RESUMO

The underlying toxicity mechanisms of microplastics on oysters have rarely been explored. To fill this gap, the present study investigated the metabolic profile and protein expression responses of oysters to microplastic stress through metabolomics and biochemical analyses. Oysters were exposed to microplastics for 21 days, and the results indicated that the microplastics induced oxidative stress, with a significant decrease in SOD activity in the 0.1 mg/L exposure group. Metabolomics revealed that exposure to microplastics disturbed many metabolic pathways, such as amino acid metabolism, lipid metabolism, biosynthesis of amino acids, aminoacyl-tRNA biosynthesis, and that different concentrations of microplastics induced diverse metabolomic profiles in oysters. Overall, the current study provides new reference data and insights for assessing food safety and consumer health risks caused by microplastic contamination.

Assuntos

Crassostrea , Microplásticos , Estresse Oxidativo , Poliestirenos , Poluentes Químicos da Água , Animais , Crassostrea/metabolismo , Crassostrea/efeitos dos fármacos , Crassostrea/química , Microplásticos/metabolismo , Poluentes Químicos da Água/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poliestirenos/química , Poliestirenos/metabolismo , Metaboloma/efeitos dos fármacos , Frutos do Mar/análise , Metabolômica , Contaminação de Alimentos/análise

RESUMO

Recently, the increasing incidence of malignant melanoma has become a major public health concern owing to its poor prognosis and impact on quality of life. Consuming foods with potent antitumor compounds can help prevent melanoma and maintain skin health. Fucoxanthin (FX), a naturally occurring carotenoid found in brown algae, possesses antitumor properties. However, its bioavailability, safety risks, and in vivo effects and mechanisms against melanoma remain unclear. This research focused on evaluating the safety and prospective antimelanoma impact of simulated gastrointestinal digestion products (FX-ID) on HaCaT and A375 cells.The results indicate that FX-ID exerts negative effects on mitochondria in A375 cells, increases Bax expression, releases Cytochrome C, and activates cleaved caspase-3, ultimately promoting apoptosis. Additionally, FX-ID influences the mitogen-activated protein kinase (MAPK) pathway by enhancing cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) levels, consequently facilitating apoptosis and inflammation without significantly impacting HaCaT cells. These findings provide insight into inhibitory mechanism of FX-ID against melanoma, guiding the development of functional foods for prevention.

Assuntos

Apoptose , Queratinócitos , Melanoma , Xantofilas , Humanos , Melanoma/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Apoptose/efeitos dos fármacos , Xantofilas/farmacologia , Xantofilas/química , Linhagem Celular Tumoral , NF-kappa B/metabolismo , NF-kappa B/genética , Digestão , Modelos Biológicos , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Antineoplásicos/farmacologia , Antineoplásicos/química , Phaeophyceae/química , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 3/genética

RESUMO

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus. Diabetic corneal neuropathy refers to the progressive damage of corneal nerves. Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature. However, growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit, which includes both the retinal vascular structures and neural tissues. Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening. However, diabetic corneal neuropathy is commonly overlooked and underdiagnosed, leading to severe ocular surface impairment. Several studies have found that these two conditions tend to occur together, and they share similarities in their pathogenesis pathways, being triggered by a status of chronic hyperglycemia. This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy, whether diabetic corneal neuropathy precedes diabetic retinopathy, as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy. We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

RESUMO

Arsenic (As) pollution in soils is a pervasive environmental issue. Biochar immobilization offers a promising solution for addressing soil As contamination. The efficiency of biochar in immobilizing As in soils primarily hinges on the characteristics of both the soil and the biochar. However, the influence of a specific property on As immobilization varies among different studies, and the development and application of arsenic passivation materials based on biochar often rely on empirical knowledge. To enhance immobilization efficiency and reduce labor and time costs, a machine learning (ML) model was employed to predict As immobilization efficiency before biochar application. In this study, we collected a dataset comprising 182 data points on As immobilization efficiency from 17 publications to construct three ML models. The results demonstrated that the random forest (RF) model outperformed gradient boost regression tree and support vector regression models in predictive performance. Relative importance analysis and partial dependence plots based on the RF model were conducted to identify the most crucial factors influencing As immobilization. These findings highlighted the significant roles of biochar application time and biochar pH in As immobilization efficiency in soils. Furthermore, the study revealed that Fe-modified biochar exhibited a substantial improvement in As immobilization. These insights can facilitate targeted biochar property design and optimization of biochar application conditions to enhance As immobilization efficiency.

Assuntos

Arsênio , Carvão Vegetal , Aprendizado de Máquina , Poluentes do Solo , Solo , Carvão Vegetal/química , Arsênio/química , Poluentes do Solo/química , Poluentes do Solo/análise , Solo/química , Modelos Químicos

RESUMO

Introduction: The therapeutic efficacy for airway allergies needs to be improved. Th2 polarization is a primary pathological feature of airway allergies. We constructed chimeric antigen-LgDNA (Lactobacillus rhamnosus DNA) nanoparticles (CAP-NPs). The effects of CAP-NPs on reconciling airway Th2 polarization were tested. Methods: In this study, disulfide bond-linked antigen-major histocompatibility complex II (MHC II)-LgDNA nanoparticles (NPs) were constructed and designated CAP-NPs. An airway Th2 polarization mouse model was established to test the effects of CAP-NPs on suppressing the Th2 response. Results: The CAP-NP components of ovalbumin (OVA), major histocompatibility complex II (MHC II), and LgDNA were confirmed in a series of laboratory tests. The CAP-NPs remained stable at pH7.2 for at least 96 h. In in vitro experiments, CAP-NPs bound to the surface of OVA-specific CD4+ T cells, which resulted in apoptosis of the antigen-specific CD4+ T cells. Removal of any of the three components from the NPs abolished the induction of apoptosis of antigen specific CD4+ T cells. CAP-NPs increased the expression of lysine-specific demethylase 5A (KDM5A) in CD4+ T cells. Histone H3K9 and the gene promoter of caspase 8 were demethylated by KDM5A, which led to transcription and expression of the caspase 8 gene. Administration of CAP-NPs significantly alleviated experimental airway Th2 polarization through activating the caspase 8-apoptosis signaling pathway. Discussion: In this paper, we constructed CAP-NPs that could induce antigen-specific CD4+ T cell apoptosis. Administration of CAP-NPs efficiently alleviated experimental airway Th2 polarization.

Assuntos

Apoptose , Nanopartículas , Ovalbumina , Células Th2 , Animais , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Nanopartículas/química , Camundongos , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Caspase 8/metabolismo , Caspase 8/genética , Feminino , DNA/química , DNA/administração & dosagem , Antígenos/administração & dosagem , Antígenos/química , Linfócitos T CD4-Positivos/efeitos dos fármacos

RESUMO

The prevalence and spread of antibiotic resistance genes (ARGs) have been a significant concern for global public health in recent years. Small rural watersheds are the smallest units of factor mobility for agricultural production in China, and their ARG profiles are the best scale of the contamination status, but the mapping and the distribution and diffusion of ARGs in the water and soil of small rural watersheds are inadequate. In this study, based on microbial metagenomics, we invested prevalence maps of 209 ARGs corresponding to typical commonly used antibiotics (including multidrug, aminoglycoside, macrolide-lincosamide-streptogramin B (MLSB), and ß-Lactamase) in water and soil in different agricultural types, as well as within water-soil interfaces in small rural watersheds in Southwest China. The results revealed that the most abundant ARGs in water and soil were consistent, but different in subtypes, and anthropogenic activities affect the transport of ARGs between water and soils. Livestock wastewater discharges influenced the diversity and abundance of ARGs in water, while in soil it is planting type and fertilizer management, and thus interfered with the co-occurrence patterns between bacteria and ARGs. Co-occurrence analysis revealed that Proteobacteria, Actinobacteria, and Bacteroidetes were the predominant ARG hosts in water and soil, but soil exhibited a more intricate ARG-bacterial association. Overall, this study provides integrated profiles of ARGs in water and soil influenced by anthropogenic activities at the small watershed scale in a typical rural area and provides a baseline for comparisons of ARGs.

RESUMO

In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8+ basaloid cells. IL11 is similarly expressed by KRT8+ alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease. Stimulation of alveolar epithelial cells with IL11 causes epithelial-to-mesenchymal transition and promotes a KRT8-high state, which stalls the beneficial differentiation of alveolar type 2 (AT2)-to-AT1 cells. Inhibition of IL11-signaling in AT2 cells in vivo prevents the accumulation of KRT8+ cells, enhances AT1 cell differentiation and blocks fibrogenesis, which is replicated by anti-IL11 therapy. These data show that IL11 inhibits reparative AT2-to-AT1 differentiation in the damaged lung to limit endogenous alveolar regeneration, resulting in fibrotic lung disease.

Assuntos

Células Epiteliais Alveolares , Diferenciação Celular , Interleucina-11 , Regeneração , Interleucina-11/metabolismo , Interleucina-11/genética , Animais , Regeneração/genética , Humanos , Camundongos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/metabolismo , Transição Epitelial-Mesenquimal/genética , Modelos Animais de Doenças , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Transdução de Sinais , Feminino

RESUMO

Background: Black men who have sex with men (BMSM) face multiple minority stressors (e.g., homophobia, racism, and presumed HIV status) that may indirectly erode their confidence in pursuing HIV testing uptake through exacerbating alcohol use disorder (AUD). Objectives: Using cross-sectional data from 203 community-based BMSM (71.4% as homosexual with a mean age of 26 years) living in a Southern US city, we conducted a causal mediation and moderation analysis to investigate in/direct pathways linking minority stressors, AUD risk, and self-efficacy of HIV testing, including how resilience may moderate these associations. Results: Our mediation analysis revealed that AUD risk accounted for 32.1% of the total effect of internalized homonegativity (ßtotal effect = -0.424; SE=0.071; p<0.001), 28.6% of the total effect of experienced homophobia (ßtotal effect = -0.684; SE=0.122; p<0.001), and 15.3% of the total effect of perceived HIV stigma (ßtotal effect = -0.361; SE=0.164; p<0.05) on HIV testing self-efficacy. Resilience significantly moderated the associations of experienced homophobia (ß = -0.049; SE=0.011; p<0.001), internalized homonegativity (ß = -0.065; SE=0.027; p<0.01), and perceived HIV stigma (ß = -0.034; SE=0.013; p<0.05) with AUD risk. Resilience also significantly moderated the associations of experienced homophobia (ß = -0.073; SE=0.021; p<0.01), internalized homonegativity (ß = -0.082; SE=0.012; p<0.001), perceived HIV stigma (ß = -0.037; SE=0.039; p<0.05), and AUD risk (ß = -0.021; SE=0.015; p<0.05) with HIV testing self-efficacy. Conclusions: Our study provides important implications in identifying multilevel sources for building resilience among BMSM to buffer the effects of minority stress on AUD risk and improve HIV testing outcomes.

RESUMO

BACKGROUND: Improvement is needed in the remedies used to control Th2 polarization. Bioengineering approaches have modified immune cells that have immunosuppressive functions. This study aims to generate modified eosinophils (Meos) in vivo and use Meos to balance Th2 polarization and reduce airway allergy. METHODS: A cell editor was constructed. The editor contained a peptide carrier, an anti-siglec F antibody, MHC II, ovalbumin, and LgDNA (DNA extracted from a probiotic, Lactobacillus rhamnosus GG). Which was designated as Cedit. Meos are eosinophils modified using Cedits. An airway Th2 polarization mouse model was established used to test the effect of Meos on suppressing airway allergy. RESULTS: The Cedits remained physically and chemically stable in solution (pH7.2) for at least 96 h. Cedits specifically bound to eosinophils, which are designated as Meos. Meos produced programmed death ligand-1 (PD-L1); the latter induced antigen specific CD4+ T cell apoptosis. Administration of Cedits through nasal instillations generated Meos in vivo, which significantly reduced the frequency of antigen specific CD4+ T cells in the airways, and mitigated airway Th2 polarization. CONCLUSIONS: We constructed Cedit, which could edit eosinophils into Meos in vivo. Meos could induce antigen specific CD4+ T cell apoptosis, and reconcile airway Th2 polarization.

Assuntos

Eosinófilos , Células Th2 , Animais , Células Th2/imunologia , Eosinófilos/imunologia , Eosinófilos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Antígenos/imunologia , Ovalbumina/imunologia , Hipersensibilidade/imunologia , Feminino , Hipersensibilidade Respiratória/imunologia , Linfócitos T CD4-Positivos/imunologia , Lacticaseibacillus rhamnosus/imunologia

RESUMO

Inflammation is a major impediment to the healing of cartilage injuries, yet bioactive scaffolds suitable for cartilage repair in inflammatory environments are extremely rare. Herein, we utilized electrospinning to fabricate a two-dimensional nanofiber scaffold (2DS), which was then subjected to gas foaming to obtain a three-dimensional scaffold (3DS). 3DS was modified with metal phenolic networks (MPNs) composed of epigallocatechin gallate (EGCG) and strontium ions (Sr2+) to afford a MPNs-modified 3D scaffold (3DS-E). Gas-foamed scaffold exhibited multilayered structure conducive to cellular infiltration and proliferation. Compared to other groups, 3DS-E better preserved chondrocytes under interleukin (IL)-1ß induced inflammatory environment, showing less apoptosis of chondrocytes and higher expression of cartilage matrix. Additionally, 3DS-E facilitated the regeneration of more mature cartilage in vivo, reduced cell apoptosis, and decreased the expression of pro-inflammatory cytokines. Taken together, 3DS-E may offer an ideal candidate for cartilage regeneration.

RESUMO

BACKGROUND: Stapled hemorrhoidopexy (SH) is currently a widely accepted method for treating the prolapse of internal hemorrhoids. Postoperative anal stenosis is a critical complication of SH. A remedy for this involves the removal of the circumferential staples of the anastomosis, followed by the creation of a hand-sewn anastomosis. Numerous studies have reported modified SH procedures to improve outcomes. We hypothesized that our modified SH technique may help reduce complications of anal stenosis after SH. AIM: To compare outcomes of staple removal at the 3- and 9-o'clock positions during modified SH in patients with mixed hemorrhoids. METHODS: This was a single-center, retrospective, observational study. Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1, 2015, and January 1, 2020, were included. The operation time, blood loss, length of hospital stay, and incidence of minor or major complications were recorded. RESULTS: Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1, 2015 and January 1, 2020, were included. Operation time, blood loss, length of hospital stay, and incidence of minor or major complications were recorded. We investigated 187 patients (mean age, 50.9 years) who had undergone our modified SH and 313 patients (mean age, 53.0 years) who had undergone standard SH. In the modified SH group, 54% of patients had previously undergone surgical intervention for hemorrhoids, compared with the 40.3% of patients in the standard SH group. The modified SH group included five (2.7%) patients with anal stenosis, while 21 (6.7%) patients in the standard SH group had complications of anal stenosis. There was a significant relationship between the rate of postoperative anal stenosis and the modified SH: 0.251 (0.085-0.741) and 0.211 (0.069-0.641) in multiple regression analysis. The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH. CONCLUSION: The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH.

RESUMO

BACKGROUND: Colorectal cancer is a common malignancy and various methods have been introduced to decrease the possibility of recurrence. Early recurrence (ER) is related to worse prognosis. To date, few observational studies have reported on the analysis of rectal cancer. Hence, we reported on the timing and risk factors for the ER of resectable rectal cancer at our institute. AIM: To analyze a cohort of patients with local and/or distant recurrence following the radical resection of the primary tumor. METHODS: Data were retrospectively collected from the institutional database from March 2011 to January 2021. Clinicopathological data at diagnosis, perioperative and postoperative data, and first recurrence were collected and analyzed. ER was defined via receiver operating characteristic curve. Prognostic factors were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. RESULTS: We included 131 patients. The optimal cut off value of recurrence-free survival (RFS) to differentiate between ER (n = 55, 41.9%) and late recurrence (LR) (n = 76, 58.1%) was 8 mo. The median post-recurrence survival (PRS) of ER and LR was 1.4 mo and 2.9 mo, respectively (P = 0.008) but PRS was not strongly associated with RFS (R² = 0.04). Risk factors included age ≥ 70 years [hazard ratio (HR) = 1.752, P = 0.047], preoperative concurrent chemoradiotherapy (HR = 3.683, P < 0.001), colostomy creation (HR = 2.221, P = 0.036), and length of stay > 9 d (HR = 0.441, P = 0.006). CONCLUSION: RFS of 8 mo was the optimal cut-off value. Although ER was not associated with PRS, it was still related to prognosis; thus, intense surveillance is recommended.

RESUMO

In this Letter, an all-fiber tunable mode converter for a mini-two-arm Mach-Zehnder interferometer (MTA-MZI) is proposed and realized for the first time to our knowledge. Employing an electric arc discharge technology, we couple a multi-mode fiber (MMF) and a single-mode fiber (SMF), resulting in an MZI characterized by centimeter-scale arms. The varied sensitivity of fiber modes to curvature makes the high-order modes of the MMF more prone to leakage when subjected to bending, leading to alterations in the output interference fringe pattern of the MZI. Through continuous monitoring of the interference fringes of the MZI, we effectively detect the mode properties within the MZI in real time. In addition, a verification experiment is conducted by introducing a peanut structure to excite further higher-order modes of light to enter the MZI in advance. Upon modifying the curvature of the MZI, these excited higher-order modes leak, causing the interference fringe pattern to revert to its initial state without a peanut structure. This experimental validation highlights the potential employment of the MTA-MZI as an all-fiber mode converter and paves the way for optical field mode conversion within an all-fiber framework.

RESUMO

PURPOSE: We evaluated the efficacy and safety of roxadustat, a first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor, for chemotherapy-induced anemia (CIA) in patients with nonmyeloid malignancies receiving multicycle treatments of chemotherapy. PATIENTS AND METHODS: In this open-label, noninferiority phase III study conducted at 44 sites in China, 159 participants age ≥18 years with CIA nonmyeloid malignancy and CIA were randomly assigned (1:1) to oral roxadustat or subcutaneous recombinant human erythropoietin-α (rHuEPO-α) three times a week for 12 weeks. Roxadustat starting dosages were 100, 120, and 150 mg three times a week for participants weighing 40-<50, 50-60, and >60 kg, respectively. rHuEPO-α starting dosage for all participants was 150 IU/kg three times a week. Both roxadustat and rHuEPO-α dosages could be modified. The primary end point was least-squares mean (LSM) change in hemoglobin (Hb) concentration from baseline to the concentration averaged over weeks 9-13. RESULTS: Of the 159 participants randomly assigned, 140 were included in the per-protocol set (roxadustat, n = 78; rHuEPO-α, n = 62). The LSM (95% two-sided CI) change from baseline to weeks 9-13 in Hb concentration was 17.1 (13.58 to 20.71) g/L with roxadustat and 15.4 (11.34 to 19.50) g/L with rHuEPO-α (mean difference [95% CI], 1.7 [-3.39 to 6.84]). The lower bound of the one-sided 97.5% CI for the treatment difference (‒3.4 g/L) was greater than the predefined noninferiority margin of ‒6.6 g/L, establishing noninferiority. Noninferiority was supported by five of six key secondary end points. Rates of adverse events were generally comparable between treatments and consistent with previous findings. CONCLUSION: Roxadustat was noninferior to rHuEPO-α in treating CIA in participants with nonmyeloid malignancies receiving multicycle treatments of myelosuppressive chemotherapy. The oral formulation of roxadustat may potentially increase compliance.

RESUMO

MAT2B works together with MAT2A to synthesize S-Adenosyl methionine (SAM) as the primary methyl donor. MAT2B, despite lacking catalytic activity, exerts regulatory control over the enzymatic activity of MAT2A. In addition to the enzymatic activity regulation, we find that, in an NADP+-dependent manner, MAT2B binds and stabilizes MAT2A. Disruption of the cellular NADP+ remodels the protein level of MAT2A. The pentose phosphatase pathway regulates the level of MAT2A protein through the interaction of NADP+ with MAT2B. Additionally, MAT2B-MAT2A interaction regulates the mRNA m6A modification and stability. In liver tumors, the Mat2a mRNA level is elevated but the protein level is decreased by the restricted NADP+. Blocking the interaction between MAT2B and MAT2A by the keto diet can suppress liver tumor growth. These findings reveal that MAT2B is essential for regulating the protein levels of MAT2A and connecting SAM synthesis to mRNA m6A.

Assuntos

Adenosina , Neoplasias Hepáticas , Metionina Adenosiltransferase , Metionina Adenosiltransferase/metabolismo , Metionina Adenosiltransferase/genética , Humanos , Adenosina/metabolismo , Adenosina/análogos & derivados , Animais , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , NADP/metabolismo , Camundongos , S-Adenosilmetionina/metabolismo , Linhagem Celular Tumoral , Ligação Proteica

RESUMO

BACKGROUND: Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. METHODS: We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. RESULTS: A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband's parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. CONCLUSIONS: WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.

Assuntos

Arritmias Cardíacas , Sequenciamento do Exoma , Predisposição Genética para Doença , Heterozigoto , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Humanos , Masculino , Arritmias Cardíacas/genética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Feminino , China , Análise Mutacional de DNA , Adulto , Povo Asiático/genética , Canais de Cálcio/genética , Pessoa de Meia-Idade , Hereditariedade , Frequência Cardíaca/genética , Potenciais de Ação , População do Leste Asiático

RESUMO

Stage I non-small cell lung cancer (NSCLC) accounts for about 15% of incident cancer cases. Prognosis is poor, with a metastasis and recurrence rate of 38% within 2 years of surgery and an overall 5-year survival rate of 54-60%. Here, we report successful apatinib monotherapy of early NSCLC in a patient who had declined surgery, radiofrequency ablation, and immunotherapy. The patient received apatinib for 64 months without clinical, laboratory, or radiographic evidence of disease progression. The curative effect was judged to be stable and safe.The role of apatinib as monotherapy for patients with early stage NSCLC who are not candidates for surgery or radiotherapy, or as an adjunct to standard therapy, deserves further study.

Assuntos

Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piridinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piridinas/uso terapêutico , Antineoplásicos/uso terapêutico , Masculino , Estadiamento de Neoplasias , Idoso , Pessoa de Meia-Idade

RESUMO

BACKGROUND: Vascular endothelial dysfunction is the initial factor involved in cardiovascular injury in patients with diabetes. Retinoic acid is involved in improving vascular complications in patients with diabetes, but its protective mechanism is still unclear. This study aimed to evaluate the effect and mechanism of All-Trans Retinoic Acid (ATRA) on endothelial dysfunction induced by diabetes. METHODS: In the present study, streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were observed, and the effects of ATRA on HG-induced endothelial dysfunction and ferroptosis were evaluated. RESULTS: ATRA treatment improved impaired vasorelaxation in diabetic aortas in an endothelium-dependent manner, and this effect was accompanied by an increase in the NO concentration and eNOS expression. Ferroptosis, characterized by lipid peroxidation and iron overload induced by HG, was improved by ATRA administration, and a ferroptosis inhibitor (ferrostatin-1, Fer-1) improved endothelial function to a similar extent as ATRA. In addition, the inactivation of phosphoinositol-3-kinase (PI3K)/protein kinases B (AKT) and Yes-Associated Protein (YAP) nuclear localization induced by HG were reversed by ATRA administration. Vascular ring relaxation experiments showed that PI3K/AKT activation and YAP inhibition had similar effects on ferroptosis and endothelial function. However, the vasodilative effect of retinoic acid was affected by PI3K/AKT inhibition, and the inhibitory effects of ATRA on ferroptosis and the improvement of endothelial function were dependent on the retinoic acid receptor. CONCLUSION: ATRA could improve vascular endothelial dysfunction by inhibiting PI3K/AKT/YAP-mediated ferroptosis induced by HG, which provides a new idea for the treatment of vascular lesions in diabetes.

RESUMO

A cerium(III)-containing silicotungstate, [H2N(CH3)2]10NaK[KCe(SiW11O39)2(H2O)]·18.5H2O (CeSiW), was successfully synthesized and characterized. Structure analysis reveals that CeSiW is composed of two {SiW11O39} units connected by one cerium(III) cation to form a typical 1:2 sandwich structure, which is further expanding into a 1D chain linked by K+ ions. The oxygen-enriched surfaces of {SiW11O39} units and open cerium sites provide abundant Lewis base and acid sites in CeSiW. As a result, CeSiW efficiently catalyzed the C3-alkenylation of oxindoles with aldehydes through the simultaneous activation of both reaction substrates on its crystal framework. Various 3-benzylidene-oxindoles are synthesized with excellent yields and high E-selectivity under solvent-free conditions.

RESUMO

In this work, an impedance probe was designed to measure ionospheric low-density plasma. The probe is made of short cylindrical dipoles with an antenna 20 cm in length and 0.25 cm in diameter, which can operate in the frequency range of 0-100 MHz. Combined with a vector network analyzer, the performance of the probe was tested in laboratory-created ionospheric-like plasma, and the results were compared with those of the Langmuir probe measurements. The densities measured by the two methods show a consistent trend, and the impedance probe data show much smaller uncertainties, which suggests that the impedance probe can achieve high-precision measurements. Furthermore, by fitting the antenna phase data, the electron-neutral collision frequency can also be obtained. Therefore, the impedance probe provides a feasible method for exploring low-density partially ionized plasma and can be expanded to actual ionospheric exploration in the future.