This study investigated the impact of environmental engineering on existing venues, venues and operations management. First, the literature analysis and field survey method are used to summarize the ...current situation of the venue. Then, 420 questionnaires are collected for statistical verification analysis, combined with the interview method to understand the deepest feelings of the people, and finally discussed with a multi-inspection method. The researcher believes that although environmental construction can improve infrastructure and human quality of life, which, after all, are experiment after completion. If, before construction, a good communication channel; obtaining consensus from the people and businesses; acquiring precise information; spraying water to reduce dust; increasing the height of the peripheral fence; planning a substitutive plan; avoiding crowds; reducing mistakes in the process; avoiding influencing the water and electricity supply and soil, water, and environment sanitation; and planning for a substitutive route and parking space with subsidy for damages are not possible, a negative image will be produced, willingness to spend will be reduced in the people due to the blocking of the view by the building (75%), the billboard will lose its functionality (63.2%), and inconvenience will be caused by the line of movement (75%) and parking space (55.9%), which are not helpful for development.
The functional outcome of intracerebral hemorrhage (ICH) in young male patients are poor than in premenopausal women. After ICH, ferrous iron accumulation causes a higher level of oxidative injury ...associated with autophagic cell death in striatum of male mice than in females. In rodent model of ferrous citrate (FC)-infusion that simulates iron accumulation after ICH, female endogenous estradiol (E
) suppresses autophagy via estrogen receptor α (ERα) and contributes to less injury severity. Moreover, E
implantation diminished the FC-induced autophagic cell death and injury in males, whose ERα in the striatum is less than females. Since, no sex difference of ERβ was observed in striatum, we delineated whether ERα and G-protein-coupled estrogen receptor 1 (GPER1) mediate the suppressions of FC-induced autophagy and oxidative injury by E
in a sex-dimorphic manner. The results showed that the ratio of constitutive GPER1 to ERα in striatum is higher in males than in females. The GPER1 and ERα predominantly mediated suppressive effects of E
on FC-induced autophagy in males and antioxidant effect of E
in females, respectively. This finding opens the prospect of a male-specific therapeutic strategy targeting GPER1 for autophagy suppression in patients suffering from iron overload after hemorrhage.
There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na
/K
-ATPase, has been implicated in the mouse model with ...manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation. CCAAT/Enhancer-Binding Protein Delta (CEBPD) is an inflammatory transcription factor that contributes to neurological disease progression. In this study, we demonstrated that the expression of CEBPD in astrocytes was increased in ouabain-treated mice. Furthermore, we observed an increase in the expression and transcript levels of CEBPD in human primary astrocytes following ouabain treatment. Transcriptome analysis revealed high MMP8 expression in human primary astrocytes following CEBPD overexpression and ouabain treatment. We confirmed that MMP8 is a CEBPD-regulated gene that mediates ouabain-induced neuroinflammation. In our animal model, treatment of ouabain-injected mice with M8I (an inhibitor of MMP8) resulted in the inhibition of manic-like behavior compared to ouabain-injected mice that were not treated with M8I. Additionally, the reduction in the activation of astrocytes and microglia was observed, particularly in the hippocampal CA1 region. Excessive reactive oxygen species formation was observed in ouabain-injected mice, and treating these mice with M8I resulted in the reduction of oxidative stress, as indicated by nitrotyrosine staining. These findings suggest that MMP8 inhibitors may serve as therapeutic agents in mitigating manic symptoms in bipolar disorder.
The purpose of this study is to explore, after the epidemic, the intelligent traffic management system, which is the key to creating a green leisure tourism environment in the move towards ...sustainable urban development. First, quantitative research, snowballing, and convenience sampling methods are used to analyze 750 questionnaires with a basic statistical test, t-test, ANOVA test, and the Pearson product–moment correlation coefficient (PPMCC) method. Qualitative research and a semi-structured interview method are used to collect the opinions of six experts on the data results. Finally, the results are discussed with the multivariate inspection method. Although the current electric bicycle system is convenient, the study found that the service quality of the airport is sufficient; that the fare of the subway is low and popular with students if the system can ease the crowd during peak hours; and that the login and security check time can be shortened, which can help improve the operating convenience of the system interface and link the information of leisure and tourism activities. On the other hand, adjusting fares, increasing seats, planning for women-only ticketing measures and travel space, providing disinfection or cleaning facilities in public areas, and improving passenger’s public health literacy and epidemic prevention cooperation will further enhance the student travel experience, improve the smart city and green tourism network, and help achieve sustainable urban tourism.
Background
We investigated the prevalence of psychiatric referral, frequency of repeat upper gastrointestinal (UGI) contrast studies, and esophagogastroduodenoscopy (EGD) in children with ineffective ...esophageal motility (IEM) before the confirmation of esophageal dysmotility.
Methods
A total of 19 children (nine boys, 10 girls; mean age, 13.80 ± 5.10 years) with symptoms of refractory gastroesophageal reflux (GER) who underwent high‐resolution esophageal impedance manometry (HRIM) were enrolled in this retrospective analysis. Refractory GER symptoms were defined as persistent symptoms even under acid‐suppression therapy for 8 weeks in this study. Clinical data including age, gender, time from symptom onset to diagnosis, and number of UGI contrast studies and EGD before diagnosis were obtained. HRM parameters and the prevalence of psychiatric referral were also analyzed.
Results
There are 14 children (73.68%) diagnosed with IEM by HRIM, and another 5 children (26.32%) diagnosed as GER disease (GERD) by EGD. A significant proportion of IEM children were misdiagnosed with psychological problems compared with the GERD children (78.57% vs 20.00%, P = 0.04). Three IEM children (21.43%) received antipsychotic and antidepressant agents before diagnosis of IEM, and all of them discontinued these medications after diagnosis. IEM children underwent a greater number of UGI contrast studies (1.07 ± 0.92 vs 0.20 ± 0.45; P = 0.02) and EGD (2.36 ± 2.50 vs 0.60 ± 0.55; P = 0.03) before HRM than GERD children.
Conclusions
Esophageal manometry for the diagnosis of IEM should be considered in children with GER symptoms refractory to acid‐suppression therapy for 8 weeks to avoid repeat UGI contrast studies, EGD, and psychological therapy.
Age-related macular degeneration (AMD) is the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris among elderly individuals and is the leading cause of ...blindness worldwide. Thus, a better understanding of the underlying mechanisms in retinal tissue activated by blue light exposure is important for developing novel treatment and intervention strategies. In this study, blue-light-emitting diodes with a wavelength of 440 nm were applied to RPE cells at a dose of 3.7 ± 0.75 mW/cm
for 24 h. ARPE-19 cells were used to investigate the underlying mechanism induced by blue light exposure. A trypan blue exclusion assay was used for the cell viability determination. Flow cytometry was used for apoptosis rate detection and autophagy analysis. An immunofluorescence microscopy analysis was used to investigate cellular oxidative stress and DNA damage using DCFDA fluorescence staining and an anti-γH2AX antibody. Blue light exposure of zebrafish larvae was established to investigate the effect on retinal tissue development in vivo. To further demonstrate the comprehensive effect of blue light on ARPE-19 cells, next-generation sequencing (NGS) was performed for an ingenuity pathway analysis (IPA) to reveal additional related mechanisms. The results showed that blue light exposure caused a decrease in cell proliferation and an increase in apoptosis in ARPE-19 cells in a time-dependent manner. Oxidative stress increased during the early stage of 2 h of exposure and activated DNA damage in ARPE-19 cells after 8 h. Furthermore, autophagy was activated in response to blue light exposure at 24-48 h. The zebrafish larvae model showed the unfavorable effect of blue light in prohibiting retinal tissue development. The RNA-Seq results confirmed that blue light induced cell death and participated in tissue growth inhibition and maturation. The current study reveals the mechanisms by which blue light induces cell death in a time-dependent manner. Moreover, both the in vivo and NGS data uncovered blue light's effect on retinal tissue development, suggesting that exposing children to blue light could be relatively dangerous. These results could benefit the development of preventive strategies utilizing herbal medicine-based treatments for eye diseases or degeneration in the future.
Heparan sulfate is essential for thymus growth Hsu, Hsuan-Po; Chen, Yun-Tzu; Chen, Yu-Ying ...
Journal of biological chemistry/The Journal of biological chemistry,
01/2021, Letnik:
296
Journal Article
Recenzirano
Odprti dostop
Thymus organogenesis and T cell development are coordinated by various soluble and cell-bound molecules. Heparan sulfate (HS) proteoglycans can interact with and immobilize many soluble mediators, ...creating fields or gradients of secreted ligands. While the role of HS in the development of many organs has been studied extensively, little is known about its function in the thymus. Here, we examined the distribution of HS in the thymus and the effect of its absence on thymus organogenesis and T cell development. We found that HS was expressed most abundantly on the thymic fibroblasts and at lower levels on endothelial, epithelial, and hematopoietic cells. To study the function of HS in the thymus, we eliminated most of HS in this organ by genetically disrupting the glycosyltransferase Ext1 that is essential for its synthesis. The absence of HS greatly reduced the size of the thymus in fetal thymic organ cultures and in vivo, in mice, and decreased the production of T cells. However, no specific blocks in T cell development were observed. Wild-type thymic fibroblasts were able to physically bind the homeostatic chemokines CCL19, CCL21, and CXCL12 ex vivo. However, this binding was abolished upon HS degradation, disrupting the CCL19/CCL21 chemokine gradients and causing impaired migration of dendritic cells in thymic slices. Thus, our results show that HS plays an essential role in the development and growth of the thymus and in regulating interstitial cell migration.
Background
The combination of atezolizumab and bevacizumab (Atezo-Bev) has become the standard first-line therapy for patients with advanced hepatocellular carcinoma (HCC), but the prognosis and ...treatment pattern after its treatment failure are unclear.
Methods
We reviewed the medical records of patients who failed first-line Atezo-Bev treatment for advanced HCC from January 2018 to May 2021 in four Taiwan medical centers. Post-first-line survival (PFLS) was defined as the date from the failure of Atezo-Bev treatment to the date of death or last follow-up.
Results
A total of 41 patients were included in the study. All patients had Child–Pugh A liver reserve before the initiation of Atezo-Bev treatment, but the liver reserve of 6 (15%) and 7 (17%) patients deteriorated to Child–Pugh B and C, respectively, after treatment failure. The median PFLS was 5.9 months. PFLS significantly differed among patients with various liver reserves after the failure of Atezo-Bev treatment (median 9.6 vs 3.8 vs 1.2 months, for Child–Pugh A, B, and C;
p
< 0.001). In total, 30 (73%) patients received second-line systemic therapy, and they exhibited significantly longer PFLS (median 8.0 vs 1.8 months,
p
= 0.033) than patients who did not. Deteriorated liver function and not receiving second-line therapy remained associated with inferior PFLS in multivariate analysis. The most common second-line therapies were sorafenib (
n
= 19, 63%) and lenvatinib (
n
= 9, 30%), with no significant differences in efficacies.
Conclusion
Receiving second-line therapy and good liver reserve were associated with favorable PFLS after the failure of first-line Atezo-Bev treatment.
Metal–organic frameworks (MOFs) are superior for multiple applications including drug delivery, sensing, and gas storage because of their tunable physiochemical properties and fascinating ...architectures. Optoelectronic application of MOFs is difficult because of their porous geometry and conductivity issues. Recently, a few optoelectronic devices have been fabricated by a suitable design of integrating MOFs with other materials. However, demonstration of laser action arising from MOFs as intrinsic gain media still remains challenging, even though some studies endeavor on encapsulating luminescence organic laser dyes into the porous skeleton of MOFs to achieve laser action. Unfortunately, the aggregation of such unstable laser dyes causes photoluminescence quenching and energy loss, which limits their practical application. In this research, unprecedently, we demonstrated ultralow-threshold (∼13 nJ/cm2) MOF laser action by a judicious choice of metal nodes and organic linkers during synthesis of MOFs. Importantly, we also demonstrated that the white random lasing from the beautiful microflowers of organic linkers possesses a porous network, which is utilized to synthesize the MOFs. The highly luminescent broad-band organic linker 1,4-NDC, which itself exhibits a strong white random laser, is used not only to achieve the stimulated emission in MOFs but also to reduce the lasing threshold. Such white lasing has multiple applications from bioimaging to the recently developed versatile Li-Fi technology. In addition, we showed that the smooth facets of MOF microcrystals can show Fabry–Perot resonant cavities having a high quality factor of ∼103 with excellent photostability. Our unique discovery of stable, nontoxic, high-performance MOF laser action will open up a new route for the development of new optoelectronic devices.
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