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1.
ACS Omega ; 9(17): 19493-19503, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38708253

RESUMO

Hydrogen sulfide (H2S) is a very toxic, acidic, and odorous gas. In this study, a calcined zeolite was used to investigate the adsorption performance of H2S. Among particle size, calcination temperature and time calcination temperature and time had significant effects on the adsorption capacity of H2S on the zeolite. The optimal calcination conditions for the zeolite were 332 °C, 1.8 h, and 10-20 mm size, and the maximum adsorption capacity of H2S was approximately 6219 mg kg-1. Calcination could broaden the channels, remove the adsorbed gases and impurities on the surface of zeolites, and increase the average pore size and point of zero net charge. As the zeolite adsorbed to saturation, it could be regenerated at the temperatures between 200 and 350 °C for 0.5 h. Compared with the natural zeolite, the adsorption capacities of dimethyl disulfide, dimethyl sulfide, toluene, CH3SH, CS2, CO2, and H2S were significantly higher on the calcined zeolite, while the adsorption capacity of CH4 was lower on the calcined zeolite. A gas treatment system by a temperature swing adsorption-regeneration process on honeycomb rotors with calcined zeolites was proposed. These findings are helpful for developing techniques for removing gas pollutants such as volatile sulfur compounds and volatile organic compounds to purify biogas and to limited toxic concentrations in the working environment.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38702170

RESUMO

Objective: To investigate the impact of the restoration of non-bracket invisible orthodontic titanium alloy implant on individuals with dental malocclusion and arch deficiency accompanied by periodontitis and local periodontal Inflammation. Method: A cohort of 120 patients presenting with dental malocclusion and defects compounded by periodontitis, were treated at our institution between January 2021 and January 2022; these patients were enrolled in a randomized controlled trial.. These patients were allocated into two groups. The control group (comprising 60 cases) underwent titanium alloy implant restoration, while the research group (also with 60 cases) received titanium alloy implant restoration following invisible orthodontic treatment without brackets. A one-year post-treatment follow-up was conducted, during which various parameters, including pain levels, aesthetic improvement, inflammatory response, dental function, oral hygiene, and the incidence of adverse events, were evaluated and compared before and after treatment between the two groups. Results: After six months of treatment, the visual analog scale (VAS) in the study group was lower than that in the control group (P < .05). After 6 months of treatment, the research team observed the changes in gingival crevicular interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Interleuckin-1 (IL-1), plaque index (PLI), and soft dirt index (DI) were all lower than those in the control group (P < .05). After 6 months of treatment, the research group had higher scores for tooth functions such as chewing, swallowing, speech expression, and occlusion than the control group, as well as higher pink and white aesthetics indexes (P < .05). The difference in the incidence rate of adverse outcomes between the research and control group was not distinct (P > .05). Conclusion: In case of dental malocclusion accompanied by periodontal disease, the utilization of titanium implants for rectifying dental arch deformities without the use of orthodontic brackets, devoid of orthodontic brackets, has demonstrated notable efficacy in alleviating patients' periodontal discomfort, their oral hygiene, and dental functionality. This modality is conducive to augmenting dental aesthetics without incurring heightened rates of unfavorable consequences, thereby enhancing treatment outcomes.

3.
Transl Cancer Res ; 13(4): 1834-1847, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38737687

RESUMO

Background: Hepatocellular carcinoma (HCC) is a major health problem with more than 850,000 cases per year worldwide. This cancer is now the third leading cause of cancer-related deaths worldwide, and the number is rising. Cancer cells develop anoikis resistance which is a vital step during cancer progression and metastatic colonization. However, there is not much research that specifically addresses the role of anoikis in HCC, especially in terms of prognosis. Methods: This study obtained gene expression data and clinical information from 371 HCC patients through The Cancer Genome Atlas (TCGA) Program and The Gene Expression Omnibus (GEO) databases. A total of 516 anoikis-related genes (ANRGs) were retrieved from GeneCard database and Harmonizome portal. Differential expression analysis identified 219 differentially expressed genes (DEGs), and univariate Cox regression analysis was utilized to select 99 ANRGs associated with the prognosis of HCC patients. A risk scoring model with seven genes was established using the least absolute shrinkage and selection operator (LASSO) regression model, and internal validation of the model was performed. Results: The identified 99 ANRGs are closely associated with the prognosis of HCC patients. The risk scoring model based on seven characteristic genes demonstrates excellent predictive performance, further validated by receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves. The study reveals significant differences in immune cell infiltration, gene expression, and survival status among different risk groups. Conclusions: The prognosis of HCC patients can be predicted using a unique prognostic model built on ANRGs in HCC.

4.
Comput Biol Med ; 175: 108549, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704901

RESUMO

In this paper, we propose a multi-task learning (MTL) network based on the label-level fusion of metadata and hand-crafted features by unsupervised clustering to generate new clustering labels as an optimization goal. We propose a MTL module (MTLM) that incorporates an attention mechanism to enable the model to learn more integrated, variable information. We propose a dynamic strategy to adjust the loss weights of different tasks, and trade off the contributions of multiple branches. Instead of feature-level fusion, we propose label-level fusion and combine the results of our proposed MTLM with the results of the image classification network to achieve better lesion prediction on multiple dermatological datasets. We verify the effectiveness of the proposed model by quantitative and qualitative measures. The MTL network using multi-modal clues and label-level fusion can yield the significant performance improvement for skin lesion classification.


Assuntos
Pele , Humanos , Pele/diagnóstico por imagem , Pele/patologia , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Redes Neurais de Computação , Algoritmos , Dermatopatias/diagnóstico por imagem
5.
Talanta ; 275: 126133, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38669957

RESUMO

Designing a working electrode is crucial for the reliable electrochemistry detection, which is applied to detect toxic and harmful substances sensitively and rapidly. Here we report the polytetrafluoroethylene decomposition-assisted electrospinning, a combination method for creating nanopore and synthesizing CeF3, to prepare the self-supporting electrode of CeF3 nanoparticles-anchored on porous carbon nanofibers (CeF3/PCNFs) for highly sensitive nitrite detection. The CeF3/PCNFs exhibits remarkable electroactivity toward nitrite detection, featuring a wide concentration range (0.5 µM-6 mM), low detection limit (10 nm) and high sensitivity (2093 µA mM-1 cm-2). It also exhibits excellent selectivity, stability and reproducibility, and powerful reliability for nitrite detection in saliva, pickles, sausages, chips, river water and tap water. This study provides a facile strategy to prepare the metal fluoride-based self-supporting electrode, which overcomes the disadvantages of chemically modified electrodes unstable and poorly reproducible, and is significant for clinical diagnosis, food safety and environmental monitoring.

7.
Clin Nutr ; 43(6): 1372-1383, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38678822

RESUMO

BACKGROUND & AIMS: Sepsis-induced disseminated intravascular coagulation (DIC) is characterised by abnormal blood clotting resulting from severe infection, contributing to organ dysfunction in sepsis. Resolvin D1 (RvD1) is an endogenous lipid mediator, synthesised from the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) through enzymatic processes involving 15-LOX and 5-LOX. RvD1 is recognised for its protective properties against various inflammatory conditions. This study aims to investigate its potential to modulate coagulation dysfunction in sepsis and to evaluate coagulation disorders in septic patients. METHODS: Sepsis models were established by intraperitoneal injection LPS (20 mg/kg) or cecal ligation and puncture (CLP) followed by injection of RvD1 (10 µg/kg) or saline. The impact of RvD1 on coagulation dysfunction was assessed by clotting time and coagulation indicators such as TAT, D-dimer, PAI-1, and fibrinogen. The activity of the coagulation system in vivo was observed by evaluating dynamic microcirculation, platelets and thrombin in mice using intravital microscopy. The effect of RvD1 on pyroptosis was investigated by measuring NOD-like receptor protein 3 (NLRP3), Caspase-1, Caspase-11, and Gasdermin D (GSDMD) levels via western blot. Caspase-1 knockout mice, GSDMD knockout mice and bone marrow-derived macrophages (BMDMs) were used to elucidate the underlying mechanisms. Lastly, the concentration of RvD1 in plasma from septic patients was quantified to explore its relationship with coagulation and pyroptosis. RESULTS: RvD1 significantly attenuated coagulation dysfunction in septic mice induced by LPS and CLP, and inhibited Caspase-1/GSDMD-dependent pyroptosis in septic mice and bone marrow-derived macrophages. In septic patients, the plasma concentrations of RvD1 was negatively correlated with both coagulation-related indicators and markers of GSDMD activation. CONCLUSION: The results suggest that RvD1 can improve coagulation dysfunction in sepsis by regulating the Caspase-1/GSDMD pyroptotic pathway. Additionally, the concentration of RvD1 in septic patient plasma is related to prognosis and DIC development. RvD1 could be a potential biomarker and a promising therapeutic alternative in sepsis-induced DIC.

8.
Water Res ; 256: 121624, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38669903

RESUMO

The algal-bacterial wastewater treatment process has been proven to be highly efficient in removing nutrients and recovering nitrogen (N). However, the recovery of the valuable N-rich biopolymer, cyanophycin, remains limited. This research explored the synthesis mechanism and recovery potential of cyanophycin within two algal-bacterial symbiotic reactors. The findings reveal that the synergy between algae and bacteria enhances the removal of N and phosphorus. The crude contents of cyanophycin in the algal-bacterial consortia reached 115 and 124 mg/g of mixed liquor suspended solids (MLSS), respectively, showing an increase of 11.7 %-20.4 % (p < 0.001) compared with conventional activated sludge. Among the 170 metagenome-assembled genomes (MAGs) analyzed, 50 were capable of synthesizing cyanophycin, indicating that cyanophycin producers are common in algal-bacterial systems. The compositions of cyanophycin producers in the two algal-bacterial reactors were affected by different lighting initiation time. The study identified two intracellular synthesis pathways for cyanophycin. Approximately 36 MAGs can synthesize cyanophycin de novo using ammonium and glucose, while the remaining 14 MAGs require exogenous arginine for production. Notably, several MAGs with high abundance are capable of assimilating both nitrate and ammonium into cyanophycin, demonstrating a robust N utilization capability. This research also marks the first identification of potential horizontal gene transfer of the cyanophycin synthase encoding gene (cphA) within the wastewater microbial community. This suggests that the spread of cphA could expand the population of cyanophycin producers. The study offers new insights into recycling the high-value N-rich biopolymer cyanophycin, contributing to the advancement of wastewater resource utilization.


Assuntos
Microalgas , Nitrogênio , Nitrogênio/metabolismo , Microalgas/metabolismo , Bactérias/metabolismo , Reatores Biológicos , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias , Proteínas de Bactérias
9.
BioDrugs ; 38(3): 369-385, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38489061

RESUMO

The remarkable advance in gene editing technology presents unparalleled opportunities for transforming medicine and finding cures for hereditary diseases. Human trials of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9)-based therapeutics have demonstrated promising results in disrupting or deleting target sequences to treat specific diseases. However, the potential of targeted gene insertion approaches, which offer distinct advantages over disruption/deletion methods, remains largely unexplored in human trials due to intricate technical obstacles and safety concerns. This paper reviews the recent advances in preclinical studies demonstrating in vivo targeted gene insertion for therapeutic benefits, targeting somatic solid tissues through systemic delivery. With a specific emphasis on hemophilia as a prominent disease model, we highlight advancements in insertion strategies, including considerations of DNA repair pathways, targeting site selection, and donor design. Furthermore, we discuss the complex challenges and recent breakthroughs that offer valuable insights for progressing towards clinical trials.


Assuntos
Sistemas CRISPR-Cas , Desenvolvimento de Medicamentos , Edição de Genes , Terapia Genética , Hemofilia A , Humanos , Hemofilia A/genética , Hemofilia A/terapia , Edição de Genes/métodos , Desenvolvimento de Medicamentos/métodos , Terapia Genética/métodos , Animais , Mutagênese Insercional
10.
Nat Commun ; 15(1): 2248, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38472227

RESUMO

Reducing the silver film to 10 nm theoretically allows higher transparency but in practice leads to degraded transparency and electrical conductivity because the ultrathin film tends to be discontinuous. Herein, we developed a thinning-back process to address this dilemma, in which silver film is first deposited to a larger thickness with high continuity and then thinned back to a reduced thickness with an ultrasmooth surface, both implemented by a flood ion beam. Contributed by the shallow implantation of silver atoms into the substrate during deposition, the thinness of silver films down to 4.5 nm can be obtained, thinner than ever before. The atomic-level surface smooth permits excellent visible transparency, electrical conductivity, and the lowest haze among all existing transparent conductors. Moreover, the ultrathin silver film exhibits the unique robustness of mechanical flexibility. Therefore, the ion-beam thinning-back process presents a promising solution towards the excellent transparent conductor for flexible optoelectronic devices.

12.
Nat Chem Biol ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553609

RESUMO

Cytosine base editors (CBEs) are effective tools for introducing C-to-T base conversions, but their clinical applications are limited by off-target and bystander effects. Through structure-guided engineering of human APOBEC3A (A3A) deaminase, we developed highly accurate A3A-CBE (haA3A-CBE) variants that efficiently generate C-to-T conversion with a narrow editing window and near-background level of DNA and RNA off-target activity, irrespective of methylation status and sequence context. The engineered deaminase domains are compatible with PAM-relaxed SpCas9-NG variant, enabling accurate correction of pathogenic mutations in homopolymeric cytosine sites through flexible positioning of the single-guide RNAs. Dual adeno-associated virus delivery of one haA3A-CBE variant to a mouse model of tyrosinemia induced up to 58.1% editing in liver tissues with minimal bystander editing, which was further reduced through single dose of lipid nanoparticle-based messenger RNA delivery of haA3A-CBEs. These results highlight the tremendous promise of haA3A-CBEs for precise genome editing to treat human diseases.

13.
Cell Div ; 19(1): 10, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532477

RESUMO

BACKGROUND: Mechanisms and consequences of Gasdermin D (GSDMD) activation in alcoholic hepatitis (AH) are unclear. In the present study, we investigated whether GSDMD induces hepatocyte pyroptosis by regulating mitochondrial dysfunction in AH. RESULTS: Liver damage in AH mice was assessed by HE staining, serum levels of AST, ALT, TC, and TG. The levels of IL-1ß, IL-18, LDH, inflammasome-associated proteins and hepatocyte death were assessed to determine pyroptosis. Mitochondrial dysfunction was assessed through various parameters including mitochondrial DNA (mtDNA) levels, ROS generation, mitochondrial membrane potential, ATP contents, levels of mitochondrial function-related proteins and morphological changes of mitochondria. AH induced gasdermin D (GSDMD) activation, leading to increased protein expression of N-terminal GSDMD (GSDMD-N), NLRP3, and Caspase 11 in liver tissues. Downregulation of GSDMD alleviated alcohol-induced hepatocyte pyroptosis. Alcohol also causes mitochondrial dysfunction in hepatocytes in AH, which was improved by inhibiting GSDMD. Furthermore, enhancing mitochondrial function suppressed alcohol-induced hepatocyte pyroptosis. Further, knockdown of GSDMD or dynamin-related protein 1 (Drp1) improved AH-induced liver injury, accompanied by a decrease in hepatocyte pyroptosis. CONCLUSION: GSDMD induces hepatocyte pyroptosis by modulating mitochondrial dysfunction during AH-induced inflammation and liver injury. These findings may pave the way to develop new therapeutic treatments for AH.

14.
Mar Drugs ; 22(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38535479

RESUMO

Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L-1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L-1), phycoerythrin (102.95 mg L-1), and polysaccharide (1.42 g L-1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum.


Assuntos
Gluconatos , Porphyridium , Ficoeritrina , Gluconato de Cálcio , Polissacarídeos
15.
Eur J Surg Oncol ; 50(4): 108240, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38457858

RESUMO

Minimally invasive surgery on treatment of early-stage cervical cancer is debatable. Traditional approaches of colpotomy are considered responsible for an inferior oncological outcome. Evidence on whether protective colpotomy could optimize minimally invasive technique and improve prognoses of women with early-stage cervical cancer remains limited. We produced a systematic review and meta-analysis to compare oncological outcomes of the patients treated by minimally invasive radical hysterectomy with protective colpotomy to those treated by open surgery according to existing literature. We explored PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to December 2022. Inclusion criteria were: (1) randomized controlled trials or observational studies published in English, (2) studies comparing minimally invasive radical hysterectomy with protective colpotomy to abdominal radical hysterectomy in early-stage cervical cancer, and (3) studies comparing survival outcomes. Two reviewers performed the screening, data extraction, and quality assessment independently. A total of 8 retrospective cohort studies with 2020 women were included in the study, 821 of whom were in the minimally invasive surgery group, and 1199 of whom were in the open surgery group. The recurrence-free survival and overall survival in the minimally invasive surgery group were both similar to that in the open surgery group (pooled hazard ratio, 0.88 and 0.78, respectively; 95% confidence interval, 0.56-1.38 and 0.42-1.44, respectively). Minimally invasive radical hysterectomy with protective colpotomy on treatment of early-stage cervical cancer had similar recurrence-free survival and overall survival compared to abdominal radical hysterectomy. Protective colpotomy could be a guaranteed approach to modifying minimally invasive technique.


Assuntos
Laparoscopia , Neoplasias do Colo do Útero , Humanos , Feminino , Gravidez , Colpotomia , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Histerectomia/métodos , Modelos de Riscos Proporcionais , Laparoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Estadiamento de Neoplasias
16.
Medicine (Baltimore) ; 103(11): e37489, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489739

RESUMO

Gastric cancer (GC) is one of the most common malignant tumors worldwide and the fourth leading cause of cancer-related deaths, with a relatively high incidence among the elderly population. Surgical resection is the mainstay treatment for GC and is currently the only cure. However, the incidence of postoperative intraabdominal infections remains high and seriously affects the prognosis. This study aimed to explore the risk factors for intraabdominal infections after radical gastrectomy in elderly patients and to establish and validate a risk prediction model. We collected the clinical data of 322 GC patients, who underwent radical gastrectomy at the General Surgery Department of China Medical University Dandong Central Hospital from January 2016 to January 2023. The patients were divided into an infected group (n = 27) and a noninfected group (n = 295) according to whether intraabdominal infections occurred postoperatively. A nomogram risk prediction model for the occurrence of postoperative intraabdominal infections was developed. All patients were randomized into a training set (n = 225) and a validation set (n = 97) in a 7:3 ratio, and the model was internally validated. Of the 322 patients, 27 (8.3%) experienced postoperative intraabdominal infections. Single-factor analysis revealed associations of intraabdominal infection with body mass index, glucose, hemoglobin, albumin, and other factors. The multifactorial analysis confirmed that body mass index, glucose, hemoglobin, albumin, surgical duration, and bleeding volume were independent risk factors for intraabdominal infections. The nomogram constructed based on these factors demonstrated excellent performance in both the training and validation sets. A nomogram model was developed and validated to predict the risk of intraabdominal infection after radical gastrectomy. The model has a good predictive performance, which could help clinicians prevent the occurrence of intraabdominal infections after radical gastrectomy in elderly patients.


Assuntos
Infecções Intra-Abdominais , Neoplasias Gástricas , Idoso , Humanos , Albuminas , Gastrectomia/efeitos adversos , Glucose , Hemoglobinas , Infecções Intra-Abdominais/etiologia , Infecções Intra-Abdominais/complicações , Nomogramas , Estudos Retrospectivos , Neoplasias Gástricas/patologia
17.
Biochem Biophys Res Commun ; 709: 149853, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38555838

RESUMO

BACKGROUND: Tibial transverse transport (TTT) can promote the healing of chronic foot ulcers, but the specific cellular and molecular mechanisms by which TTT promotes wound healing remain unclear. METHODS: New Zealand White rabbits were selected to induce foot ulcer models. The treatment included unilateral TTT surgery and bilateral TTT surgery. Observation of tissue neovascularization structure by HE staining and CD31 immunofluorescence detection. Collagen fiber formation was detected through the Masson staining. The mobilization of endothelial progenitor cell (EPCs) were analyzed by VEGFR2 immunofluorescence detection and flow cytometry detection of the number of VEGFR2/Tie-2-positive cells in peripheral blood. ELISA and qPCR assay were performed to detect VEGFA and CXCL12 levels. RESULTS: The complete healing time of ulcer surfaces in sham, unilateral and bilateral TTT groups was about 22 days, 17 days and 13 days, respectively. TTT treatment significantly increased the deposition of granulation tissue and epithelialization of wounds. It also led to an increase in collagen fiber content and the level of the microvascular marker CD31. Furthermore, TTT treatment upregulated the levels of VEGFA and CXCL12 in peripheral blood and wound tissues, as well as increased the expression of VEGFR2 in wound tissues and the proportion of VEGFR2/Tie-2 in peripheral blood. Moreover, these effects of TTT treatment in the bilateral group was more significant than that in the unilateral group. CONCLUSIONS: TTT may facilitate wound fibroblasts to release VEGFA and CXCL12, causing EPC mobilization, thus promoting angiogenesis and ulcer wound healing.


Assuntos
Angiogênese , Células Progenitoras Endoteliais , Úlcera , Cicatrização , Animais , Coelhos , Colágeno
18.
J Med Chem ; 67(6): 5075-5092, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38483150

RESUMO

Aberrantly elevated adenosine in the tumor microenvironment exerts its immunosuppressive functions through adenosine receptors A2AR and A2BR. Antagonism of A2AR and A2BR has the potential to suppress tumor growth. Herein, we report a systemic assessment of the effects of an indole modification at position 4, 5, 6, or 7 on both A2AR/A2BR activity and selectivity of novel 2-aminopyrimidine compounds. Substituting indole at the 4-/5-position produced potent A2AR/A2BR dual antagonism, whereas the 6-position of indole substitution gave highly selective A2BR antagonism. Molecular dynamics simulation showed that the 5-cyano compound 7ai had a lower binding free energy than the 6-cyano compound 7aj due to water-bridged hydrogen bond interactions with E169 or F168 in A2AR. Of note, dual A2AR/A2BR antagonism by compound 7ai can profoundly promote the activation and cytotoxic function of T cells. This work provided a strategy for obtaining novel dual A2AR/A2BR or A2BR antagonists by fine-tuning structural modification.


Assuntos
Pirimidinas , Receptor A2A de Adenosina , Receptor A2B de Adenosina , Receptor A2A de Adenosina/metabolismo , Receptor A2B de Adenosina/metabolismo , Adenosina/metabolismo , Indóis
19.
ACS Appl Mater Interfaces ; 16(11): 13525-13533, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38467516

RESUMO

Flexible electronics have been of great interest in the past few decades for their wide-ranging applications in health monitoring, human-machine interaction, artificial intelligence, and biomedical engineering. Currently, transfer printing is a popular technology for flexible electronics manufacturing. However, typical sacrificial intermediate layer-based transfer printing through chemical reactions results in a series of challenges, such as time consumption and interface incompatibility. In this paper, we have developed a time-saving, wafer-recyclable, eco-friendly, and multiscale transfer printing method by using a stable transferable photoresist. Demonstration of photoresist with various, high-resolution, and multiscale patterns from the donor substrate of silicon wafer to different flexible polymer substrates without any damage is conducted using the as-developed dry transfer printing process. Notably, by utilizing the photoresist patterns as conformal masks and combining them with physical vapor deposition and dry lift-off processes, we have achieved in situ fabrication of metal patterns on flexible substrates. Furthermore, a mechanical experiment has been conducted to demonstrate the mechanism of photoresist transfer printing and dry lift-off processes. Finally, we demonstrated the application of in situ fabricated electrode devices for collecting electromyography and electrocardiogram signals. Compared to commercially available hydrogel electrodes, our electrodes exhibited higher sensitivity, greater stability, and the ability to achieve long-term health monitoring.

20.
Front Oncol ; 14: 1353580, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425337

RESUMO

Introduction: The etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions. Methods: This retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions. Results: Among the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had non-neoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04). Conclusions: Chinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection.

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