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Dual control policies aim to effectively reduce energy consumption and carbon emission by setting targets for total volume and intensity control. With global climate change becoming increasingly serious. China, as a large energy-consuming and carbon-emitting country, faces a huge challenge to reduce carbon emissions. The transition from the "dual control of energy consumption" to the "dual control of carbon emissions" in China is necessary to optimize energy structures, promote energy conservation, reduce carbon emissions, and reach carbon neutrality. This study utilizes multi-regional input-output models to evaluate the results toward both goals from production-based, consumption-based, and income-based perspectives. The findings indicate that "dual control of carbon emissions" is a more precise approach than "dual control of energy consumption". Some provinces have met the latter goal while still falling short of the former. Provinces having met their production-based energy intensity and carbon emission intensity targets, but having failed their consumption-based and income-based targets, are identified to develop a comprehensive and accurate assessment of these targets. A net outflow of embodied energy and carbon emissions is observed among provinces in less-developed central and southern regions to more-developed eastern and northern regions. Suggestions and policy implications based on these findings include establishing a comprehensive evaluation of energy and carbon intensity, considering both consumption-based and income-based perspectives, as well as facilitating enhanced cooperation among developed and developing provinces.
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Carbon , Climate Change , ChinaABSTRACT
OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome. Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events, but its underlying mechanism is not completely understood. The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent. METHODS: AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse. Acupuncture was done at the Gok-Ji (LI11) acupoints. AD-like symptoms were assessed by lesion scores, scratching behavior, and histopathological changes; intestinal barrier function was measured by fecal output, serum lipopolysaccharide levels, histopathological changes, and mRNA expression of markers involved in intestinal permeability and inflammation. Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples. RESULTS: Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening, and also significantly altered gut microbiota structure as revealed by ß-diversity indices and analysis of similarities. These beneficial effects were eliminated by antibiotic depletion of gut microbiota, but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice. Interestingly, AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability, atrophy of the mucosal structure (reduced villus height and crypt depth), decreased expression of tight junctions and mucus synthesis genes, and increased expression of inflammatory mediators in the ileum. Acupuncture attenuated these abnormalities, which was gut microbiota-dependent. CONCLUSION: Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier, providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD. Please cite this article as: Yeom M, Ahn S, Hahm DH, Jang SY, Jang SH, Park SY, Jang JH, Park J, Oh JY, Lee IS, Kim K, Kwon SK, Park HJ. Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice. J Integr Med. 2024; Epub ahead of print.
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Introduction: In vitro fertilization (IVF) is a technology that assists couples experiencing infertility to conceive children. However, unsuccessful attempts can lead to significant physical and financial strain. Some individuals opt for electro-acupuncture (EA) during IVF, even though there is limited evidence regarding the efficacy of this practice. Thus, this pilot study aims to explore the effectiveness and safety of EA during IVF on pregnancy outcomes. Methods and analysis: This clinical trial is a parallel, randomized, sham-controlled study. It aims to include a total of 118 infertile women who intend to undergo IVF. The participants will be randomly divided into three groups in a 1:1:1 ratio: the EA + IVF group, the placebo electro-acupuncture (pEA) +IVF group, and the IVF control group. All of the patients will be required to use ovarian stimulation drugs, while those in the EA + IVF and pEA + IVF groups will receive acupuncture treatment at three sessions per week (every other day) until trigger day with a minimum five session. The primary outcome of this trial will focus on the clinical pregnancy rate (CPR). CPR is defined as the rate of achieving clinical pregnancy from the first fresh/frozen embryo transfer cycle with an ultrasound-confirmed gestational sac in the uterine cavity. The secondary outcomes will assess embryology data, biochemical pregnancy rate, early miscarriage rate, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Fertile Quality of Life (FertiQoL), patient retention rate, treatment adherence, and safety outcomes. Ethics and dissemination: Ethics approval was obtained from the Ethics Committee of Sichuan Jinxin Xi'nan Women and Children Hospital (number 2021-007). The results will be disseminated through peer-reviewed publications. The participants gave informed consent to participate in the study before taking part in it. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2300074455.
Subject(s)
Electroacupuncture , Fertilization in Vitro , Pregnancy Outcome , Pregnancy Rate , Humans , Female , Pregnancy , Fertilization in Vitro/methods , Electroacupuncture/methods , Pilot Projects , Adult , Infertility, Female/therapy , Ovulation Induction/methods , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Myocardial infarction (MI) and the ensuing heart failure (HF) remain the main cause of morbidity and mortality worldwide. One of the strategies to combat MI and HF lies in the ability to accurately predict the onset of these disorders. Alterations in mitochondrial homeostasis have been reported to be involved in the pathogenesis of various cardiovascular diseases (CVDs). In this regard, perturbations to mitochondrial dynamics leading to impaired clearance of dysfunctional mitochondria have been previously established to be a crucial trigger for MI/HF. In this study, we found that MI patients could be classified into three clusters based on the expression levels of mitophagy-related genes and consensus clustering. We identified a mitophagy-related diagnostic 5-genes signature for MI using support vector machines-Recursive Feature Elimination (SVM-RFE) and random forest, with the area under the ROC curve (AUC) value of the predictive model at 0.813. Additionally, the single-cell transcriptome and pseudo-time analyses showed that the mitoscore was significantly upregulated in macrophages, endothelial cells, pericytes, fibroblasts and monocytes in patients with ischemic cardiomyopathy, while sequestosome 1 (SQSTM1) exhibited remarkable increase in the infarcted (ICM) and non-infarcted (ICMN) myocardium samples dissected from the left ventricle compared with control samples. Lastly, through analysis of peripheral blood from MI patients, we found that the expression of SQSTM1 is positively correlated with troponin-T (Pâ¯<â¯0.0001, Râ¯=â¯0.4195, R2â¯=â¯0.1759). Therefore, this study provides the rationale for a cell-specific mitophagy-related gene signature as an additional supporting diagnostic for CVDs.
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An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N-oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO-induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ-free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO-related POCD and improving the quality of life for elderly patients.
Subject(s)
Cognitive Dysfunction , Disease Models, Animal , Femoral Fractures , Gastrointestinal Microbiome , Methylamines , Animals , Methylamines/metabolism , Methylamines/adverse effects , Mice , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/etiology , Male , Femoral Fractures/metabolism , Femoral Fractures/complications , Microglia/metabolism , Fecal Microbiota Transplantation , Mice, Inbred C57BL , Postoperative Cognitive Complications/metabolism , Postoperative Cognitive Complications/etiology , Cytokines/metabolism , Brain/metabolismABSTRACT
Carbon-carbon coupling is a basic design principle for the synthesis of porous organic polymers, which are widely used in gas adsorption/separation, photocatalysis, energy storage, etc. However, the C(sp3)-C(sp3) coupling reaction to construct porous organic polymers remains an important yet elusive objective due to its low reactivity and unknown side reactions. Herein, we report that nickel bis(1,5-cyclooctadiene) (Ni(COD)2), which was a famous catalyst for C(sp2)-C(sp2) coupling reactions, enables highly efficient C(sp3)-C(sp3) homo-coupling reactions to construct porous linear crystalline polymers and flexible three-dimensional porous aromatic frameworks (PAFs) under mild reaction conditions. The resulting linear polymers generated with dibromomethyl arenes have good crystallinity and high melting points (T m = 286 °C) due to controllability of reaction sites. Furthermore, the PAFs (PAF-64, PAF-65 and PAF-66) stemmed from tri-/tetra-bromomethyl arenes show high surface area (S BET = 390 m2 g-1) and high methane-storage capacity (up to 313 cm3 cm-3) because of their flexible frameworks. This work sheds new light on the construction of novel porous polymers through C(sp3)-C(sp3) coupling reactions and the development of methane-storage materials.
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Durable repellent surfaces of high transparency find key applications in daily life and industry. Nevertheless, developing anti-reflective coatings with omni-repellency, concerted multi-function, and desirable durability remains a daunting challenge. Here, a highly comprehensive coating is designed based on the combination of structural design and molecular design. The resulting silica hybrid coating not only manifests enhanced transparency and exceptional omniphobicity, but also achieves integration of multi-function (e.g., anti-smudge, anti-icing, and anti-corrosion). The unprecedented durability of the coating is evidenced by maintaining slipperiness after rigorous treatments, such as 2.5 × 105-cycle mechanical abrasion with a high loading pressure of 100 kPa, 1000-cycle adhesion/peeling and soaking in extreme pH solutions, etc. This work provides a design blueprint for manufacturing versatile and durable coatings for wide-ranging applications.
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BACKGROUND: Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). METHODS: Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 µg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a-/-) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons. RESULTS: Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx. CONCLUSIONS: Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization. SIGNIFICANCE STATEMENT: This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.
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This paper contributes current research by investigating the extent to which equity linkage networks impact enterprise green transition in sustainable development. By adopting a complex network approach, we constructed a common shareholding network based on the top ten shareholders of listed industrial enterprises in Shanghai and Shenzhen A-shares from 2013 to 2022. The empirical results indicate that enterprises closer to the centre of the equity linkage network tend to have higher degrees of green transition. This impact is facilitated through three mechanism channels of capital flow, information exchange, and knowledge transfer within the network. We find enterprises at the core of the network can effectively reduce their financing constraints on enterprises, mitigate risks associated with external environmental uncertainties and managerial myopia, and promote knowledge exchange and innovation cooperation between enterprises. We have also discovered that the centrality of equity network has a greater impact on promoting transition in state-owned, large-scale enterprises, and enterprises with less heavy pollution and the network effect can be enhanced by strong regional environmental regulations. The above findings not only provide policy makers with policy recommendations to guide the enterprises green transition, but also provide industry practitioners with practical paths and directions, which can help promote the green development process of the whole society.
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Background: Many studies have reported the use of preoperative oral carbohydrates (CHO) in children, but the results are inconsistent. The aim of this meta-analysis is to assess the effectiveness and safety of oral CHO administration in children prior to surgery, with the goal of offering a dependable reference for clinical nursing practices and surgical interventions. Methods: Two authors searched PubMed, Clinical trials, Web of Science, Embase, Cochrane Library, China national knowledge infrastructure (CNKI), Wanfang and Weipu databases for randomized controlled trial (RCT) on the effects of preoperative oral CHO in children up to April 12, 2024. We used RevMan 5.4 software for data analysis. Results: Nine RCTs involving a total of 1279 children were included. The meta-analysis showed that there was statistical difference in the pH of gastric juice (MD = 1.54, 95%CI: 1.40-1.67, p < .001), intraoperative sedation score (MD = 0.62, 95%CI: 0.27-0.97, p < .001), and the incidence of postoperative nausea and vomiting (OR = 0.40, 95%CI: 0.20-0.80, p = .009) between the CHO and control groups. There was no statistical difference in the RGV (MD = -0.23, 95%CI: -0.47-0.01, p = .06) and the postoperative blood glucose level (MD = -0.91, 95%CI: -5.03-3.21, p = .67) between the CHO and control groups. Egger regression analysis showed that there were no publication biases amongst the synthesized outcomes (all p > .05). Conclusion: The administration of oral CHO to children before surgery is safe and practicable. There is a need for additional, well-conducted studies with more participants to further elucidate the role of preoperative CHO administration.
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A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates numerous primary sequence changes, and novel methods are needed to accurately predict combinations of mutations that maintain or enhance function. Models of sequence co-variation (e.g., EVcouplings), which leverage extensive information about various protein properties and activities from homologous protein sequences, have proven effective for many applications including structure determination and mutation effect prediction. We apply EVcouplings to computationally design variants of the model protein TEM-1 ß-lactamase. Nearly all the 14 experimentally characterized designs were functional, including one with 84 mutations from the nearest natural homolog. The designs also had large increases in thermostability, increased activity on multiple substrates, and nearly identical structure to the wild type enzyme. This study highlights the efficacy of evolutionary models in guiding large sequence alterations to generate functional diversity for protein design applications.
Subject(s)
Evolution, Molecular , Mutation , Protein Engineering , beta-Lactamases , beta-Lactamases/genetics , beta-Lactamases/metabolism , beta-Lactamases/chemistry , Protein Engineering/methods , Models, Molecular , Amino Acid Sequence , Enzyme Stability , Protein ConformationABSTRACT
The two-dimensional quantum anomalous Hall (QAH) effect is direct evidence of non-trivial Berry curvature topology in condensed matter physics. Searching for QAH in 2D materials, particularly with simplified fabrication methods, poses a significant challenge in future applications. Despite numerous theoretical works proposed for the QAH effect with C = 2 in graphene, neglecting magnetism sources such as proper substrate effects lacks experimental evidence. In this work, we propose the QAH effect in graphene/MnBi2Te4 (MBT) heterostructure based on density-functional theory (DFT) calculations. The monolayer MBT introduces spin-orbital coupling, Zeeman exchange field, and Kekulé distortion as a substrate effect into graphene, resulting in QAH with C = 1 in the heterostructure. Our effective Hamiltonian further presents a rich phase diagram that has not been studied previously. Our work provides a new and practical way to explore the QAH effect in monolayer graphene and the magnetic topological phases by the flexibility of MBT family materials.
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MAPK pathway-driven tumorigenesis, often induced by BRAFV600E, relies on epithelial dedifferentiation. However, how lineage differentiation events are reprogrammed remains unexplored. Here, we demonstrate that proteostatic reactivation of developmental factor, TBX3, accounts for BRAF/MAPK-mediated dedifferentiation and tumorigenesis. During embryonic development, BRAF/MAPK upregulates USP15 to stabilize TBX3, which orchestrates organogenesis by restraining differentiation. The USP15-TBX3 axis is reactivated during tumorigenesis, and Usp15 knockout prohibits BRAFV600E-driven tumor development in a Tbx3-dependent manner. Deleting Tbx3 or Usp15 leads to tumor redifferentiation, which parallels their overdifferentiation tendency during development, exemplified by disrupted thyroid folliculogenesis and elevated differentiation factors such as Tpo, Nis, Tg. The clinical relevance is highlighted in that both USP15 and TBX3 highly correlates with BRAFV600E signature and poor tumor prognosis. Thus, USP15 stabilized TBX3 represents a critical proteostatic mechanism downstream of BRAF/MAPK-directed developmental homeostasis and pathological transformation, supporting that tumorigenesis largely relies on epithelial dedifferentiation achieved via embryonic regulatory program reinitiation.
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Carcinogenesis , Proto-Oncogene Proteins B-raf , T-Box Domain Proteins , Animals , Female , Humans , Mice , Carcinogenesis/genetics , Carcinogenesis/metabolism , Carcinogenesis/pathology , Cell Differentiation , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Gene Expression Regulation, Neoplastic , MAP Kinase Signaling System/genetics , Mice, Knockout , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , T-Box Domain Proteins/metabolism , T-Box Domain Proteins/genetics , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , Proteostasis/geneticsABSTRACT
Glycated hemoglobin (HbA1c), originating from the non-enzymatic glycosylation of ßVal1 residues in hemoglobin (Hb), is an essential biomarker indicating average blood glucose levels over a period of 2 to 3 months without external environmental disturbances, thereby serving as the gold standard in the management of diabetes instead of blood glucose testing. The emergence of HbA1c biosensors presents affordable, readily available options for glycemic monitoring, offering significant benefits to small-scale laboratories and clinics. Utilizing nanomaterials coupled with high-specificity probes as integral components for recognition, labeling, and signal transduction, these sensors demonstrate exceptional sensitivity and selectivity in HbA1c detection. This review mainly focuses on the emerging probes and strategies integral to HbA1c sensor development. We discussed the advantages and limitations of various probes in sensor construction as well as recent advances in diverse sensing strategies for HbA1c measurement and their potential clinical applications, highlighting the critical gaps in current technologies and future needs in this evolving field.
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Biosensing Techniques , Glycated Hemoglobin , Glycated Hemoglobin/analysis , Biosensing Techniques/methods , Humans , Diabetes Mellitus/diagnosis , Diabetes Mellitus/blood , Blood Glucose/analysisABSTRACT
Cells defend against oxidative stress by enhancing antioxidant capacity, including stress-activated metabolic alterations, but the underlying intracellular signaling mechanisms remain unclear. This paper reports that immunoglobulin superfamily containing leucine-rich repeat (ISLR) functions as a redox sensor that responds to reactive oxygen species (ROS) stimulation and modulates the antioxidant capacity by suppressing pyruvate kinase isozyme M2 (PKM2) activity. Following oxidative stress, ISLR perceives ROS stimulation through its cysteine residue 19, and rapidly degrades in the autophagy-lysosome pathway. The downregulated ISLR enhances the antioxidant capacity by promoting the tetramerization of PKM2, and then enhancing the pyruvate kinase activity, PKM2-mediated glycolysis is crucial to the ISLR-mediated antioxidant capacity. In addition, our results demonstrated that, in triple-negative breast cancer, cisplatin treatment reduced the level of ISLR, and PKM2 inhibition sensitizes tumors to cisplatin by enhancing ROS production; and argued that PKM2 inhibition can synergize with cisplatin to limit tumor growth. Our results demonstrate a molecular mechanism by which cells respond to oxidative stress and modulate the redox balance.
Subject(s)
Antioxidants , Oxidation-Reduction , Oxidative Stress , Reactive Oxygen Species , Humans , Oxidation-Reduction/drug effects , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Antioxidants/metabolism , Antioxidants/pharmacology , Oxidative Stress/drug effects , Animals , Cisplatin/pharmacology , Female , Membrane Proteins/metabolism , Thyroid Hormones/metabolism , Thyroid Hormone-Binding Proteins , Mice , Pyruvate Kinase/metabolism , Glycolysis/drug effects , Autophagy/drug effects , Carrier Proteins/metabolism , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/enzymologyABSTRACT
BACKGROUND: The conversion from a temporary to a permanent stoma (PS) following rectal cancer surgery significantly impacts the quality of life of patients. However, there is currently a lack of practical preoperative tools to predict PS formation. The purpose of this study is to establish a preoperative predictive model for PS using machine learning algorithms to guide clinical practice. METHODS: In this retrospective study, we analyzed clinical data from a total of 655 patients who underwent anterior resection for rectal cancer, with 552 patients from one medical center and 103 from another. Through machine learning algorithms, five predictive models were developed, and each was thoroughly evaluated for predictive performance. The model with superior predictive accuracy underwent additional validation using both an independent testing cohort and the external validation cohort. The Shapley Additive exPlanations (SHAP) approach was employed to elucidate the predictive factors influencing the model, providing an in-depth visual analysis of its decision-making process. RESULTS: Eight variables were selected for the construction of the model. The support vector machine (SVM) model exhibited superior predictive performance in the training set, evidenced by an AUC of 0.854 (95 % CI:0.803-0.904). This performance was corroborated in both the testing set and external validation set, where the model demonstrated an AUC of 0.851 (95%CI:0.748-0.954) and 0.815 (95%CI:0.710-0.919), respectively, indicating its efficacy in identifying the PS. CONCLUSIONS: The model(https://yangsu2023.shinyapps.io/psrisk/) indicated robust predictive performance in identifying PS after anterior resection for rectal cancer, potentially guiding surgeons in the preoperative stratification of patients, thus informing individualized treatment plans and improving patient outcomes.
Subject(s)
Machine Learning , Rectal Neoplasms , Surgical Stomas , Humans , Rectal Neoplasms/surgery , Female , Male , Retrospective Studies , Middle Aged , Aged , Support Vector Machine , Quality of Life , Proctectomy/methods , AlgorithmsABSTRACT
Clear cell renal cell carcinoma (ccRCC), the most common type of renal cell carcinoma (RCC), is not sensitive to traditional radiotherapy and chemotherapy. The polyphenolic compound Gallic acid (GA) can be naturally found in a variety of fruits, vegetables and plants. Autophagy, an intracellular catabolic process, regulates the lysosomal degradation of organelles and portions in cytoplasm. It was reported that autophagy and GA could affect the development of several cancers. Therefore, the aim of the present study was to evaluate the effects of GA on ccRCC development and clarify the role of autophagy in this process. In the present study, the effects of GA on the proliferation, migration and invasion of ccRCC cells were investigated in vitro by Cell Counting Kit8, colony formation, flow cytometry, wound healing and Transwell migration assays, respectively. Additionally, the effects of GA on ccRCC growth and metastasis were evaluated using hematoxylineosin and immunohistochemical staining in vivo. Moreover, it was sought to explore the underlying molecular mechanisms using transmission electron microscopy, western blotting and reverse transcriptionquantitative PCR analyses. In the present study, it was revealed that GA had a more potent viability inhibitory effect on ccRCC cells (786O and ACHN) than the effect on normal renal tubular epithelial cell (HK2), which demonstrated that GA selectively inhibits the viability of cancer cells. Furthermore, it was identified that GA dosedependently inhibited the proliferation, migration and invasion of ccRCC cells in vitro and in vivo. It was demonstrated that GA promoted the release of autophagy markers, which played a role in regulating the PI3K/Akt/Atg16L1 signaling pathway. All the aforementioned data provided evidence for the great potential of GA in the treatment of ccRCC.
Subject(s)
Autophagy-Related Proteins , Autophagy , Carcinoma, Renal Cell , Cell Movement , Cell Proliferation , Gallic Acid , Kidney Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Humans , Gallic Acid/pharmacology , Autophagy/drug effects , Signal Transduction/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/metabolism , Cell Proliferation/drug effects , Cell Line, Tumor , Mice , Phosphatidylinositol 3-Kinases/metabolism , Cell Movement/drug effects , Animals , Autophagy-Related Proteins/metabolism , Autophagy-Related Proteins/genetics , Xenograft Model Antitumor Assays , Disease Progression , Male , Female , Gene Expression Regulation, Neoplastic/drug effects , Carrier Proteins/metabolismABSTRACT
OBJECTIVES: To observe the effect of electroacupuncture (EA) at different intensities on nociceptive discharges of wide dynamic range (WDR) neurons in the spinal dorsal horns (DHs) of rats, so as to explore its regulatory characteristics on nociceptive signals at the spinal level. METHODS: A total of 25 male SD rats were used in the present study. A microelectrode array was used to record the discharge activity of WDR neurons in the lumbar spinal DHs of normal rats. After finding the WDR neuron, electrical stimulation (pulse width of 2 ms) was administered to the plantar receptive field (RF) for determining its response component of discharges according to the latency of action potential generation (Aß ï¼»0 to 20 msï¼½, Aδ ï¼»20 to 90 msï¼½, C ï¼»90 to 500 msï¼½ and post-discharge ï¼»500 to 800 msï¼½). High-intensity electrical stimulation was continuously applied to the RF at the paw's plantar surface to induce DHs neuronal windup response. Subsequently, EA stimulation at different intensities (1 mA and 2 mA) was applied to the left "Zusanli"(ST36) at a frequency of 2 Hz/15 Hz for 10 min. The induction of WDR neuronal windup was then repeated under the same conditions. The quantity of nociceptive discharge components and the windup response of WDR neurons before and after EA stimulations at different intensities were compared. RESULTS: Compared to pre-EA, both EA1 mA and EA2 mA significantly reduced the number of Aδ and C component discharges of WDR neurons during stimulation, as well as post-discharge (P<0.01, P<0.001). The inhibitory rate of C component by EA2 mA was significantly higher than that by EA1 mA (P<0.05). Meanwhile, both EA1 mA and EA2 mA attenuated the windup response of WDR neurons (P<0.05, P<0.01), and the effect of EA2 mA was stronger than that of EA1 mA (P<0.05). Further analysis showed that when EA1 mA and EA2 mA respectively applied to both non-receptive field (non-RF) and RF, a significant reduction in the number of Aδ component, C component and post-discharge was observed (P<0.05, P<0.01). EA2 mA at the non-RF and RF demonstrated a significant inhibitory effect on the windup response of WDR neurons (P<0.01, P<0.05), but EA1 mA only at the non-RF showed a significant inhibitory effect on the windup response (P<0.01). CONCLUSIONS: EA can suppress nociceptive discharges of spinal DHs WDR neurons in rats. The inhibitory impact of EA is strongly correlated with the location and intensity of EA stimulation, and EA2 mA has a stronger inhibitory effect than EA1 mA.
Subject(s)
Acupuncture Points , Electroacupuncture , Rats, Sprague-Dawley , Animals , Male , Rats , Humans , Nociception , Spinal Cord Dorsal Horn/physiopathology , Posterior Horn Cells/physiology , Action PotentialsABSTRACT
Diode effects are of great interest for both fundamental physics and modern technologies. Electrical diode effects (nonreciprocal transport) have been observed in Weyl systems. Optical diode effects arising from the Weyl fermions have been theoretically considered but not probed experimentally. Here, we report the observation of a nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetization introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). We demonstrate a six-fold change of the measured SHG intensity between opposite propagation directions over a bandwidth exceeding 250 meV. Supported by density-functional theory, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of this broadband effect. We further demonstrate current-induced magnetization switching and thus electrical control of the NODE. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials and further opens new pathways for the unidirectional manipulation of light.