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Hepatocellular carcinoma (HCC) is an aggressive cancer that has an effect on human health. As a first-line drug for HCC, despite its excellent efficacy, lenvatinib (Len) is prone to developing drug resistance in HCC patients. The N6-methyladenosine (m6A) modification is not only related to the development of HCC but also shows great potential in overcoming HCC resistance. Using Dot Blot, our group first screened a small molecule m6A regulator, lobeline (Lob), from a library of 390 compounds (mostly natural products). In vitro experiments demonstrated that Lob could significantly enhance the sensitivity to Len of Len-resistant HCC (HCC/Len) and inhibit migration of resistant cells. In Len-resistant cell-derived and patient-derived xenograft models, Lob could reverse the resistant phenotype, with reductions in tumor volume of 68% and 60%, respectively. Furthermore, MeRIP-m6A sequencing results indicated that the underlying molecular mechanism of Lob reversal of HCC drug resistance was related to UBE3B. Taken together, this study highlighted that Lob, a plant derived natural product, could reverse the resistance of HCC to Len by regulating the m6A levels. It is hoped that this will provide a pharmacological research basis for the clinical treatment of HCC patients.
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Intestinal metaplasia (IM) is a premalignant condition that increases the risk for subsequent gastric cancer (GC). Traditional Chinese medicine generally plays a role in the treatment of IM, and the phytochemical naringenin used in Chinese herbal medicine has shown therapeutic potential for the treatment of gastric diseases. However, naringenin's specific effect on IM is not yet clearly understood. Therefore, this study identified potential gene targets for the treatment of IM through bioinformatics analysis and experiment validation. Two genes (MTTP and APOB) were selected as potential targets after a comparison of RNA-seq results of clinical samples, the GEO dataset (GSE78523), and naringenin-related genes from the GeneCards database. The results of both cell and animal experiments suggested that naringenin can improve the changes in the intestinal epithelial metaplasia model via MTTP/APOB expression. In summary, naringenin likely inhibits the MTTP/APOB axis and therefore inhibits IM progression. These results support the development of naringenin as an anti-IM agent and may contribute to the discovery of novel IM therapeutic targets.
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N6-methyladenosine (m6A) methylation is a vital epigenetic mechanism associated with drug addiction. However, the relationship between m6A modification and oxycodone rewarding is less well explored. Based on an open field test, the present study evaluated oxycodone rewarding using chromatin immunoprecipitation PCR, immunofluorescence, and RNA sequencing. A marked increase in METTL14 protein and a decrease in PP1α protein due to oxycodone abundance in the striatal neurons were observed in a dose- and time-dependent manner. Oxycodone markedly increased LSD1 expression, and decreased H3K4me1 expression in the striatum. In the open field test, intra-striatal injection of METTL14 siRNA, HOTAIR siRNA, or LSD1 shRNA blocked oxycodone-induced increase in locomotor activity. The downregulation of PP1α was also inhibited after treatment with METTL14/HOTAIR siRNA and LSD1 shRNA. Enhanced binding of LSD1 with CoRest and of CoRest with the PP1α gene induced by oxycodone was also reversed by LSD1 shRNA. In addition, H3K4me1 demethylation was also blocked by the treatment. In summary, the investigation confirmed that METTL14-mediated upregulation of HOTAIR resulted in the repression of PP1α, which in turn facilitated the recruitment of LSD1, thus catalyzing H3K4me1 demethylation and promoting oxycodone addiction.
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Metiltransferases , Oxicodona , RNA Longo não Codificante , Animais , Masculino , Camundongos , Corpo Estriado/metabolismo , Corpo Estriado/efeitos dos fármacos , Desmetilação , Histona Desmetilases/metabolismo , Histona Desmetilases/genética , Histonas/metabolismo , Lisina/análogos & derivados , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos Endogâmicos C57BL , Oxicodona/farmacologia , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 1/genética , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/genética , Regulação para CimaRESUMO
BACKGROUND: The meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund's adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll-like receptor (TLR) ligands as compared to CFA. METHODS: A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein-3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme-linked immunosorbent assay quantified antigen-specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes. RESULTS: TLR ligands demonstrated efficacy in inducing PV-like symptoms in wild-type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self-antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study. CONCLUSIONS: The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis. KEY POINTS/HIGHLIGHTS: Immunization with desmoglein 3 and Toll-like receptor (TLR) ligands effectively induces pemphigus symptoms in wild-type mice, whereas complete Freund's adjuvant (CFA) fails. TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model. CFA promoted regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10, leading to more effective immune responses.
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Adjuvantes Imunológicos , Modelos Animais de Doenças , Pênfigo , Receptores Toll-Like , Animais , Pênfigo/imunologia , Camundongos , Receptores Toll-Like/metabolismo , Receptores Toll-Like/imunologia , Receptores Toll-Like/agonistas , Adjuvantes Imunológicos/farmacologia , Adjuvante de Freund/imunologia , Camundongos Endogâmicos C57BL , Ligantes , Ovalbumina/imunologia , FemininoRESUMO
Numerous studies have suggested that the perceived built environment is shaped by the objective built environment and influences human physical activity. However, the empirical examination of this pathway remains scant. Addressing this gap, our study investigates whether the built environment affects leisure-time physical activity through its impact on the perceived built environment, utilizing data collected from 760 residents in Fuzhou, China. Structural Equation Modeling results reveal a modest correlation between objective and perceived built environment elements, with the objective built environment being a stronger predictor of leisure-time physical activity. Notably, perceived recreational facilities significantly mediate the relationship between objective recreational facilities and leisure-time physical activity, accounting for 15% of the variance in physical activity due to objective recreational facilities. This mediation effect is consistent across subpopulations, irrespective of residential self-selection biases. These results highlight the imperative for urban planning and policy to extend beyond mere spatial allocation of amenities to enhancing both the actual and perceived accessibility of these facilities, thus underlining the study's profound implications for public health and urban development strategies.
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Ambiente Construído , Cidades , Exercício Físico , Atividades de Lazer , Humanos , China , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Planejamento Ambiental , Adulto Jovem , Planejamento de CidadesRESUMO
Ion back-diffusion hinders the practical application of conventional flow-electrode capacitive deionization (FCDI) under long-term operational conditions. To address this challenge, the present study integrated cation intercalation deionization (CID) with FCDI. A novel PFCDI-CID system was developed by utilizing a modified Prussian blue analogues owing to their enhanced rheological and electrochemical properties. The PFCDI-CID system achieved a high charge efficiency of 89.77% and an energy-normalized removal salt of 0.69 mol kJ-1 in single-cycle (SC) mode with the flow electrodes mass fraction of 2% and a desalinized water chamber-to-concentrated saline water chamber ratio of 2:1. Furthermore, under continuous operation for 12 h in SC mode, the PFCDI-CID system maintained stable desalination performance within the first 2 h. Over an extended duration, the average charge efficiency of the PFCDI-CID system was maintained at 88.44%, with an average energy-normalized removal salt of 0.65 mol kJ-1. The mechanism revealed that the desalination process involving the Prussian blue analogues primarily involves Na+ intercalation, accompanied by a small amount of electro-sorption process. This system exhibits the characteristics of conventional FCDI while enabling desalination and concentration of simulated saline water during brine discharge, thereby mitigating the impact of ion back-diffusion and broadening the application scope of FCDI.
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Cátions , Eletrodos , Ferrocianetos , Purificação da Água , Purificação da Água/métodos , Ferrocianetos/químicaRESUMO
The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be studied. In our study, rewarding memory was assessed by using conditioned place preference (CPP) in male mice. Next generation sequencing and chromatin immunoprecipitation-PCR were used to explore the molecular mechanisms. Oxycodone significantly decreased PP1α mRNA and protein levels in hippocampal neurons. Oxycodone significantly increased KDM1A and H3K4me1 levels, while significantly decreased H3K4me2 levels in a time- and dose-dependent manner. Behavioral data demonstrated that intraperitoneal injection of ORY-1001 (KDM1A inhibitor) or intra-hippocampal injection of KDM1A siRNA/shRNA blocked the acquisition and expression of oxycodone CPP and facilitated the extinction of oxycodone CPP. The decrease of PP1α was markedly blocked by the injection of ORY-1001 or KDM1A siRNA/shRNA. Oxycodone-induced enhanced binding of CoRest with KDM1A and binding of CoRest with the PP1α promoter was blocked by ORY-1001. The level of H3K4me2 demethylation was also decreased by the treatment. The results suggest that oxycodone-induced upregulation of KDM1A via demethylation of H3K4me2 promotes the binding of CoRest with the PP1α promoter, and the subsequent decrease in PP1α expression in hippocampal neurons may contribute to oxycodone reward.
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Epigênese Genética , Histona Desmetilases , Oxicodona , Animais , Masculino , Epigênese Genética/efeitos dos fármacos , Camundongos , Oxicodona/farmacologia , Histona Desmetilases/metabolismo , Histona Desmetilases/genética , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Recompensa , Condicionamento Psicológico/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Histonas/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Memória/efeitos dos fármacosRESUMO
In the context of global climate change, recurrent freeze-thaw cycles (FTC) and concurrent exposure to polystyrene nanoplastics (PSNPs) directly impact crop growth and indirectly affect resilience to abiotic stress. In January 2023, experiments at the Environmental Biology Laboratory, Jilin University, Changchun, China, exposed rye seedlings to 100 nm PSNPs at concentrations of 0, 10, 50, and 100 mg/L for seven days, followed by three FTC. Scanning electron microscopy (SEM) demonstrated that PSNPs migrated from the roots to the leaves, with FTC significantly exacerbating their accumulation within plant tissues. Transmission electron microscopy (TEM) observations showed that FTC disrupted normal cell division, and combined stress from NPs damaged plant organs, particularly chloroplasts, thereby substantially inhibiting photosynthesis. FTC delayed plant phenological stages. Under combined stress, malondialdehyde (MDA) accumulation in plant tissues increased by 15.6%, while hydrogen peroxide (H2O2) content decreased. Simultaneously, the activities of peroxidase (POD) and catalase (CAT) increased by 34.2% and 38.6%, respectively. Molecular docking unveiled that PSNPs could bind to the active center of POD/CAT through hydrogen bonding or hydrophobic interactions. The Integrated Biomarker Response (IBR) index highlighted FTC as a crucial determinant for pronounced effects. Moreover, an apparent dose-dependent effect was observed, with antioxidant enzyme activities in rye seedlings induced by low pollutant concentrations and inhibited by high concentrations. These results indicate that FTC and PSNPs can disrupt plant membrane systems and cause severe oxidative damage. Overall, this study provides compelling scientific evidence of the risks associated with NPs exposure in plants subjected to abiotic stress.
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Congelamento , Poliestirenos , Secale , Plântula , Plântula/efeitos dos fármacos , Plântula/metabolismo , Poliestirenos/toxicidade , Secale/efeitos dos fármacos , Secale/metabolismo , Peroxidase/metabolismo , Catalase/metabolismo , Nanopartículas/toxicidade , Simulação de Acoplamento Molecular , Malondialdeído/metabolismoRESUMO
INTRODUCTION: Steroid-induced necrosis of the femoral head (SINFH) is a femoral head necrotic disease caused by prolonged use of hormones. Wen-Dan decoction is used in Chinese clinical practice for the treatment of steroid-induced necrosis of the femoral head (SINFH). However, the mechanism and active compounds of Wen-Dan decoction used to treat SINFH are not well understood. OBJECTIVES: We studied the mechanism of action of Wen-Dan decoction in treating steroidinduced necrosis of the femoral head (SINFH) via network pharmacology and in vivo experiments. METHODS: The active compounds of Wen-Dan decoction and SINFH-related target genes were identified through public databases. Then, network pharmacological analysis was conducted to explore the potential key active compounds, core targets and biological processes of Wen-Dan decoction in SINFH. The potential mechanisms of Wen-Dan decoction in SINFH obtained by network pharmacology were validated through in vivo experiments. RESULTS: We identified 608 DEGs (differentially expressed genes) (230 upregulated, 378 downregulated) in SINFH. GO analysis revealed that the SINFH-related genes were mainly involved in neutrophil activation and the immune response. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the SINFH-related genes were mainly associated with cytokine receptor interactions, lipids, atherosclerosis, and tuberculosis. We identified 147 active ingredients of Wen-Dan decoction; the core ingredient was quercetin, and licorice was an active ingredient. Moreover, 277 target genes in the treatment of SINFH with Wen-Dan decoction were identified, and NCF1, PTGS2, and RUNX2 were selected as core target genes. QRT-PCR of peripheral blood from SINFH patients showed higher levels of PGTS2 and NCF1 and showed lower levels of RUNX2 compared to controls. QRT-PCR analysis of peripheral blood and femoral bone tissue from a mouse model of SINFH showed higher levels of PGTS2 and NCF1 and lower levels of RUNX2 in the experimental animals than the controls, which was consistent with the bioinformatics results. HE, immunohistochemistry, and TUNEL staining confirmed a significant reduction in hormone-induced femoral head necrosis in the quercetintreated mice. HE, immunohistochemistry, and TUNEL staining confirmed significant improvement in hormone-induced femoral head necrosis in the quercetin-treated mice. CONCLUSION: We provide new insights into the genes and related pathways involved in SINFH and report that PTGS2, RUNX2, and NCF1 are potential drug targets. Quercetin improved SINFH by promoting osteogenesis and inhibiting apoptosis.
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Medicamentos de Ervas Chinesas , Necrose da Cabeça do Fêmur , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Animais , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/induzido quimicamente , Camundongos , Humanos , MasculinoRESUMO
Genetic variants of the OX40 ligand (OX40L) locus are associated with the risk of systemic lupus erythematosus (SLE), it is unclear how the OX40L blockade delays the lupus phenotype. Therefore, we examined the effects of an anti-OX40L antibody in MRL/Lpr mice. Next, we investigated the effect of anti-OX40L on immunosuppression in keyhole limpet hemocyanin-immunized C57BL/6J mice. In vitro treatment of anti-OX40L in CD4+ T and B220+ B cells was used to explore the role of OX40L in the pathogenesis of SLE. Anti-OX40L alleviated murine lupus nephritis, accompanied by decreased production of anti-dsDNA and proteinuria, as well as lower frequencies of splenic T helper (Th) 1 and T-follicular helper cells (Tfh). In keyhole limpet hemocyanin-immunized mice, decreased levels of immunoglobulins and plasmablasts were observed in the anti-OX40L group. Anti-OX40L reduced the number and area of germinal centers. Compared with the control IgG group, anti-OX40L downregulated CD4+ T-cell differentiation into Th1 and Tfh cells and upregulated CD4+ T-cell differentiation into regulatory T cells in vitro. Furthermore, anti-OX40L inhibited toll-like receptor 7-mediated differentiation of antibody-secreting cells and antibody production through the regulation of the SPIB-BLIMP1-XBP1 axis in B cells. These results suggest that OX40L is a promising therapeutic target for SLE.
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Nefrite Lúpica , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Ligante OX40 , Receptores OX40 , Transdução de Sinais , Animais , Camundongos , Nefrite Lúpica/imunologia , Ligante OX40/metabolismo , Transdução de Sinais/imunologia , Receptores OX40/imunologia , Receptores OX40/metabolismo , Receptores OX40/genética , Linfócitos B/imunologia , Feminino , Hemocianinas/imunologia , Modelos Animais de Doenças , Células Th1/imunologia , Anticorpos Antinucleares/imunologia , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
In spite of the competitive performance at room temperature, the development of sodium-ion batteries (SIBs) is still hindered by sluggish electrochemical reaction kinetics and unstable electrode/electrolyte interphase under subzero environments. Herein, a low-concentration electrolyte, consisting of 0.5M NaPF6 dissolving in diethylene glycol dimethyl ether solvent, is proposed for SIBs working at low temperature. Such an electrolyte generates a thin, amorphous, and homogeneous cathode/electrolyte interphase at low temperature. The interphase is monolithic and rich in organic components, reducing the limitation of Na+ migration through inorganic crystals, thereby facilitating the interfacial Na+ dynamics at low temperature. Furthermore, it effectively blocks the unfavorable side reactions between active materials and electrolytes, improving the structural stability. Consequently, Na0.7Li0.03Mg0.03Ni0.27Mn0.6Ti0.07O2//Na and hard carbon//Na cells deliver a high capacity retention of 90.8 % after 900 cycles at 1C, a capacity over 310â mAh g-1 under -30 °C, respectively, showing long-term cycling stability and great rate capability at low temperature.
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To explore the moderating role of dyadic appraisal in the association between dyadic coping and diabetes management efficacy. Two hundred seventy six middle-aged and older couple pairs with one spouse who had diabetes were recruited from 14 community healthcare centers across Guangzhou. The moderating role of dyadic appraisal was investigated using the actor-partner interdependence moderation model. When both couples considered diabetes to be a shared condition, statistically-significant associations were found between patients' negative (ß = -22.7, p = 0.008) and neutral behaviors (ß = 13.6, p = 0.017), plus spouses' positive behaviors (ß = 22.8, p = 0.009) on their own diabetes management efficacy, respectively (i.e. actor effects); as well as between spouses' positive (ß = 16.8, p = 0.028), negative (ß = -28.5, p < 0.001), and neutral behaviors (ß = 16.9, p = 0.006) on patient's diabetes management efficacy (i.e. partner effects). Dyadic appraisal moderates the association between dyadic coping and diabetes management efficacy.
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Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, and atopic dermatitis. Thus, blocking CYSLTR1 may be a promising strategy for psoriasis immunotherapy. We prepared a montelukast sodium cream and solution and investigated their effects on psoriasis-like skin lesions induced by imiquimod (IMQ). After the treatment, serum, skin, and spleen samples were collected for evaluation. We treated human T helper (Th) 17 cells with montelukast in vitro to study its effect on Th17 differentiation and nuclear factor kappa-B (NF-κB) signaling. We also created a keratinocyte proliferation model induced by M5 cytokines and assessed the influence of montelukast on key psoriasis-related genes. We induced psoriasis in CYSLTR1 knockout (KO) mice using IMQ to explore the role of CYSLTR1 in psoriasis development. Montelukast sodium cream and solution effectively reduced the psoriasis area and severity index (PASI) and alleviated disease symptoms in IMQ-induced mice. Furthermore, reduced infiltration of inflammatory cells (Th1, Th17, and T follicular helper [Tfh] cells), decreased mRNA expression of cytokines in the skin (interleukin [IL]-17/F and IL-23), and lower serum concentrations of various cytokines (IL-2, IL-6, IL-13, and IL-17A/F) were observed. Montelukast cream and solution also decreased spleen size and the proportion of Th17 and Tfh cells, and significantly inhibited NF-κB signaling-related genes after application. Moreover, montelukast inhibited Th17 cell differentiation and suppressed NF-κB signaling in vitro. CYSLTR1 KO mice induced with IMQ showed improvement in PASI scores, serum IL-17A/F levels, and lower Th1 and Th17 cells in the spleen and skin compared to wild-type mice. Montelukast also suppressed the proliferation and inflammatory response of keratinocytes by regulating NF-κB signaling. Collectively, our results strongly indicate that inhibition of CYSLTR1 signaling to target the Th17 response holds significant promise as a therapeutic approach to manage psoriasis.
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Acetatos , Ciclopropanos , NF-kappa B , Psoríase , Quinolinas , Sulfetos , Humanos , Animais , Camundongos , Interleucina-17 , Células Th17 , Psoríase/tratamento farmacológico , Diferenciação Celular , CitocinasRESUMO
Cancer is a heterogeneous disease. Although both tumor metabolism and tumor immune microenvironment are recognized as driving factors in tumorigenesis, the relationship between them is still not well-known, and potential combined targeting approaches remain to be identified. Here, we demonstrated a negative correlation between the expression of NAMPT, an NAD+ metabolism enzyme, and PD-L1 expression in various cancer cell lines. A clinical study showed that a NAMPTHigh PD-L1Low expression pattern predicts poor prognosis in patients with various cancers. In addition, pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65, and blocking PD-L1 would induce NAMPT expression through a HIF-1-dependent glycolysis pathway. Based on these findings, we designed and synthesized a dual NAMPT/PD-L1 targeting compound, LZFPN-90, which inhibits cell growth in a NAMPT-dependent manner and blocks the cell cycle, subsequently inducing apoptosis. Under co-culture conditions, LZFPN-90 treatment contributes to the proliferation and activation of T cells and blocks the growth of cancer cells. Using mice bearing genetically manipulated tumors, we confirmed that LZFPN-90 exerted target-dependent antitumor activities, affecting metabolic processes and the immune system. In conclusion, our results demonstrate the relevance of NAD+-related metabolic processes in antitumor immunity and suggest that co-targeting NAD+ metabolism and PD-L1 represents a promising therapeutic approach.
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Antígeno B7-H1 , Neoplasias , Humanos , Animais , Camundongos , NAD , Neoplasias/patologia , Proliferação de Células , Apoptose , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
The electrochemiluminescence (ECL) signal is largely determined by the electron transfer efficiency. Therefore, in the nanomaterial-involved ECL system, the structure-related electron distribution could affect the electron transfer efficiency and further alter the ECL intensity. These features make the design of versatile ECL-based analytical techniques for probing the correlated structure possible. And it is generally accepted that the increased crystallinity of nanomaterials usually leads to a uniform electron distribution, which provides higher conductivity. Therefore, the crystallinity-improved conductivity could facilitate electron transfer, promote the electrochemical activity of support materials, and boost the efficiency of the ECL reaction. In this study, we have demonstrated that the ECL signal of the graphitic carbon nitride reporter was proportional to the crystallinity of layered double hydroxides (LDHs), which meets the supposition well. On the basis of this phenomenon, an ECL-based crystallinity analysis approach has been established using CdAl-LDHs as the model materials. The universality of this proposed technique was further validated by the rapid and accurate crystallinity determination of ZnAl-LDH samples with diverse crystallinities. This work not only contributes an alternative to the X-ray diffraction technique for the rapid screening of crystallinity in layered materials but also opens a new avenue for the design of ECL-based structure analysis techniques toward nanomaterials and even organic materials by involving electron transfer regulation correlation.
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Hyperspectral digital holography (HSDH) is a versatile holographic imaging technique that offers large unambiguous depth range and spectroscopic information. In this Letter, we propose a novel, to the best of our knowledge, HSDH system that is realized by using an electro-optical frequency comb (EOFC) via injection locking. In comparison with conventional dual-comb HSDH, the proposed system only requires one EOFC and few other devices, which not only simplifies the system structure and reduces the cost but also improves the imaging speed. We validated the system using an EOFC with 20 optical frequencies spaced at 18 GHz intervals. In a total measurement time of 0.5 s, we successfully captured images of two targets that were 0.74 mm apart without phase ambiguity and obtained the transmission spectrum of an absorbing gas simultaneously. This work provides valuable insights for HSDH systems relying on an optical frequency comb.
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Objective: To study the correlation between episcleral vein pressure (EVP) with intraocular pressure (IOP), exophthalmos, and optic nerve injury in thyroid-associated ophthalmopathy (TAO) patients and to explore the possibility of higher EVP as an intervention indicator in TAO patients. Methods: This study was a case-control study, including the TAO group and normal control group. TAO group: 15 patients (30 eyes) were diagnosed with TAO complicated with exophthalmos. Normal control group: 14 cases, 28 eyes. EVP, IOP, exophthalmos, retinal nerve fiber layer thickness, and visual field were measured, respectively in the two groups. Non-parametric test was used to compare the difference between EVP and IOP between the two groups, test the correlation between EVP and IOP or exophthalmos, and analyze the clinical characteristics of optic nerve injury in patients with elevated IOP in the TAO group. Results: The EVP in the TAO group (15.30±3.48 mmHg) was significantly higher than the normal control group (8.82±1.44 mmHg) (P < .001). The IOP in the TAO group (18.55±8.13 mmHg) was significantly higher than in the normal control group (12.98±2.10 mmHg) (P < .001) (3) There was a positive linear correlation between EVP (X) and IOP (Y) in TAO group: Y = 0.9684x + 3.737 (rs>0, P < .05); There was a positive linear correlation between EVP (Y) and exophthalmos (X) in TAO group: Y = 0.9218x - 2.691 (rs>0, P < .05); Some TAO patients with elevated EVP had the related manifestations of optic nerve function impairment: thinning of retinal nerve fiber layer and loss of visual field. However, there was no clear correlation between EVP and the thickness of the optic nerve fiber layer (P = .4354). Conclusion: The increase of EVP is an important factor leading to elevated IOP in TAO patients, which may be used as an indicator for intervention treatment in TAO patients. EVP can be used to indirectly evaluate orbital pressure. TAO patients can develop secondary glaucoma with irreversible optic nerve damage due to the continuous Elevation of EVP.
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The processing of traditional Chinese medicine (TCM) plays an important role in the clinical application, which usually has the function of "increasing efficiency and reducing toxicity". Polygonum multiflorum (PM) has been reported to induce hepatotoxicity, while it is believed that the toxicity is reduced after processing. Studies have shown that the hepatotoxicity of PM is closely related to the changes in chemical components before and after processing. However, there is no comprehensive investigation on the chemical changes of PM during the processing progress. In this research, we established a comprehensive method to profile both small molecule compounds and polysaccharides from raw and different processed PM samples. In detail, an online two-dimensional liquid chromatography coupled with quadrupole-orbitrap mass spectrometry (2D-LC/Q-Orbitrap MS) was utilized to investigate the small molecules, and a total of 150 compounds were characterized successfully. After multivariate statistical analysis, 49 differential compounds between raw and processed products were screened out. Furthermore, an accurate and comprehensive method for quantification of differential compounds in PM samples was established based on ultra-high performance liquid chromatography/Q-Orbitrap-MS (UHPLC/Q-Orbitrap-MS) within 16 min. In addition, the changes of polysaccharides in different PM samples were analyzed, and it was found that the addition of black beans and steaming times would affect the content and composition of polysaccharides in PM significantly. Our work provided a reference basis for revealing the scientific connotation of the processing technology and increasing the quality control and safety of PM.
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Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Fallopia multiflora , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/química , Fallopia multiflora/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , PolissacarídeosRESUMO
Ganoderma lucidum (G. lucidum) is a rare medicinal fungus with various beneficial properties. One of its main components, ganoderic acids (GAs), are important triterpenoids known for their sedative and analgesic, hepatoprotective, and anti-tumor activities. Understanding the growth and development of the G. lucidum fruiting body is crucial for determining the optimal time to harvest them. In this study, we used nuclear magnetic resonance (NMR) spectroscopy to systematically characterize the metabolites of G. lucidum at seven distinct developmental stages. We also measured the contents of seven kinds of GAs using LC-MS/MS. A total of 49 metabolites were detected in G. lucidum, including amino acids, sugars, organic acids and GAs. During the transition from the bud development period (I) to the budding period (II), we observed a rapid accumulation of glucose, tyrosine, nicotinamide ribotide, inosine and GAs. After the budding period, the contents of most metabolites decreased until the mature period (VII). In addition, the contents of GAs showed an initial raising, followed by a decline during the elongation period, except for GAF, which exhibited a rapid raise during the mature stage. We also detected the expression of several genes involved in GA synthesis, finding that most genes including 16 cytochrome P450 monooxygenase were all down-regulated during periods IV and VII compared to period I. These findings provide valuable insights into the dynamic metabolic profiles of G. lucidum throughout its growth stage, and it is recommended to harvest G. lucidum at period IV.
Assuntos
Ascomicetos , Reishi , Triterpenos , Reishi/genética , Reishi/química , Cromatografia Líquida , Reação em Cadeia da Polimerase em Tempo Real , Espectrometria de Massas em Tandem , Espectroscopia de Ressonância Magnética , Ascomicetos/genéticaRESUMO
Abnormal fatty acid metabolism is recognized as a key driver of tumor development and progression. Although numerous inhibitors have been developed to target this pathway, finding drugs with high specificity that do not disrupt normal cellular metabolism remains a formidable challenge. In this paper, we introduced a novel real-time NMR-based drug screening technique that operates within living cells. This technique provides a direct way to putatively identify molecular targets involved in specific metabolic processes, making it a powerful tool for cell-based drug screening. Using 2-13C acetate as a tracer, combined with 3D cell clusters and a bioreactor system, our approach enables real-time detection of inhibitors that target fatty acid metabolism within living cells. As a result, we successfully demonstrated the initial application of this method in the discovery of traditional Chinese medicines that specifically target fatty acid metabolism. Elucidating the mechanisms behind herbal medicines remains challenging due to the complex nature of their compounds and the presence of multiple targets. Remarkably, our findings demonstrate the significant inhibitory effect of P. cocos on fatty acid synthesis within cells, illustrating the potential of this approach in analyzing fatty acid metabolism events and identifying drug candidates that selectively inhibit fatty acid synthesis at the cellular level. Moreover, this systematic approach represents a valuable strategy for discovering the intricate effects of herbal medicine.