How to effectively and accurately evaluate and analyze the volatility and reliability of travel speed on urban road before and after students back to school is a hot and key problem in urban road ...traffic congestion governance research. The Beijing 3rd Ring Road was taken as the research object and the impacts of the students back to school on the volatility and reliability of the travel speed of road sections were qualitatively and quantitatively analyzed based on the road section travel speed data during the weekday morning peak (7:00–8:59). The results showed that the travel speed of the Beijing 3rd Ring Road had cyclicity, time variability, large-scale volatility, and light congestion during the weekday morning peak, and the volatility and reliability indexes of the travel speed of road sections significantly decreased under the impact of the students back to school. The data showed that after the students back to school, the maximum reduction ratio of average travel speed was larger than 55%, and the maximum travel speed reliability reduction value was larger than 0.85 based on the evaluation model of travel speed reliability of car commuters. The research results provide data and theoretical support for urban road traffic congestion mitigation and governance.
Objective The study aims to investigate the protective effect of Mingjing granule (MG) in a fibrovascular membrane rat model of neovascular age-related macular degeneration (nAMD) and explore the ...underlying mechanism. Methods The nAMD fibrovascular membrane model was established by two-stage laser photocoagulation. BN rats were randomly divided into four groups: the model group was gavaged with distilled water, the anti-VEGF group was given an intravitreous injection of ranibizumab, the MG + anti-VEGF group was gavaged with MG combined with an intravitreous injection of ranibizumab, and the normal group not modeled only fed conventionally. Lesions were evaluated by color fundus photograph, optical coherence tomography, fundus fluorescein angiography, and retinal pigment epithelial–choroid–sclera flat mount. The changes in the retinal structure were observed by histopathology. The expression of inflammatory cell markers F4/80, Iba-1, and glial fibrillary acidic protein (GFAP); the fibrosis-related factors collagen-1, fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor-beta (TGF-β); and the complement system-related factors C3a and C3aR in the retina were detected by immunofluorescence or qRT-PCR. Results The current study revealed that MG + anti-VEGF administration more significantly reduced the thickness of fibrovascular lesions, suppressed vascular leakage (exudation area and mean density value), inhibited the area of fibrovascular lesions, and restrained the formation of the fibrovascular membrane than the anti-VEGF agent alone in the two-stage laser-induced rat model. The fluorescence intensities of F4/80, Iba-1, collagen-1, fibronectin, TGF-β, and C3aR showed more significant inhibition in MG + anti-VEGF-treated rats than the anti-VEGF agent alone. The mRNA expression levels of F4/80, Iba-1, GFAP, collagen-1, fibronectin, α-SMA, TGF-β, and C3a showed lower levels in rats treated with MG + anti-VEGF than the anti-VEGF agent alone. Conclusion Combining MG with anti-VEGF treatment inhibits the growth of the fibrovascular membrane more effectively than using anti-VEGF treatment alone. The mechanism underlying this effect may involve limiting inflammatory cell aggregation, controlling complement system activation, and decreasing the expression of the fibrotic protein.
Electrical activity has a crucial impact on the development and survival of neurons. Numerous recent studies have shown that noninvasive electrical stimulation (NES) has neuroprotective action in ...various retinal disorders.
To systematically review the literature on in vivo studies and provide a comprehensive summary of the neuroprotective action and the mechanisms of NES on retinal disorders.
Based on the PRISMA guideline, a systematic review was conducted in PubMed, Web of Science, Embase, Scopus and Cochrane Library to collect all relevant in vivo studies on "the role of NES on retinal diseases" published up until September 2023. Possible biases were identified with the adopted SYRCLE's tool.
Of the 791 initially gathered studies, 21 articles met inclusion/exclusion criteria for full-text review. The results revealed the neuroprotective effect of NES (involved whole-eye, transcorneal, transscleral, transpalpebral, transorbital electrical stimulation) on different retinal diseases, including retinitis pigmentosa, retinal degeneration, high-intraocular pressure injury, traumatic optic neuropathy, nonarteritic ischemic optic neuropathy. NES could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and visual function with high security, and its mechanism of action might be related to promoting the secretion of neurotrophins and growth factors, decreasing inflammation, inhibiting apoptosis. The quality scores of included studies ranged from 5 to 8 points (a total of 10 points), according to SYRCLE's risk of bias tool.
This systematic review indicated that NES exerts neuroprotective effects on retinal disease models mainly through its neurotrophic, anti-inflammatory, and anti-apoptotic capabilities. To assess the efficacy of NES in a therapeutic setting, however, well-designed clinical trials are required in the future.
Reservoirs are an essential part of modern society, serving a variety of critical functions while exerting an uncertain and debatable impact on the surrounding climate and environment. The ...precipitation‐temperature coupling relationship and the associated compound extreme events are critical climatic factors for humans and ecosystems, but how reservoirs would affect these factors is unknown. Here, we found that sites near reservoirs had higher sensitivity of precipitation extremes to temperature increases, as well as an increased frequency of compound precipitation‐temperature extreme events, based on a global‐scale analysis of reservoir and meteorological observations and a paired comparison approach. Additionally, these reservoir climate effects are closely correlated with reservoir size and are more pronounced in warm‐dry climates. It highlights the potential climate risks associated with reservoirs which have important implications for strengthening a community's resilience in the face of these challenges.
Plain Language Summary
The interactive effects of reservoirs on changes in meteorological variables have a great impact on the local community, including water security, energy production, and agriculture. Previous studies have focused on changes in individual variables such as precipitation or temperature, which however are interconnected; these individual variables do not fully represent the many changes that can occur as a result of reservoir construction. This study conducted a global scale analysis based on observations, for the first time, quantifying the changes in the precipitation‐temperature coupling features caused by reservoirs. The results show significant differences between sites near and far from reservoirs in the sensitivity of precipitation extremes to temperature increases, as well as the frequency of compound hot‐wet and hot‐dry events. The effects of large reservoirs in warm and dry regions were most pronounced, leading to increased compound precipitation‐temperature extreme events. Given that the construction of additional dams is regarded as one of the best available options for meeting future increases in water and energy demands, these findings aid in anticipating and mitigating any adverse effects of reservoirs on local climate and have important implications for regional climate prediction under the influence of human activities.
Key Points
This study presents the first global‐scale analysis of changes in precipitation‐temperature coupling relationships caused by reservoirs
Reservoirs intensify the sensitivity of precipitation extremes to temperature and frequency of compound precipitation‐temperature extremes
Reservoirs have the most pronounced climate impacts in warm and arid regions
Retinitis pigmentosa (RP) is an inherited disease characterized by a progressive loss of rod photoreceptors of the eye, leading to irreversible blindness. To date, to our knowledge, no clinical ...prospective studies have been undertaken that could document the effect of interventions that could reverse or reduce the progression of this disease. The application of microcurrent stimulation (ES) of the eye in the treatment of chronic eye diseases such as glaucoma and age-related macular degeneration has been used over several decades and has been reported to have beneficial effects to reduce the progression of these blinding diseases and has been supported by animal studies and smaller clinical studies, but to date, no large randomized clinical trials on the use of microcurrent therapy have been published. More recent clinical reports have also shown beneficial effects of ES on slowing the progression of RP but also lacks data from robust prospective clinical outcome studies. To our knowledge, this is the first prospective randomized study to evaluate the safety and clinical effectiveness of transpalpebral electrical stimulation (TpES) on the progression of RP.
Randomized prospective study using N-of-1 trial 3 single-blind, crossover comparisons. The intervention period of each comparison is divided into treatment period and control period which are randomized arranged. Twelve participants will be strictly recruited in N-of-1 trial by the researcher in accordance with the inclusion and exclusion criteria. The main outcome of interest examined after each cycle of the 8-week intervention period is the assessment of the visual field (VF). Other variables of interest are best corrected visual acuity (BCVA), retinal function using electroretinogram (ERG), and visual function using NEI VFQ-25 questionnaire. Objective assessments of retinal changes will be undertaken using optical coherence tomography (OCT) and fundus autofluorescence (FAF).
The trial will evaluate the efficacy and safety of microcurrent stimulation on RP and provide high-quality evidence for clinical application through N-of-1 trial.
Chinese Clinical Trial Registry; ChiCTR2300067357; https://www.chictr.org.cn/showproj.html?proj=174635 . Registered on 5 January 2023.
Background: Tauroursodeoxycholic acid (TUDCA) is a naturally produced hydrophilic bile acid that has been used for centuries in Chinese medicine. Numerous recent in vitro and in vivo studies have ...shown that TUDCA has neuroprotective action in various models of retinal disorders.
Objective: To systematically review the scientific literature and provide a comprehensive summary on the neuroprotective action and the mechanisms involved in the cytoprotective effects of TUDCA.
Methods: A systematic review was conducted in accordance with the PRISMA (The Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Systematic literature search of United States National Library of Medicine (PubMed), Web of Science, Embase, Scopus and Cochrane Library was performed, which covered all original articles published up to July 2022. The terms, "TUDCA" in combination with "retina", "retinal protection", "neuroprotection" were searched. Possible biases were identified with the adopted SYRCLE's tool.
Results: Of the 423 initially gathered studies, 24 articles met inclusion/exclusion criteria for full-text review. Six of them were in vitro experiments, 17 studies reported in vivo data and one study described both in vitro and in vivo data. The results revealed the effect of TUDCA on different retinal diseases, such as retinitis pigmentosa (RP), diabetic retinopathy (DR), retinal degeneration (RD), retinal ganglion cell (RGC) injury, Leber's hereditary optic neuropathy (LHON), choroidal neovascularization (CNV), and retinal detachment (RDT). The quality scores of the in vivo studies were ranged from 5 to 7 points (total 10 points), according to SYRCLE's risk of bias tool. Both in vitro and in vivo data suggested that TUDCA could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and function, and its mechanism of actions might be related with inhibiting apoptosis, decreasing inflammation, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, and reducing angiogenesis.
Conclusion: This systematic review demonstrated that TUDCA has neuroprotective effect on in vivo and in vitro models of retinal disorders, reinforcing the currently available evidence that TUDCA could be a promising therapeutic agent in retinal diseases treatment. However, well designed clinical trials are necessary to appraise the efficacy of TUDCA in clinical setting.
Currently, excessive carbon emission is causing visible damage to the ecosystem and will lead to long-term environmental degradation in the future. The manufacturing industry is one of the main ...contributors to the carbon emission problem. Therefore, the reduction of carbon emissions should be considered at all levels of production activities. In this paper, the carbon emission as a parvenu indicator is considered parallelly with the nobleman indicator, makespan, in the flexible job-shop scheduling problem. Firstly, the carbon emission is modeled based on the energy consumption of machine operation and the coolant treatment during the production process. Then, a deep reinforcement learning-based scheduling model is proposed to handle the carbon emission-aware flexible job-shop scheduling problem. The proposed model treats scheduling as a Markov decision process, where the scheduling agent and the scheduling environment interact repeatedly via states, actions, and rewards. Next, a deep neural network is employed to parameterize the scheduling policy. Then, the proximal policy optimization algorithm is conducted to drive the deep neural network to learn the objective-oriented optimal mapping from the states to the actions. The experimental results verify that the proposed deep reinforcement learning-based scheduling model has prominent optimization and generalization abilities. Moreover, the proposed model presents a nonlinear optimization effect over the weight combinations.
Although tea leaves are rich in secondary metabolites, not enough transcriptomic information is available to aid understanding of the molecular mechanisms underlying plant growth, development, and ...secondary metabolite production. In this study, a total of 437,908 reads were generated from the tea leaf transcriptome using 454 sequencing. De novo assembly yielded 25,637 unigenes, 22,872 of which were annotated by BLAST searches against public databases. Most of these unigenes mapped to carbohydrate metabolism, energy metabolism and secondary metabolite biosynthetic pathways. Some abundant transcripts related to photomorphogenesis and development in plants, including ubiquitin/26S proteasome, lipid transfer protein, PPR-containing protein, small GTPase, expansin, transport inhibitor response 1 and thioredoxin, were identified in the transcriptome. Most of the genes encoding the main enzymes involved in flavonoid, caffeine and theanine biosynthesis were also found, and six
MYB
and two
bHLH
genes known to regulate flavonoid synthesis were identified. ABC transporter and glutathione S-transferase, generally responsible for secondary metabolite transport, and CYP450, broadly involved in oxidation steps in secondary metabolism, were also present in a large number of unigenes. Additionally, 3,767 EST-SSRs were identified as potential molecular markers in our unigenes. A total of 100 PCR primer pairs used in initial screening tests among 20 tea genotypes successfully identified 36 polymorphic loci. Overall, the tea leaf transcriptome sequences generated in this study reveal novel gene expression profiles and offer important clues for further study of the molecular mechanism of tea leaf growth, development and secondary metabolite synthesis. The thousands of EST-SSR markers identified will facilitate marker-assisted selection in tea breeding.
A simple and fast HPLC analysis method for phenolic compounds, purine alkaloids and theanine in various Camellia species was developed. Using an amide-C16 column, catechins, gallic acid, caffeine, ...theobromine, theacrine, theophyline and theanine could be rapidly separated within 45
min with a gradient elution system. Excellent linearity was observed for all 14 compounds in the range studied, with correlation coefficients between 0.9994 and 0.9999. Limit of detection and limit of quantification of the 14 compounds varied from 0.0001 to 0.072
ng/μL and 0.0004 to 0.24
ng/μL, respectively. Four kinds of Camellia species were analyzed using this method. In traditional cultivated tea trees,
Camellia sinensis and
Camellia assamica, the main purine alkaloid was caffeine and main phenolic compound was (−)-epigallocatechin gallate (EGCG). The main purine alkaloids in
Camellia ptilophylla and
C. assamica var.
kucha were theobromine and theacrine; their contents were 4.001±0.1184% dry weight and 2.116±0.0270% dry weight, respectively. The main phenolic compounds in
C. ptilophylla and
C. assamica var.
kucha were (−)-gallocatechin gallate (GCG) and EGCG respectively. The content of theanine in the four Camellia species samples ranged from 0.136±0.0026% to 1.485±0.0491% dry weight.
Background
Recently, attention has been paid to the protective properties of active ingredients in
Salvia miltiorrhiza
(AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the ...present systematic review is to evaluate the chemoprotective effects and mechanisms of AISM on
in vitro and in vivo
models of doxorubicin-induced cardiotoxicity (DIC).
Methods
According to the PRISMA guideline, the current systematic review was conducted in the Web of Science, PubMed, Embase, and the Cochrane Library to collect all relevant
in vitro and in vivo
studies on “the role of AISM on DIC” published up until May 2023. The SYRCLE's tool was used to identify potential risk of bias.
Results
Twenty-two eligible articles were included in this systematic review. Eleven types of active ingredients in
Salvia miltiorrhiza
were used for DIC, which have the following effects: improvement of physical signs and biochemical indicators, reduction of cardiac function damage caused by DIC, protection of heart tissue structure, enhancement of myocardial cell viability, prevention of cardiomyocyte apoptosis, increase of the chemosensitivity of cancer cells to Doxorubicin,
etc
. The cardioprotective mechanism of AISM involves inhibiting apoptosis, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, decreasing inflammation, improving mitochondrial structure and function, affecting cellular autophagy and calcium homeostasis. The quality scores of included studies ranged from 4 to 7 points (a total of 10 points), according to SYRCLE's risk of bias tool.
Conclusion
This systematic review demonstrated that AISM have chemoprotective effects on DIC
in vivo
and
in vitro
models through several main mechanisms such as anti-apoptosis, antioxidant effects, anti-ER stress, and anti-inflammatory.
