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Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.
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Neoplasias Primárias Desconhecidas , Medicina de Precisão , Humanos , Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/terapia , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/diagnóstico , Medicina de Precisão/métodos , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Aprendizado de Máquina , Prognóstico , Genômica/métodos , Biópsia Líquida/métodosRESUMO
Arthritis causes Fos-like 2 (Fosl2) inactivation, and various immune cells contribute to its pathogenesis. However, little is known about the role of Fosl2 in hematopoiesis and the possible pathological role of Fosl2 inactivation in the hematopoietic system in arthritis. In this study, we show that Fosl2 maintains hematopoietic stem cell (HSC) quiescence and differentiation while controlling the inflammatory response via macrophages. Fosl2-specific deletion in the hematopoietic system caused the expansion of HSCs and myeloid cell growth while affecting erythroid and B cell differentiation. Fosl2 inactivation enhanced macrophage M1 polarization and stimulated proinflammatory cytokines and myeloid growth factors, skewing HSCs toward myeloid cell differentiation, similar to hematopoietic alterations in arthritic mice. Loss of Fosl2 mediated by Vav-iCre also displays an unexpected deletion in embryonic erythro-myeloid progenitor-derived osteoclasts, leading to osteopetrosis and anemia. The reduced bone marrow cellularity in Vav-iCreFosl2f/f mice is a consequence of the reduced bone marrow space in osteopetrotic mice rather than a direct role of Fosl2 in hematopoiesis. Thus, Fosl2 is indispensable for erythro-myeloid progenitor-derived osteoclasts to maintain the medullary cavity to ensure normal hematopoiesis. These findings improve our understanding of the pathogenesis of bone-destructive diseases and provide important implications for developing therapeutic approaches for these diseases.
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Antígeno 2 Relacionado a Fos , Células-Tronco Hematopoéticas , Osteopetrose , Animais , Camundongos , Artrite/patologia , Transtornos da Insuficiência da Medula Óssea/patologia , Diferenciação Celular , Hematopoese/genética , Osteopetrose/genética , Osteopetrose/patologia , Antígeno 2 Relacionado a Fos/genéticaRESUMO
Metal phthalocyanine molecules with Me-N4 centers have shown promise in electrocatalytic CO2 reduction (eCO2R) for CO generation. However, iron phthalocyanine (FePc) is an exception, exhibiting negligible eCO2R activity due to a higher CO2 to *COOH conversion barrier and stronger *CO binding energy. Here, amine functional groups onto atomic-Fe-rich carbon dots (Af-Fe-CDs) are introduced via a one-step solvothermal molecule fusion approach. Af-Fe-CDs feature well-defined Fe-N4 active sites and an impressive Fe loading (up to 8.5 wt%). The synergistic effect between Fe-N4 active centers and electron-donating amine functional groups in Af-Fe-CDs yielded outstanding CO2-to-CO conversion performance. At industrial-relevant current densities exceeding 400 mA cm-2 in a flow cell, Af-Fe-CDs achieved >92% selectivity, surpassing state-of-the-art CO2-to-CO electrocatalysts. The in situ electrochemical FTIR characterization combined with theoretical calculations elucidated that Fe-N4 integration with amine functional groups in Af-Fe-CDs significantly reduced energy barriers for *COOH intermediate formation and *CO desorption, enhancing eCO2R efficiency. The proposed synergistic effect offers a promising avenue for high-efficiency catalysts with elevated atomic-metal loadings.
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BACKGROUND: The emergence of severe sepsis is contingent upon the occurrence of a cytokine storm (CS), a multifaceted process intricately entwined with the temporal dimension, thereby rendering the infection response remarkably intricate. Consequently, it becomes imperative to discern and accurately identify the optimal timing for interventions, predicated upon the dynamic timeline of inflammatory changes. Moreover, the administration of exogenous low-dose pro-inflammatory agents has exhibited the potential to impede the relentless progression of the inflammatory cascade. Hence, the present study aims to scrutinize the impact of exogenous Local Inflammatory Response (eLIR) on the body surface in the context of the inflammatory cascade during sepsis, within a temporal framework, with a particular emphasis on the point of exacerbation of inflammation. METHODS: Rats were induced sterile sepsis by intraperitoneal injection of zymosan (ZY) at an appropriate dosage. The temporal progression of inflammatory changes and eLIR effects were described based on the trend of serum crucial inflammatory cytokines, tring to quest time-point of inflammatory aggravation in sepsis. Then, the varying degrees of surface inflammation caused by eLIR on this time point leading to the final effects on the inflammatory cascade response were explored. In addition, given the authentic pathological progression of sepsis, further observation was conducted on the impact of another intervention timing of eLIR on the inflammatory cascade. The survival rate was measured. Serum and organ related inflammatory cytokines were detected, and organ histopathology was investigated. RESULTS: In present study, a dosage of 600 mg/kg ZY was found to be optimal for the sterile sepsis model. Initiating eLIR 6 h prior to ZY injection, the maximum effect point of eLIR could be precisely align with the inflammatory aggravation point of sterile sepsis. Initiating eLIR at this time, 3 sessions of eLIR were found to be more effective than 1 or 2 sessions in mitigating inflammatory responses during the initial stage of inflammation and the peak of inflammation. Notably, the findings also suggested that this intervention improve survival rate. In addition, the anti-inflammatory efficacy has been substantially diminished by the prompt initiation of 3 sessions of eLIR immediately after ZY injection at the onset of sepsis. Similarly, the current findings did not demonstrate a statistically significant enhancement in survival rates with eLIR at this time point. CONCLUSIONS: Compared with the initial stage of inflammation, low-scale inflammation caused by a certain intensity of eLIR (3 sessions) on the body surface can more effectively pry the inflammation aggravation time-point, thereby shifting the pro-inflammatory to anti-inflammatory milieu, impeding the disproportionate cytokines release in inflammatory diseases, slowing down the inflammatory cascade, and improving the survival rate of sepsis.
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Síndrome da Liberação de Citocina , Sepse , Ratos , Animais , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas , Inflamação/tratamento farmacológico , Sepse/complicações , Sepse/tratamento farmacológico , Anti-Inflamatórios/uso terapêuticoRESUMO
Axially chiral cycloalkylidenes are interesting but less developed axially chiral molecules. Here, a bispidine-based chiral amine catalytic system was developed to promote efficiently the asymmetric Knoevenagel condensation of N-protected oxindoles and benzofuranones with 4-substituted cyclohexanones. A variety of alkylidenecycloalkanes with stable axial chirality were obtained in good yields and fairly good er (enantiomeric ratio). Based on the absolute configuration determination of product and DFT calculations, a possible mechanism of stereoselective induction was proposed.
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Water possesses unique advantages, including abundance, environmental friendliness and mild effects. Undoubtedly, it is an ideal solvent or reagent in chemical syntheses. Water also shows unique abilities in catalytic asymmetric synthesis. It can accelerate reaction rates, improve diastereo- or enantioselectivities, initiate reactions, diversify chemo, diastereo- or enantioselectivities through various effects (hydrophobic, hydrogen bonding, protonation). Several reviews have demonstrated the positive effects of water in asymmetric synthesis. In this review, we summarize water-enabling strategies in the last decade, and focus on advances which reveal how water affects a reaction.
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Multifunctional thermally activated delayed fluorescence (TADF) materials are currently a trending research subject for luminescence layer materials of organic light-emitting diodes (OLEDs). Among these, circularly polarized thermally activated delayed fluorescence (CP-TADF) materials have the advantage of being able to directly achieve highly efficient circularly polarized luminescence (CPL). The simultaneous integration of outstanding luminescence efficiency and excellent luminescence asymmetry factor (glum) is a major constraint for the development of CP-TADF materials. Therefore, on the basis of first-principles calculations in conjunction with the thermal vibration correlation function (TVCF) method, we study CP-TADF molecules with different donors to explore the feasibility of using the donor substitution strategy for optimizing the CPL and TADF properties. The results indicate that molecules with the phenothiazine (PTZ) unit as the donor possess small energy difference, a great spin-orbit coupling constant and a rapid reverse intersystem crossing rate, which endow them with remarkable TADF features. Meanwhile, compared with the reported molecules, the three designed molecules exhibit better CPL properties with higher glum values. Effective molecular design strategies by donor engineering to modulate the CPL and TADF properties are theoretically proposed. Our findings reveal the relationship between molecular structures and luminescence properties of CP-TADF molecules and further provide theoretical design strategies for optimizing the CPL and TADF properties.
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Thermally activated delayed fluorescence (TADF) molecules with through-space charge transfer (TSCT) have attracted much attention in recent years because of their ability to simultaneously reduce the energy difference (ΔEST) and enlarge the spin-orbit coupling (SOC). In this paper, 40 molecules are theoretically designed by changing the different substitution positions of the donors and acceptors, and systematically investigated based on the first-principles calculations and excited-state dynamics study. It is found that the emission wavelengths of v-shaped molecules with intramolecular TSCT are larger than those of the molecules without TSCT. Therefore, the intramolecular TSCT can induce the red-shift of the emission and realize the deep-red/near-infrared emission. Besides intramolecular TSCT can simultaneously increase the SOC as well as the oscillator strength and reduce the ΔEST. In addition, PXZ or PTZ can also favor the realization of smaller ΔEST and red-shift emission. Our calculations suggest that intramolecular TSCT and suitable donors (-PXZ or -PTZ) are an effective strategy for the design of efficient deep red/near-infrared TADF emitters.
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As a typical thermally activated delayed fluorescence (TADF) emitter with green emission, 4CzIPN has attracted much attention recently. Most studies indicated that 4CzIPN doped in different hosts presented different performances; thus, the hosts should have an obvious influence on its photophysical properties. Herein, the influence of four kinds of hosts, including m-CzPym, m-CzTrz, p-CzPym, and p-CzTrz, on the photophysical properties of 4CzIPN is investigated. Molecular dynamics simulations were performed to simulate the host-guest conformations, and the photophysical properties were studied using the combined quantum mechanics/molecular mechanics method coupled with the thermal-vibration correlation function method. It is found that 4CzIPN in doped films has larger transition dipole moments and spin-orbital coupling constants compared to that in nondoped films. Faster radiative decay, intersystem crossing rates, and higher fluorescence efficiency could be obtained in doped films. Our work helps to better understand the photophysical properties of 4CzIPN in doped films and may favor the design of new hosts.
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Organic emitters with a simultaneous combination of aggregation-induced emission (AIE) and thermally activated delayed fluorescence (TADF) characteristics are in great demand due to their excellent comprehensive performances toward efficient organic light-emitting diodes (OLEDs), biomedical imaging, and the telecommunications field. However, the development of efficient AIE-TADF materials remains a substantial challenge. In this work, light-emitting properties of two AIE-TADF molecules with different bridging groups ICz-BP and ICz-DPS are theoretically investigated in the solid state with the combined quantum mechanics/molecular mechanics (QM/MM) method and the thermal vibration correlation function (TVCF) theory. The research indicates that the CâO bridging bond in ICz-BP is more favorable than the SâO bridging bond in ICz-DPS for enhancing the planarity of the acceptor, increasing conjugation, and thereby elevating the transition dipole moment density. Simultaneously, the stacking pattern of ICz-BP in the solid facilitates a reduction in energy gap between S1 and T1 (ΔEST), achieving rapid reverse intersystem crossing rate (kRISC). Furthermore, compared to toluene, the stacking patterns of ICz-BP and ICz-DPS in the solid effectively suppress the out-of-plane wagging vibration of the acceptor, thereby inhibiting the loss of nonradiative energy in the excited state and realizing aggregation-induced emission. Moreover, the charge transport properties of both electrons and holes in ICz-BP are found to be higher than the corresponding rates in ICz-DPS, attributed to the smaller internal reorganization energy of ICz-BP in the solid state. Additionally, the calculations reveal a more balanced charge transport characteristic in ICz-BP, contributing to efficient exciton recombination and emission and ultimately mitigating efficiency roll-off. Based on these computational results, we aim to unveil the relationship between molecular structure and light-emitting properties, aiding in the design and development of efficient AIE-TADF devices.
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Qingxuan Zhike granules (QXZKG), a traditional Chinese patent medication, has shown therapeutic potential against acute lung injury (ALI). However, the precise mechanism underlying its lung-protective effects requires further investigation. In this study, integrated network pharmacology, molecular docking, and lipidomics were used to elucidate QXZKG's regulatory effect on lipid metabolism in lipopolysaccharide-induced ALI. Animal experiments were conducted to substantiate the efficacy of QXZKG in reducing pro-inflammatory cytokines and mitigating pulmonary pathology. Network pharmacology analysis identified 145 active compounds that directly targeted 119 primary targets of QXZKG against ALI. Gene Ontology function analysis emphasized the roles of lipid metabolism and mitogen-activated protein kinase (MAPK) cascade as crucial biological processes. The MAPK1 protein exhibited promising affinities for naringenin, luteolin, and kaempferol. Lipidomic analysis revealed that 12 lipids showed significant restoration following QXZKG treatment (p < 0.05, FC >1.2 or <0.83). Specifically, DG 38:4, DG 40:7, PC O-40:8, TG 18:1_18:3_22:6, PI 18:2_20:4, FA 16:3, FA 20:3, FA 20:4, FA 22:5, and FA 24:5 were downregulated, while Cer 18:0;2O/24:0 and SM 36:1;2O/34:5 were upregulated in the QXZKG versus model groups. This study enhances our understanding of the active compounds and targets of QXZKG, as well as the potential of lipid metabolism in the treatment of ALI.
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Lesão Pulmonar Aguda , Medicamentos de Ervas Chinesas , Metabolismo dos Lipídeos , Lipidômica , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Lipidômica/métodos , Camundongos , Pulmão/efeitos dos fármacos , Pulmão/metabolismoRESUMO
Dexamethasone, a glucocorticoid commonly used in pediatric patients, has potent anti-inflammatory and immunosuppressive properties. However, it is associated with side effects such as reduced lung function and decreased immunity. Pulmonary surfactant lipids are closely linked to lung disease and play a role in reducing surface tension, immune response and antiviral activity. The dysregulation of lipid metabolism is closely associated with lung disease. Hence, untargeted lipidomics may be instrumental in elucidating the effects of dexamethasone on pulmonary surfactant lipids. We obtained surfactant lipid samples from the bronchoalveolar lavage fluid of young mice injected subcutaneously with dexamethasone and conducted a comprehensive lipidomic analysis, comparing them with a control group. We observed a decrease in lipids, such as phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine, and an increase in ceramide, fatty acid, diacylglycerol and monoglyceride, which may impact lung health. This study revealed the influence of dexamethasone on pulmonary surfactant lipids, offering new insights into adverse reactions in clinical settings.
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Líquido da Lavagem Broncoalveolar , Dexametasona , Lipidômica , Lipídeos , Surfactantes Pulmonares , Animais , Lipidômica/métodos , Dexametasona/farmacologia , Surfactantes Pulmonares/análise , Surfactantes Pulmonares/metabolismo , Camundongos , Líquido da Lavagem Broncoalveolar/química , Lipídeos/química , Lipídeos/análise , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos/efeitos dos fármacos , MasculinoRESUMO
Mycoplasma pneumoniae is a significant contributor to lower respiratory infections in children. However, the lipidomics and metabolics bases of childhood M. pneumoniae infections remain unclear. In this study, lipidomics and metabolomics analyses were conducted using UHPLC-LTQ-Orbitrap XL mass spectrometry and gas chromatography-triple quadrupole mass spectrometry on plasma (n = 65) and urine (n = 65) samples. MS-DIAL software, in combination with LipidBlast and Fiehn BinBase DB, identified 163 lipids and 104 metabolites in plasma samples, as well as 208 metabolites in urine samples. Perturbed lipid species (adjusted p < 0.05) were observed, including lysophosphatidylethanolamines, phosphatidylinositols, phosphatidylcholines, phosphatidylethanol amines, and triglycerides. Additionally, differential metabolites (adjusted p < 0.05) exhibited associations with amino acid metabolism, nucleotide metabolism, and energy metabolism. Thirteen plasma metabolites, namely l-hydroxyproline, 3-phosphoglycerate, citric acid, creatine, inosine, ribitol, α tocopherol, cholesterol, cystine, serine, uric acid, tagatose, and glycine, showed significant associations with disease severity (p < 0.05) and exhibited distinct separation patterns in M. pneumoniae-infected bronchitis and pneumonia, with an area under the curve of 0.927. Nine of them exhibited either positive or negative correlations with neutrophil or lymphocyte percentages. These findings indicated significant systemic metabolic shifts in childhood M. pneumoniae infections, offering valuable insights into the associated metabolic alterations and their relationship with disease severity.
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Líquidos Corporais , Pneumonia por Mycoplasma , Humanos , Criança , Lipidômica , Metabolômica , PlasmaRESUMO
Allergic rhinitis (AR) is a prevalent upper airway chronic inflammatory disease in children worldwide. The role of bioactive lipids in the regulation of AR has been recognized, but the underlying serum lipidomic basis of its pathology remains unclear. We utilized ultra-performance liquid chromatography (UPLC)-Q-Exactive Orbitrap/mass spectrometry (MS) to investigate the serum lipidomic profiles of children with AR. The lipidomic analysis identified 42 lipids that were differentially expressed (p < 0.05, fold change > 2) between the AR (n = 75) and normal control groups (n = 44). Specifically, the serum levels of diacylglycerol (DG), triacylglycerol (TG), fatty acid (FA), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine, phosphatidyl-ethanolamine, and cardiolipins were significantly higher in the AR group. The diagnostic potential of the identified lipids was further evaluated using receiver operating characteristic curve analysis. The analysis revealed that five lipids, including FA 30:7, LPC O-18:1, LPC 18:0, LPC 16:0, and DG 34:0, had area under the curve values greater than 0.9 (p < 0.05). Furthermore, serum levels of IgE and IL-33, markers of AR severity, were found to have a significant positive correlation (p < 0.05) with DGs, LPCs, TGs, and FAs in AR patients. This study revealed the lipid disorders associated with AR and its severity, providing new insights into the pathological process of AR.
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Lipidômica , Lipídeos , Rinite Alérgica , Humanos , Criança , Lipidômica/métodos , Masculino , Feminino , Rinite Alérgica/sangue , Lipídeos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Biomarcadores/sangue , Pré-Escolar , Interleucina-33/sangue , Índice de Gravidade de Doença , Imunoglobulina E/sangue , Adolescente , Espectrometria de Massas/métodosRESUMO
Objective: To explore the effectiveness of online-offline teaching combined with SimMan 3G simulation teaching in improving theoretical knowledge and practical skills for critical illnesses in cardiology among undergraduate students. Methods: This randomized controlled trial compared traditional bedside teaching (control group, n=120) with an innovative approach combining online education and SimMan 3G simulation teaching (experimental group, n=120) among 240 undergraduate clinical medicine students. The control group received traditional bedside teaching, while the experimental Group received a combination of online teaching plus a SimMan 3G simulation teaching. Subsequently, the theoretical and clinical practice scores and the students' satisfaction scores about the teaching methods and teaching effects were collected and analyzed. Results: The experimental group demonstrated a statistically significant improvement in both theoretical (89.42±11.28 vs. 76.49±17.42) and clinical practice scores (18.04±4.32 vs. 15.33±3.94) compared to the control group, alongside a higher satisfaction score. Conclusions: The integration of online-offline teaching with SimMan 3G simulation teaching offers a promising model for enhancing cardiology education, suggesting a valuable direction for curriculum development in medical training programs.
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Background: A statin alone or non-statins as add-ons have been introduced to intensive low-density lipoprotein cholesterol (LDL-C) -lowering therapy in patients at risk for high cardiovascular disease (CVD). The purpose of this study was to evaluate the effectiveness and safety of different rosuvastatin-based regimens for patients at high risk. Methods: Three hundred patients at high CVD risk were randomly assigned to the statin group (rosuvastatin, 20 mg/d), statin_EZ group (statin 10 mg/d + ezetimibe 10 mg/d), statin_pcsk group (statin 10 mg/d + alirocumab 75 mg/2 weeks) or combine3 group (statin 10 mg/d + ezetimibe 10 mg/d + alirocumab 75 mg/2 weeks). The primary outcome measure was cholesterol levels after 24 weeks of follow-up. Secondary outcomes included safety markers and the proportion of patients achieving the 70 mg/dL (1.8 mmol/L) target for LDL-C. A logistic regression model was performed to explore the factors affecting lipid target achievement. Results: The total cholesterol (TC) and LDL-C levels in the four groups after treatment were significantly lower than those before treatment. TC and LDL-C levels after treatment were significantly different among the four groups (p < 0.05). The levels in both the combine3 and statin_pcsk9 groups were significantly lower than those in the statin and statin_EZ groups (p < 0.05), but there was no significant difference between the combine3 and statin_pcsk9 groups. Fifty-one participants (69%) in the statin_pcsk9 group and 56 participants (78%) in the combine3 group achieved the target. Body mass index (BMI) and hypertensive status were related to LDL-C target achievement. The incidence of adverse events in the four groups was low. Conclusions: The combination of a statin and a PCSK9 inhibitor was safe and more effective for the treatment of high-risk CVD patients, while the addition of ezetimibe was unable to significantly lower lipid levels any further. The rate of achieving the target was higher in patients with hypertension and a low BMI. Clinical Trial Registration: Chinese Clinical Trial Registry, Identifier: ChiCTR2200058389, Date of Registration: 2022-04-08.
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Liver cancer is a significant global health concern, prompting the search for innovative therapeutic solutions. Yadanziolide A (Y-A), a natural derivative of Brucea javanica, has emerged as a promising candidate for cancer treatment; however, its efficacy and underlying mechanisms in liver cancer remain incompletely understood. In this study, we conducted a comprehensive evaluation of Y-A's effects on liver cancer cells using a range of in vitro assays and an orthotopic liver cancer mouse model. Our findings reveal that Y-A exerts dose-dependent cytotoxic effects on liver cancer cells, significantly inhibiting proliferation, migration, and invasion at concentrations ≥ 0.1 µM. Furthermore, Y-A induces apoptosis, as evidenced by increased apoptotic cell populations and apoptosome formation. In vivo studies confirm that Y-A inhibits tumor growth and reduces liver damage in mouse models. Mechanistically, Y-A targets the TNF-α/STAT3 pathway, inhibiting STAT3 and JAK2 phosphorylation, thereby activating apoptotic pathways and suppressing tumor cell growth. These results suggest that Y-A has promising anticancer activity and potential utility in liver cancer therapy.
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A catalytic asymmetric dearomatization reaction of benzyl 1-naphthyl ethers accelerated by a chiral N,N'-dioxide/Co(II) complex is disclosed. The reaction proceeds via an enantioselective [1,3] O-to-C rearrangement through a tight ion-pair pathway, providing a wide array of α-naphthalenone derivatives bearing an all-carbon quaternary center in high yields with excellent ee values.
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Polygalacturonase inhibitor protein (PGIP) restricts fungal growth and colonization and functions in plant immunity. Gray mold in cucumber is a common fungal disease caused by Botrytis cinerea, and is widespread and difficult to control in cucumber (Cucumis sativus L.) production. In this study, Cucumis sativus polygalacturonase-inhibiting protein 2 (CsPGIP2) was found to be upregulated in response to gray mold in cucumber. CsPGIP2 was detected in the endoplasmic reticulum, cell membrane, and cell wall after transient transformation of protoplasts and tobacco. A possible interaction between Botrytis cinerea polygalacturonase 3 (BcPG3) and CsPGIP2 was supported by protein interaction prediction and BiFC analysis. Transgenic Arabidopsis plants expressing CsPGIP2 were constructed and exhibited smaller areas of gray mold infection compared to wild type (WT) plants after simultaneous inoculation. Evans blue dye (EBD) confirmed greater damage for WT plants, with more intense dyeing than for the transgenic Arabidopsis. Interestingly, compared to WT, transgenic Arabidopsis exhibited higher superoxide dismutase (AtSOD1) expression, antioxidant enzyme activities, lignin content, net photosynthetic rate (Pn), and photochemical activity. Our results suggest that CsPGIP2 stimulates a variety of plant defense mechanisms to enhance transgenic Arabidopsis resistance against gray mold disease.
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Arabidopsis , Botrytis , Cucumis sativus , Resistência à Doença , Doenças das Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas , Cucumis sativus/microbiologia , Cucumis sativus/genética , Cucumis sativus/imunologia , Arabidopsis/genética , Arabidopsis/microbiologia , Arabidopsis/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Botrytis/patogenicidade , Resistência à Doença/genética , Plantas Geneticamente Modificadas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
OBJECTIVE: To determine the oral health status of patients on maintenance hemodialysis (MHD) and to identify the factors influencing their oral health. METHODS: This observational study included 1,186 patients with chronic kidney disease who received MHD across 33 hospitals in China. The patients were recruited for a questionnaire survey between April and August 2023 at Beijing Chaoyang Hospital using stratified sampling. Data collection tools included the General Information Questionnaire for Maintenance Hemodialysis Patients, the Oral Health Assessment Tool, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale. Spearman's rank correlation coefficients were used to assess the relationships between the oral health of patients on MHD and continuous variables such as sleep quality and emotional status. Multiple linear regression analysis was employed to explore the relationship between oral health and various variables. RESULTS: The oral health scores of the patients ranged from 8 to 22, with a mean score of 12.54 ± 2.63. The final model of the multiple linear regression analysis indicated a goodness of fit of 22.19%. Independent factors affecting the oral health of patients included smoking, the proportion of medical expenses, water consumption, sleep quality, and anxiety scores (all P < 0.05). High levels of smoking, substantial medical expenses, poor sleep quality, and elevated anxiety scores were risk factors for poor oral health (all P < 0.05). Adequate daily water intake served as a protective factor for oral health (P < 0.05). CONCLUSION: This study proposes targeted interventions to enhance the management and improvement of oral health in patients on hemodialysis, aiming to provide highly personalised and effective oral health care. These interventions are expected to improve oral health outcomes in future clinical practice.