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Identifying genotype-by-environment interaction (GEI) is challenging because the GEI analysis generally has low power. Large-scale consortium-based studies are ultimately needed to achieve adequate power for identifying GEI. We introduce Multi-Trait Analysis of Gene-Environment Interactions (MTAGEI), a powerful, robust, and computationally efficient framework to test gene-environment interactions on multiple traits in large data sets, such as the UK Biobank (UKB). To facilitate the meta-analysis of GEI studies in a consortium, MTAGEI efficiently generates summary statistics of genetic associations for multiple traits under different environmental conditions and integrates the summary statistics for GEI analysis. MTAGEI enhances the power of GEI analysis by aggregating GEI signals across multiple traits and variants that would otherwise be difficult to detect individually. MTAGEI achieves robustness by combining complementary tests under a wide spectrum of genetic architectures. We demonstrate the advantages of MTAGEI over existing single-trait-based GEI tests through extensive simulation studies and the analysis of the whole exome sequencing data from the UKB.
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Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Humanos , Fenótipo , Simulação por ComputadorRESUMO
Fibers, originating from nature and mastered by human, have woven their way throughout the entire history of human civilization. Recent developments in semiconducting polymer materials have further endowed fibers and textiles with various electronic functions, which are attractive in applications such as information interfacing, personalized medicine, and clean energy. Owing to their ability to be easily integrated into daily life, soft fiber electronics based on semiconducting polymers have gained popularity recently for wearable and implantable applications. Herein, we present a review of the previous and current progress in semiconducting polymer-based fiber electronics, particularly focusing on smart-wearable and implantable areas. First, we provide a brief overview of semiconducting polymers from the viewpoint of materials based on the basic concepts and functionality requirements of different devices. Then we analyze the existing applications and associated devices such as information interfaces, healthcare and medicine, and energy conversion and storage. The working principle and performance of semiconducting polymer-based fiber devices are summarized. Furthermore, we focus on the fabrication techniques of fiber devices. Based on the continuous fabrication of one-dimensional fiber and yarn, we introduce two- and three-dimensional fabric fabricating methods. Finally, we review challenges and relevant perspectives and potential solutions to address the related problems.
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Cancer-associated fibroblasts (CAFs) are the main components in the tumor microenvironment. Tumors activate fibroblasts from quiescent state into activated state by secreting cytokines, and activated CAFs may in turn promote tumor progression and metastasis. Therefore, studies targeting CAFs could enrich the therapeutic options for tumor treatment. In this study, we demonstrate that the content of lipid droplets and the expression of autophagosomes were higher in CAFs than in peri-tumor fibroblasts (PTFs), which was inhibited by 5-(tetradecyloxy)-2-furoic acid(TOFA). The expression of CD36 in CAFs was higher than that in PTFs at both mRNA and protein levels. Inhibition of CD36 activity using either the CD36 inhibitor SSO or siRNA had a significant negative impact on the proliferation and migration abilities of CAFs, which was associated with reduced levels of relevant activated genes (α-SMA, FAP, Vimentin) and cytokines (IL-6, TGF-ß and VEGF-α). SSO also inhibited HCC growth and tumorigenesis in nude mice orthotopically implanted with CAFs and HCC cells. Our data further show that CD36+CAFs affected the expression of PD-1 in CTLs leading to CTL exhaustion, and that patients with high CD36 expression in CAFs were correlated with shorter overall survival (OS). Together, our data demonstrate that CAFs were active in lipid metabolism with increased lipid content and lipophagy activity. CD36 may play a key role in the regulation of the biological behaviors of CAFs, which may influence the proliferation and migration of tumor cells by reprograming the lipid metabolism in tumor cells. Thus, CD36 could be an effective therapeutic target for the treatment of HCC.
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Fibroblastos Associados a Câncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Carcinoma Hepatocelular/patologia , Fibroblastos Associados a Câncer/patologia , Neoplasias Hepáticas/patologia , Camundongos Nus , Reprogramação Metabólica , Linhagem Celular Tumoral , Fibroblastos/metabolismo , Citocinas/metabolismo , Microambiente Tumoral , Proliferação de CélulasRESUMO
The electrochemical nitrogen oxidation reaction (NOR) holds significant potential to revolutionize the traditional nitrate synthesis processes. However, the progression in NOR has been notably stymied due to the sluggish kinetics of initial N2 adsorption and activation processes. Herein, the research embarks on the development of a CeO2-Co3O4 heterostructure, strategically engineered to facilitate the electron transfer from CeO2 to Co3O4. This orchestrated transfer operates to amplify the d-band center of the Co active sites, thereby enhancing N2 adsorption and activation dynamics by strengthening the CoâN bond and diminishing the resilience of the N≡N bond. The synthesized CeO2-Co3O4 manifests promising prospects, showcasing a significant HNO3 yield of 37.96 µg h-1 mgcat -1 and an elevated Faradaic efficiency (FE) of 29.30% in a 0.1 m Na2SO4 solution at 1.81 V versus RHE. Further substantiating these findings, an array of in situ methodologies coupled with DFT calculations vividly illustrate the augmented adsorption and activation of N2 on the surface of CeO2-Co3O4 heterostructure, resulting in a substantial reduction in the energy barrier pertinent to the rate-determining step within the NOR pathway. This research carves a promising pathway to amplify N2 adsorption throughout the electrochemical NOR operations and delineates a blueprint for crafting highly efficient NOR electrocatalysts.
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There is a noticeable gap in the literature regarding research on halogen-substitution-regulated ferroelectric semiconductors featuring multiple phase transitions. Here, a new category of 1D perovskite ferroelectrics (DFP)2SbX5 (DFP+ = 3,3-difluoropyrrolidium, X- = I-, Br-, abbreviated as I-1 and Br-2) with twophase transitions (PTs) is reported. The first low-temperature PT is a mmmFmm2 ferroelectric PT, while the high-temperature PT is a counterintuitive inverse temperature symmetry-breaking PT. By the substitution of iodine with bromine, the Curie temperature (Tc) significantly increases from 348 K of I-1 to 374 K of Br-2. Their ferroelectricity and pyroelectricity are improved (Ps value from 1.3 to 4.0 µC cm-2, pe value from 0.2 to 0.48 µC cm-2 K-1 for I-1 and Br-2), while their optical bandgaps increased from 2.1 to 2.7 eV. A critical slowing down phenomenon is observed in the dielectric measurement of I-1 while Br-2 exhibits the ferroelastic domain. Structural and computational analyses elucidate that the order-disorder movement of cations and the distortion of the chain perovskite [SbX5]2- anions skeleton lead to PT. The semiconductor properties are determined by [SbX5]2- anions. The findings contribute to the development of ferroelectric semiconductors and materials with multiple PTs and provide materials for potential applications in the optoelectronic field.
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BACKGROUND: Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated. METHODS: Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining. RESULTS: Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control. CONCLUSIONS: Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.
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Carcinoma Pulmonar de Lewis , Macrófagos , Animais , Camundongos , Carcinoma Pulmonar de Lewis/radioterapia , Carcinoma Pulmonar de Lewis/patologia , Linhagem Celular Tumoral , Indazóis/farmacologia , Macrófagos/metabolismo , Propionatos/farmacologia , Análise de Sequência de RNA , Microambiente Tumoral/genética , Análise de Célula Única , Quimiocina CCL8RESUMO
BACKGROUND AND AIMS: Monocarboxylate transporter (MCT) 4 is a high-affinity lactate transporter that is primarily involved in the maintenance of intracellular pH homeostasis and highly expressed in different tumors. However, the role of MCT4 in modulating immune responses against HCC remains unknown. APPROACH AND RESULTS: In this study, we demonstrated that MCT4 was overexpressed in HCC, which was associated with poor prognosis in patients. Genetic or pharmacological inhibition of MCT4 using VB124 (a highly potent MCT4 inhibitor) suppressed HCC tumor growth in immunocompetent mice model by enhancing CD8 + T cell infiltration and cytotoxicity. Such improved immunotherapy response by MCT4 targeting was due to combined consequences characterized by the alleviated acidification of tumor microenvironment and elevated the chemokine (C-X-C motif) ligand (CXCL) 9/CXCL10 secretion induced by reactive oxygen species/NF-κB signaling pathway. Combining MCT4 inhibition improved the therapeutic benefit of anti-programmed cell death 1 immunotherapy in HCC and prolonged mice survival. Moreover, higher MCT4 expression was observed in tumor tissues from nonresponder patients with HCC receiving neoadjuvant therapy with toripalimab. CONCLUSIONS: Our results revealed that lactate exportation by MCT4 has a tumor-intrinsic function in generating an immunosuppressive HCC environment and demonstrated the proof of the concept of targeting MCT4 in tailoring HCC immunotherapeutic approaches.
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Carcinoma Hepatocelular , Imunoterapia , Neoplasias Hepáticas , Transportadores de Ácidos Monocarboxílicos , Animais , Camundongos , Carcinoma Hepatocelular/terapia , Ácido Láctico/metabolismo , Neoplasias Hepáticas/terapia , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Microambiente Tumoral , HumanosRESUMO
In recent years, increasing attention has been paid to photoelectrochemical (PEC) hydrogen production owing to the utilization of sustainable solar energy and its promising performance. Silicon-based composites are generally considered ideal materials for PEC hydrogen production. However, slow reaction kinetics and poor stability are still key factors hindering the development of silicon-based photoelectrocatalysts. Herein, we present an n+-p Si pyramidal photocathode assembly method to load reduced graphene oxide (rGO) onto the surface of the n+-p Si pyramid by covalently linking (Si/rGO). rGO is utilized as a conductive layer to reduce the interfacial charge-transfer resistance. Then, MoS2 can be successfully electrodeposited on the surface of Si/rGO to form the Si/rGO/MoS2 composite, which possesses excellent PEC hydrogen evolution performance with a high and stable photocurrent of -41.6 mA cm-2 and a hydrogen evolution rate of about 18.1 µmol min-1 cm-2 under 0 V (vs RHE). The covalently linking rGO layer effectively enhances the transfer of photogenerated carriers between the Si substrate and MoS2. MoS2 provides abundant hydrogen evolution active sites, which accelerate the surface reaction kinetics, as well as a protective layer for the Si pyramidal array structure. This work provides a low-cost, convenient, and efficient way of preparing silicon-based photocathodes.
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In the quest for proficient electrocatalysts for ammonia's electrocatalytic nitrogen reduction, cobalt oxides, endowed with a rich d-electron reservoir, have emerged as frontrunners. Despite the previously evidenced prowess of CoO in this realm, its ammonia yield witnesses a pronounced decline as the reaction unfolds, a phenomenon linked to the electron attrition from its Co2+ active sites during electrocatalytic nitrogen reduction reaction (ENRR). To counteract this vulnerability, we harnessed electron-laden phosphorus (P) elements as dopants, aiming to recalibrate the electronic equilibrium of the pivotal Co active site, thereby bolstering both its catalytic performance and stability. Our empirical endeavors showcased the doped P-CoO's superior credentials: it delivered an impressive ammonia yield of 49.6 and, notably, a Faradaic efficiency (FE) of 9.6% at -0.2 V versus RHE, markedly eclipsing its undoped counterpart. Probing deeper, a suite of ex-situ techniques, complemented by rigorous theoretical evaluations, was deployed. This dual-pronged analysis unequivocally revealed CoO's propensity for an electron-driven valence metamorphosis to Co3+ post-ENRR. In stark contrast, P-CoO, fortified by P doping, exhibits a discernibly augmented ammonia yield. Crucially, P's intrinsic ability to staunch electron leakage from the active locus during ENRR ensures the preservation of the valence state, culminating in enhanced catalytic dynamism and fortitude. This investigation not only illuminates the intricacies of active site electronic modulation in ENRR but also charts a navigational beacon for further enhancements in this domain.
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Lauric acid (LA), a saturated fatty acid with 12 carbon atoms, is widely regarded as a healthy fatty acid that plays an important role in disease resistance and improving immune physiological function. The objective of this study was to determine the effects of dietary lauric acid on the growth performance, antioxidant capacity, non-specific immunity and intestinal microbiology, and evaluate the potential of lauric acids an environmentally friendly additive in swimming crab (Portunus trituberculatus) culture. A total of 192 swimming crabs with an initial body weight of 11.68 ± 0.02 g were fed six different dietary lauric acid levels, the analytical values of lauric acid were 0.09, 0.44, 0.80, 1.00, 1.53, 2.91 mg/g, respectively. There were four replicates per treatment and 8 juvenile swimming crabs per replicate. The results indicated that final weight, percent weight gain, specific growth rate, survival and feed intake were not significantly affected by dietary lauric acid levels; however, crabs fed diets with 0.80 and 1.00 mg/g lauric acid showed the lowest feed efficiency among all treatments. Proximate composition in hepatopancreas and muscle were not significantly affected by dietary lauric acid levels. The highest activities of amylase and lipase in hepatopancreas and intestine were found at crabs fed diet with 0.80 mg/g lauric acid (P < 0.05), the activity of carnitine palmityl transferase (CPT) in hepatopancreas and intestine significantly decreased with dietary lauric acid levels increasing from 0.09 to 2.91 mg/g (P < 0.05). The lowest concentration of glucose and total protein and the activity of alkaline phosphatase in hemolymph were observed at crabs fed diets with 0.80 and 1.00 mg/g lauric acid among all treatments. The activity of GSH-Px in hepatopancreas significantly increased with dietary lauric acid increasing from 0.09 to 1.53 mg/g, MDA in hepatopancreas and hemolymph was not significantly influenced by dietary lauric acid levels. The highest expression of cat and gpx in hepatopancreas were exhibited in crabs fed diet with 1.00 mg/g lauric acid, however, the expression of genes related to the inflammatory signaling pathway (relish, myd88, traf6, nf-κB) were up-regulated in the hepatopancreas with dietary lauric acid levels increasing from 0.09 to 1.00 mg/g, moreover, the expression of genes related to intestinal inflammatory, immune and antioxidant were significantly affected by dietary lauric acid levels (P < 0.05). Crabs fed diet without lauric acid supplementation exhibited higher lipid drop area in hepatopancreas than those fed the other diets (P < 0.05). The expression of genes related to lipid catabolism was up-regulated, however, and the expression of genes related to lipid synthesis was down-regulated in the hepatopancreas of crabs fed with 0.80 mg/g lauric acid. Lauric acid improved hepatic tubular integrity, and enhanced intestinal barrier function by increasing peritrophic membrane (PM) thickness and upregulating the expression of structural factors (per44, zo-1) and intestinal immunity-related genes. In addition, dietary 1.00 mg/g lauric acid significantly improved the microbiota composition of the intestinal, increased the abundance of Actinobacteria and Rhodobacteraceae, and decreased the abundance of Vibrio, thus maintaining the microbiota balance of the intestine. The correlation analysis showed that there was a relationship between intestinal microbiota and immune-antioxidant function. In conclusion, the dietary 1.00 mg/g lauric acid is beneficial to improve the antioxidant capacity and intestinal health of swimming crab.
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Ração Animal , Antioxidantes , Braquiúros , Dieta , Suplementos Nutricionais , Microbioma Gastrointestinal , Ácidos Láuricos , Animais , Braquiúros/imunologia , Braquiúros/efeitos dos fármacos , Braquiúros/crescimento & desenvolvimento , Braquiúros/microbiologia , Ácidos Láuricos/farmacologia , Ácidos Láuricos/administração & dosagem , Ração Animal/análise , Antioxidantes/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Distribuição Aleatória , Relação Dose-Resposta a DrogaRESUMO
This experiment was conducted to explore the effects of dietary vitamin C supplementation on non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab (Scylla paramamosain). Mud crabs with an initial weight of 14.67 ± 0.13 g were randomly divided into 6 treatments and fed diets with 0.86 (control), 44.79, 98.45, 133.94, 186.36 and 364.28 mg/kg vitamin C, respectively. The experiment consisted of 6 treatments, each treatment was designed with 4 replicates and each replicate was stocked with 8 crabs. After 42 days of feeding experiment, 2 crabs were randomly selected from each replicate, and a total of 8 crabs in each treatment were carried out 72 h low-temperature challenge experiment. The results showed that crabs fed diets with 186.36 and 364.28 mg/kg vitamin C significantly improved the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in hemolymph and hepatopancreas (P < 0.05). Crabs fed diet with 133.94 mg/kg vitamin C significantly decreased the concentration of nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in hemolymph (P < 0.05). Diet with 133.94 mg/kg vitamin C was improved the activity of polyphenol oxidase (PPO) and the concentration of albumin (ALB) in hemolymph. Crabs fed diet with 133.94 mg/kg vitamin C showed lower concentration of malondialdehyde (MDA) in hemolymph and hepatopancreas than those fed the other diets. Meanwhile, crabs fed diet with 98.45 mg/kg vitamin C showed higher activity of total superoxide dismutase (T-SOD) in hemolymph, and crabs fed diet with 133.94 mg/kg vitamin C showed higher activity of T-SOD in hepatopancreas. Crabs fed diet with 186.36 mg/kg vitamin C significantly decreased the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GSH-PX) in hepatopancreas (P < 0.05). In normal temperature, crabs fed diets with 133.94 mg/kg vitamin C significantly up-regulated the expression levels of gpx (glutathione peroxidase) and trx (thioredoxin) in hepatopancreas compared with the control treatment (P < 0.05). The highest expression levels of relish, il16 (interleukin 16), caspase 2 (caspase 2), p38 mapk (p38 mitogen-activated protein kinases) and bax (bcl-2 associated x protein) in hepatopancreas were found at crabs fed control diet (P < 0.05). Moreover, crabs fed diet with 133.94 mg/kg vitamin C showed higher expression levels of alf-3 (anti-lipopolysaccharide factor 3) and bcl-2 (B-cell lymphoma 2) in hepatopancreas than those fed the other diets (P < 0.05). Under low-temperature stress, crabs fed diet with 133.94 mg/kg vitamin C significantly improved the expression levels of hsp90 (heat shock protein 90), cat (catalase), gpx, prx (thioredoxin peroxidase) and trx in hepatopancreas (P < 0.05). In addition, dietary with 133.94 vitamin C significantly up-regulated the expression levels of alf-3 and bcl-2 (P < 0.05). Based on two slope broken-line regression analysis of activity of PPO against the dietary vitamin C level, the optimal dietary vitamin C requirement was estimated to be 144.81 mg/kg for juvenile mud crab. In conclusion, dietary 133.94-144.81 mg/kg vitamin C significantly improved the non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab.
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The discovery of enzyme-like catalytic characteristics in nanomaterials triggers the generation of nanozymes and their multifarious applications. As a class of artificial mimetic enzymes, nanozymes are widely recognized to have better stability and lower cost than natural bio-enzymes, but the lack of catalytic specificity hinders their wider use. To solve the problem, several potential strategies are explored, among which molecular imprinting attracts much attention because of its powerful capacity for creating specific binding cavities as biomimetic receptors. Attractively, introducing molecularly imprinted polymers (MIPs) onto nanozyme surfaces can make an impact on the latter's catalytic activity. As a result, in recent years, MIPs featuring universal fabrication, low cost, and good stability have been intensively integrated with nanozymes for biochemical detection. In this critical review, we first summarize the general fabrication of nanozyme@MIPs, followed by clarifying the potential effects of molecular imprinting on the catalytic performance of nanozymes in terms of selectivity and activity. Typical examples are emphatically discussed to highlight the latest progress of nanozyme@MIPs applied in catalytic analysis. In the end, personal viewpoints on the future directions of nanozyme@MIPs are presented, to provide a reference for studying the interactions between MIPs and nanozymes and attract more efforts to advance this promising area.
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Hepatocellular adenoma (HCA) represents a rare benign hepatic neoplasm with potential for malignant transformation into hepatocellular carcinoma (HCC), yet the underlying mechanism remains elusive. In this study, we investigated the genomic landscape of this process to identify therapeutic strategies for blocking malignant transformation. Using micro-detection techniques, we obtained specimens of adenoma, cancerous neoplasm and adjacent normal liver from three patients undergoing hepatic resection surgery. Whole-exome sequencing (WES) was performed, and genomic interactions between HCA and HCC components within the same tumour were evaluated using somatic variant calling, copy number variation (CNV) analysis, clonality evaluation and mutational signature analysis. Our results revealed genomic heterogeneity among patient cases, yet within each sample, HCA and HCC tissues exhibited a similar mutational landscape, suggesting a high degree of homology. Using nonnegative matrix factorization and phylogenetic trees, we identified shared and distinct mutational characteristics and uncovering necessary pathways associated with HCA-HCC malignant transformation. Remarkably, we found that HCA and HCC shared a common monoclonal origin while displaying significant genetic diversity within HCA-HCC tumours, indicating fundamental genetic connections or evolutionary pathways between the two. Moreover, elevated immune therapy-related markers in these patients suggested heightened sensitivity to immune therapy, providing novel avenues for the treatment of hepatic malignancies. This study sheds light on the genetic mechanisms underlying HCA-HCC progression, offering potential targets for therapeutic intervention and highlighting the promise of immune-based therapies in managing hepatic malignancies.
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Adenoma de Células Hepáticas , Carcinoma Hepatocelular , Transformação Celular Neoplásica , Sequenciamento do Exoma , Neoplasias Hepáticas , Mutação , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/genética , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/patologia , Masculino , Feminino , Variações do Número de Cópias de DNA , Pessoa de Meia-Idade , Análise Mutacional de DNARESUMO
BACKGROUND: Acute pancreatitis (AP) has become a significant global health concern, and a high body mass index (BMI) has been identified as a key risk factor exacerbating this condition. Within this context, lipid metabolism assumes a critical role. The complex relationship between elevated BMI and AP, mediated by lipid metabolism, markedly increases the risk of complications and mortality. This study aimed to accurately define the correlation between BMI and AP, incorporating a comprehensive analysis of the interactions between individuals with high BMI and AP. METHODS: Mendelian randomization (MR) analysis was first applied to determine the causal relationship between BMI and the risk of AP. Subsequently, three microarray datasets were obtained from the GEO database. This was followed by an analysis of differentially expressed genes and the application of weighted gene coexpression network analysis (WGCNA) to identify key modular genes associated with AP and elevated BMI. Functional enrichment analysis was then performed to shed light on disease pathogenesis. To identify the most informative genes, machine learning algorithms, including Random Forest (RF), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), were employed. Subsequent analysis focused on the colocalization of the Quantitative Trait Loci (eQTL) data associated with the selected genes and Genome-Wide Association Studies (GWAS) data related to the disease. Preliminary verification of gene expression trends was conducted using external GEO datasets. Ultimately, the diagnostic potential of these genes was further confirmed through the development of an AP model in mice with a high BMI. RESULTS: A total of 21 intersecting genes related to BMI>30, AP, and lipid metabolism were identified from the datasets. These genes were primarily enriched in pathways related to cytosolic DNA sensing, cytokineâcytokine receptor interactions, and various immune and inflammatory responses. Next, three machine learning techniques were utilized to identify HADH as the most prevalent diagnostic gene. Colocalization analysis revealed that HADH significantly influenced the risk factors associated with BMI and AP. Furthermore, the trend in HADH expression within the external validation dataset aligned with the trend in the experimental data, thus providing a preliminary validation of the experimental findings.The changes in its expression were further validated using external datasets and quantitative real-time polymerase chain reaction (qPCR). CONCLUSION: This study systematically identified HADH as a potential lipid metabolism-grounded biomarker for AP in patients with a BMI>30.
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Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Pancreatite , Locos de Características Quantitativas , Humanos , Pancreatite/genética , Camundongos , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Perfilação da Expressão Gênica , Transcriptoma/genética , Aprendizado de Máquina , Metabolismo dos Lipídeos/genética , Redes Reguladoras de Genes , Fatores de RiscoRESUMO
Moutan Cortex (MC) is a traditional Chinese medicine that contains abundant medicinal components, such as paeonol, paeoniflorin, etc. Paeonol is the main active component of MC. In this study, paeonol was extracted from MC through an ultrasound-assisted extraction process, which is based on single-factor experiments and response surface methodology (RSM). Subsequently, eight macroporous resins of different properties were used to purify paeonol from MC. The main components of the purified extract were identified by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS/MS). The results indicate the optimal parameters are as follows: liquid-to-material ratio 21:1 mL/g, ethanol concentration 62%, ultrasonic time 31 min, ultrasonic temperature 36 °C, ultrasonic power 420 W. Under these extraction conditions, the actual yield of paeonol was 14.01 mg/g. Among the eight tested macroporous resins, HPD-300 macroporous resin was verified to possess the highest adsorption and desorption qualities. The content of paeonol increased from 6.93% (crude extract) to 41.40% (purified extract) after the HPD-300 macroporous resin treatment. A total of five major phenolic compounds and two principal monoterpene glycosides were characterized by comparison with reference compounds. These findings will make a contribution to the isolation and utilization of the active components from MC.
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Acetofenonas , Medicamentos de Ervas Chinesas , Paeonia , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/químicaRESUMO
Modulating the arrangement of superstructures through noncovalent interactions has a significant impact on macroscopic shape and the expression of unique properties. Constructing π-interaction-driven hierarchical three-dimensional (3D) superstructures poses challenges on account of limited directional control and weak intermolecular interactions. Here we report the construction of a 3D diamondoid superstructure, named π-Diamond, employing a ditopic strained Z-shaped building block comprising a porphyrin unit as bow-limb double-strapped with two m-xylylene units as bowstrings. This superstructure, reminiscent of diamond's tetrahedral carbon composition, is composed of double-walled tetrahedron (DWT) driven solely by π-interactions. Hetero-π-stacking interactions between porphyrin and m-xylylene panels drive the assembly of four building blocks predominantly into a DWT, which undergoes extension to create an adamantane unit and eventually a diamondoid superstructure wherein each porphyrin panel is shared by two neighboring tetrahedra through hetero-π-stacking. π-Diamond exhibits a solid-state fluorescent quantum yield 44 times higher than that of tetraphenylporphyrin along with excellent photocatalytic performance. The precise 3D directionality of π-interactions, achieved through strained multipanel building blocks, revolutionizes the assembly of hierarchical 3D superstructures driven by π-interactions.
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Pyroelectric materials hold significant potential for energy harvesting, sensing, and imaging applications. However, achieving high-performance pyroelectricity across a wide temperature range near room temperature remains a significant challenge. Herein, we demonstrate a single crystal of Fe(II) spin-crossover compound shows remarkable pyroelectric properties accompanied by a thermally controlled spin transition. In this material, the uniaxial alignment of polar molecules results in a polarization of the lattice. As the molecular geometry is modulated during a gradual spin transition, the polar axis experiences a colossal thermal expansion with a coefficient of 796×10-6â K-1. Consequently, the material's polarization undergoes significant modulation as a secondary pyroelectric effect. The considerable shift in polarization (pyroelectric coefficient, p=3.7-22â nC K-1cm-2), coupled with a low dielectric constant (ϵ'=4.4-5.4) over a remarkably wide temperature range of 298 to 400â K, suggests this material is a high-performance pyroelectric. The demonstration of pyroelectricity combined with magnetic switching in this study will inspire further investigations in the field of molecular electronics and magnetism.
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A pyrene-fused dimerized electron acceptor has been successfully synthesized and subsequently incorporated as the third component in ternary organic solar cells (OSCs). Diverging from the traditional dimerized acceptors with a linear configuration, this novel electron acceptor displays a distinctive "butterfly-like" structure, comprising two Y-acceptors as wings fused with a pyrene-based backbone. The extended π-conjugated backbone and the electron-donating nature of pyrene enable the new acceptor to show low solubility, elevated glass transition temperature (Tg ), and low-lying frontier energy levels. Consequently, the new dimerized acceptor seamlessly integrates as the third component into ternary OSCs, enhancing electron transporting properties, reducing non-radiative voltage loss, and elevating open-circuit voltage. These merits have enabled the ternary OSCs to show an exceptional efficiency of 19.07%, a marked improvement compared to the 17.6% attained in binary OSCs. More importantly, the high Tg exhibited by the pyrene-fused electron acceptor helps to stabilize the morphology of the photoactive layer thermal-treated at 70 °C, retaining 88.7% efficiency over 600â hours. For comparison, binary OSCs experience a decline to 73.7% efficiency after the same duration. These results indicate that the "butterfly-like" design and the incorporation of a pyrene unit is a promising strategy in the development of dimerized electron acceptors for OSCs.
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Designing and synthesizing narrow band gap acceptors that exhibit high photoluminescence quantum yield (PLQY) and strong crystallinity is a highly effective, yet challenging, approach to reducing non-radiative energy losses (âµEnr) and boosting the performance of organic solar cells (OSCs). We have successfully designed and synthesized an A-D-A type fused-ring electron acceptor, named DM-F, which features a planar molecular backbone adorned with bulky three-dimensional camphane side groups at its central core. These bulky substituents effectively hinder the formation of H-aggregates of the acceptors, promoting the formation of more J-aggregates and notably elevating the PLQY of the acceptor in the film. As anticipated, DM-F showcases pronounced near-infrared absorption coupled with impressive crystallinity. Organic solar cells (OSCs) leveraging DM-F exhibit a high EQEEL value and remarkably low âµEnr of 0.14â eV-currently the most minimal reported value for OSCs. Moreover, the power conversion efficiency (PCE) of binary and ternary OSCs utilizing DM-F has reached 16.16 % and 20.09 %, respectively, marking a new apex in reported efficiency within the OSCs field. In conclusion, our study reveals that designing narrow band gap acceptors with high PLQY is an effective way to reduce âµEnr and improve the PCE of OSCs.
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One-unit-cell, single-crystal, hexagonal CuInP2 S6 atomically thin sheets of≈0.81â nm in thickness was successfully synthesized for photocatalytic reduction of CO2 . Exciting ethene (C2 H4 ) as the main product was dominantly generated with the yield-based selectivity reaching ≈56.4 %, and the electron-based selectivity as high as ≈74.6 %. The tandem synergistic effect of charge-enriched Cu-In dual sites confined on the lateral edge of the CuInP2 S6 monolayer (ML) is mainly responsible for efficient conversion and high selectivity of the C2 H4 product as the basal surface site of the ML, exposing S atoms, can not derive the CO2 photoreduction due to the high energy barrier for the proton-coupled electron transfer of CO2 into *COOH. The marginal In site of the ML preeminently targets CO2 conversion to *CO under light illumination, and the *CO then migrates to the neighbor Cu sites for the subsequent C-C coupling reaction into C2 H4 with thermodynamic and kinetic feasibility. Moreover, ultrathin structure of the ML also allows to shorten the transfer distance of charge carriers from the interior onto the surface, thus inhibiting electron-hole recombination and enabling more electrons to survive and accumulate on the exposed active sites for CO2 reduction.