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Molecular vibrational spectroscopies, including infrared absorption and Raman scattering, provide molecular fingerprint information and are powerful tools for qualitative and quantitative analysis. They benefit from the recent development of deep-learning-based algorithms to improve the spectral, spatial, and temporal resolutions. Although a variety of deep-learning-based algorithms, including those to simultaneously extract the global and local spectral features, have been developed for spectral classification, the classification accuracy is still far from satisfactory when the difference becomes very subtle. Here, we developed a lightweight algorithm named patch-based convolutional encoder (PACE), which effectively improved the accuracy of spectral classification by extracting spectral features while balancing local and global information. The local information was captured well by segmenting the spectrum into patches with an appropriate patch size. The global information was extracted by constructing the correlation between different patches with depthwise separable convolutions. In the five open-source spectral data sets, PACE achieved a state-of-the-art performance. The more difficult the classification, the better the performance of PACE, compared with that of residual neural network (ResNet), vision transformer (ViT), and other commonly used deep learning algorithms. PACE helped improve the accuracy to 92.1% in Raman identification of pathogen-derived extracellular vesicles at different physiological states, which is much better than those of ResNet (85.1%) and ViT (86.0%). In general, the precise recognition and extraction of subtle differences offered by PACE are expected to facilitate vibrational spectroscopy to be a powerful tool toward revealing the relevant chemical reaction mechanisms in surface science or realizing the early diagnosis in life science.
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Spectrum-structure correlation is playing an increasingly crucial role in spectral analysis and has undergone significant development in recent decades. With the advancement of spectrometers, the high-throughput detection triggers the explosive growth of spectral data, and the research extension from small molecules to biomolecules accompanies massive chemical space. Facing the evolving landscape of spectrum-structure correlation, conventional chemometrics becomes ill-equipped, and deep learning assisted chemometrics rapidly emerges as a flourishing approach with superior ability of extracting latent features and making precise predictions. In this review, the molecular and spectral representations and fundamental knowledge of deep learning are first introduced. We then summarize the development of how deep learning assist to establish the correlation between spectrum and molecular structure in the recent 5 years, by empowering spectral prediction (i.e., forward structure-spectrum correlation) and further enabling library matching and de novo molecular generation (i.e., inverse spectrum-structure correlation). Finally, we highlight the most important open issues persisted with corresponding potential solutions. With the fast development of deep learning, it is expected to see ultimate solution of establishing spectrum-structure correlation soon, which would trigger substantial development of various disciplines.
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There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.
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Dioscorea alata L. (Dioscoreaceae) is a widely cultivated tuber crop with variations in tuber color, offering potential value as health-promoting foods. This study focused on the comparison of D. alata tubers possessing two distinct colors, white and purple, to explore the underlying mechanisms of color variation. Flavonoids, a group of polyphenols known to influence plant color and exhibit antioxidant properties, were of particular interest. The total phenol and total flavonoid analyses revealed that purple tubers (PTs) have a significantly higher content of these metabolites than white tubers (WTs) and a higher antioxidant activity than WTs, suggesting potential health benefits of PT D. alata. The transcriptome analysis identified 108 differentially expressed genes associated with the flavonoid synthesis pathway, with 57 genes up-regulated in PTs, including CHS, CHI, DFR, FLS, F3H, F3'5'H, LAR, ANS, and ANR. The metabolomics analysis demonstrated that 424 metabolites, including 104 flavonoids and 8 tannins, accumulated differentially in PTs and WTs. Notably, five of the top ten up-regulated metabolites were flavonoids, including 6-hydroxykaempferol-7-O-glucoside, pinocembrin-7-O-(6â³-O-malonyl)glucoside, 6-hydroxykaempferol-3,7,6-O-triglycoside, 6-hydroxykaempferol-7-O-triglycoside, and cyanidin-3-O-(6â³-O-feruloyl)sophoroside-5-O-glucoside, with the latter being a precursor to anthocyanin synthesis. Integrating transcriptome and metabolomics data revealed that the 57 genes regulated 20 metabolites within the flavonoid synthesis pathway, potentially influencing the tubers' color variation. The high polyphenol content and antioxidant activity of PTs indicate their suitability as nutritious and health-promoting food sources. Taken together, the findings of this study provide insights into the molecular basis of tuber color variation in D. alata and underscore the potential applications of purple tubers in the food industry and human health promotion. The findings contribute to the understanding of flavonoid biosynthesis and pigment accumulation in D. alata tubers, opening avenues for future research on enhancing the nutritional quality of D. alata cultivars.
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Dioscorea , Transcriptoma , Humanos , Dioscorea/genética , Dioscorea/metabolismo , Antioxidantes , Antocianinas/metabolismo , Flavonoides , Perfilación de la Expresión Génica , Metabolómica , Glucósidos , Color , Regulación de la Expresión Génica de las PlantasRESUMEN
Spinal intradural (subdural and subarachnoid) hematoma following percutaneous kyphoplasty is an extremely rare complication. In this report, we described a case of 2 episodes of subarachnoid hemorrhage with delayed paralysis after kyphoplasty. A 73-year-old man underwent percutaneous kyphoplasty in our hospital an osteoporotic vertebral fracture at the T12 level. On the 55 h after kyphoplasty for T12 osteoporotic vertebral fracture, he developed paralysis of the lower limbs. An emergency posterior decompression from T8 to L2 was performed. And the subarachnoid hematomas were removed. Postoperatively, the neurological symptoms improved rapidly. However, 2 weeks after the operation, the patient experienced a setback with severe neurological decline (paraplegia with sensory and autonomic dysfunction). An emergency posterior decompression from T5 to L2 was performed. The subarachnoid hematomas were removed. This case reflects the cause and progression of spinal subdural hematoma. Previous literature has debated the best treatment approach for spinal subarachnoid hemorrhage, but the prognosis of patients is heavily dependent on precise symptom evaluation and localization.
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Seeking high-performance photoresists is an important item for semiconductor industry due to the continuous miniaturization and intelligentization of integrated circuits. Polymer resin containing carbonate group has many desirable properties, such as high transmittance, acid sensitivity and chemical formulation, thus serving as promising photoresist material. In this work, a series of aqueous developable CO2-sourced polycarbonates (CO2-PCs) were produced via alternating copolymerization of CO2 and epoxides bearing acid-cleavable cyclic acetal groups in the presence of tetranuclear organoborane catalyst. The produced CO2-PCs were investigated as chemical amplification resists in deep ultraviolet (DUV) lithography. Under the catalysis of photogenerated acid, the acetal (ketal) groups in CO2-PC were hydrolysed into two equivalents of hydroxyl groups, which change the exposed area from hydrophobicity to hydrophilicity, thus enabling the exposed area to be developed with water. Through normalized remaining thickness analysis, the optimal CO2-derived resist achieved a remarkable sensitivity of 1.9â mJ/cm2, a contrast of 7.9, a favorable resolution (750â nm, half pitch), and a good etch resistance (38 % higher than poly(tert-butyl acrylate)). Such performances outperform commercial KrF and ArF chemical amplification resists (i.e., polyhydroxystyrene-derived and polymethacrylate-based resists), which endows broad application prospects in the field of DUV (KrF and ArF) and extreme ultraviolet (EUV) lithography for nanomanufacturing.
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Being characterized by the self-adaption and high accuracy, the deep learning-based models have been widely applied in the 1D spectroscopy-related field. However, the "black-box" operation and "end-to-end" working style of the deep learning normally bring the low interpretability, where a reliable visualization is highly demanded. Although there are some well-developed visualization methods, such as Class Activation Mapping (CAM) and Gradient-weighted Class Activation Mapping (Grad-CAM), for the 2D image data, they cannot correctly reflect the weights of the model when being applied to the 1D spectral data, where the importance of position information is not considered. Here, aiming at the visualization of Convolutional Neural Network-based models toward the qualitative and quantitative analysis of 1D spectroscopy, we developed a novel visualization algorithm (1D Grad-CAM) to more accurately display the decision-making process of the CNN-based models. Different from the classical Grad-CAM, with the removal of the gradient averaging (GAP) and the ReLU operations, a significantly improved correlation between the gradient and the spectral location and a more comprehensive spectral feature capture were realized for 1D Grad-CAM. Furthermore, the introduction of difference (purity or linearity) and feature contribute in the CNN output in 1D Grad-CAM achieved a reliable evaluation of the qualitative accuracy and quantitative precision of CNN-based models. Facing the qualitative and adulteration quantitative analysis of vegetable oils by the combination of Raman spectroscopy and ResNet, the visualization by 1D Grad-CAM well reflected the origin of the high accuracy and precision brought by ResNet. In general, 1D Grad-CAM provides a clear vision about the judgment criterion of CNN and paves the way for CNN to a broad application in the field of 1D spectroscopy.
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Pathogenic bacterial infections, exacerbated by increasing antimicrobial resistance, pose a major threat to human health worldwide. Extracellular vesicles (EVs), secreted by bacteria and acting as their "long-distance weapons", play an important role in the occurrence and development of infectious diseases. However, no efficient methods to rapidly detect and identify EVs of different bacterial origins are available. Here, label-free Raman spectroscopy in combination with a new deep learning model of the attentional neural network (aNN) was developed to identify pathogen-derived EVs at Gram±, species, strain, and even down to physiological levels. By training the aNN model with a large Raman data set from six typical pathogen-derived EVs, we achieved the identification of EVs with high accuracies at all levels: exceeding 96% at the Gram and species levels, 93% at the antibiotic-resistant and sensitive strain levels, and still above 87% at the physiological level. aNN enabled Raman spectroscopy to interrogate the bacterial origin of EVs to a much higher level than previous methods. Moreover, spectral markers underpinning EV discrimination were uncovered from subtly different EV spectra via an interpretation algorithm of the integrated gradient. A further comparative analysis of the rich Raman biochemical signatures of EVs and parental pathogens clearly revealed the biogenesis process of EVs, including the selective encapsulation of biocomponents and distinct membrane compositions from the original bacteria. This developed platform provides an accurate and versatile means to identify pathogen-derived EVs, spectral markers, and the biogenesis process. It will promote rapid diagnosis and allow the timely treatment of bacterial infections.
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Infecciones Bacterianas , Aprendizaje Profundo , Vesículas Extracelulares , Bacterias , Biomarcadores/análisis , Vesículas Extracelulares/química , Humanos , Espectrometría Raman/métodosRESUMEN
In recent years, the risk from environmental pollution caused by chloramphenicol (CAP) has emerged as a serious concern worldwide, especially for the co-selection of antibiotic resistance microorganisms simultaneously exposed to CAP and salts. In this study, the multistage contact oxidation reactor (MCOR) was employed for the first time to treat the CAP wastewater under the co-existence of CAP (10-80 mg/L) and salinity (0-30 g/L NaCl). The CAP removal efficiency reached 91.7% under the co-existence of 30 mg/L CAP and 10 g/L NaCl in the influent, but it fluctuated around 60% with the increase of CAP concentration and salinity. Trichococcus and Lactococcus were the major contributors to the CAP and salinity shock loads. Furthermore, the elevated CAP and salinity selection pressures inhibited the spread of CAP efflux pump genes, including cmlA, tetC, and floR, and significantly affected the composition and abundance of antibiotic resistance genes (ARGs). As the potential hosts of CAP resistance genes, Acinetobacter, Enterococcus, and unclassified_d_Bacteria developed resistance against high osmotic pressure and antibiotic environment using the efflux pump mechanism. The results also revealed that shifting of potential host bacteria significantly contributed to the change in ARGs. Overall, the co-existence of CAP and salinity promoted the enrichment of core genera Trichococcus and Lactococcus; however, they inhibited the proliferation of ARGs. KEY POINTS: ⢠Trichococcus and Lactococcus were the core bacteria related to CAP biodegradation ⢠Co-existence of CAP and salinity inhibited proliferation of cmlA, tetC, and floR ⢠The microorganism resisted the CAP using the efflux pump mechanism.
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Cloranfenicol , Microbiota , Cloranfenicol/farmacología , Antibacterianos/farmacología , Salinidad , Cloruro de Sodio , Genes Bacterianos , Farmacorresistencia Microbiana/genética , Aguas Residuales/análisis , Bacterias/genéticaRESUMEN
OBJECTIVES: We aimed to investigate the value of performing gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) radiomics for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) based on multiple sequences. METHODS: We randomly allocated 165 patients with HCC who underwent partial hepatectomy to training and validation sets. Stepwise regression and the least absolute shrinkage and selection operator algorithm were used to select significant variables. A clinicoradiological model, radiomics model, and combined model were constructed using multivariate logistic regression. The performance of the models was evaluated, and a nomogram risk-prediction model was built based on the combined model. A concordance index and calibration curve were used to evaluate the discrimination and calibration of the nomogram model. RESULTS: The tumour margin, peritumoural hypointensity, and seven radiomics features were selected to build the combined model. The combined model outperformed the radiomics model and the clinicoradiological model and had the highest sensitivity (90.89%) in the validation set. The areas under the receiver operating characteristic curve were 0.826, 0.755, and 0.708 for the combined, radiomics, and clinicoradiological models, respectively. The nomogram model based on the combined model exhibited good discrimination (concordance index = 0.79) and calibration. CONCLUSIONS: The combined model based on radiomics features of Gd-EOB-DTPA enhanced MRI, tumour margin, and peritumoural hypointensity was valuable for predicting HCC microvascular invasion. The nomogram based on the combined model can intuitively show the probabilities of MVI.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Medios de Contraste , Gadolinio DTPA , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.
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Factores de Crecimiento de Fibroblastos , Hipertensión Renal , Nefritis , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Línea Celular , Acetato de Desoxicorticosterona , Factores de Crecimiento de Fibroblastos/sangre , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/uso terapéutico , Humanos , Hipertensión Renal/inducido químicamente , Hipertensión Renal/tratamiento farmacológico , Hipertensión Renal/metabolismo , Hipertensión Renal/patología , Interleucina-6/metabolismo , Riñón/metabolismo , Riñón/patología , Masculino , Ratones Endogámicos C57BL , Nefritis/inducido químicamente , Nefritis/tratamiento farmacológico , Nefritis/metabolismo , Nefritis/patología , Estrés Oxidativo , Proteínas Recombinantes/uso terapéutico , Cloruro de Sodio Dietético , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Glioblastoma is the most common intracranial primary malignant tumor, which leads to the poor quality of life of patients and has a high recurrence rate. Chemotherapy is a vital part in the treatment of this disease. Tetrandrine(Tet) is an active ingredient extracted from the root of the Chinese medicinal plant Stephania tetrandra, which has been proved with a wide range of pharmacological effects including anti-tumor. However, there are few studies regarding the effect of Tet on glioma. In this study, MTT and BrdU assays were employed to detect the effect of Tet on the proliferation of LN229 glioblastoma cells; flow cytometry was used to analyze the cycle distribution and apoptosis; plate cloning assay and soft agar colony formation assay were performed to study the colony formation ability of LN229 cells exposed to Tet; scratch assay and Transwell assay were conducted to detect the ability of migration and invasion; Western blot was adopted to the exploration of the molecular mechanism. The MTT and BrdU assays showed that Tet inhibited the proliferation of LN229 cells in a time-and dose-dependent manner. The plate cloning assay and soft agar colony formation assay showed that Tet weakened the colony formation of LN229 cells in vitro; cytometry assay showed that Tet blocked cells in the G_1 phase and promoted cell apoptosis; scratch and Transwell assays proved that Tet inhibited the migration and invasion of LN229 cells; Western blot results showed that Tet down-regulated the expression levels of CDK2, CDK6, cyclin D1, cyclin E1, snail, slug, vimentin, and N-cadherin, while up-regulated the level of E-cadherin. The results indicate that Tet has a certain inhibitory effect on the proliferation, migration, and invasion of LN229 glioblastoma cells, and such effect may be related to the participation of Tet in the regulation of c-Myc/p27 axis and snail signaling pathway.
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Glioblastoma , Apoptosis , Bencilisoquinolinas , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Humanos , Calidad de VidaRESUMEN
Traumatic brain injury (TBI) is a worldwide public health and medical problem. Oxidative stress is recognized as an important contributing factor in the pathogenesis of TBI. The present study was designed to explore the anti-oxidative effect of Nuclear factor erythroid 2-related factor 2 (Nrf2) on brain damage induced by traumatic injury in a mouse model. Moderate weight-drop impact head injury was induced in adult male mice. The mice were randomly divided into four groups: Nrf2(+/+) sham-operation, Nrf2(-/-) sham-operation, Nrf2(+/+) TBI, and Nrf2(-/-) TBI group. Neurological scores were evaluated 24 h after TBI, followed by collection of the brain specimens. Brain edema was detected by the wet-dry ratio method. The expression of NOX2 protein in the brain specimen was investigated using Western Blot analysis and immunohistochemical staining. In addition, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were evaluated in the brain tissues. Twenty-four hours after TBI, our results showed Nrf2(+/+) TBI mice have more severe neurological deficits and brain edema than Nrf2(+/+) sham group. On the other hand, the Nrf2(-/-) TBI mice were found to have significantly increased neurological deficits and brain edema, compared to Nrf2(+/+) TBI mice (P < 0.05). At the same time, we found that the expression of NOX2 protein, MDA level were significantly increased in Nrf2(-/-) mice, while SOD activity was considerably decreased after TBI compared to Nrf2(+/+) mice (P < 0.05). We demonstrated that deletion of Nrf2 exacerbates brain injury after TBI in mice, suggesting that Nrf2 may play an important role in protecting brain injury after TBI, possibly by modulating oxidative stress.
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Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Eliminación de Gen , Factor 2 Relacionado con NF-E2/deficiencia , Estrés Oxidativo , Animales , Western Blotting , Encéfalo/metabolismo , Encéfalo/patología , Edema Encefálico/patología , Inmunohistoquímica , Masculino , Malondialdehído/metabolismo , Glicoproteínas de Membrana/metabolismo , Ratones Endogámicos ICR , NADPH Oxidasa 2 , NADPH Oxidasas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Evidence has shown that the activation of the autophagy pathway after experimental subarachnoid hemorrhage (SAH) protects against neuronal damage. Tert-butylhydroquinone (tBHQ), a commonly used nuclear factor erythroid 2-related factor 2 (Nrf2) activator, was found to significantly enhance autophagy activation. The aim of this study was to explore the effect of tBHQ treatment on early stage brain injury at 24 h after SAH. The results showed that tBHQ treatment failed to stimulate an effective anti-oxidative effect at 24 h after the SAH operation, but succeeded in ameliorating early brain injury, including alleviated brain edema, BBB disruption, neuronal degeneration and neurological deficits. Further exploration found that tBHQ treatment significantly increased the expression of Beclin-1 and the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II to LC3-I, suggesting that autophagy was enhanced after tBHQ treatment. Moreover, tBHQ treatment restored Bcl-2 and Bax expression and reduced caspase-3 cleavage, suggesting the protective effect of tBHQ treatment in ameliorating brain injury after SAH. Furthermore, tBHQ enhanced autophagy activation, decreased neuronal degeneration and improved the neurological score after SAH in Nrf2-deficient mice. Taken together, these findings suggest that tBHQ treatment exerts neuro-protective effects against EBI following SAH by enhancing Nrf2-independent autophagy. Therefore, tBHQ is a promising therapeutic agent against EBI following SAH.
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Autofagia/efectos de los fármacos , Lesiones Encefálicas/prevención & control , Modelos Animales de Enfermedad , Hidroquinonas/farmacología , Factor 2 Relacionado con NF-E2/fisiología , Hemorragia Subaracnoidea/complicaciones , Animales , Barrera Hematoencefálica , Lesiones Encefálicas/etiología , RatonesRESUMEN
BACKGROUND: Traumatic brain injury (TBI) is a worldwide health problem, identified as a major cause of death and disability. Increasing evidence has shown that oxidative stress plays an important role in TBI pathogenesis. The antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), is a known mediator in protection against TBI-induced brain damage. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect against TBI-induced oxidative stress. METHODS: Adult male imprinting control region mice were randomly divided into three groups: (1) sham + vehicle group; (2) TBI + vehicle group; and (3) TBI + tBHQ group. Closed-head brain injury was applied using the Feeney weight-drop method. We accessed the neurologic outcome of mice at 24 h after TBI, and subsequently measured protein levels of Nrf2 and the NOX2 subunit of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), the concentration of malondialdehyde, superoxide dismutase activity, and brain edema. RESULT: The NOX2 protein level was increased fivefold in the TBI + vehicle group, whereas pretreatment with tBHQ markedly attenuated the NOX2 protein expression relative to that in the TBI + vehicle group. TBI increased Nrf2 formation by 5% compared with the sham group, whereas treatment with tBHQ further upregulated the Nrf2 protein level by 12% compared with the sham group. The level of the oxidative damage marker malondialdehyde was reduced by 29% in the TBI + tBHQ group compared with the TBI + vehicle group, Moreover, pretreatment with tBHQ significantly increased the antioxidant enzyme superoxide dismutase activity. Administration of tBHQ also significantly decreased TBI-induced brain edema and neurologic deficits. CONCLUSIONS: Pretreatment with tBHQ effectively attenuated markers of cerebral oxidative stress after TBI, thus supporting the testing of tBHQ as a potential neuroprotectant and adjunct therapy for TBI patients.
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Antioxidantes/uso terapéutico , Edema Encefálico/prevención & control , Lesiones Encefálicas/tratamiento farmacológico , Hidroquinonas/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Animales , Daño Encefálico Crónico/etiología , Daño Encefálico Crónico/prevención & control , Edema Encefálico/etiología , Lesiones Encefálicas/complicaciones , Evaluación Preclínica de Medicamentos , Masculino , Malondialdehído/metabolismo , Glicoproteínas de Membrana/metabolismo , Ratones , NADPH Oxidasa 2 , NADPH Oxidasas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Examen Neurológico , Distribución Aleatoria , Superóxido Dismutasa/metabolismoRESUMEN
Dioscorea alata, commonly known as "greater yam", is a vital crop in tropical and subtropical regions of the world, yet it faces significant threats from anthracnose disease, mainly caused by Colletotrichum gloeosporioides. However, exploring disease resistance genes in this species has been challenging due to the difficulty of genetic mapping resulting from the loss of the flowering trait in many varieties. The receptor-like kinase (RLK) gene family represents essential immune receptors in plants. In this study, genomic analysis revealed 467 RLK genes in D. alata. The identified RLKs were distributed unevenly across chromosomes, likely due to tandem duplication events. However, a considerable number of ancient whole-genome or segmental duplications dating back over 100 million years contributed to the diversity of RLK genes. Phylogenetic analysis unveiled at least 356 ancient RLK lineages in the common ancestor of Dioscoreaceae, which differentially inherited and expanded to form the current RLK profiles of D. alata and its relatives. The analysis of cis-regulatory elements indicated the involvement of RLK genes in diverse stress responses. Transcriptome analysis identified RLKs that were up-regulated in response to C. gloeosporioides infection, suggesting their potential role in resisting anthracnose disease. These findings provide novel insights into the evolution of RLK genes in D. alata and their potential contribution to disease resistance.
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The greater yam (Dioscorea alata), a widely cultivated and nutritious food crop, suffers from widespread yield reduction due to anthracnose caused by Colletotrichum gloeosporioides. Latent infection often occurs before anthracnose phenotypes can be detected, making early prevention difficult and causing significant harm to agricultural production. Through comparative genomic analysis of 60 genomes of 38 species from the Colletotrichum genus, this study identified 17 orthologous gene groups (orthogroups) that were shared by all investigated C. gloeosporioides strains but absent from all other Colletotrichum species. Four of the 17 C. gloeosporioides-specific orthogroups were used as molecular markers for PCR primer designation and C. gloeosporioides detection. All of them can specifically detect C. gloeosporioides out of microbes within and beyond the Colletotrichum genus with different sensitivities. To establish a rapid, portable, and operable anthracnose diagnostic method suitable for field use, specific recombinase polymerase amplification (RPA) primer probe combinations were designed, and a lateral flow (LF)-RPA detection kit for C. gloeosporioides was developed, with the sensitivity reaching the picogram (pg) level. In conclusion, this study identified C. gloeosporioides-specific molecular markers and developed an efficient method for C. gloeosporioides detection, which can be applied to the prevention and control of yam anthracnose as well as anthracnose caused by C. gloeosporioides in other crops. The strategy adopted by this study also serves as a reference for the identification of molecular markers and diagnosis of other plant pathogens.
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BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Flavonoides , Humanos , Niño , Ratones , Masculino , Animales , Adolescente , FN-kappa B/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Quinasas Activadas por AMP , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológicoRESUMEN
BACKGROUND: Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS. RESULTS: We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells. CONCLUSIONS: Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. Video Abstract.
Asunto(s)
Ácido Elágico , Encefalomielitis Autoinmune Experimental , Microbioma Gastrointestinal , Esclerosis Múltiple , Propionatos , Ácido Elágico/farmacología , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/microbiología , Propionatos/metabolismo , Ratones , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/microbiología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Femenino , Autoinmunidad/efectos de los fármacos , Disbiosis/microbiología , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/inmunología , Humanos , Administración OralRESUMEN
Phthalate acid esters (PAEs) are one of the most widely used plasticizers globally, extensively employed in various decoration materials. However, studies on the impact of these materials on indoor environmental PAE pollution and their effects on human health are limited. In this study, forty dust samples were collected from four types of stores specializing in decoration materials (flooring, furniture boards, wall coverings, and household articles). The levels, sources, exposure doses, and potential health risks of PAEs in dust from decoration material stores were assessed. The total concentrations of Σ9PAE (the sum of nine PAEs) in dust from all decoration-material stores ranged from 46,100 ng/g to 695,000 ng/g, with a median concentration of 146,000 ng/g. DMP, DEP, DBP, and DEHP were identified as the predominant components. Among all stores, furniture board stores exhibited the highest Σ9PAE (159,000 ng/g, median value), while flooring stores exhibited the lowest (95,300 ng/g). Principal component analysis (PCA) showed that decoration materials are important sources of PAEs in the indoor environment. The estimated daily intakes of PAEs through non-dietary dust ingestion and dermal-absorption pathways among staff in various decoration-material stores were 60.0 and 0.470 ng/kg-bw/day (flooring stores), 113 and 0.780 ng/kg-bw/day (furniture board stores), 102 and 0.510 ng/kg-bw/day (wall covering stores), and 114 and 0.710 ng/kg-bw/day (household article stores). Particularly, staff in wall-covering and furniture-board stores exhibited relatively higher exposure doses of DEHP. Risk assessment indicated that although certain PAEs posed potential health risks, the exposure levels for staff in decoration material stores were within acceptable limits. However, staff in wall covering stores exhibited relatively higher risks, necessitating targeted risk-management strategies. This study provides new insights into understanding the risk associated with PAEs in indoor environments.