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Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = -0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = -0.4451) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = -0.3868) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.
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BACKGROUNDS: To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. METHODS: We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25-65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. RESULTS: A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. CONCLUSIONS: In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Persona de Mediana Edad , Masculino , Femenino , China/epidemiología , Adulto , Estudios Transversales , Anciano , Factores de Riesgo , Encuestas y Cuestionarios , Enfermedad AgudaRESUMEN
With an extremely high dimensionality, the spatial degree of freedom of entangled photons is a key tool for quantum foundation and applied quantum techniques. To fully utilize the feature, the essential task is to experimentally characterize the multiphoton spatial wave function including the entangled amplitude and phase information at different evolutionary stages. However, there is no effective method to measure it. Quantum state tomography is costly, and quantum holography requires additional references. Here, we introduce quantum Shack-Hartmann wavefront sensing to perform efficient and reference-free measurement of the biphoton spatial wave function. The joint probability distribution of photon pairs at the back focal plane of a microlens array is measured and used for amplitude extraction and phase reconstruction. In the experiment, we observe that the biphoton amplitude correlation becomes weak while phase correlation shows up during free-space propagation. Our work is a crucial step in quantum physical and adaptive optics and paves the way for characterizing quantum optical fields with high-order correlations or topological patterns.
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Subcutaneous granuloma annulare (SGA) is a rare clinicopathologic subtype of granuloma annulare characterized by the presence of subcutaneous nodules. There are no present reviews synthesizing the clinical features and treatment modalities in SGA. We conducted a systematic review following PRISMA guidelines [CRD42022344672] on all peer-reviewed English-language studies that reported one or more cases of SGA. A total of 97 studies, comprising 26 case series and 71 case reports with 324 patients, were included for analysis. Most cases were predominantly pediatric, with 78.9% of the cases identified being age 16 or lower and a median age of diagnosis of 6. There was no overall gender predisposition. Although over two-thirds of patients did not have any comorbidities, diabetes mellitus was the most common comorbidity present in 4% of cases. The most common feature of SGA was nodules, which were present in 99.6% of patients. Pain or tenderness was reported in 15.4%, and erythema of overlying skin in 11.0% of cases. Surgical excision was performed in 96/141 (68.1%) patients. Among the 27/141 (18.0%) patients who were conservatively managed, 87.0% spontaneously improved, including 60.0% who completely self-resolved. Topical and intralesional steroids were used in 3.40% and 1.85% of patients, respectively, resulting in complete or partial resolution in 54.6% and 100%. Among patients who were followed up, 83/324 (25.6%) patients experienced recurrence after a median duration of 26 weeks. SGA is predominantly a pediatric disease that frequently occurs on the limbs and the head. Juxta-articular lesions are more commonly observed in adults than in children. Surgical excision is common and effective in most patients. Spontaneous improvement occurs in most untreated cases, and intralesional steroids but not topical steroids may be beneficial for non-resolving cases and to reduce time to resolution.
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Background: Integrating immune checkpoint inhibitors with multi-target tyrosine kinase inhibitors presents an innovative and hopeful strategy in liver cancer treatment. Nonetheless, a degree of resistance to this treatment is noticeable in certain patients. Alternative splicing (AS) represents a common biological process that controls the variety of life functions via isoforms. Purpose: Investigating how gene AS affects the effectiveness of combined immunotherapy in treating hepatocellular carcinoma (HCC). Methods: Our retrospective examination focused on AS's effect on immune therapy effectiveness, utilizing accessible tissue sequencing and clinical records for HCC. For corroborating our results, we gathered samples of drug-resistant HCC tissue, nearby tissues, HCC tissue with high drug responsiveness, and healthy liver tissue from clinical studies. Results: The study revealed a link between the frequency of AS occurrences, the expression levels of programmed cell death 1 ligand 1, and the resistance to tumor medications. Our study detailed the AS occurrences in HCC, leading to the creation of a risk-assessment function and a predictive model using AS data. The results of our study revealed that the risk score effectively distinguished between various immune subtypes and the effectiveness of immune therapy. Additional examination of the chosen AS occurrences uncovered their effects on both the immune microenvironment and cellular immunity. Our investigation also delved into the regulatory framework of AS, uncovering the role of stringently controlled splicing factors in the emergence of tumors and the modulation of the body's immune response. Conclusions: Increased AS in HCC diminishes the efficacy of immunotherapy; conversely, more AS in peritumoral tissue elevates the likelihood of tumor immune evasion.
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Empalme Alternativo , Carcinoma Hepatocelular , Inmunoterapia , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/inmunología , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/inmunología , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Biomarcadores de Tumor/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Estudios Retrospectivos , Pronóstico , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Biología Computacional/métodos , Resultado del TratamientoRESUMEN
Two-dimensional (2D) magnetic materials offer a promising platform for nanoscale spintronics and for exploration of novel physical phenomena. Here, we predict a diverse range of magnetic orders in cobalt-based 2D single septuple layers CoX2Y4, namely, CoBi2Te4, CoBi2Se2Te2, CoBi2Se4, and CoSb2Te4. Notably, CoBi2Te4 presents intrinsic non-collinear antiferromagnetism (AFM), while the others display collinear AFM. The emergence of AFM in all CoX2Y4 materials is attributed to the antiferromagnetic 90° Co-Te(Se)-Co superexchange coupling. The origin of non-collinear/collinear orders lies in competing Heisenberg exchange interactions within the Co triangular lattice. A pivotal factor governing the non-collinear order of CoBi2Te4 is the vanishingly small ratio of exchange coupling between next-nearest neighbour Co and the nearest neighbour Co (J2/J1 â¼ 0.01). Furthermore, our investigation into strain effects on CoX2Y4 lattices demonstrates the tunability of the magnetic state of CoSb2Te4 from collinear to non-collinear. Our prediction of the unique non-collinear AFM in 2D suggests the potential for observing extraordinary magnetic phenomena in 2D, including non-collinear scattering and magnetic domain walls.
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A convenient and efficient synthesis of structurally diverse indazolo[1,2-a]indazolones via a Rh(III)-catalyzed [4 + 1] annulation of 1-arylindazolones with alkynyl cyclobutanols has been achieved by combining C-H and C-C bond cleavage. This cascade reaction features readily available starting materials, good functional group tolerance, broad substrate scope, and excellent atom-economy.
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The photoconversion of CO2 into valuable chemical products using solar energy is a promising strategy to address both energy and environmental challenges. However, the strongly adsorbed CO2 frequently impedes the seamless advancement of the subsequent reaction by significantly increasing the reaction activation energy. Here, we present a BiFeO3 material with lattice strain that collaboratively regulates the d/p-2π* orbitals hybridization between metal sites and *CO2 as well as *COOH intermediates to achieve rapid conversion of solidly adsorbed CO2 to critical *COOH intermediates, accelerating the overall CO2 reduction kinetics. Quasi in-situ X-ray photoelectron spectroscopy and in-situ Fourier Transform infrared spectroscopy combined with theoretical calculation reveals that the optimized Fe sites enhance the adsorption and activation effect of CO2, and continuous internal electrons are rapidly transferred to the reaction sites and injected into the surface *CO2 and *COOH under the condition of illumination, which promotes the rapid formation and stability of *COOH. Certainly, the performance of CO2 photoreduction to CO is improved by 12.81-fold compared with the base material. This work offers a new perspective for the rapid photoreduction process of strongly adsorbed CO2.
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Acetyl tripeptide-30 citrulline, a commercialized bio-active peptide, is widely used in anti-wrinkle formulations. Volunteer-based tests have demonstrated that topical application of products containing acetyl tripeptide-30 citrulline significantly reduces the visibility of stretch marks. However, there is still a lack of research dedicated to systematically and holistically evaluating its cosmetic properties and elucidating its mechanisms of action. In this study, we assessed the cosmetic potential of acetyl tripeptide-30 citrulline using human immortalized keratinocytes (HaCaT) and mouse embryonic fibroblasts (3T3). Our findings reveal that acetyl tripeptide-30 citrulline exhibits anti-inflammatory and antioxidant activities in skin cells, particularly effective against the inflammatory markers cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and the extent of inhibition of reactive oxygen species (ROS) production ranged from 95 % to 340 %. Moreover, acetyl tripeptide-30 citrulline specifically up-regulates Collagen IV and down-regulates matrix metalloproteinase-9 (MMP9), enhances the expression of skin barrier proteins transglutaminase 1 (TGM1) and filaggrin (FLG), thereby demonstrating its reparative capabilities. Additionally, acetyl tripeptide-30 citrulline increases the expression of the water channel protein aquaporin 3 (AQP3), thus improving skin hydration function. These results substantiate the previously proclaimed cosmetic attributes of acetyl tripeptide-30 citrulline and support its efficacy as an anti-aging agent in dermatological applications.
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BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.
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Epilepsia , Ferroptosis , Fármacos Neuroprotectores , Troglitazona , Animales , Ratones , Epilepsia/tratamiento farmacológico , Epilepsia/inducido químicamente , Ferroptosis/efectos de los fármacos , Ferroptosis/fisiología , Fármacos Neuroprotectores/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/metabolismo , Ácido Glutámico/metabolismo , Masculino , Ácido Kaínico/toxicidad , Ratones Endogámicos C57BL , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéuticoRESUMEN
As an important class of nitrogen-containing fused heterocyclic compounds, imidazo[1,2-a]pyridines often exhibit significant biological activities, such as analgesic, anticancer, antiosteoporosis, anxiolytic, etc. Using Y(OTf)3 as a Lewis acid catalyst, a simple and efficient method has been developed for the synthesis of C3-alkylated imidazo[1,2-a]pyridines through the three-component aza-Friedel-Crafts reaction of imidazo[1,2-a]pyridines, aldehydes, and amines in the normal air atmosphere without the protection of inert gas and special requirements for anhydrous and anaerobic conditions. A series of imidazo[1,2-a]pyridine derivatives were obtained with moderate to good yields, and their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Furthermore, this conversion has the advantages of simple operation, excellent functional group tolerance, high atomic economy, broad substrate scope, and can achieve gram-level reactions. Notably, this methodology may be conveniently applied to the further design and rapid synthesis of potential biologically active imidazo[1,2-a]pyridines with multifunctional groups.
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OBJECTIVE: The purpose of this study is to compare radiological and clinical outcomes between alternate levels (C4 and C6) and all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. METHODS: Ninety-six patients who underwent C3-6 unilateral open-door laminoplasty with alternate levels mini-plate fixation (54 patients in group A) or all levels mini-plate fixation (42 patients in group B) between September 2014 and September 2019 were reviewed in this study. Radiologic and clinical outcomes were assessed. Clinical results included Visual Analogue Scale (VAS) of axial neck pain and Japanese Orthopedic Association (JOA) score. Radiographic results included cervical range of motion (ROM), cervical curvature index (CCI), and the spinal canal expansive parameters including open angle, anteroposterior diameter (APD), and Pavlov`s ratio. RESULTS: There was no significant difference in VAS, JOA score, ROM, and CCI between two groups. There was no significant difference in canal expansion postoperatively between two groups. However, open angle, APD, and Pavlov`s ratio in group A decreased significantly during the follow-up. In group B, APD, Pavlov`s ratio, and open angle were maintained until the final follow-up. There was no hardware failure or lamina reclosure occurred in both groups during the follow-up. The mean cost of group B was higher than that of group A. CONCLUSIONS: Despite the differences in the maintenance of canal expansion, alternate levels mini-plate fixation can achieve similar clinical outcomes as all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. As evidenced in this study, we believe C3-6 laminoplasty with alternate levels (C4 and C6) mini-plate fixation is an economical, effective, and safe treatment method.
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Placas Óseas , Vértebras Cervicales , Laminoplastia , Humanos , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Laminoplastia/métodos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Masculino , Anciano , Resultado del Tratamiento , Rango del Movimiento Articular , Adulto , Dolor de Cuello/etiología , Dolor de Cuello/cirugíaRESUMEN
The deployment of DNA damage response (DDR) combats various forms of DNA damage, ensuring genomic stability. Cancer cells' propensity for genomic instability offers therapeutic opportunities to selectively kill cancer cells by suppressing the DDR pathway. DNA-dependent protein kinase (DNA-PK), a nuclear serine/threonine kinase, is crucial for the non-homologous end joining (NHEJ) pathway in the repair of DNA double-strand breaks (DSBs). Therefore, targeting DNA-PK is a promising cancer treatment strategy. This review elaborates on the structures of DNA-PK and its related large protein, as well as the development process of DNA-PK inhibitors, and recent advancements in their clinical application. We emphasize our analysis of the development process and structure-activity relationships (SARs) of DNA-PK inhibitors based on different scaffolds. We hope this review will provide practical information for researchers seeking to develop novel DNA-PK inhibitors in the future.
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Proteína Quinasa Activada por ADN , Inhibidores de Proteínas Quinasas , Humanos , Proteína Quinasa Activada por ADN/antagonistas & inhibidores , Proteína Quinasa Activada por ADN/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Relación Estructura-Actividad , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Estructura Molecular , Desarrollo de Medicamentos , AnimalesRESUMEN
This study investigates lightweight and efficient candidates for sound absorption to address the growing demand for sustainable and eco-friendly materials in noise attenuation. Juncus effusus (JE) is a natural fiber known for its unique three-dimensional network, providing a viable and sustainable filler for enhanced sound absorption in honeycomb panels. Microperforated-panel (MPP) honeycomb absorbers incorporating JE fillers were fabricated and designed, focusing on optimizing the absorber designs by varying JE filler densities, geometrical arrangements, and MPP parameters. At optimal filling densities, the MPP-type honeycomb structures filled with JE fibers achieved high noise reduction coefficients (NRC) of 0.5 and 0.7 at 20 mm and 50 mm thicknesses, respectively. Using an analytical model and an artificial neural network (ANN) model, the sound absorption characteristics of these absorbers were successfully predicted. This study demonstrates the potential of JE fibers in improving noise mitigation strategies across different industries, offering more sustainable and efficient solutions for construction and transportation.
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PURPOSE: To study the stability of physicochemical properties and sterilizing effect about two commercially available hypochlorous acid (HClO) products under simulated clinical conditions, and to evaluate the compatibility of HClO on soft and hard tissues and cells in oral cavity. METHODS: Samples of HClO solution with different production processes were prepared, to detect the changes of physicochemical indexes of each sample over time under simulated clinical conditions (shielded from light at 20-25 â, open the cover for 5 minutes every day), including free available chlorine, oxidation-reduction potential and pH. Through suspension quantitative germicidal test, the antibiosis-concentration curve of HClO solution was made, so as to calibrate the change of antibacterial ability of disinfectant with the decrease of available chlorine content during storage. Pulp, tongue and dentine were immersed in PBS, 100 ppm HClO, 200 ppm HClO and 3% NaClO. The influence on soft and hard tissues was evaluated by weighing method and microhardness test. The toxic effects of HClO, NaClO and their 10-fold diluent on human gingival fibroblasts were determined by CCK-8 cytotoxicity assay. GraphPad PRIS 8.0 software was used to analyze the data. RESULTS: Under simulated conditions, the free available chlorine (FAC) of HClO solution decayed with time, and the attenuation degree was less than 20 ppm within 1 month. The bactericidal effect of each HClO sample was still higher than 5log after concentration decay. There was no obvious dissolution and destruction to soft and hard tissues for HClO(Pï¼0.05). The cell viability of HClO to human gingival fibroblast cells (HGFC) was greater than 80%, which was much higher than 3% NaClO (Pï¼0.001). CONCLUSIONS: The bactericidal effect and stability of HClO solution can meet clinical needs, which has low cytotoxicity and good histocompatibility. It is expected to become a safe and efficient disinfection product in the field of living pulp preservation and dental pulp regeneration.
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Fibroblastos , Ácido Hipocloroso , Boca , Ácido Hipocloroso/química , Humanos , Boca/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Encía/citología , Encía/efectos de los fármacos , Irritantes , Desinfectantes/farmacología , Desinfectantes/química , Antibacterianos/farmacología , Antibacterianos/químicaRESUMEN
Organic synthesis methods initiated by visible light have received increasing attention from synthetic chemists. Reactions initiated by EDA complexes do not require the use of toxic or expensive photoredox catalysts, unlike traditional photoreaction processes. However, this kind of reaction requires a particular structure for the substrate, so it is important to study the detailed and systematic reaction mechanism for its design. EDA complexes of substituted 1H-indole and substituted benzyl bromide derivatives were studied by density functional theory (DFT). The difference between EDA complexes with substituents of different kinds and locations were compared by theoretical study and a new EDA complex was predicted.
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OBJECTIVE: This study focuses on dose-response investigation using a codon-optimized and de novo -synthesized E-Selectin/AAV2 (E-Sel/AAV2) vector in preparation for Investigational New Drug (IND)-enabling of subsequent clinical studies. BACKGROUND: Gene therapy is a potential solution for patients suffering from chronic limb-threatening ischemia (CLTI). Understanding the dose for effective gene delivery is crucial for future IND-enabling studies. METHODS: Expression of the codon-optimized E-Selectin gene was assessed by flow cytometry following in vitro cell transfection assay and RT-qPCR for murine limbs injected in vivo with AAV-m-E-Selectin (E-Sel/AAV2). Dose-response studies involved three cohorts of FVB/NJ mice (n=6/group) with escalating log doses of E-Selectin/AAV2 injected intramuscularly (IM) in divided aliquots, ranging from 2×10 9 VG to 2×10 11 VG, into ischemic limbs created by left femoral artery/vein ligation/excision and administration of nitric oxide synthase inhibitor, L-NAME. Limb perfusion, extent of gangrene free limb, functional limb recovery and therapeutic angiogenesis were assessed. RESULTS: Codon-optimized E-Sel/AAV2 gene therapy exhibits superior expression level than WT E-Sel/AAV2 gene therapy both in vitro and in vivo . Mice treated with a high dose (2×10 11 VG) of E-Sel/AAV2 showed significantly improved perfusion indices, lower Faber's scores, increased running stamina and neovascularization compared with lower doses tested with control groups, indicating a distinct dose-dependent response. No toxicity was detected in any of the animal groups studied. CONCLUSION: E-Sel/AAV2 Vascular Regeneration Gene Therapy (VRGT) holds promise for enhancing the recovery of ischemic hindlimb perfusion and function, with the effective dose identified in this study as 2×10 11 VG aliquots injected IM.
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OBJECTIVE: To explore the value of treatment choice and clinical prognosis for Riolan's arch in chronic superior mesenteric artery (SMA) ischaemic disease in vascular surgery. METHODS: The clinical data of 215 patients with SMA ischaemic disease (41 cases with Riolan's arch and 174 cases without) admitted to the Department of Vascular Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University (China) from January 2019 to April 2023 were reviewed. Clinical characteristics, imaging findings, treatment, perioperative complications, and patient follow-up data were analysed to observe the impact of Riolan's arch on the prognosis of patients with SMA ischaemic disease. RESULTS: There were significant differences in body mass index (Riolan's arch group: 22.82 ± 3.28 vs 24.03 ± 4.26 in non-Riolan's arch group, P = 0.049), Takayasu's arteritis (4.9% vs 0, respectively, P = 0.036), and secondary intervention (3.3% vs 1.9%, respectively, P < 0.001) between the two groups. Propensity score matching was used to exclude the effect of baseline data on patient outcomes. There were significant differences related to therapy method (conservative treatment, Riolan's arch group: 24.1% vs 39.7% in the non-Riolan's arch group; operative treatment, Riolan's arch group: 51.7% vs 20.7% in the non-Riolan's arch group, P = 0.014), as well as in-hospital time (9.79 ± 4.20 vs 6.86 ± 4.32, respectively, P = 0.011). There was no statistically significant difference in Kaplan-Meier curves between the two groups (log-rank test P = 0.476). CONCLUSIONS: Riolan's arch plays an important compensatory role in SMA ischaemic disease, especially in chronic disease. We found significant differences in the treatment methods and length of hospital stay of Riolan's arch, which may suggest that Riolan's arch has some reference value in the choice of treatment mode.
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Arteria Mesentérica Superior , Humanos , Masculino , Femenino , Persona de Mediana Edad , Arteria Mesentérica Superior/cirugía , Arteria Mesentérica Superior/diagnóstico por imagen , Pronóstico , Resultado del Tratamiento , Enfermedad Crónica , Isquemia Mesentérica/cirugía , Isquemia Mesentérica/terapia , AncianoRESUMEN
Background: A pivotal determinant for the success of tissue regeneration lies in the establishment of sufficient vasculature. Utilizing autologous tissue grafts from donors offers the dual advantage of mitigating the risk of disease transmission and circumventing the necessity for post-transplant immunosuppression, rendering it an exemplary vascularization strategy. Among the various potential autologous donors, adipose tissue emerges as a particularly auspicious source, being both widely available and compositionally rich. Notably, adipose-derived microvascular fragments (ad-MVFs) are a promising candidate for vascularization. ad-MVFs can be isolated from adipose tissue in a short period of time and show high vascularized capacity. In this study, we extracted ad-MVFs from adipose tissue and utilized their strong angiogenic ability to accelerate bone repair by promoting vascularization. Methods: ad-MVFs were extracted from the rat epididymis using enzymatic hydrolysis. To preserve the integrity of the blood vessels, gelatin methacryloyl (GelMA) hydrogel was chosen as the carrier for ad-MVFs in three-dimensional (3D) culture. The ad-MVFs were cultured directly on the well plates for two-dimensional (2D) culture as a control. The morphology of ad-MVFs was observed under both 2D and 3D cultures, and the release levels of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) were assessed under both culture conditions. In vitro studies investigated the impact of ad-MVFs/GelMA hydrogel on the toxicity, osteoblastic activity, and mineralization of rat bone marrow mesenchymal stem cells (rBMSCs), along with the examination of osteogenic gene and protein expression. In vivo experiments involved implanting the ad-MVFs/GelMA hydrogel into critical-size skull defects in rats, and its osteogenic ability was evaluated through radiographic and histological methods. Results: ad-MVFs were successfully isolated from rat adipose tissue. When cultured under 2D conditions, ad-MVFs exhibited a gradual disintegration and loss of their original vascular morphology. Compared with 2D culture, ad-MVFs can not only maintain the original vascular morphology, but also connect into a network in hydrogel under 3D culture condition. Moreover, the release levels of VEGF and BMP-2 were significantly higher than those in 2D culture. Moreover, the ad-MVFs/GelMA hydrogel exhibited superior osteoinductive activity. After implanting into the skull defect of rats, the ad-MVFs/GelMA hydrogel showed obvious effects for angiogenesis and osteogenesis. The translational potential of this article: The utilization of autologous adipose tissue as a donor presents a more direct route toward clinical translation. Anticipated future clinical applications envision the transformation of discarded adipose tissue into a valuable resource for personalized tissue repair, thereby realizing a paradigm shift in the utilization of this abundant biological material.