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Achieving high-efficiency perovskite solar cells (PSCs) hinges on the precise control of the perovskite film crystallization process, often improved by the inclusion of additives. While dimethyl sulfoxide (DMSO) is traditionally used to manage this process, its removal from the films is problematic. In this work, methyl phenyl sulfoxide (MPSO) was employed instead of DMSO to slow the crystallization rate, as MPSO is more easily removed from the perovskite structure. The electron delocalization associated with the benzene ring in MPSO decreases the electron density around the oxygen atom in the sulfoxide group, thus reducing its interaction with PbI2. This strategy not only sustains the formation of a crystallization-slowing intermediate phase but also simplifies the elimination of the additive. Consequently, the optimized PSCs achieved a leading power conversion efficiency (PCE) of 25.95% along with exceptional stability. This strategy provides a novel method for fine-tuning perovskite crystallization to enhance the overall performance of photovoltaic devices.
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Human microbes are closely associated with a variety of complex diseases and have emerged as drug targets. Identification of microbe-related drugs is becoming a key issue in drug development and precision medicine. It can also provide guidance for solving the increasingly serious problem of drug resistance enhancement in viruses. METHODS: In this paper, we have proposed a novel model of layer attention graph convolutional network for microbe-drug association prediction. First, multiple biological data have been integrated into a heterogeneous network. Then, the heterogeneous network has been incorporated into a graph convolutional network to determine the embedded microbe and drug. Finally, the microbe-drug association scores have been obtained by decoding the embedding of microbe and drug based on the layer attention mechanism. RESULTS: To evaluate the performance of our proposed model, leave-one-out crossvalidation (LOOCV) and 5-fold cross-validation have been implemented on the two datasets of aBiofilm and MDAD. As a result, based on the aBiofilm dataset, our proposed model has attained areas under the curve (AUC) of 0.9178 and 0.9022 on global LOOCV and local LOOCV, respectively. Based on aBiofilm dataset, the proposed model has attained an AUC value of 0.9018 and 0.8902 on global LOOCV and local LOOCV, respectively. In addition, the average AUC and standard deviation of the proposed model for 5- fold cross-validation on the aBiofilm and MDAD datasets were 0.9141±6.8556e-04 and 0.8982±7.5868e-04, respectively. Also, two kinds of case studies have been further conducted to evaluate the proposed models. CONCLUSION: Traditional methods for microbe-drug association prediction are timeconsuming and laborious. Therefore, the computational model proposed was used to predict new microbe-drug associations. Several evaluation results have shown the proposed model to achieve satisfactory results and that it can play a role in drug development and precision medicine.
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Redes Neurais de Computação , Humanos , Bactérias/efeitos dos fármacosRESUMO
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Connexin is a transmembrane protein involved in gap junctions (GJs) formation. Our previous study found that connexin 37 (Cx37), encoded by gap junction protein alpha 4 (GJA4), expressed on fibroblasts acts as a promoter of CRC and is closely related to epithelial-mesenchymal transition (EMT) and tumor immune microenvironment. However, to date, the mechanism concerning the malignancy of GJA4 in tumor stroma has not been studied. METHODS: Hematoxylin-eosin (HE) and immunohistochemical (IHC) staining were used to validate the expression and localization of GJA4. Using single-cell analysis, enrichment analysis, spatial transcriptomics, immunofluorescence staining (IF), Sirius red staining, wound healing and transwell assays, western blotting (WB), Cell Counting Kit-8 (CCK8) assay and in vivo experiments, we investigated the possible mechanisms of GJA4 in promoting CRC. RESULTS: We discovered that in CRC, GJA4 on fibroblasts is involved in promoting fibroblast activation and promoting EMT through a fibroblast-dependent pathway. Furthermore, GJA4 may act synergistically with M2 macrophages to limit T cell infiltration by stimulating the formation of an immune-excluded desmoplasic barrier. Finally, we found a significantly correlation between GJA4 and pathological staging (P < 0.0001) or D2 dimer (R = 0.03, P < 0.05). CONCLUSION: We have identified GJA4 expressed on fibroblasts is actually a promoter of the tumor mesenchymal phenotype. Our findings suggest that the interaction between GJA4+ fibroblasts and M2 macrophages may be an effective target for enhancing tumor immunotherapy.
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Based on the PM1 mass concentration data from all the air quality monitoring stations in China from 2014 to 2017, the temporal and spatial distribution characteristics of PM1 concentration were studied using the time series statistical and spatial hierarchical clustering methods, and the PM1 spatiotemporal evolution characteristics were revealed. Combined with AOD data of the MODIS remote-sensing satellite, the temporal and spatial variation in PM1-AOD correlation was analyzed on a fine scale. The results showed that, from 2014 to 2017, the annual average PM1 concentration in China decreased yearly, the seasonal PM1 concentration showed the characteristics of "high in winter and low in summer," and the monthly average PM1 concentration showed a "U"-shaped variation. An "M"-shaped PM1 variation pattern was presented before and after the holidays. Weekly variation showed that high PM1 values occurred on Mondays and Fridays, and low ones occurred on Sundays. Based on the spatial clustering method, the national average annual PM1 concentration in China was divided into seven categories, and the overall spatial distribution pattern was "high in the east and low in the west and high in the north and low in the south." The highest and the lowest values of average PM1 concentration occurred in central China(54.59 µg·m-3) and in Xinjiang-Qinghai-Xizang(11.37 µg·m-3), respectively. The PM1-AOD relationship was positively correlated as a whole, the highest correlation coefficient was 0.55 in central China, and the lowest value was 0.36 in central and southern China.
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Bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP) are a group of antibacterial proteins that play an important role in the host's innate immune defense against pathogen infection. In this study, two BPI/LBPs, named ToBPI1/LBP (1434 bp in length, 478 amino acids) and ToBPI2/LBP (1422 bp in length, 474 amino acids), were identified from the golden pompano. ToBPI1/LBP and ToBPI2/LBP were significantly expressed in immune-related tissues after being challenged with Streptococcus agalactiae and Vibrio alginolyticus. The two BPI/LBPs showed significant antibacterial activity against Gram-negative Escherichia coli and Gram-positive S. agalactiae and Streptococcus iniae. In contrast, the antibacterial activity against Staphylococcus aureus, Corynebacterium glutamicum, Vibrio parahaemolyticus, V. alginolyticus and Vibrio harveyi was low and decreased with time. The membrane permeability of bacteria treated with recombinant ToBPI1/LBP and ToBPI2/LBP was significantly enhanced. These results suggest that ToBPI1/LBP and ToBPI2/LBP may play important immunological roles in the immune response of the golden pompano to bacteria. This study will provide basic information and new insights into the immune response mechanism of the golden pompano to bacteria and the function of BPI/LBP.
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Infecções Bacterianas , Peixes , Animais , Sequência de Aminoácidos , Sequência de Bases , Filogenia , Peixes/genética , AntibacterianosRESUMO
Cryptococcosis is a globally distributed infectious fungal disease. However, much remains unknown about its molecular epidemiology in many parts of the world. In this study, we analyzed 86 clinical Cryptococcus neoformans isolates from 14 regions in Jiangxi Province in south central China. Each isolate was from a different patient and 35 of the 86 (40.7%) patients were infected with HIV. All strains belonged to serotype A and mating type α (MATα). Genotyping based on DNA sequences at seven nuclear loci revealed eight sequence types (STs) among the 86 isolates, including two novel STs that have not been reported from other parts of the world. ST5 was the dominant genotype and our comparative analyses showed that these genotypes in Jiangxi likely originated by dispersal from other regions within and outside of China and/or mutations from another genotype within Jiangxi. Though none of the isolates was resistant to the five tested antifungal drugs (flucytosine, amphotericin B, fluconazole, itraconazole, and voriconazole), obvious differences in their minimum inhibitory concentrations were observed, even among isolates of the same ST. Our results suggest that continuous monitoring should be conducted to understand the changing dynamics of C. neoformans in this and other regions.
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Antifúngicos/farmacologia , Criptococose/epidemiologia , Cryptococcus neoformans/genética , Farmacorresistência Fúngica/genética , Genes Fúngicos Tipo Acasalamento , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China/epidemiologia , Criptococose/genética , Criptococose/microbiologia , Cryptococcus neoformans/classificação , Cryptococcus neoformans/isolamento & purificação , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Filogenia , Sorotipagem , Adulto JovemRESUMO
AIM: To investigate the role of activating transcription factor 4 (ATF4) in glucose deprivation (GD) induced colorectal cancer (CRC) drug resistance and the mechanism involved. METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RT-PCR and Western blot were used to detect the mRNA and protein expression of drug resistance gene 1 (MDR1), respectively. RESULTS: GD protected CRC cells from drug-induced apoptosis (oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug re-sensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells. CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression.