-n-butylphthalide (NBP) treatment reduced contusion volume after TBI.•NBP treatment blocked apoptotic neuronal cell death.•NBP treatment suppressed inflammation.•Chronic intranasal NBP delivery increased regeneration in the post-TBI brain.•NBP promoted functional recovery and prevented post-TBI depression.
Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells ...(DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles.
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