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•Evaluating urban carbon emissions helps to achieve carbon reduction targets.•The carbon emission efficiency of 105 cities in the Yangtze River Economic Belt was evaluated.•The ...evolution of carbon emissions of 105 cities in the Yangtze River Economic Belt was explored.•Joint use of Geographic detector and Tobit model to analyze seven driving factors.•Results are beneficial to the regional collaborative management of carbon emissions.
As an important economic growth pole and ecological area in China, the urban agglomeration of the Yangtze River Economic Belt (YREB) is the key to carbon emission reduction. Exploring the spatial–temporal evolution and driving variables of its carbon emission efficiency (CEE) is crucial for realizing the goals of carbon peaking and carbon neutrality. The super-efficiency SBM model, the nuclear density method, and the spatial autocorrelation method were used to discuss the spatial–temporal CEE characteristics of 105 cities in the YREB. On the driving factors of carbon emissions, the geographic detector and the Tobit model were combined to explore the spatial differentiation characteristics of the driving factors from the perspective of heterogeneity, and concurrently analyze the single-factor’s effecting intensity and impacting direction, as well as the dual-factors’ interaction effects. The findings indicated that the CEE of YREB generally showed a slow upward trend during 2006–2021. From the perspective of time dynamic evolution, the differentiation of efficiency intensified, and the overall development was toward the high efficiency level. Furthermore, the results of spatial pattern evolution showed that the CEE presents the pattern of “downstream areas > midstream areas > upstream areas”, “high in the east and low in the west”, “hot in the east and cold in the west”, while the spatial clustering effect was significant, showing the distributions of low-low clustering or high-high clustering. Moreover, the results of the geographic detector showed that government intervention, economic growth, and technological progress were the main driving factors. In addition, the interactions government intervention and the other factors were significantly detected. Tobit regression results showed that technological advancement and economic growth had a favorable impact on CEE, but foreign investment, urbanization, and government involvement had negative impacts. In the future, the correlations between provinces and cities should be strengthened and amplified to promote the integrated green development, as well as to improve the ecological environments.
Purpose
The main purpose of our systematic review was to investigate the effect of peer-led intervention on self-stigma in individuals with mental health problems. Secondary purpose was investigating ...the impact of peer intervention on clinical symptoms, recovery-related outcomes, and disclosure-related outcomes.
Methods
Five electronic databases were searched from 1975 to 2021. Literature databases were searched for randomized controlled trials. From the perspective of key outcomes, a meta-analysis of the effects of peer-led interventions on changing stigma was conducted.
Results
A meta-analysis of randomized controlled trials targeting different target groups with mental health problems (e.g., adolescents, college students, family members of mentally ill persons, unemployed persons, etc.) was conducted. It was found that, at the end of the intervention, intervention had a positive effect on main outcomes such as self-stigma and stress from stigma. As for secondary outcomes, there was no significant influence on clinical symptoms. There was a positive effect on rehabilitation and empowerment, but without a statistical significance. There was a statistically significant effect on self-efficacy and professional help seeking. There was a statistically significant effect on confidentiality and disclosure-related distress in the Honest Open Proud (HOP) subgroup. There was no significant influence on confidentiality and withdrawal in the non-HOP subgroup.
Conclusion
Peer-led intervention can reduce self-stigma and stigma pressure and might improve recovery and empowerment. It increases self-efficacy and willingness to seek professional help, but has no significant effect on clinical symptoms and withdrawal. HOP intervention has positive effects on disclosure-related confidentiality and pain.
Systematic Review Registration
https://www.crd.york.ac.uk/PROSPERO
, identifier: CRD42021287584.
Although immune checkpoint therapy has significantly improved the prognosis of patients with melanoma, urgent attention still needs to be paid to the low patient response rates and the challenges of ...precisely identifying patients before treatment. Therefore, it is crucial to investigate novel immunosuppressive mechanisms and targets in the tumor microenvironment in order to reverse tumor immune escape. In this study, we found that the cell cycle checkpoint Aurora kinase B (AURKB) suppressed the anti-tumor immune response, and its inhibitor, Tozasertib, effectively activated T lymphocyte cytokine release in vitro and anti-tumor immunity in vivo. Tozasertib significantly inhibited melanoma xenograft tumor growth by decreasing the number of inhibitory CD4+ Treg cells in the tumors, which, in turn, activated CD8+ T cells. Single-cell analysis revealed that AURKB suppressed anti-tumor immunity by increasing MIF-CD74/CXCR4 signaling between tumor cells and lymphocytes. Our study suggests that AURKB is a newly identified anti-tumor immunity suppressor, whose inhibitors may be developed as novel anti-tumor immunity drugs and may have synergistic anti-melanoma effects with immune checkpoint therapies.
Dopamine deficiency is mainly caused by apoptosis of dopaminergic nerve cells in the substantia nigra of the midbrain and the striatum and is an important pathologic basis of Parkinson's disease ...(PD). Recent research has shown that dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission plays a crucial role in dopaminergic nerve cell apoptosis. However, the upstream regulatory mechanism remains unclear. Our study showed that Drp1 knockdown inhibited aberrant mitochondrial fission and apoptosis. Importantly, we found that ROCK1 was activated in an MPP
-induced PD cell model and that ROCK1 knockdown and the specific ROCK1 activation inhibitor Y-27632 blocked Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cells by suppressing Drp1 dephosphorylation/activation. Our in vivo study confirmed that Y-27632 significantly improved symptoms in a PD mouse model by inhibiting Drp1-mediated aberrant mitochondrial fission and apoptosis. Collectively, our findings suggest an important molecular mechanism of PD pathogenesis involving ROCK1-regulated dopaminergic nerve cell apoptosis via the activation of Drp1-induced aberrant mitochondrial fission.
IR‐783 is a kind of heptamethine cyanine dye that exhibits imaging, cancer targeting and anticancer properties. A previous study reported that its imaging and targeting properties were related to ...mitochondria. However, the molecular mechanism behind the anticancer activity of IR‐783 has not been well demonstrated. In this study, we showed that IR‐783 inhibits cell viability and induces mitochondrial apoptosis in human breast cancer cells. Exposure of MDA‐MB‐231 cells to IR‐783 resulted in the loss of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) depletion, mitochondrial permeability transition pore (mPTP) opening and cytochrome c (Cyto C) release. Furthermore, we found that IR‐783 induced dynamin‐related protein 1 (Drp1) translocation from the cytosol to the mitochondria, increased the expression of mitochondrial fission proteins mitochondrial fission factor (MFF) and fission‐1 (Fis1), and decreased the expression of mitochondrial fusion proteins mitofusin1 (Mfn1) and optic atrophy 1 (OPA1). Moreover, knockdown of Drp1 markedly blocked IR‐783‐mediated mitochondrial fission, loss of MMP, ATP depletion, mPTP opening and apoptosis. Our in vivo study confirmed that IR‐783 markedly inhibited tumour growth and induced apoptosis in an MDA‐MB‐231 xenograft model in association with the mitochondrial translocation of Drp1. Taken together, these findings suggest that IR‐783 induces apoptosis in human breast cancer cells by increasing Drp1‐mediated mitochondrial fission. Our study uncovered the molecular mechanism of the anti‐breast cancer effects of IR‐783 and provided novel perspectives for the application of IR‐783 in the treatment of breast cancer.
Biopharmaceutical technology is one of the most promising biotechnologies in the world. With the development of modern biotechnology, biopharmaceuticals are thriving and developing rapidly as a ...global high-tech biotechnology industry, bringing the unprecedented market prospects to biopharmaceuticals in China and the world. Today, world is witnessing that Chinese biopharmaceutical industry is booming and growing up. The national biopharmaceutical industry of China, especially the development and industrialization of biological medicines with genetic engineering drugs as its core fields, has already reached a certain market scale after over 20 years of development. The biopharmaceutical industry will be one of the most active economic sectors in China, whereas the biotechnological revolution with modern biopharmaceutical technology has become the lifeblood of maintaining human health and food safety in the future. The article systematically analyzed and evaluated the current status and trend and explored the main existing problems of Chinese biopharmaceutical industry with some development strategies in a challenging perspective. It probes into Chinese biopharmaceutical industry and its bases too. The future development prospects of Chinese national biopharmaceutical industry are much optimistic but challenging.
Background: Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop ligandgated
ion-channel (LGIC) superfamily, which also includes the GABA, glycine, and serotonin receptors.
Many nAChR ...subunits have been identified and shown to be involved in signal transduction
on binding to them of either the neurotransmitter acetylcholine or exogenous ligands such as
nicotine. The nAChRs are pentameric assemblies of homologous subunits surrounding a central
pore that gates cation flux, and they are expressed at neuromuscular junctions throughout the nervous
system.
Methods and Results: Because different nAChR subunits assemble into a variety of pharmacologically
distinct receptor subtypes, and different nAChRs are implicated in various physiological functions
and pathophysiological conditions, nAChRs represent potential molecular targets for drug
addiction and medical therapeutic research. This review intends to provide insights into recent advances
in nAChR signaling, considering the subtypes and subunits of nAChRs and their roles in
nicotinic cholinergic systems, including structure, diversity, functional allosteric modulation, targeted
knockout mutations, and rare variations of specific subunits, and the potency and functional
effects of mutations by focusing on their effects on nicotine addiction (NA) and smoking cessation
(SC). Furthermore, we review the possible mechanisms of action of nAChRs in NA and SC based
on our current knowledge.
Conclusion: Understanding these cellular and molecular mechanisms will lead to better translational
and therapeutic operations and outcomes for the prevention and treatment of NA and other
drug addictions, as well as chronic diseases, such as Alzheimer’s and Parkinson’s. Finally, we put
forward some suggestions and recommendations for therapy and treatment of NA and other chronic
diseases.
Purpose
– An extensive search of the literature revealed a dearth of research on the demotivational factors affecting the performance and productivity level of site-based construction project ...managers. Following the announcement of awarding the FIFA 2022 World Cup hosting rights to the State of Qatar, the State is pledging to spend tens of Billions of Dollars on hundreds of new construction projects. Therefore, the purpose of this paper is to identify, explore, and rank the relative importance of the demotivational factors influencing the productivity of the State's construction management force.
Design/methodology/approach
– A structured questionnaire survey comprising 38 potential demotivational factors, which were shortlisted based on relevant previous studies on the impact of motivation on construction productivity, and numerous interviews with local industry professionals, was distributed to a relatively large sample of site-resident project managers. Using the “Relative Importance Index” technique, the influence ranks of the factors explored were determined.
Findings
– The results obtained reveal the following as the prominent demotivational factors influencing the productivity of construction project managers: lack of financial incentive schemes; slow decision-making process by owners; remuneration scale; delay in responding to Requests For Information (RFI); shortage of skilled labour force; shortage of materials; clarity and completeness of technical specifications; frequent changing orders during execution; drawings quality level; and rework.
Research limitations/implications
– It is clear, based on the outcomes, that the cultural background of individuals, and the prevalent practices within the environment in which they operate, are two critical factors in determining their motivation drivers. Hence, it is prudent to explore the dominant culture and values of the management workforce, in addition to the characteristics of the working environment, before trying to apply relevant motivational theories, or even implement new management strategies.
Practical implications
– The results demonstrate that, within the geographical setting and cultural aspects of the sample surveyed, “tributes” and “pecuniary” may be interpreted to have the largest effect on the productivity of construction project managers.
Originality/value
– The findings not only contribute to the overall body of knowledge related to the effect of the motivation phenomenon on the productivity of the construction operation, but can also be used to provide industry practitioners with guidance for focusing, acting upon, and controlling the significant demotivational factors affecting the efficiency of the construction project management force practicing in State.
This experiment explored the dietary effects of green tea (Camellia sinensis) in feed supplementation on the development of broiler chicks. Totally, two hundred and seventy‐day‐old male broiler ...chicks were assigned to 27 broiler groups each with 10 individuals (initial mean body weight 44.2 ± 1.3 g) in a 4 × 2 factorial arrangement. Each chicken group was supplemented with the feed additives of green tea powder. The trial data were measured and obtained based on the records of carcass traits and intestine characteristics of broiler chicken fed with four different additive levels of green tea (0.25%, 0.50%, 0.75%, and 1.00%). The experiment lasted for two trial periods of 21 days and 42 days for each treatment of the green tea supplement with full records of broiler traits. There were interesting results recorded in the majority of broiler intestinal traits between the two trial periods. There are a few significant differences (p < .05) observed among multiple comparisons of some intestinal traits in broiler chicks such as colon diameter (p = .022) and jejunum width (p = .01). The most significant differences exist in these intestinal traits of chicken right and left cecum among broiler chicks fed with dietary green tea powder (p < .05). The other intestinal characteristics of broiler chicks were recorded from single treatment are insignificantly distinguished compared with the control groups. There are also some near significant differences of chicken intestinal carcass traits and characteristics. These results and experimental data of this study extend the current knowledge on the dietary effects of green tea in chicken raising and feeding with dietary supplementation.
This experiment explored the dietary effects of green tea (Camellia sinensis) in feed supplementation on the development of broiler chicks. Significant statistics of broiler chicken intestine traits of colon diameter and jejunum width were affected by different additive levels of green tea at the 42nd day of age. The trial results suggest that there are some significant improvements in two traits, i.e. colon diameter (overall p = .022) and jejunum width (overall p = .01) among broiler chicks fed with green tea.
Artesunate (ART), a natural product isolated from traditional Chinese plant Artemisia annua, has not been extensively explored for its anti-melanoma properties. In our study, we found that ART ...inhibited melanoma cell proliferation and induced melanoma cell ferroptosis. Mechanistic study revealed that ART directly targets Ido1, thereby suppressing Hic1-mediated transcription suppression of Hmox1, resulting in melanoma cell ferroptosis. In CD8.sup.+ T cells, ART does not cause cell ferroptosis due to the low expression of Hmox1. It also targets Ido1, elevating tryptophan levels, which inhibits NFATc1-mediated PD1 transcription, consequently activating CD8.sup.+ T cells. Our study uncovered a potent and synergistic anti-melanoma efficacy arising from ART-induced melanoma cell ferroptosis and concurrently enhancing CD8.sup.+ T cell-mediated immune response both in vivo and in vitro through directly targeting Ido1. Our study provides a novel mechanistic basis for the utilization of ART as an Ido1 inhibitor and application in clinical melanoma treatment.
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