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BACKGROUND: Essential micronutrient Boron (B) plays crucial roles in plant survival and reproduction but becomes toxic in higher quantities. Although plant cells have different B transport systems, B homeostasis is mainly maintained by two transporter protein families: B exporters (BOR) and nodulin-26-like intrinsic proteins (NIP). Their diversity and differential expression are responsible for varied B tolerance among plant varieties and species. Longan is a highly admired subtropical fruit with a rising market in China and beyond. In the present study, we cultured Shixia (SX) and Yiduo (YD), two differently characterized Longan cultivars, with foliar B spray. We analyzed their leaf physiology, fruit setting, B content, and boron transporter gene expression of various tissue samples. We also traced some of these genes' subcellular localization and overexpression effects. RESULTS: YD and SX foliage share similar microstructures, except the mesophyll cell wall thickness is double in YD. The B spray differently influenced their cellular constituents and growth regulators. Gene expression analysis showed reduced BOR genes expression and NIP genes differential spatiotemporal expression. Using green fluorescent protein, two high-expressing NIPs, NIP1 and NIP19, were found to translocate in the transformed tobacco leaves' cell membrane. NIPs transformation of SX pollen was confirmed using magnetic beads and quantified using a fluorescence microscope and polymerase chain reaction. An increased seed-setting rate was observed when YD was pollinated using these pollens. Between the DlNIP1 and DlNIP19 transformed SX pollen, the former germinated better with increasing B concentrations and, compared to naturally pollinated plants, had a better seed-setting rate in YDâ × SXâ. CONCLUSION: SX and YD Longan have different cell wall structures and react differently to foliar B spray, indicating distinct B tolerance and management. Two B transporter NIP genes were traced to localize in the plasma membrane. However, under high B concentrations, their differential expression resulted in differences in Jasmonic acid content, leading to differences in germination rate. Pollination of YD using these NIPs transformed SX pollen also showed NIP1 overexpression might overcome the unilateral cross incompatibility between YDâ × SXâ and can be used to increase Longan production.
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Boro , Proteínas de Membrana Transportadoras , Boro/metabolismo , Transporte Biológico , Proteínas de Membrana Transportadoras/genética , Plantas/metabolismo , Proteínas de Transporte/metabolismo , HomeostaseRESUMO
In factories, human posture recognition facilitates human-machine collaboration, human risk management, and workflow improvement. Compared to optical sensors, inertial sensors have the advantages of portability and resistance to obstruction, making them suitable for factories. However, existing product-level inertial sensing solutions are generally expensive. This paper proposes a low-cost human motion capture system based on BMI 160, a type of six-axis inertial measurement unit (IMU). Based on WIFI communication, the collected data are processed to obtain the displacement of human joints' rotation angles around XYZ directions and the displacement in XYZ directions, then the human skeleton hierarchical relationship was combined to calculate the real-time human posture. Furthermore, the digital human model was been established on Unity3D to synchronously visualize and present human movements. We simulated assembly operations in a virtual reality environment for human posture data collection and posture recognition experiments. Six inertial sensors were placed on the chest, waist, knee joints, and ankle joints of both legs. There were 16,067 labeled samples obtained for posture recognition model training, and the accumulated displacement and the rotation angle of six joints in the three directions were used as input features. The bi-directional long short-term memory (BiLSTM) model was used to identify seven common operation postures: standing, slightly bending, deep bending, half-squatting, squatting, sitting, and supine, with an average accuracy of 98.24%. According to the experiment result, the proposed method could be used to develop a low-cost and effective solution to human posture recognition for factory operation.
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Captura de Movimento , Postura , Humanos , Fenômenos Biomecânicos , Movimento , Rotação , Movimento (Física)RESUMO
ß-acetoxyisovalerylalkannin (ß-AIVA) is one of shikonin/alkannin derivative, which were mainly extracted from Boraginaceae family. The effects of ß-AIVA on human melanoma A375 cells and U918 cells were investigated in vitro. The CCK-8 assay showed that ß-AIVA inhibited proliferation of cells. Results from flow cytometry, ROS assay and JC-1 assay showed that ß-AIVA increased late apoptosis rate, induced the production of ROS and promoted mitochondrial depolarization in cells. ß-AIVA regulated expressions of BAX and Bcl-2 proteins, and increased the expression of cleaved caspase-9 and cleaved caspase-3. These findings suggest that ß-AIVA may be a potential therapeutic drug for treating melanoma.
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Melanoma , Humanos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Linhagem Celular Tumoral , Mitocôndrias , Proliferação de CélulasRESUMO
R2R3-MYB is an important transcription factor family that regulates plant growth and development. Root development directly affects the absorption of water and nutrients by plants. Therefore, to understand the regulatory role of R2R3-MYB transcription factor family in root development of longan, this study identified the R2R3-MYB gene family members at the genome-wide level, and analyzed their phylogenetic characteristics, physical and chemical properties, gene structure, chromosome location and tissue expression. The analysis identified 124 R2R3-MYB family members in the longan genome. Phylogenetic analysis divided these members into 22 subfamilies, and the members of the unified subfamily had similar motifs and gene structures. The result of qRT-PCR showed that expression levels of DlMYB33, DlMYB34, DlMYB59, and DlMYB77 were significantly higher in main roots than in lateral as opposed to those of DlMYB35, DlMYB69, DlMYB70, and DlMYB83, which were significantly lower. SapBase database prediction and miRNAs sequencing results showed that 34 longan miRNAs could cleave R2R3-MYB, including 17 novel miRNAs unique to longan. The qRT-PCR and subcellular localization experiments of DlMYB92 and DlMYB98 showed that DlMYB92 is a key factor that regulates transcription in the nucleus and participates in the regulation of longan lateral root development. Longan also has a conserved miRNA-MYB-lateral root development regulation mechanism. This study provides a reference for further research on the transcriptional regulation of the miRNA-R2R3-MYB module in the root development of longan.
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Genes myb , MicroRNAs , Filogenia , MicroRNAs/genética , Fatores de Transcrição/genéticaRESUMO
Cardiovascular diseases(CVD) with high morbidity and mortality pose severe threats to human life. Allicin, a main active ingredient of garlic, possesses multiple pharmaceutical activities. It not only exerts cardioprotective effects but also prevents the risk factors for CVD. Allicin exerts cardioprotective effects via a variety of mechanisms, including inhibiting oxidative stress, apoptosis, autophagy, and inflammatory responses, regulating lipid metabolism and gut microbiota, inducing hydrogen sulfide production, and dilating vessels. Despite the valuable cardioprotective effects, the instability of allicin has hindered the basic research and clinical application. This paper reviews the progress in the cardioprotective effects and mechanisms of allicin in the last decade and summarizes the methods to improve the stability of allicin. In addition, this review provides a reference for further research and development of allicin in cardiovascular protection.
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Doenças Cardiovasculares , Dissulfetos , Humanos , Coração , Ácidos Sulfínicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Preparações FarmacêuticasRESUMO
This study aimed to explore the effect and mechanism of acetylalkannin from Arnebia euchroma on the proliferation, migration, and invasion of human melanoma A375 cells. A375 cells were divided into a blank group, and low-, medium-, and high-dose acetylalkannin groups(0.5, 1.0, and 2.0 µmol·L~(-1)). The MTT assay was used to detect cell proliferation. Cell scratch and transwell migration assays were used to detect cell migration ability, and the transwell invasion assay was used to detect cell invasion ability. Western blot was used to detect the protein expression of migration and invasion-related N-cadherin, vimentin, matrix metalloproteina-se-9(MMP-9), and Wnt/ß-catenin pathway-related Wnt1, Axin2, glycogen synthase kinase-3ß(GSK-3ß), phosphorylated GSK-3ß(p-GSK-3ß), ß-catenin, cell cycle protein D_1(cyclin D_1), and p21. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) was used to detect the mRNA expression of E-cadherin, matrix metalloproteinase-2(MMP-2), N-cadherin, vimentin, ß-catenin, snail-1, and CD44. MTT results showed that the cell inhibition rates in the acetylalkannin groups significantly increased as compared with that in the blank group(P<0.01). The results of cell scratch and transwell assays showed that compared with the blank group, the acetylalkannin groups showed reduced cell migration and invasion, and migration and invasion rates(P<0.05, P<0.01) and weakened horizontal and vertical migration and invasion abilities. Western blot results showed that compared with the blank group, the high-dose acetylalkannin group showed increased expression of Axin2 protein(P<0.05), and decreased expression of N-cadherin, vimentin, MMP-9, Wnt1, p-GSK-3ß, ß-catenin, cyclin D_1, and p21 proteins(P<0.05, P<0.01). The expression of GSK-3ß protein did not change significantly. PCR results showed that the overall trend of MMP-2, N-cadherin, vimentin, ß-catenin, snail-1, and CD44 mRNA expression was down-regulated(P<0.01), and the expression of E-cadherin mRNA increased(P<0.01). Acetylalkannin can inhibit the proliferation, migration, and invasion of human melanoma A375 cells, and its mechanism of action may be related to the regulation of Wnt/ß-catenin signaling pathway.
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Boraginaceae , Melanoma , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Vimentina/genética , Vimentina/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Linhagem Celular Tumoral , Via de Sinalização Wnt , Caderinas/genética , Melanoma/tratamento farmacológico , Melanoma/genética , Ciclina D/metabolismo , Proliferação de Células , Boraginaceae/genética , RNA Mensageiro , Movimento CelularRESUMO
This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.
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Doença de Alzheimer , Berberis , NF-kappa B , Farmacologia em Rede , Antocianinas , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Fator 88 de Diferenciação Mieloide , Doenças Neuroinflamatórias , Receptor 4 Toll-Like , Proteínas I-kappa BRESUMO
We find that the relative error of a fiber optic current sensor (FOCS) increases quadratically with the electric current to be measured, causing unacceptable inaccuracy for direct current (DC) measurements beyond 100â kA. We prove analytically and confirm experimentally that such a nonlinear relative error escalation (REE) mainly originates from the residual linear birefringence of the spun fiber used in the FOCS. We propose and demonstrate that by first measuring residual linear birefringence, together with the circular birefringence of the spun fiber, the REE of the FOCS can be significantly reduced from -1.22% to -0.15% at 200â kA DC by a compensation scheme using the measured birefringences in the quadratic expression we derived. Further reduction of the REE to -0.02% at 200â kA DC can be obtained if the quadratic relation between the REE and the current under test is experimentally obtained. Our work points to a new direction for drastically improving the accuracy of FOCS at large currents and shall prove beneficial for scientists and engineers working in the field of current sensing.
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The purpose of this investigation was to establish a mathematical model for determining the dissolution of diclofenac sodium and codeine phosphate simultaneously. Based on the dual-wavelength isosbestic point spectrophotometry, the dissolution of diclofenac sodium and codeine phosphate tablets was determined using Fiber-Optic Dissolution Test (FODT) instrument capable of real-time measurement. Dissolution curves showed that the dissolution process of diclofenac sodium was similar to that of codeine phosphate. The dissolution profile of diclofenac sodium and codeine phosphate at 45 min was concordant with that stated in Chinese pharmacopoeia. There was no significant difference between results obtained from FODT and HPLC (p>0.05). A fibre-optic dissolution test system assisted by the mathematical separation model of linear equations was able to detect the dissolution of diclofenac sodium and codeine phosphate simultaneously. The dissolution profiles and overall data, which can directly reflect the dissolution speed at each time point, can provide the basis for establishing standards for the quality evaluation of drugs.
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Química Farmacêutica/métodos , Codeína/análise , Diclofenaco/análise , Tecnologia de Fibra Óptica/métodos , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/metabolismo , Codeína/metabolismo , Diclofenaco/metabolismo , Solubilidade , Espectrofotometria/métodos , ComprimidosRESUMO
Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins H-J (1-3), with four known compounds (4-7), were isolated from the air-dried aerial parts of Hypericum acmosepalum. Especially, compounds 1 and 2 were identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). Their structures were established by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of seven compounds were evaluated. Compounds 1 and 5 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.[Formula: see text].
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Hypericum , Células Hep G2 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , FloroglucinolRESUMO
Silicon-based devices offer great potential for quantum key distribution (QKD) with the benefits of miniaturization, scalability, complexity, and improved performance. Based on the planar lightwave circuit technology, a 200 ps delay-time asymmetric Mach-Zehnder interferometer (AMZI) decoding chip was designed and fabricated that can adjust the power ratio of the two arms by introducing a variable beam splitter. The measured delay time is approximately 200 ps, and the two output pulses' peaks can be balanced by loading an appropriate voltage on the variable beam splitter. The classical interference visibility of the AMZI versus temperature was studied, and it is highly temperature dependent. The interference visibility can reach as high as 99.72% under appropriate temperature control. This AMZI can act as a passive decoder in fiber-based QKD systems.
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The segmentation of buildings in remote-sensing (RS) images plays an important role in monitoring landscape changes. Quantification of these changes can be used to balance economic and environmental benefits and most importantly, to support the sustainable urban development. Deep learning has been upgrading the techniques for RS image analysis. However, it requires a large-scale data set for hyper-parameter optimization. To address this issue, the concept of "one view per city" is proposed and it explores the use of one RS image for parameter settings with the purpose of handling the rest images of the same city by the trained model. The proposal of this concept comes from the observation that buildings of a same city in single-source RS images demonstrate similar intensity distributions. To verify the feasibility, a proof-of-concept study is conducted and five fully convolutional networks are evaluated on five cities in the Inria Aerial Image Labeling database. Experimental results suggest that the concept can be explored to decrease the number of images for model training and it enables us to achieve competitive performance in buildings segmentation with decreased time consumption. Based on model optimization and universal image representation, it is full of potential to improve the segmentation performance, to enhance the generalization capacity, and to extend the application of the concept in RS image analysis.
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Apostichopus japonicus is a species of sea cucumber that is extensively bred as a marine delicacy because of its high nutritive and medicinal value. Immunostimulants are usually used to enhance the immunity of sea cucumber against diseases, but the physiological function of immunostimulants is poorly understood. In this study, we fed A. japonicus individuals with a diet supplemented with different concentrations of tussah immunoreactive substances (TIS), and then subjected their intestines to iTRAQ-based proteomic analysis. A total of 51 differentially expressed proteins were detected in response to TIS, 13 proteins were upregulated, while 38 proteins were reduced. These proteins are involved in phagocytosis, tissue protection, cell apoptosis and energy metabolism. Among these 51 proteins, 7 proteins (GLO2, ACOX, CTTN, MARK, FADD, CSTA and CASP6) related to immunity with functional annotation in sea cucumber were further analyzed. In addition, the upregulated expression of 4 immune-related proteins (GLO2, ACOX, CTTN and MARK) was validated by qRT-PCR. The findings of this study gave further insight into the mechanism by which TIS might enhance the immunity of A. japonicus.
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Adjuvantes Imunológicos/farmacologia , Imunidade Humoral/genética , Imunidade Inata/genética , Proteoma , Stichopus/genética , Stichopus/imunologia , Adjuvantes Imunológicos/administração & dosagem , Ração Animal/análise , Animais , Dieta , Suplementos Nutricionais/análise , Intestinos/imunologiaRESUMO
In order to research and enhance bioavailability of chlorogenic acid and rutin(CA-R) via the oral route, chitosan coated composite phospholipid liposomes (C-CPLs) were applied to study on preparation, permeability and pharmacokinetic of C-CA-R-CPLs. TheC-CA-R-CPLs were prepared by the method of ethanol injection. The entrapment efficiency (EE), average particle sizes, polymer disperse index (PDI), zeta potential, shape and in vitro drug release were investigated to characterize physicochemical parameters of C-CA-R-CPLs. The penetration properties from C-CA-R-CPLs were studied through Caco-2 cells model and the pharmacokinetics in Sprague-Dawley (SD) rats were evaluated by rat jugular vein intubation tube. The EE of C-CA-R-CPLs of CA and R was 91.3±2.13% and 92.6±2.44%, particle size of C-CA-R-CPLs was 176.7±2.3 nm, PDI was 0.207±0.014 and zeta potential of 12.61±1.33 mV. CA-R-CPLs and C-CA-R-CPLs were spherical or elliptical sphere and the bilayer of the CPL was observed obviously under transmission electron. The Cmax, t1/2 and AUC0-12 h values of CA and R for groups of C-CA-R-CPLs were significantly increased.In conclusion, TheC-CA-R-CPLs as a novel nano-formulation have potential to be used to enhance the oral bioavailability of poorlywater-soluble drugs after oral administration.
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Permeabilidade da Membrana Celular/efeitos dos fármacos , Quitosana/farmacocinética , Ácido Clorogênico/farmacocinética , Portadores de Fármacos/farmacocinética , Fosfolipídeos/farmacocinética , Rutina/farmacocinética , Animais , Células CACO-2 , Permeabilidade da Membrana Celular/fisiologia , Quitosana/administração & dosagem , Quitosana/síntese química , Ácido Clorogênico/administração & dosagem , Ácido Clorogênico/síntese química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Humanos , Lipossomos , Masculino , Fosfolipídeos/administração & dosagem , Fosfolipídeos/síntese química , Ratos , Ratos Sprague-Dawley , Rutina/administração & dosagem , Rutina/síntese químicaRESUMO
Although chemical vapor deposition is the most common method to synthesize transition metal dichalcogenides (TMDs), several obstacles, such as the high annealing temperature restricting the substrates used in the process and the required transfer causing the formation of wrinkles and defects, must be resolved. Here, we present a novel method to grow patternable two-dimensional (2D) transition metal disulfides (MS2) directly underneath a protective coating layer by spin-coating a liquid chalcogen precursor onto the transition metal oxide layer, followed by a laser irradiation annealing process. Two metal sulfides, molybdenum disulfide (MoS2) and tungsten disulfide (WS2), are investigated in this work. Material characterization reveals the diffusion of sulfur into the oxide layer prior to the formation of the MS2. By controlling the sulfur diffusion, we are able to synthesize continuous MS2 layers beneath the top oxide layer, creating a protective coating layer for the newly formed TMD. Air-stable and low-power photosensing devices fabricated on the synthesized 2D WS2 without the need for a further transfer process demonstrate the potential applicability of TMDs generated via a laser irradiation process.
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It is currently unclear how sharpness discrimination ability is distributed across a wide range of edge sharpness and the effect of contact area on haptic perception. We 3D printed triangular prisms with various edge sharpness and half-edge widths in the full-scale range and conducted 2AFC tasks to gain the haptic threshold distribution. Results show that the distribution curves of the sharpness threshold and its contact area have a similar inflection point at 115 °, implying a boundary between medium-low and high stimuli. It is also found that Weber fractions in the medium stimulus range follow Weber's Law and are consistent with previous studies but lower than the mean of Weber fractions in the high stimulus range. Besides, there is no significant difference in upper and lower thresholds in the medium-low stimulus range but a significant difference in the high stimulus range with the higher upper threshold. Variations in contact area do not affect sharpness discrimination ability when the half-edge width exceeds 2 mm. However, decreasing the half-edge width from 2 mm to 1 mm significantly reduces haptic sensitivity. Our findings offer preliminary evidence contributing to understanding haptic perception in edge sharpness discrimination, encompassing the properties of objects and object-individual interfaces.
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Discriminação Psicológica , Limiar Sensorial , Percepção do Tato , Humanos , Percepção do Tato/fisiologia , Limiar Sensorial/fisiologia , Discriminação Psicológica/fisiologia , Adulto , Masculino , Feminino , Adulto Jovem , Estimulação Física , Tato/fisiologiaRESUMO
Introduction: Glioblastoma (GBM) presents significant challenges due to its malignancy and limited treatment options. Precision treatment requires subtyping patients based on prognosis. Disulfidptosis, a novel cell death mechanism, is linked to aberrant glucose metabolism and disulfide stress, particularly in tumors expressing high levels of SLC7A11. The exploration of disulfidptosis may provide a new perspective for precise diagnosis and treatment of glioblastoma. Methods: Transcriptome sequencing was conducted on samples from GBM patients treated at Tiantan Hospital (January 2022 - December 2023). Data from CGGA and TCGA databases were collected. Consensus clustering based on disulfidptosis features categorized GBM patients into two subtypes (DRGclusters). Tumor immune microenvironment, response to immunotherapy, and drug sensitivity were analyzed. An 8-gene disulfidptosis-based subtype predictor was developed using LASSO machine learning algorithm and validated on CGGA dataset. Results: Patients in DRGcluster A exhibited improved overall survival (OS) compared to DRGcluster B. DRGcluster subtypes showed differences in tumor immune microenvironment and response to immunotherapy. The predictor effectively stratified patients into high and low-risk groups. Significant differences in IC50 values for chemotherapy and targeted therapy were observed between risk groups. Discussion: Disulfidptosis-based classification offers promise as a prognostic predictor for GBM. It provides insights into tumor immune microenvironment and response to therapy. The predictor aids in patient stratification and personalized treatment selection, potentially improving outcomes for GBM patients.
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Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Multiômica , Imunoterapia , Algoritmos , Morte Celular , Microambiente TumoralRESUMO
Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.
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Biofilmes , Fluorocarbonos , Gálio , Staphylococcus aureus Resistente à Meticilina , Oxigênio , Protoporfirinas , Infecções Estafilocócicas , Terapia por Ultrassom , Animais , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Camundongos , Gálio/química , Gálio/farmacologia , Protoporfirinas/química , Protoporfirinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Oxigênio/química , Infecções Estafilocócicas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos Endogâmicos BALB C , Feminino , PentanosRESUMO
Introduction: Synergistic medication, a crucial therapeutic strategy in cancer treatment, involves combining multiple drugs to enhance therapeutic effectiveness and mitigate side effects. Current research predominantly employs deep learning models for extracting features from cell line and cancer drug structure data. However, these methods often overlook the intricate nonlinear relationships within the data, neglecting the distribution characteristics and weighted probability densities of gene expression data in multi-dimensional space. It also fails to fully exploit the structural information of cancer drugs and the potential interactions between drug molecules. Methods: To overcome these challenges, we introduce an innovative end-to-end learning model specifically tailored for cancer drugs, named Dual Kernel Density and Positional Encoding (DKPE) for Graph Synergy Representation Network (DKPEGraphSYN). This model is engineered to refine the prediction of drug combination synergy effects in cancer. DKPE-GraphSYN utilizes Dual Kernel Density Estimation and Positional Encoding techniques to effectively capture the weighted probability density and spatial distribution information of gene expression, while exploring the interactions and potential relationships between cancer drug molecules via a graph neural network. Results: Experimental results show that our prediction model achieves significant performance enhancements in forecasting drug synergy effects on a comprehensive cancer drug and cell line synergy dataset, achieving an AUPR of 0.969 and an AUC of 0.976. Discussion: These results confirm our model's superior accuracy in predicting cancer drug combinations, providing a supportive method for clinical medication strategy in cancer.
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Longan (Dimocarpus Longan) is one of the most important fruit crops in Southern China. Lack of available Mg in acidic soil conditions is a limitation to further increasing longan yield. Magnesium transporter (MGT/MRS2) mediates the uptake, transport, and redistribution of Mg2+ in higher plants. To understand the role of MGTs family members in longan Mg deficiency. We identified and analyzed the protein characteristics, phylogeny, expression changes, subcellular localization, and transcriptional regulation of DlMGTs members. The results showed that, twelve DlMGTs are localized in the cell membrane, chloroplast, and nucleus. The evolutionary differences in MGTs between herbaceous and woody species in different plants. The DlMGTs promoters contained many cis-acting elements and transcription factor binding sites related to the hormone, environmental, and stress response. Subcellular localization assays showed that DlMGT1 localizes in the cell membrane of Arabidopsis protoplasts. The candidate transcription factor DlGATA16, which may regulate the expression of DlMGT1, was localized in the nucleus of tobacco leaves. Dual luciferase analysis demonstrated that DlGATA16 is a potential factor regulating the transcriptional activity of DlMGT1. In this study, we identified and analyzed DlMGTs on a genome-wide scale and the subcellular localization and interaction of DlMGT1 and DlGATA16, which has important implications for further functional analysis studies of MGTs and the use of MGT for longan genetic improvement.