Search

To investigate the impact of aging on the sources, volatility, and viscosity of organic aerosol (OA) in Chinese outflows, a high-resolution time-of-flight aerosol mass spectrometer (HR-AMS) coupled with a thermodenuder (TD) was deployed in the spring of 2018 in Dongying, which is a regional receptor site of metropolitan emissions in the North China Plain (NCP). The average mass concentration of PM1 is 31.5±22.7 µg m−3, which is mainly composed of nitrate (33 %) and OA (25 %). The source apportionment results show that the OA is mainly contributed by oxygenated OA (OOA) from secondary sources, including background-OOA (33 %) representing a background concentration of OA (2.6 µg m−3) in the NCP area, and transported-OOA (33 %) oxidized from urban emissions. The other two factors include aged hydrocarbon-liked OA (aged-HOA, 28 %) from transported vehicle emissions and biomass burning OA (BBOA, 5 %) from local open burning. The volatility of total OA (average C*=3.2×10-4 µg m−3) in this study is generally lower than that reported in previous field studies, which is mainly due to the high OA oxidation level resulting from aging processes during transport. The volatilities of OA factors follow the order of background-OOA (average C*=2.7×10-5 µg m−3)

This study aimed to explore the role of p53/p21 in osteoarthritis (OA). OA animal model was established by the anterior cruciate ligamentotomy (ACLT). 24 rats were randomly divided into control, OA, OA+p53 inhibitor and OA+pyroptosis inducer groups (n = 6). In the knee joint tissue, microstructural changes were analysed by Micro-CT. Histopathological changes were stained by HE and safranin-fast green. NLRP3 and Caspase-1 were detected by immunohistochemistry. The chondrocytes C-28I2 were divided into control, LPS+ ATP and p53 inhibitor groups. The cell viability, apoptosis, and LDH release were measured by MTT assay, TUNEL staining and LDH kit. The expression of p53/p21 and pyroptosis pathways were examined by western blot. The p53 inhibitor reduced the relative volume of trabecular bone (BV/TV) and trabecular bone thickness (Tb.Th), while increased trabecular separation (Tb.Sp). Moreover, the p53 inhibitor improved histopathological changes in the knee joint, attenuated cartilage damage, and reduced the expression of p53/p21 and pyroptosis pathways-related proteins. In vitro assay showed that the p53 inhibitor increased C-28I2 cell activity, reduced LDH release and apoptosis and reduced p53/p21 and pyroptosis pathways-related proteins. Totally, p53 inhibitors improved the cartilage tissue and chondrocyte damage, inhibited cell pyroptosis and the progression of OA.

The nano-punching characteristics of single-crystalline aluminum are investigated using the quasi-continuum (QC) method. Four variables (i.e., crystal orientation, workpiece thickness, clearance between the punch and the substrate, and the taper angle of punch) are used to explore their effect during the nano-punching process. The shear stress distribution is used to express the punching effect on the punch and on both sides of the substrates. Besides, fracture strength, residual flash, and the atomic displacement vector are observed and discussed regarding the behaviors of the nano-punching process under various conditions. Based on the results, the Al workpiece with the X[111]Y[−110] orientation presents less lattice resistance during the punching process. Besides, the thickness of the workpiece has a significant effect on the punching quality. Workpieces with thickness values of 5 and 10 Å are more suitable for punching, due to stable loading and unloading stress–displacement curves and less residual flash on the cutting surfaces of these workpieces. In contrast, the effect of clearance has less impact on the punching behaviors of thinner workpieces. However, for thicker workpieces (i.e., 15 and 20 Å), a larger clearance will likely cause more residual flash. Furthermore, the taper angle of the punch should not be larger than 10°, otherwise, it might damage the workpiece and the substrate.

Triazole resistance in the human fungal pathogen Aspergillus fumigatus has been a growing challenge in clinic treatment with triazole drugs such as itraconazole. The fast evolvement of triazole resistance in A. fumigatus in the ecosystem has drawn great attention, and there has been a possible link between the application of triazole fungicides in agriculture and triazole resistance in A. fumigatus. The change in susceptibility of A. fumigatus exposed to the new chiral triazole fungicide mefentrifluconazole was investigated in this study.The results indicated that triazole resistance in A. fumigatus was acquired with exposure to mefentrifluconazole at a level of greater than or equal to 2 mg LThe results suggest that triazole resistance in A. fumigatus could be resulted from the selection of mefentrifluconazole at concentrations larger than 2 mg L

Medium-chain acyl-CoA dehydrogenase (MCAD) is one of the significant enzymes involved in the β-oxidation of mitochondrial fatty acids. MCAD deficiency affects the β-oxidation of fatty acid and leads to lipid deposition in multiple organs, but little is known about its importance in nonalcoholic steatohepatitis (NASH). Empagliflozin is revealed to effectively improve NASH by increasing research, whereas the specific mechanism still has to be explored. Human liver tissues of patients with or without NASH were obtained for proteomic analysis to screen proteins of interest. db/db mice were given empagliflozin by gavage for 8 weeks. The expression of MCAD and signaling molecules involved in hepatic lipid metabolism was evaluated in human liver, mice and HL7702 cells. We found that the MCAD levels in the liver were significantly reduced in NASH patients compared to patients without NASH. Protein–protein interaction network analysis showed that MCAD was highly correlated with forkhead box A2 (FOXA2) and protein kinase AMP-activated catalytic subunit alpha (PRKAA). AMPK/FOXA2/MCAD signaling pathway was detected to be inhibited in the liver of NASH patients. Decreased expression of MCAD was also observed in the livers of db/db mice and hepatocyte treated with palmitic acid and glucose. Of note, empagliflozin could upregulate MCAD expression by activating AMPK/FOXA2 signaling pathway, reduce lipid deposition and improve NASH in vivo and in vitro. This research demonstrated that MCAD is a key player of hepatic lipid deposition and its targeting partially corrects NASH. MCAD thus may be a potential therapeutic target for the treatment of NASH.

Three-dimensional (3D) laser nanoprinting allows maskless manufacturing of diverse nanostructures with nanoscale resolution. However, 3D manufacturing of inorganic nanostructures typically requires nanomaterial-polymer composites and is limited by a photopolymerization mechanism, resulting in a reduction of material purity and degradation of intrinsic properties. We developed a polymerization-independent, laser direct writing technique called photoexcitation-induced chemical bonding. Without any additives, the holes excited inside semiconductor quantum dots are transferred to the nanocrystal surface and improve their chemical reactivity, leading to interparticle chemical bonding. As a proof of concept, we printed arbitrary 3D quantum dot architectures at a resolution beyond the diffraction limit. Our strategy will enable the manufacturing of free-form quantum dot optoelectronic devices such as light-emitting devices or photodetectors.

In today’s society, the pressure of family care is increasing and people’s demand for childcare services is increasing. At the same time, the government also pays more attention to the problem of 0 ∼ 3-year-old infant care services which are desperately needed in every society throughout the world. General studies have been carried out in literature where results show that in families with only one child, long working hours and with more than two children, the three factors of children’s age gap, attention to nursery facilities, attention to environment and food safety have a negative impact on people’s demand for nursery services. From these studies, we have extracted three vital factors that have a positive impact on people’s demand for childcare services: grandparents’ help to take care of children, parents’ age, and psychological tolerance of childcare service fees. In this paper, we have utilized one of the most commonly used methodology, i.e., big data, to smoothly resolve the accessibility issue of urban non-profit public nursery services. In order to verify and evaluate our claim, we have implemented the proposed scheme and compared the results which shows that exceptional performance of the propose scheme.

In order to design effective public health policies to combat the COVID-19 pandemic, local governments and organizations must be able to forecast the expected number of cases in their area. Although researchers have developed individual models for predicting COVID-19 based on sensor data without requiring a test, less research has been conducted on how to leverage those individual predictions in forecasting virus spread for determining hierarchical predictions from the community level to the state level. The Multi-Level Adaptive and Dynamic Biosensor Epidemic Model, or m-ADBio, is designed to improve on the traditional SEIR model used to forecast the spread of COVID-19. In this study, the predictive performance of m-ADBio is examined at the state, county, and community levels through numerical experimentation. We find that the model improves over SEIR at all levels, but especially at the community level, where the m-ADBio model with sensor-based initial values yielded no statistically significant difference between the forecasted cases and the true observed data -meaning that the model was highly accurate. Therefore, the m-ADBio model is expected to provide a more timely and accurate forecast to help policymakers optimize pandemic management strategy. IEEE

Although azoxystrobin has been widely applied on various crops, little is known about the bioavailability of azoxystrobin in the soil-vegetable system. In this study, the uptake, accumulation and translocation of azoxystrobin as affected by soil characteristics and plant species were respectively investigated. The accumulation amount of azoxystrobin in pakchoi increased as soil adsorption decreased and was positively associated with its concentration in pore water (C

Optimal feature extraction for multi-category motor imagery brain-computer interfaces (MI-BCIs) is a research hotspot. The common spatial pattern (CSP) algorithm is one of the most widely used methods in MI-BCIs. However, its performance is adversely affected by variance in the operational frequency band and noise interference. Furthermore, the performance of CSP is not satisfactory when addressing multi-category classification problems. In this work, we propose a fusion method combining Filter Banks and Riemannian Tangent Space (FBRTS) in multiple time windows. FBRTS uses multiple filter banks to overcome the problem of variance in the operational frequency band. It also applies the Riemannian method to the covariance matrix extracted by the spatial filter to obtain more robust features in order to overcome the problem of noise interference. In addition, we use a One-Versus-Rest support vector machine (OVR-SVM) model to classify multi-category features. We evaluate our FBRTS method using BCI competition IV dataset 2a and 2b. The experimental results show that the average classification accuracy of our FBRTS method is 77.7% and 86.9% in datasets 2a and 2b respectively. By analyzing the influence of the different numbers of filter banks and time windows on the performance of our FBRTS method, we can identify the optimal number of filter banks and time windows. Additionally, our FBRTS method can obtain more distinctive features than the filter banks common spatial pattern (FBCSP) method in two-dimensional embedding space. These results show that our proposed method can improve the performance of MI-BCIs.

This study aimed to clarify the effect of early glucocorticoid (GC) application on achieving minimal manifestation (MM) status or better in the treatment of myasthenia gravis (MG) in the early clinical phase. A retrospective analysis was performed on 366 patients with MG who had received immunotherapy in the Henan Institute of Medical and Pharmaceutical Sciences Myasthenia Gravis Biobank from January 2015 to September 2022. Patients were divided into two groups: the early mono-GC group (treated with GC within 6 months of MG onset) and delayed mono-GC group. Kaplan-Meier analysis showed that the early mono-GC group achieved MM status earlier and more frequently (Log-rank test, P = 0.0052; hazard ratio [HR], 1.59; P = 0.007). The early mono-GC group had a lower maintenance oral GC dose than delayed mono-GC group. In multivariate Cox regression analysis, early mono-GC (HR, 0.68; P = 0.026), early-onset MG (EOMG) (HR, 0.53; P = 0.004), ocular MG (OMG) (HR, 0.58; P = 0.002), and Myasthenia Gravis Foundation of America (MGFA) IV-V typing (HR, 2.51; P = 0.035) were associated with MM. In conclusion, EOMG, OMG, and low MGFA typing were positive predictors of treatment goals. Early intervention with GC leads to better long-term outcomes and reduces the necessary maintenance dose of oral GC for patients with MG.

Metal halide perovskites exhibit intriguing properties for optoelectronic and electronic applications. Understanding their intrinsic photoexcitation and band-tail dynamics is essential for exploring novel functionality and improving device performance. This report addresses the band-tail luminescence of lead bromide perovskite (APbBr3) single crystals, where A is methylammonium, formamidinium, and cesium. Using time-resolved photoluminescence (PL) spectroscopy, the dynamics of well-defined dual emission peaks are unambiguously resolved from the picosecond to the microsecond scale. Whereas the long-lived states exhibit similar recombination dynamics at high temperatures, a clear, fast transition occurs between the high and low energy states at low temperatures, indicating direct communication between these two states. These time-resolved PL spectra shed light on the intrinsic optical properties of metal halide perovskites.

Supplementary Table S2 shows LRRC15 IHC expression in tumor and stroma of patients with sarcoma treated ABBV-085 monotherapy at 3.6 or 4.2 mg/kg

PDF file - 160K

Cisplatin chemotherapy is standard care for many cancers but is toxic to the kidneys. How this toxicity occurs is uncertain. In this study, we identified apurinic/apyrimidinic endonuclease 2 (APE2) as a critical molecule upregulated in the proximal tubule cells (PTC) following cisplatin-induced nuclear DNA and mitochondrial DNA damage in cisplatin-treated C57B6J mice. The APE2 transgenic mouse phenotype recapitulated the pathophysiological features of C-AKI (acute kidney injury, AKI) in the absence of cisplatin treatment. APE2 pulldown-MS analysis revealed that APE2 binds myosin heavy-Chain 9 (MYH9) protein in mitochondria after cisplatin treatment. Human MYH9-related disorder is caused by mutations in MYH9 that eventually lead to nephritis, macrothrombocytopenia, and deafness, a constellation of symptoms similar to the toxicity profile of cisplatin. Moreover, cisplatin-induced C-AKI was attenuated in APE2-knockout mice. Taken together, these findings suggest that cisplatin promotes AKI development by upregulating APE2, which leads to subsequent MYH9 dysfunction in PTC mitochondria due to an unrelated role of APE2 in DNA damage repair. This postulated mechanism and the availability of an engineered transgenic mouse model based on the mechanism of C-AKI provides an opportunity to identify novel targets for prophylactic treatment of this serious disease.Significance:These results reveal and highlight an unexpected role of APE2 via its interaction with MYH9 and suggest that APE2 has the potential to prevent acute kidney injury in patients with cisplatin-treated cancer.

Table S1: MS/MS analyses of APE2 pull-down proteins in 293T cells

Supplementary Figure S1 shows the study design.

Supplementary Figure S2 shows LRRC15 RNA data from NanoString and clinical response in nonresponder (n=19) and responder (n=5) patients with sarcoma

Supplementary Table S3 shows patient demographics and baseline characteristics

Normal morphology in other organs.

Slight increase of APE2 expression in mouse PTCs after carboplatin and oxaliplatin treatment.

Supplementary Table S1 shows inclusion and exclusion criteria for each treatment arm that enrolled patients

Purpose: Fenretinide (4-HPR) is a cytotoxic retinoid with minimal systemic toxicity that has shown clinical activity against recurrent high-risk neuroblastoma. To identify possible synergistic drug combinations for future clinical trials, we determined whether ABT-737, a small-molecule BH3-mimetic that inhibits most proteins of the antiapoptotic Bcl-2 family, could enhance 4-HPR activity in neuroblastoma.Experimental Design: Eleven neuroblastoma cell lines were tested for the cytotoxic activity of 4-HPR and ABT-737 as single agents and in combination using the DIMSCAN fluorescence digital imaging cytotoxicity assay. The effect of these agents alone and in combination on mitochondrial membrane depolarization and apoptosis (by flow cytometry), cytochrome c release, caspases, Bax-α, t-Bid, and Bak activation, and subcutaneous xenografts in nu/nu mice was also determined.Results: Multilog synergistic cytotoxicity was observed for the drug combination in all of the 11 neuroblastoma cell lines tested, including MDR lines and those insensitive to either drug as single agents. 4-HPR + ABT-737 induced greater mitochondrial membrane depolarization and mitochondrial cytochrome c release, greater activation of caspases, Bax-α, t-Bid, and Bak, and a higher level of apoptosis than either drug alone. In vivo, 4-HPR + ABT-737 increased the event-free survival of the MDR human neuroblastoma line CHLA-119 implanted subcutaneously in nu/nu mice (194.5 days for the combination vs. 68 days for ABT-737 and 99 days for 4-HPR).Conclusion: Thus, the combination of 4-HPR with a BH3-mimetic drug warrants clinical trials in recurrent neuroblastoma. Clin Cancer Res; 17(22); 7093–104. ©2011 AACR.

Supplementary Figure S3 shows T-cell infiltration in patients with breast cancer

Background: The nuclear receptor Nur77 has been demonstrated to play a vital role in the inflammatory response and cellular metabolisms, and its ligands exhibit efficacy in the treatment of inflammation-related diseases (e.g., improving mouse acute lung injury (ALI) and obesity. Recently, ω-3 polyunsaturated fatty acid-ethanolamine derivatives (ω-3 PUFA-EAs), including DPA-EA and DHA-EA, have been reported as new Nur77-targeting anti-inflammatory agents. However, the lipid-lowering effect of ω-3 PUFA-EAs is still unknown, and lipid profile changes induced by Nur77-targeting anti-inflammatory agents also remain unclear.Objective: This study aimed to evaluate the lipid-lowering effect and the underlying mechanism of DPA-EA acting as Nur77-targeting anti-inflammatory agents. It also aimed to investigate the in vitro and in vivo lipid-lowering effects of the DPA-EA and DHA-EA mixture prepared from algae oil.Methods: The in vitro lipid-lowing effect of DPA-EA and its mixture with DHA-EA was first evaluated in palmitic acid-stimulated HepG2 Cells. To confirm the lipid-lowering effect and explore the underlying mechanism, we performed untargeted lipidomic analysis using ultra-performance liquid chromatography/triple quadrupole-time-of-flight (TOF) mass spectrometry coupled with multivariate statistical analysis, with another Nur77-targeting anti-inflammatory compound Celastrol (Cel) as a reference. Finally, we examined the anti-obesity effect of the DPA-EA and DHA-EA mixture synthesized from algae oil in a high-fat diet (HFD)-fed mice model.Results: DPA-EA significantly alleviated lipid accumulation with lower toxicity than Celastrol. Nur77-targeting compounds DPA-EA and Celastrol could simultaneously reduce 14 lipids (9 TGs, 2 PCs, 1 PA, 1 SM, and 1 LacCer) and increase 13 lipids (4 DGs, 6 LPEs, 2 PEs, and 1PC) in Pal-stimulated HepG2 cells. However, Cer lipids were more sensitive to DPA-EA, while the over-downregulation of SM lipids might be associated with the off-target toxicity of Celastrol. The mixture of DPA-EA and DHA-EA synthesized from algae oil could significantly decrease TG, TC, and LDL levels and increase HDL levels in HFD-fed mice, exerting an excellent anti-obesity effect.Conclusion: Nur77-targeting anti-inflammatory compound DAP-EA could promote the hydrolysis of PEs and TGs to ameliorate lipid accumulation. The DPA-EA and DHA-EA mixture prepared from algae oil might be a potential therapeutic agent for obesity and other inflammation-related diseases.

Data harmonization is the process by which each of the variables from different research studies are standardized to similar units resulting in comparable datasets. These data may be integrated for more powerful and accurate examination and prediction of outcomes for use in the intelligent and smart electronic health software programs and systems. Prospective harmonization is performed when researchers create guidelines for gathering and managing the data before data collection begins. In contrast, retrospective harmonization is performed by pooling previously collected data from various studies using expert domain knowledge to identify and translate variables. In nutritional epidemiology, dietary data harmonization is often necessary to construct the nutrient and food databases necessary to answer complex research questions and develop effective public health policy. In this paper, we review methods for effective data harmonization, including developing a harmonization plan, which common standards already exist for harmonization, and defining variables needed to harmonize datasets. Currently, several large-scale studies maintain harmonized nutrient databases, especially in Europe, and steps have been proposed to inform the retrospective harmonization process. As an example, data harmonization methods are applied to several U.S longitudinal diet datasets. Based on our review, considerations for future dietary data harmonization include user agreements for sharing private data among participating studies, defining variables and data dictionaries that accurately map variables among studies, and the use of secure data storage servers to maintain privacy. These considerations establish necessary components of harmonized data for smart health applications which can promote healthier eating and provide greater insights into the effect of dietary patterns on health.