RESUMO
Implant-associated infections and delayed osseointegration are major challenges for the clinical success of titanium implants. To enhance antibacterial effects and promote early osseointegration, we developed a synergistic photothermal (PTT)/photodynamic (PDT) therapy strategy based on near-infrared (NIR) responsive biomimetic micro/nano titanate/TiO2-X heterostructure coatings (KMNW and NaMNS) in situ constructed on the surface of titanium implants. Specifically, KMNW and NaMNS significantly enhanced photothermal conversion capabilities, achieving localized high temperatures of 48-51 °C and promoting substantial amounts of reactive oxygen species production under 808 nm irradiation. In vitro antibacterial experiments demonstrated that KMNW achieved the highest antibacterial rates against Staphylococcus aureus and Escherichia coli, at 98.78 and 98.33% respectively. Moreover, by mimicking the three-dimensional fibrous network of the extracellular matrix during bone healing, both KMNW and NaMNS markedly promoted the proliferation and osteogenic differentiation of osteoblasts. In vivo implantation studies further confirmed these findings, with KMNW and NaMNS exhibiting superior antibacterial performance under NIR irradiationâ94.45% for KMNW and 92.66% for NaMNS. Moreover, KMNW and NaMNS also significantly promoted new bone formation and improved osseointegration in vivo. This study presents a promising PTT/PDT therapeutic strategy for dentistry and orthopedics by employing NIR-responsive biomimetic coatings to combat implant-associated infection and accelerate osseointegration.
RESUMO
BACKGROUND: The modified Xiaoyao San (MXS) formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer, which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival. However, the molecular mechanisms underlying that remain unclear. AIM: To investigate the role and mechanisms of MXS in ameliorating hepatic injury, steatosis and inflammation. METHODS: A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis (NASH) model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes. Liver tissues were collected for western blotting and immunohistochemistry (IHC) assays. Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining. The serum samples were collected for biochemical assays and NMR-based metabonomics analysis. The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH. RESULTS: MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation, inflammation and hepatic fibrosis in the pathogenesis of NASH. The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis. Mechanistically, we found that MXS protected against NASH by attenuating the sex hormone-related metabolism, especially the metabolism of male hormones. CONCLUSION: MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones. Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.
RESUMO
Using bone regeneration scaffolds to repair craniomaxillofacial bone defects is a promising strategy. However, most bone regeneration scaffolds still exist some issues such as a lack of barrier structure, inability to precisely match bone defects, and necessity to incorporate biological components to enhance efficacy. Herein, inspired by a periosteum-bone complex, a class of multifunctional hierarchical porous poly(lactic-co-glycolic acid)/baicalein scaffolds is facilely prepared by the union of personalized negative mold technique and phase separation strategy and demonstrated to precisely fit intricate bone defect cavity. The dense up-surface of the scaffold can prevent soft tissue cell penetration, while the loose bottom-surface can promote protein adsorption, cell adhesion, and cell infiltration. The interior macropores of the scaffold and the loaded baicalein can synergistically promote cell differentiation, angiogenesis, and osteogenesis. These findings can open an appealing avenue for the development of personalized multifunctional hierarchical materials for bone repair.
RESUMO
Introduction: Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Methods: Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. Results: A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), p = 0.009; OR 0.461, 95% CI (0.241-0.883), p = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. Conclusion: In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.
RESUMO
Photocatalytic degradation of organic pollutants in water is of great significance to the sustainable development of the environment, but encounters limited efficiency when a single compound is used. Thus, there have been enormous efforts to find novel photocatalytic heterostructured composites with high performance. In this work, a novel S-scheme heterostructure is constructed with BiOBr and Zn2+ doped C4N3 (Zn-C4N3) by a solvothermal method for efficient photodegradation of tetracycline (TC), a residual antibiotic difficult to be removed from the aquatic environment. Thanks to Zn2+-doping induced improvement in chemical affinity between Zn-C4N3 and BiOBr, well-formed Zn-C4N3/BiOBr heterostructured hollow spheres are formed. This structure can efficiently suppress fast recombination of photogenerated electron-hole pairs to enhance the photocatalytic activity of BiOBr dramatically. At a room temperature of 25 °C and neutral pH 7, the catalyst can degrade a significant portion of TC pollutants within 30 min under visible light. Also, the Zn-C4N3/BiOBr heterostructure displays good stability after recycling experiments. Free radical capture experiments and ESR tests show that ËO2- is the main active substance for photocatalytic degradation of TC. This study provides new insights for constructing heterostructures with an intimate interface between the two phases for photocatalytic applications.
RESUMO
OBJECTIVE: This study aims to develop a predictive model for the detection of gastric cancer risk utilizing non-invasive parameters and to assess the model's effectiveness in risk stratification for gastric cancer (GC). METHODS: A case-control study was conducted among inpatients with various gastric diseases. These individuals were categorized into two groups: the gastric cancer group (138 cases) and the chronic non-atrophic gastritis (CNAG) group (319 cases). We employed a comprehensive panel of hematological, biochemical, and coagulation parameters derived from routine blood tests. Random Forest and Logistic regression analysis was used for feature selection and model building. Statistical analyses were performed using R version 4.2.3. RESULTS: Logistic regression analysis was employed to establish risk prediction models for GC, incorporating variables such as D-dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 724 (CA724), and hemoglobin (HGB). A visual nomogram was generated as the final prediction model. The area under the receiver operating characteristic curve (AUC) for the training and test sets were 0.8093 [95% confidence interval (CI), 0.7541-0.8644], and 0.8076 [95% CI 0.7237-0.8915], respectively. Furthermore, we have developed an HTML file, featuring the Logistic equation, which enables real-time assessment of GC risk scores. CONCLUSION: The performance of this predictive model demonstrates its adequacy, making it a valuable and cost-effective noninvasive tool for identifying early gastric cancer (EGC) in patients. Consequently, this model may facilitate the implementation of targeted preventive and intervention strategies in clinical practice.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/sangue , Neoplasias Gástricas/epidemiologia , Masculino , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Idoso , Testes Sorológicos/métodos , Curva ROC , Fatores de Risco , Antígenos Glicosídicos Associados a Tumores/sangue , Nomogramas , Modelos Logísticos , Adulto , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Medição de Risco/métodosRESUMO
PURPOSE: To construct a venous thromboembolism (VTE) risk assessment model specifically for inpatients with cancer. METHOD: Patients were included according to the inclusion criteria. Univariate and multivariate analyses of all variables were included to develop a VTE risk assessment model applicable to the derivation cohort. Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were used to test the fit degree and identification validity of the model. The patient data from separate validation cohorts verified the external population. RESULT: A total of 944 cancer patients were included in this study. Alfalfa-inpatient-CAT model, a risk assessment model for VTE in hospitalized cancer patients, was established, which mainly includes hypertension, surgical history (nearly one month), history of VTE, peripherally inserted central venous catheters (PICC), chemotherapy, PT < 12.85 s, D-dimer ≥ 1.805 µg/mL, hemoglobin ≤ 114.5 g/L, CRP ≥ 7.575 mg/L. Hosmer-Lemeshow test results showed P = 0.353 > 0.05, (χ2 = 8.872, Df = 8). The area under ROC curve was 0.906 [95%CI (0.881-0.930), P < 0.001]. The authenticity evaluation in the model database showed that the risk of thrombosis in the high-risk group (score ≥ 3) was 72.63%, significantly higher than that in the low-risk group (score 0-2) (27.37%) [χ2 = 144.00, Df = 1, P < 0.001]. CONCLUSION: This study developed a new VTE risk assessment model - Alfalfa-inpatient-CAT model - for hospitalized cancer patients at high risk of thrombosis. This model has a good fitting degree and discriminant validity. It is expected to provide some reference for the clinical treatment of inpatients with cancer through continuous optimization.
Assuntos
Pacientes Internados , Medicago sativa , Neoplasias , Tromboembolia Venosa , Humanos , Neoplasias/complicações , Masculino , Medição de Risco/métodos , Feminino , Pessoa de Meia-Idade , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/diagnóstico , Idoso , Fatores de Risco , Curva ROC , Adulto , Trombose/etiologiaRESUMO
Breast cancer susceptibility 1/2 (BRCA1/2) genes play a crucial role in DNA damage repair, yet mutations in these genes increase the susceptibility to tumorigenesis. Exploiting the synthetic lethality mechanism between BRCA1/2 mutations and poly(ADP-ribose) polymerase (PARP) inhibition has led to the development and clinical approval of PARP inhibitor (PARPi), representing a milestone in targeted therapy for BRCA1/2 mutant tumors. This approach has paved the way for leveraging synthetic lethality in tumor treatment strategies. Despite the initial success of PARPis, resistance to these agents diminishes their efficacy in BRCA1/2-mutant tumors. Investigations into PARPi resistance have identified replication fork stability and homologous recombination repair as key factors sensitive to PARPis. Additionally, studies suggest that replication gaps may also confer sensitivity to PARPis. Moreover, emerging evidence indicates a correlation between PARPi resistance and cisplatin resistance, suggesting a potential overlap in the mechanisms underlying resistance to both agents. Given these findings, it is imperative to explore the interplay between replication gaps and PARPi resistance, particularly in the context of platinum resistance. Understanding the impact of replication gaps on PARPi resistance may offer insights into novel therapeutic strategies to overcome resistance mechanisms and enhance the efficacy of targeted therapies in BRCA1/2-mutant tumors.
Assuntos
Proteína BRCA1 , Proteína BRCA2 , Resistencia a Medicamentos Antineoplásicos , Mutação , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Proteína BRCA2/genética , Proteína BRCA1/genética , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Neoplasias/genética , Neoplasias/tratamento farmacológicoRESUMO
As one of the biomarkers of coagulation system-related diseases, the detection of thrombin is of practical importance. Thus, this study developed a portable biosensor based on a personal glucometer for rapid detection of thrombin activity. Fibrinogen was used for the detection of thrombin, and the assay principle was inspired by the blood coagulation process, where thrombin hydrolyzes fibrinogen to produce a fibrin hydrogel, and the amount of invertase encapsulated in the fibrin hydrogel fluctuates in accordance with the activity of thrombin in the sample solution. The quantitative assay is conducted by measuring the amount of unencapsulated invertase available to hydrolyze the substrate sucrose, and the signal readout is recorded using a personal glucometer. A linear detection range of 0-0.8 U/mL of thrombin with a limit of detection of 0.04 U/mL was obtained based on the personal glucometer sensing platform. The results of the selectivity and interference experiments showed that the developed personal glucometer sensing platform is highly selective and accurate for thrombin activity. Finally, the reliability of the portable glucometer method for rapid thrombin detection in serum samples was investigated by measuring the recovery rate, which ranged from 92.8% to 107.7%. In summary, the fibrin hydrogel sensing platform proposed in this study offers a portable and versatile means for detecting thrombin using a personal glucometer. This approach not only simplifies the detection process, but also eliminates the need for large instruments and skilled operators, and substantially reduces detection costs.
Assuntos
Técnicas Biossensoriais , Coagulação Sanguínea , Fibrina , Hidrogéis , Trombina , Trombina/análise , Humanos , Hidrogéis/química , Automonitorização da GlicemiaRESUMO
Zirconia faces challenges in dental implant applications due to its inherent biological inertness, which compromises osseointegration, a critical factor for the long-term success of implants that rely heavily on specific cell adhesion and enhanced osteogenic activity. Here, we fabricated a dual-functional coating that incorporates strontium ions, aimed at enhancing osteogenic activity, along with an integrin-targeting sequence to improve cell adhesion by mussel byssus-inspired surface chemistry. The results indicated that although the integrin-targeting sequence at the interface solely enhances osteoblast adhesion without directly increasing osteogenic activity, its synergistic interaction with the continuously released strontium ions from the coating, as compared to the release of strontium ions alone, significantly enhances the overall osteogenic effect. More importantly, compared to traditional polydopamine surface chemistry, the coating surface is enriched with amino groups capable of undergoing various chemical reactions and exhibits enhanced stability and aesthetic appeal. Therefore, the synergistic interplay between strontium and the functionally customizable surface offers considerable potential to improve the success of zirconia implantation.
RESUMO
BACKGROUND: Currently published studies have not observed consistent results on the efficacy and safety of direct oral anticoagulants (DOACs) use in patients with chronic kidney disease (CKD) combined with atrial fibrillation (AF). Therefore, this study conducted a meta-analysis of the efficacy and safety of DOACs for patients with AF complicated with CKD. METHODS: Database literature was searched up to May 30, 2023, to include randomized controlled trials (RCT) involving patients with AF complicated with CKD DOACs and vitamin K antagonists (VKAs). Stroke, systemic embolism (SE), and all-cause mortality were used as effectiveness indicators, and major bleeding, intracranial hemorrhage (ICH), fatal bleeding, gastrointestinal bleeding (GIB), and clinically relevant non-major bleeding (CRNMB) were used as safety outcomes. RESULTS: Nine RCT studies were included for analysis according to the inclusion criteria. Results of the efficacy analysis showed that compared with VKAs, DOACs reduced the incidence of stroke/SE (OR = 0.75, 95% CI 0.67-0.84) and all-cause deaths (OR = 0.84, 95% CI 0.75-0.93) in patients with AF who had comorbid CKD. Safety analyses showed that compared with VKAs, DOACs improved safety by reducing the risk of major bleeding (OR = 0.76, 95%CI 0.65-0.90), ICH (OR = 0.46, 95%CI 0.38-0.56), and fatal bleeding (OR = 0.75, 95%CI 0.65-0.87), but did not reduce the incidence of GIB and CRNMB. CONCLUSION: Compared with VKAs, DOACs may increase efficacy and improve safety in AF patients with CKD (90 ml/min> Crcl≥15 ml/min), and shows at least similar efficacy and safety in AF patients with Kidney failure (Crcl<15 ml/min).
RESUMO
Biomacromolecules have attracted interest as spraying additives due to their degradability, renewability, and non-toxicity. However, microscopic mechanism of the biomacromolecules regulating the droplet behavior on fruits and vegetables is still unclear. In this study, konjac glucomannan (KGM) was used to improve the spraying efficiency and the fresh-keeping performance of tea polyphenols solution. KGM increased effective spreading ratio on hydrophilic surfaces and retention ratio of the main droplet on hydrophobic surfaces, thus improving spraying efficiency. Computational fluid dynamics and Brown dynamics simulations were implemented to investigate KGM behaviors during droplets colliding on hydrophilic and hydrophobic surfaces. Most KGM molecules extended and then collapsed in gradually weakened shear flow. Meanwhile, on the hydrophobic surface, most KGM molecules were continuously stretched by the unstable flow field. As the KGM extended, the kinetic energy of droplets converted into elastic energy stored in the KGM, promoting the stability of droplets on target surfaces and improving the spraying efficiency. The KGM molecular weight of 3.8 × 105 Da was optimal from the point of energy storage density. This study provides more understanding of the mechanism of biomacromolecules on spraying efficiency and guidance to develop biomass spraying additives for fruit and vegetable preservation.
Assuntos
Frutas , Verduras , Peso Molecular , Mananas/farmacologia , Mananas/química , Interações Hidrofóbicas e HidrofílicasRESUMO
MOTIVATION: The process of analyzing high throughput sequencing data often requires the identification and extraction of specific target sequences. This could include tasks, such as identifying cellular barcodes and UMIs in single-cell data, and specific genetic variants for genotyping. However, existing tools, which perform these functions are often task-specific, such as only demultiplexing barcodes for a dedicated type of experiment, or are not tolerant to noise in the sequencing data. RESULTS: To overcome these limitations, we developed Flexiplex, a versatile and fast sequence searching and demultiplexing tool for omics data, which is based on the Levenshtein distance and thus allows imperfect matches. We demonstrate Flexiplex's application on three use cases, identifying cell-line-specific sequences in Illumina short-read single-cell data, and discovering and demultiplexing cellular barcodes from noisy long-read single-cell RNA-seq data. We show that Flexiplex achieves an excellent balance of accuracy and computational efficiency compared to leading task-specific tools. AVAILABILITY AND IMPLEMENTATION: Flexiplex is available at https://davidsongroup.github.io/flexiplex/.
Assuntos
Ferramenta de Busca , Software , Análise de Sequência de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Processamento Eletrônico de DadosRESUMO
Food packaging detection devices have attracted attention to optimize storage situations and reduce food spoilage. However, low-cost and highly sensitive multifunctional sensors for detecting both food freshness and packaging pressure are still lacking. In this study, a multifunctional sensor was developed consisting of a MXene coated alcohol-soluble polyurethane fiber network (MXene/APU) and composite biohydrogel films made of konjac glucomannan, chitosan, and blueberry anthocyanin (KCB). Based on the pressure sensitivity of MXene/APU and the color changes of KCB in response to pH values, the sensor can detect internal package bulging, external squeezing, and food deterioration. The pressure sensor shows a sensitivity of 1.16 kPa-1, a response time of 200 ms, a wide strain range of 1092%, and stability over multiple loops. The pressure sensor could detect human motion and identify surface morphologies. The excellent sensor performance was attributed to the porous structure and large specific surface area of microfiber networks, conductivity of MXene nanosheets, and protective effect of KCB films coated on the conductive membrane. Besides, the microfluidic blow-spinning method used to prepare microfiber networks showed the advantages of low energy consumption and high production efficiency. Based on the color changes of blueberry anthocyanin loaded in KCB films in response to pH, the sensor realized sensitive spoilage detection of food containing protein. This study provides a new multifunctional food packaging sensing device and a greater understanding of the optimization and application of related devices.
Assuntos
Antocianinas , Hidrogéis , Nitritos , Elementos de Transição , Humanos , Biomassa , Embalagem de AlimentosRESUMO
Two-dimensional (2D) materials are an excellent platform for surface-enhanced Raman spectroscopy (SERS). For ReS2, the Raman enhancement effect can be highly improved through the dipole-dipole interactions and synergistic resonance effects in the phase-engineering ReS2 films. However, the performance of the substrate can be improved further through regulating the electronic interaction between the ReS2 and probe molecules. Herein, a dynamic coulomb repulsion strategy is proposed to trigger an electronic state redistribution by asymmetric electrostatic interactions. With the phase-engineering ReS2/graphene heterostructure as a prototype, under laser excitation, the generated hot electrons in graphene and ReS2 can repel each other due to Coulomb interaction, which breaks the symmetrical distribution of hot electrons in ReS2, and increases the electronic concentration at the interface between ReS2 and the probe molecule. With R6G as the probe molecule, the asymmetric electron distribution and synergistic resonance effects on their interface improve the limit of detection to 10-12 M with an EF of 2.15 × 108. Meanwhile, the heterostructure also shows good uniformity, stability as well as unique anisotropy. This strategy can be generalized to other 2D heterostructures to obtain the ultrasensitive SERS substrates.
RESUMO
An unprecedented palladium-catalysed fragmentary esterification-induced allylic alkylation (FEAA) of cyclic vinylogous anhydrides (CVAs) and allyl carbonates has been disclosed. The protocol features broad sp3-rich scaffold tolerance, rendering highly functionalized 1,6 and 1,7-dicarbonyls in up to high yields and diastereoselectivities. Three-component FEAA is also well tolerant to generate 1,6-dicarbonyls through the addition of extra O/N-nucleophiles. Furthermore, cyclic allyl carbonate-involved FEAA provides an efficient approach for the synthesis of structurally complex medium-sized rings.
RESUMO
The sophisticated hierarchical structure that precisely combines contradictory mechanical and biological characteristics is ideal for biomaterials, but it is challenging to achieve. Herein, we engineer a spatiotemporally hierarchical guided bone regeneration (GBR) membrane by rational bilayer integration of densely porous N-halamine functionalized bacterial cellulose nanonetwork facing the gingiva and loosely porous chitosan-hydroxyapatite composite micronetwork facing the alveolar bone. Our GBR membrane asymmetrically combine stiffness and flexibility, ingrowth barrier and ingrowth guiding, as well as anti-bacteria and cell-activation. The dense layer has a mechanically matched space maintenance capacity toward gingiva, continuously blocks fibroblasts, and prevents bacterial invasion with multiple mechanisms including release-killing, contact-killing, anti-adhesion, and nanopore-blocking; the loose layer is ultra-soft to conformally cover bone surfaces and defect cavity edges, enables ingrowth of osteogenesis-associated cells, and creates a favorable osteogenic microenvironment. As a result, our all-in-one porous membrane possesses full protective abilities in GBR.
Assuntos
Regeneração Óssea , Membranas Artificiais , Porosidade , Regeneração Óssea/fisiologia , Osteogênese , Materiais Biocompatíveis/químicaRESUMO
The lack of low-cost methods to synthesize large-area graphene-based materials is still an important factor that limits the practical application of graphene devices. Herein, we present a facile method for producing large-area graphene oxide-metal (GO-M) films, which are size controllable and transferable. The sensor constructed using the GO-M film exhibited humidity sensitivity while being unaffected by pressure. The relationship between the sensor's resistance and relative humidity followed an exponential trend. The GO-Mg sensor was the most sensitive among all the tested sensors. The facile synthesis of GO-M films will accelerate the widespread utilization of graphene-based materials.