RESUMO
Kuwanon C is a unique flavonoid found in the mulberry family, characterized by two isopentenyl groups. While previous research has focused on various properties of kuwanon C, such as antioxidant, hypoglycemic, antimicrobial, food preservation, skin whitening, and nematode lifespan extension, little attention has been given to its potential role in oncological diseases. In this study, we investigate the antitumor effect of kuwanon C in cervical cancer cells and elucidate its specific mechanism of action. We assessed the antitumor effects of kuwanon C using various experimental techniques, including cell proliferation assay, wound healing assays, EdU 488 proliferation assay, mitochondrial membrane potential assay, ROS level assay, cell cycle, apoptosis analysis, and studies on kuwanon C target sites and molecular docking. The results revealed that kuwanon C significantly impacted the cell cycle progression of HeLa cells, disrupted their mitochondrial membrane potential, and induced a substantial increase in intracellular ROS levels. Moreover, kuwanon C exhibited notable anti-proliferative and pro-apoptotic effects on HeLa cells, surpassing the performance of commonly used antitumor drugs such as paclitaxel and cisplatin. Notably, kuwanon C demonstrated superior efficacy while also being more easily accessible compared to paclitaxel. Our study demonstrates that kuwanon C exerts potent antitumor effects by its interaction with the mitochondrial and endoplasmic reticulum membranes, induces a significant production of ROS, disrupts their normal structure, inhibits cell cycle progression, and stimulates apoptotic signaling pathways, ultimately resulting in the death of HeLa tumor cells. As an isopentenyl compound derived from Morus alba, kuwanon C holds great promise as a potential candidate for the development of effective antitumor drugs.
Assuntos
Apoptose , Proliferação de Células , Retículo Endoplasmático , Potencial da Membrana Mitocondrial , Mitocôndrias , Espécies Reativas de Oxigênio , Humanos , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Células HeLa , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Simulação de Acoplamento Molecular , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacosRESUMO
Defect inspection of existing buildings is receiving increasing attention for digitalization transfer in the construction industry. The development of drone technology and artificial intelligence has provided powerful tools for defect inspection of buildings. However, integrating defect inspection information detected from UAV images into semantically rich building information modeling (BIM) is still challenging work due to the low defect detection accuracy and the coordinate difference between UAV images and BIM models. In this paper, a deep learning-based method coupled with transfer learning is used to detect defects accurately; and a texture mapping-based defect parameter extraction method is proposed to achieve the mapping from the image U-V coordinate system to the BIM project coordinate system. The defects are projected onto the surface of the BIM model to enrich a surface defect-extended BIM (SDE-BIM). The proposed method was validated in a defect information modeling experiment involving the No. 36 teaching building of Nantong University. The results demonstrate that the methods are widely applicable to various building inspection tasks.
RESUMO
A rhodium-catalyzed [4 + 2] cycloaddition of ynamines and 2-(cyanomethyl)phenylboronates has been developed, leading to efficient and excellent regioselective synthesis of valuable indole-linked aromatic compounds in a concise and flexible approach. Interestingly, this strategy was successful in the construction of C···N axially chiral indoles with high enantiocontrol by the introduction of a new phosphoramidite ligand (Xie-Phos).
RESUMO
Objective: This study aims to analyze the application effect of IMB (Information-Motivation-Behavioral skills) model rehabilitation nursing, which focuses on enhancing patient knowledge, motivation, and skills for disease management in patients with diabetes and end-stage renal disease receiving maintenance hemodialysis and its impact on the patient's nutritional status. Methods: Eighty-four patients with diabetes and end-stage renal disease undergoing maintenance hemodialysis were selected as study subjects at our hospital. All patients met the inclusion criteria and were divided into two groups based on the nursing interventions received. The control group (n=42) received routine rehabilitation nursing intervention, while the observation group (n=42) received IMB-guided rehabilitation nursing intervention. The effects of nursing intervention, psychological conditions, nutritional status, and quality of life were evaluated using standardized measurement tools. Psychological conditions were assessed using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). Nutritional status was evaluated through measurements of albumin (ALB), body composition analysis (BBC), hemoglobin (Hb), triceps skinfold thickness (TSF), arm circumference (A.C.), and arm muscle circumference (AMC). Quality of life was assessed using the SF-36 Health Survey. Comparative analysis was conducted to examine the differences between the two groups in terms of the aforementioned outcomes. Results: The results of the study revealed compelling data showcasing the effectiveness of the nursing intervention. Notably, after the nursing intervention, ALB (albumin) levels in the observation group increased by 12%, indicating a significant improvement in nutritional status. This increase signifies enhanced protein synthesis and improved overall metabolic functioning among the patients. Additionally, the SF-36 scores, reflecting the quality of life, demonstrated a substantial improvement of 15 points in the observation group following the nursing intervention. This improvement indicates a significant enhancement in various aspects of health-related quality of life, such as physical functioning, mental health, social functioning, and overall well-being. Furthermore, the total nursing effective rate in the observation group was an impressive 97.62%, surpassing the 80.95% rate in the control group. This statistically significant difference (P < .05) emphasizes the superior outcomes achieved through the nursing intervention in the observation group. Moreover, when comparing psychological conditions, the SAS scores in the observation group after the nursing intervention were significantly lower than those in the control group by 8 points (P < .05). Similarly, the SDS scores in the observation group showed a significant decrease of 10 points compared to the control group (P < .05). These findings indicate a substantial reduction in anxiety and depression levels among patients in the observation group. Conclusion: The findings of this study have significant implications for patient care and highlight potential areas for future research. The results suggest that integrating IMB-guided approaches into hemodialysis care protocols could significantly enhance patient well-being. The notable improvements in nutritional status, as indicated by the increase in ALB levels, and the substantial enhancement in quality of life, as reflected by the improvement in SF-36 scores, underscore the effectiveness of the nursing intervention. These findings have important implications for clinical practice, emphasizing the need for broader implementation of IMB-guided approaches in diverse clinical settings. By incorporating these interventions into routine hemodialysis care, healthcare providers can potentially improve patient outcomes and enhance their overall quality of life. Furthermore, these results also highlight potential areas for future research. Additional studies could explore the long-term effects of the nursing intervention on patient health outcomes, sustainability of the improvements observed, and the cost-effectiveness of implementing IMB-guided approaches in hemodialysis settings. Moreover, investigating the feasibility and efficacy of these interventions in different patient populations could further expand our understanding and inform tailored approaches for specific subgroups.
RESUMO
Breast cancer ranks as the most prevalent malignancy, presenting persistent therapeutic challenges encompassing issues such as drug resistance, recurrent occurrences, and metastatic progression. Therefore, there is a need for targeted drugs that are less toxic and more effective against breast cancer. Kuwanon C, an isoamylated flavonoid derived from mulberry resources, has shown promise as a potential candidate due to its strong cytotoxicity against cancer cells. The present study focused on investigating the anticancer activity of kuwanon C in two human breast cancer cell lines, MDA-MB231 and T47D cells. MTS assay results indicated a decrease in cell proliferation with increasing concentrations of kuwanon C. Furthermore, kuwanon C upregulated the expression levels of the cyclin-dependent kinase inhibitor p21 and effectively inhibited cell DNA replication and induced DNA damage. Flow cytometry confirmed that kuwanon C induced cell apoptosis and upregulated the expression levels of pro-apoptotic proteins (Bax and c-caspase3). Additionally, it stimulated the production of reactive oxygen species (ROS) in the cells. Transmission electron microscopy and Fluo-4 AM-calcium ion staining experiments provided insights into the endoplasmic reticulum (ER), revealing that kuwanon C induced ER stress. Kuwanon C upregulated the expression levels of unfolded protein response-related proteins (ATF4, GADD34, HSPA5, and DDIT3). Overall, the present findings suggested that kuwanon C exerts a potent inhibitory effect on breast cancer cell proliferation through modulating of the p21, induction of mitochondrial-mediated apoptosis, activation of ER stress and induction of DNA damage. These results position kuwanon C as a potential targeted therapeutic agent for breast cancer.
Assuntos
Apoptose , Neoplasias da Mama , Proliferação de Células , Chaperona BiP do Retículo Endoplasmático , Humanos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Feminino , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Antineoplásicos/química , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Flavonoides/química , Transdução de Sinais/efeitos dos fármacosRESUMO
Catalytic cross-coupling by transition metals has revolutionized the formation of C-C bonds in organic synthesis. However, the challenge of forming multiple alkyl-alkyl bonds in crowded environments remains largely unresolved. Here, we report the regioselective functionalization of olefins with sp3-hybridized organohalides and organozinc reagents using a simple (terpyridine)iron catalyst. Aliphatic groups of various sizes are successfully installed on either olefinic carbon, furnishing a diverse array of products with congested cores featuring C- or heteroatom-substituted stereocenters. The method enables access to valuable but synthetically challenging C(sp3)-rich molecules, including alicyclic compounds bearing multiple contiguous stereocenters through annulation cascades. Mechanistic and theoretical studies suggest a stepwise iron-mediated radical carbometallation pathway followed by outer-sphere C-C bond formation, which potentially opens the door to a broader scope of transformations and new chemical space.
RESUMO
A mild method for the C-H/S-H coupling of pyrazol-5-amines and thiophenols was developed via electrochemistry, giving diverse amino pyrazole thioether derivatives in 37-98% yields. This electrochemical reaction is sustainable and an atom-efficient approach with good functional group tolerance and scalability by avoiding metal and external chemical oxidants.
RESUMO
We developed an electrochemical approach for benzylic C(sp3)-H imidation by virtue of the in situ generated oxygen-centered radicals (OCRs). The electrochemical imidation provides a complementary approach to giving distinct imide products compared with previous acyloxylation products. This protocol exhibits good site selectivity and broad substrate generality. Moreover, the utility of the OCR-mediated protocol was extended to the electrochemical oxidation of silane, and its robustness was also highlighted by the imidation of complex substrates, which would otherwise be inaccessible for previous approaches. A plausible reaction mechanism was proposed to rationalize the experimental observations.
RESUMO
An electrochemical oxidative cross-coupling strategy for the synthesis of N-sulfenylsulfoximines from sulfoximines and thiols was accomplished, giving diverse N-sulfenylsulfoximines in moderate to good yields. Moreover, this strategy can be extended to construct the N-P bond of N-phosphinylated sulfoximines. With electrons as reagents, the oxidative dehydrogenation cross-coupling reaction proceeds smoothly in the absence of traditional redox reagents.
RESUMO
Nowadays, flexible multifunctional composites are attracting much attention and are practically being used in various emerging electronic devices. However, most composites suffer from the disadvantages of high loadings of conductive fillers, complicated preparation processes, and low energy conversion efficiency. In this article, Caffeic acid-modified multiwalled carbon nanotubes (C-MWCNTs)/poly(3,4-ethylene dioxythiophene):polystyrene sulfonic acid (PEDOT:PSS)/polyimide (PI) composite films (CPFs) were prepared using a simple layer-by-layer deposition method. The "reinforced concrete" structure of the C-MWCNTs/PEDOT:PSS layer ensures high electrical conductivity of the film, while the PI layer provides excellent mechanical properties (72.69 MPa). The composite film exhibits excellent electrothermal response and thermal stability up to approximately 125 °C at 5 V. In addition, the good conductivity of the film provides its electromagnetic shielding effectiveness (32.69 dB). With these advantages, we expect that flexible CPFs will be widely utilized in wearable devices, electromagnetic interference (EMI) shielding applications, and thermal management of personal or electronic devices.
RESUMO
With the popularization of 5G technology and the development of science and technology, flexible and transparent conductive films (TCF) are increasingly used in the preparation of optoelectronic devices such as electromagnetic shielding devices, transparent flexible heaters, and solar cells. Silver nanowires (AgNW) are considered the best material for replacing indium tin oxide to prepare TCFs due to their excellent comprehensive properties. However, the loose overlap between AgNWs is a significant reason for the high resistance. This article investigates a sandwich structured conductive network composed of AgNW and Ti3C2Tx MXene for high-performance EMI shielding and transparent electrical heaters. Polyethylene pyrrolidone (PVP) solution was used to hydrophilic modify PET substrate, and then MXene, AgNW, and MXene were assembled layer by layer using spin coating method to form a TCF with a sandwich structure. One-dimensional AgNW is used to provide electron transfer channels and improve light penetration, while two-dimensional MXene nanosheets are used for welding AgNWs and adding additional conductive channels. The flexible TCF has excellent transmittance (85.1 % at 550 nm) and EMI shielding efficiency (27.1 dB). At the voltage of 5 V, the TCF used as a heater can reach 85.6 °C. This work offers an innovative approach to creating TCFs for the future generation.
RESUMO
This study presents the fabrication of a novel porous composite of graphene oxide-montmorillonite (GO-MMT) through the modification of montmorillonite using the freeze-drying method for the purpose of Pb removal. The characterization of the GO-MMT composite was conducted using scanning electron microscopy, Fourier transform infrared spectrometry, and X-ray diffraction. The results from batch adsorption experiments revealed that the GO-MMT composite exhibited a superior capacity for Pb removal compared to MMT. Furthermore, a single factor experiment confirmed that the dosage of the GO-MMT composite or GO, pH, temperature, and reaction time all significantly influenced the adsorption of Pb by the GO-MMT composite, MMT, or GO. This superiority can be attributed to the presence of oxygen-containing functional groups, the site-blocking effect, and the ion exchange mechanism exhibited by the GO-MMT composite.
Assuntos
Grafite , Poluentes Químicos da Água , Bentonita/química , Chumbo , Adsorção , Grafite/química , Poluentes Químicos da Água/químicaRESUMO
Atherosclerosis (AS) is a pivotal pathological basis of cardiovascular and cerebrovascular diseases, and circular RNAs (circRNAs) has been disclosed to exert a vital part in the progression of AS. However, the functions of circ_0004872 in the progression of AS is indistinct. In this context, we aimed to elucidate the role of circ_0004872 and the potential mechanism in AS. The level of circ_0004872, miR-424-5p and fibroblast growth factor receptor substrate 2 (FRS2) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was monitored by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine (EDU) assays. The invasion and migration capabilities of VSMCs were tested by transwell assays and wound-healing assay, respectively. Western blot was adopted to check the protein levels of CyclinD1, Vimentin and FRS2. Dual-luciferase reporter and RNA immunoprecipitation assay were executed to manifest the interaction between miR-424-5p and circ_0004872 or FRS2. The level of circ_0004872 was increased in the serum samples of AS patients and ox-LDL-exposed VSMCs. Ox-LDL exposure triggered cell proliferation, invasion and migration ability of VSMCs. depletion of circ_0004872 partly weakened ox-LDL-mediated effects in VSMCs. Mechanistically, circ_0004872 functioned as a sponge of miR-424-5p, and miR-424-5p inhibition partly alleviated circ_0004872 deficiency-mediated influences in VSMCs. Additionally, miR-424-5p interacted with FRS2, and miR-424-5p constrained dysfunction in ox-LDL-stimulated VSMCs via reducing FRS2 level. Notably, circ_0004872 functioned as a sponge of miR-424-5p to elevate FRS2 expression. Circ_0004872 accelerated ox-LDL-induced damage via mediating miR-424-5p/FRS2 axis.
RESUMO
Crohn's disease (CD) is caused by immune, environmental, and genetic factors. It can involve the entire gastrointestinal tract, and although its prevalence is rapidly increasing its etiology remains unclear. Emerging biological and small-molecule drugs have advanced the treatment of CD; however, a considerable proportion of patients are non-responsive to all known drugs. To achieve a breakthrough in this field, innovations that could guide the further development of effective therapies are of utmost urgency. In this review, we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases, and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data. The supporting evidence is fully summarized, including the existence of lymphatic system dysfunction, recognition of the inside-out model, disorders of immune cells, changes in cell plasticity, partial overlap of the underlying mechanisms, and common gut-derived fatty and bile acid metabolism. Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases, especially CD, as this model is good at presenting and mimicking lymphatic dysfunction. More importantly, the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.
Assuntos
Doença de Crohn , Vasos Linfáticos , Humanos , Animais , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Peixe-Zebra , Sistema LinfáticoRESUMO
Here, an Ir/Zn-cocatalyzed atroposelective [2+2+2] cycloaddition of 1,6-diynes and ynamines was developed, forging various functionalized CâN axially chiral indoles and pyrroles in generally good to excellent yields (up to 99%), excellent chemoselectivities, and high enantioselectivities (up to 98% enantiomeric excess) with wide substrate scope. This cocatalyzed strategy not only provided an alternative promising and reliable way for asymmetric alkyne [2+2+2] cyclotrimerization in an easy handle but also settled the issues of previous [Rh(COD)2]BF4-catalyzed system on the construction of CâN axial chirality such as complex operations, limited substrate scope, and low efficiency. In addition, control experiments and theoretical calculations disclosed that Zn(OTf)2 markedly reduced the barrier of migration insertion to significantly increase reaction efficiency, which was distinctly different from previous work on the Lewis acid for improving reaction yield through accelerating oxidative addition and reductive elimination.
RESUMO
A simple and efficient method for the ruthenium-catalyzed 1,6-hydroalkylation of para-quinone methides (p-QMs) with ketones via the in situ activation of C(sp3)-H bonds has been disclosed. Without the need for preactivation of the substrates and oxidant, a broad range of p-QMs and ketones are well tolerated, producing the expected 1,6-hydroalkylation products with moderate to good yields. Step-by-step control experiments and DFT calculation were conducted systematically to gain insights for the plausible reaction mechanism. This finding may have potential application in the selective diarylmethylation of ketones at the α-C position in organic synthesis.
RESUMO
The enantioselective transformation of easily accessible 1,2-diketones represents a quick pathway towards enantioenriched molecules. Herein, we disclose a copper-catalyzed atroposelective formal [4+1] annulation of 1,2-diketones with vinyl cations, enabling the efficient and atom-economical construction of axially chiral arylpyrroles bearing 1,3-dioxole moieties with good to excellent enantioselectivities under mild reaction conditions. Importantly, this methodology constitutes the first enantioselective formal [4+1] annulation of 1,2-diketones.
RESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging. CASE SUMMARY: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen. The patient had no history of hepatitis, did not drink alcohol, and had no family history of cancer. Abdominal contrast-enhanced computed tomography (CT) revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm, with blood supplied by the left inferior phrenic artery. The patient underwent laparoscopic surgery, and HCC was identified by postoperative pathology. Additionally, specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC. The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery. Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis. CONCLUSION: This asymptomatic ectopic HCC case described achieved an excellent result due to early detection, radical resection, and systematic surveillance.
RESUMO
One-carbon homologation reactions based on one-carbon insertion into the N-O bond of heterocycles have received tremendous interest over the past decades. However, these protocols have to rely on the use of hazardous and not easily accessible diazo compounds as precursors, and examples of the relevant asymmetric catalysis have not been reported. Here we show that a copper-catalyzed intermolecular formal (5 + 1) annulation of 1,5-diynes with 1,2,5-oxadiazoles involving one-carbon insertion into the heterocyclic N-O bond via non-diazo approach. This method enables practical and atom-economic synthesis of valuable pyrrole-substituted oxadiazines in generally moderate to good yields under mild reaction conditions. In addition, the possibility of such an asymmetric formal (5 + 1) annulation also emerges.