Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing ...therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPβ, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBPβ, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner. By recruiting the methyltransferase DOT1L, C/EBPβ can maintain an open chromatin state by H3K79 methylation of multiple drug-resistance genes, thereby augmenting the chemoresistance of tumor cells. Therefore, we propose a new path against cancer epigenetics in which identifying and targeting the key regulators of epigenetics such as C/EBPβ may provide more precise therapeutic options in ovarian cancer.
Interfaces play a decisive role in perovskite solar cells’ power conversion efficiency and their long‐term durability. Small‐molecule hole‐transporting materials (HTMs) have grabbed enormous ...attention due to their structural flexibility, material properties, and stabilities, allowing for improved operational durability in perovskite photovoltaics. This study synthesizes and investigates a new class of benzimidazole‐based small molecules, named YJS001 and YJS003, serving as the HTMs to enable high‐efficiency mixed‐cation mixed‐halide perovskite solar cells. The benzimidazole‐based materials are dopant‐free HTMs composed of donor and acceptor building blocks that are designed to engineer the energy level alignment near the HTM/perovskite interface. Mixed‐cation mixed‐halide perovskites can be grown uniformly on both HTMs with large crystalline grains. It is discovered that the donor‐rich YJS003‐based solar cell exhibits a high open‐circuit voltage of 1.09 V with a champion power conversion efficiency of over 20%. Power‐dependent current–voltage characteristics of the solar cells are analyzed, from which the high performance of YJS003's excellent hole mobility and well‐aligned energy level is attributed. This work introduces a new class of benzimidazole‐based small molecules as HTMs, that paves the path for dopant free interface material development for commercialization of perovskite solar cells.
Two new hole‐transporting materials (HTMs) with acceptor‐rich (YJS001) and donor‐rich (YJS003) are synthesized and characterized for hybrid perovskite photovoltaics applications. Under similar conditions, the efficiency of HTM YJS001 and YJS003‐based devices is 17.43% and 20.81%, respectively. The superior performance of YJS003 over YJS001 is attributed to higher open‐circuit voltage and fill factor from good hole transport, lower trap density, and lower electric resistance of cells.
The study on atmospheric polycyclic aromatic hydrocarbons (PAHs) in China has regional and global significance to understand the large scale atmospheric transport of PAHs. In this study, 16 US EPA ...priority PAHs were analyzed in more than 500 pairs of gas and particle phases samples, which were collected on the same schedule on a weekly basis from August 2008 to July 2009 at 11 urban sites (6 northern cities and 5 southern cities) across China. The average concentration was 239 ± 329 ng/m3 and 165 ± 164 ng/m3 for the northern cities and the southern cities, respectively. Different seasonal variations of atmospheric PAHs were observed between northern cities and southern cities, which were mainly caused by the different temperature effects in winter. Identified by principal component analysis, coal combustion and vehicle exhaust were the major sources of atmospheric PAHs in northern and southern cities of China, respectively. The temperature dependences of atmospheric PAHs were also different, which were caused by the different influences of temperature on identified sources. To our knowledge, this is the first comprehensive study to report the difference with concentrations, seasonal variations, sources and temperature dependences of atmospheric PAHs between northern cities and southern cities in China.
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•More than 500 pairs of gas and particle phases were collected for PAHs analysis.•3-ring and 4-ring PAHs were the predominate homologues in atmosphere.•Significant difference between northern and southern cities was found in winter.•Coal combustion and vehicle exhaust were major sources of atmospheric PAHs.•Temperatures dependences of atmospheric PAHs were influenced by sources.
An effective collection of multiple photogenerated electrons for VOCs oxidation by mean of broadband light absorption and unidirectional electron flow to surface reactive sites by synergetic ...contributions of Pt electron trapping and oxygen defective WO3 via facile one-step room-temperature strategy.
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•Oxygen vacancies are controllably tuned in Pt/WO3 by different NaBH4 concentrations.•Vo-rich Pt/WO3 enhances light harvesting and charge carriers separation.•Multiple charge collection is realized by synergetic Pt and oxygen defective WO3.•Efficient solar light promoted VOCs degradation is achieved in Vo-rich Pt/WO3.
Solar heterogeneous photocatalysis is a highly desirable way for the degradation of volatile organic compounds. Controlled creation of intrinsic oxygen vacancies can significantly modulate the optical and electronic properties of metal oxide semiconductors. However, poor charge utilization in defective metal oxides restrains their photocatalysis efficiency by the sluggish interfacial reaction dynamics. Herein, we demonstrate an effective photogenerated carriers collection for VOCs oxidation by mean of broadband light absorption and unidirectional electron flow to surface reactive sites by synergetic contribution of Pt nanoparticles acting as electron trapping and WO3 with abundant oxygen vacancies via facile one-step room-temperature NaBH4 treatment strategy. The optimized Vo-rich (oxygen vacancies-rich) Pt/WO3 nanosheets is able to achieve effective charge carrier utilization in a high toluene conversion of 98% even at a high CO2 yield of 95% with a quantum efficiency of 55.7% and good stability under solar light irradiation. This work highlights using oxygen vacancies-rich semiconductor as a promising support to design efficient and durable photocatalyst with collaborative optimizing charge separation and utilization, which will provide valuable insights on the defect engineering for photoredox catalysis applications toward efficient solar-to-chemical energy conversion.
Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation ...resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage‐mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3‐associated phagocytosis (LAP), a non‐canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G‐protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL‐induced efferocytosis, anti‐colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3‐associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease.
Synopsis
Enhancement of efferocytosis has been regarded as an emerging strategy for inflammatory diseases, while pharmacological approaches to modulate efferocytosis are poorly defined. Our study identified a natural compound, columbamine (COL), that can activate LC3‐associated efferocytosis and attenuate DSS‐induced colitis by biasedly targeting FPR2 on macrophages. This study provides a novel therapeutic strategy for inflammatory diseases, including colitis, via enhancing FPR2‐mediated efferocytosis.
COL has been identified as a novel efferocytosis enhancer that ameliorates mouse colitis.
COL binds to and biasedly activates FPR2, leading to enhanced efferocytosis in macrophages.
FPR2 emerges as a promising therapeutic target for the treatment of inflammatory diseases through modulating LC3‐associated efferocytosis in macrophages.
Enhancement of efferocytosis has been regarded as an emerging strategy for inflammatory diseases, while pharmacological approaches to modulate efferocytosis are poorly defined. Our study identified a natural compound, columbamine (COL), that can activate LC3‐associated efferocytosis and attenuate DSS‐induced colitis by biasedly targeting FPR2 on macrophages. This study provides a novel therapeutic strategy for inflammatory diseases, including colitis, via enhancing FPR2‐mediated efferocytosis.
•The thermal energy flow model with time delay under CF-VT for DHN is proposed.•The model for DHN under different heating regulation modes is distinguished.•An optimal scheduling strategy of DIHPS ...under VF-CT and CF-VT is proposed.•The total thermal capacity of buildings is less under CF-VT than VF-CT.•Thermal inertia of DHN restrict flexibility of DIHPS with multiple energy stations.
Utilizing multiple energy supply solutions and the thermal inertia of buildings are considered as an efficient method for improving energy conservation and the operational flexibility of Combined Heat and Power (CHP) for wind power integration in a district integrated heat and power system (DIHPS). However, to truly take advantage of these, many factors such as the energy price, the variable efficiency of devices, and especially the different heating regulation modes (the quantity regulation and the quality regulation mode) are imperative to be considered for variable situations of the practical project. Therefore, in this paper, an integrated hydraulic-thermal model of the district heating network (DHN) under the quantity regulation mode is introduced, and a novel thermal energy flow model with transmission time delay under the quality regulation mode is firstly proposed to simulate the dynamic thermal energy distribution of the DHN with multiple heat sources. Then, in terms of different heating regulation modes, the different thermal capacity of buildings to increase the flexibility of the DIHPS is studied. Moreover, an optimal scheduling method considering different energy stations and the thermal inertia of buildings under different heating regulation modes is proposed to guide the operation of the DIHPS in variable actual engineering applications for the sake of operational economics and wind power utilization. Finally, numerical cases have been compared based on a modified testing system. The results demonstrate that under the quantity regulation mode the coordination of energy stations effectively reduces the daily operation cost by 17.4%. The thermal inertia of buildings give a saving rate of 6.4% and he penalty cost of wind power is reduced by 36.3% further. Moreover, the total thermal capacity of buildings to reduce the operation cost and the wind power curtailment is less under the quality regulation mode. It results that the daily operation cost increases by 4.1%. In addition, towards the DIHPS with multiple energy stations in our case, the thermal inertia of pipes cloud not reduce the daily operation cost.
Background:
Surgical treatment is indicated for unstable acromioclavicular (AC) joint dislocation. The hook plate (HP) technique is a commonly used treatment method, but the use of the suture button ...(SB) technique is increasing.
Purpose:
To conduct a meta-analysis of clinical studies evaluating patient outcomes between the SB and HP techniques for acute unstable AC joint dislocation.
Study Design:
Meta-analysis.
Methods:
A literature search of the Embase, PubMed, and Cochrane Library databases was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Cohort studies and case-control studies comparing the SB and HP procedures for acute unstable AC joint dislocation were included. Statistical analysis was performed with RevMan (v 5.3.5).
Results:
Eight clinical studies that met the inclusion criteria were identified and included a total of 204 patients treated with the SB technique and 195 patients with the HP technique. Patients treated with the SB technique had a higher Constant score (mean difference MD, 3.95; 95% CI, 1.20-6.70; P = .005) and a lower visual analog scale pain score (MD, –0.75; 95% CI, –1.12 to 0.37; P < .0001) when compared with the HP technique. No significant differences in operation time (MD, –0.38; 95% CI, –7.14 to 6.37; P = .91), coracoclavicular distance (MD, –0.07; 95% CI, –0.49 to 0.35; P = .75), complications (odds ratio, 0.59; 95% CI, 0.22-1.54; P = .28), and loss of reduction (odds ratio, 2.55; 95% CI, 0.66-9.83; P = .17) were found between the SB and HP techniques. The subgroup analysis showed that the arthroscopic SB technique resulted in a higher Constant score (MD, 6.75; 95% CI, 4.21-9.29; P < .00001) as compared with the HP technique, but no differences were observed between the open SB and HP techniques (MD, 0.69; 95% CI, –0.82 to 2.20; P = .37).
Conclusion:
This meta-analysis demonstrated that the SB technique resulted in better functional outcomes and a reduced visual analog scale pain score when compared with the HP technique. However, for operation time, coracoclavicular distance, complications, and loss of reduction, there were no statistically significant differences between the techniques. Compared with the open procedure, arthroscopic SB may be superior for better functional outcomes.
•We firstly clarify the relationship between the hepatic protection of CSGS and its antidepressant effect through metabonomics and qRT-PCR.•Metabonomics demonstrated that CSGS mainly regulated ...phospholipids and bile acid metabolism against hepatic injury induced by CUMS.•The mRNA expression levels of apoptosis-associated genes and four genes related to the perturbed metabolic pathways were regulated by CSGS.
Chaihu-Shu-Gan-San (CSGS) is a famous classic traditional Chinese medicines (TCM) formula for treatment of liver stagnancy recorded in a famous book of traditional Chinese medicine, Jing Yue Quan Shu published in 1624. It has been extensively accepted as an antidepressant in China and its mechanism of action is still not clear. Previously we have found that hepatic injury happens in chronic unpredicted mild stress (CUMS). Thus, the protection of CSGS against hepatic injury induced by CUMS treatment was explored by metabonomics study and gene expression of the rat liver tissue. The results indicated that CSGS improved 8 of the 18 perturbed potential biomarkers in liver tissues of rats treated with CUMS, and involved in regulating phospholipids and bile acid metabolism against hepatic injury induced by CUMS in rat. The expressions of two apoptosis associated genes (Bcl-2 and Bax) and four genes (Pnpla6, Pla2g15, Baat and Gad1) related to the perturbed metabolic pathways were further investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Both metabonomics and studies of genetic influences on metabolites demonstrated that CSGS inhibited hepatocyte apoptosis, and regulated phospholipids and bile acid metabolism against hepatic injury induced by CUMS in rat. Exploring the protection of CSGS against hepatic injury related to depression further clarify the relationship between CUMS-induced depression and hepatic injury, and also provide a novel insight to understand the underlying antidepressive mechanism of CSGS.
Osteoarthritis (OA) refers to a chronic joint disease characterized by degenerative changes of articular cartilage and secondary bone hyperplasia. Since articular cartilage has a special structure, ...namely the absence of blood vessels as well as the low conversion rate of chondrocytes in the cartilage matrix, the treatment faces numerous clinical challenges. Traditional OA treatment (
., arthroscopic debridement, microfracture, autologous or allogeneic cartilage transplantation, chondrocyte transplantation) is primarily symptomatic treatment and pain management, which cannot contribute to regenerating degenerated cartilage or reducing joint inflammation. Also, the generated mixed fibrous cartilage tissue is not the same as natural hyaline cartilage. Mesenchymal stem cells (MSCs) have turned into the most extensively explored new therapeutic drugs in cell-based OA treatment as a result of their ability to differentiate into chondrocytes and their immunomodulatory properties. In this study, the preliminary results of preclinical (OA animal model)/clinical trials regarding the effects of MSCs on cartilage repair of knee joints are briefly summarized, which lay a solid application basis for more and deeper clinical studies on cell-based OA treatment.
Autophagy impairment is commonly implicated in the pathological characteristic of Alzheimer's disease (AD). Presenilin 1 (PS1) expression in human brain gradually decreases with age and its mutations ...account for the most common cases of early-onset familial Alzheimer's disease (FAD). The dominant autophagy phenotypes occur in PS1-knockout and PS1 mutant neurons; it is still unknown whether PS1 deficiency causes serious autophagy impairment in neural stem cells (NSCs). Herein, we generated the heterozygote and homozygote of PS1 knockout in human induced pluripotent stem cells (iPSCs) via CRISPR/Cas9-based gene editing and differentiated them into human NSCs. In these human PS1-deficient NSCs, reduced autophagosome formation and downregulated expression of autophagy-lysosome pathway (ALP)-related mRNAs, as well as proteins were observed. Mechanistically, ERK/CREB inhibition and GSK3β activation had key roles in reducing TFEB expression in PS1-knockout NSCs. Pharmacological inhibition of GSK3β upregulated the expression of TFEB and ALP-related proteins in PS1-knockout NSCs, whereas this effect could be blocked by CREB inhibition. These findings demonstrate that PS1 deficiency causes autophagy suppression in human NSCs via downregulating ERK/CREB signaling.
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