Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 732
Filtrar
1.
J Drug Target ; : 1-17, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38625591

RESUMEN

Portulacerebroside A (PCA), a cerebroside compound extracted from Portulaca oleracea L., has been shown to suppress hepatocellular carcinoma (HCC) cells. This study aims to investigate the effectiveness of trimethyl chitosan-cysteine (TMC-Cys) nanocarrier in delivering PCA for HCC management and to elucidate the molecular mechanisms behind PCA's function. TMC-Cys nanocarriers notably augmented PCA's function, diminishing the proliferation, migration, and invasiveness of HCC cells in vitro, reducing hepatocellular tumorigenesis in immunocompetent mice, and impeding metastasis of xenograft tumors in nude mice. Comprehensive bioinformatics analyses, incorporating Super-PRED systems alongside pathway enrichment analysis, pinpointed toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR) as two promising targets of PCA, enriched in immune checkpoint pathway. PCA/nanocarrier (PCA) reduced levels of TLR4 and EGFR and their downstream proteins, including programmed cell death ligand 1, thereby increasing populations and activity of T cells co-cultured with HCC cells in vitro or in primary HCC tumors in mice. However, these effects were counteracted by additional artificial activation of TLR4 and EGFR. In conclusion, this study provides novel evidence of PCA's function in immunomodulation in addition to its direct tumor suppressive effect. TMC-Cys nanocarriers significantly enhance PCA efficacy, indicating promising application as a drug delivery system.

2.
Fitoterapia ; : 105965, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38631599

RESUMEN

Four new diterpenoids, including three secolathyrane diterpenoids (1-3) and one lathyrane diterpenoid (4), together with seven known diterpenoids, were obtained in the shelled seeds of Euphorbia lathyris. In particular, 1-3 possess a rare split ring structure, and currently only one compound with the same skeleton has been identified in E. lathyris. Compound 4 furnishes an unprecedented oxygen bridge structure. The structures were identified using various spectral techniques, including NMR, HR-ESI-MS, single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD). The biosynthetic pathway of 1-4 was inferred. Furthermore, the cytotoxic activities of all compounds (1-11) were measured on three human tumor cells. New compounds 2 and 3 showed moderate cytotoxic activities against U937 cells with IC50 values of 22.18 and 25.41 µM, respectively.

3.
Biomacromolecules ; 25(4): 2438-2448, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38502912

RESUMEN

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.


Asunto(s)
Quitosano , Hidrogeles , Hidrogeles/farmacología , Cicatrización de Heridas , Antibacterianos/farmacología , Ciprofloxacina , Vendajes
4.
J Mater Chem B ; 12(14): 3417-3435, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38525920

RESUMEN

Due to the increasing aging population and the advancements in transcatheter aortic valve replacement (TAVR), the use of bioprosthetic heart valves (BHVs) in patients diagnosed with valvular disease has increased substantially. Commercially available glutaraldehyde (GA) cross-linked biological valves suffer from reduced durability due to a combination of factors, including the high cell toxicity of GA, subacute thrombus, inflammation and calcification. In this study, oxidized chondroitin sulfate (OCS), a natural polysaccharide derivative, was used to replace GA to cross-link decellularized bovine pericardium (DBP), carrying out the first crosslinking of DBP to obtain OCS-BP. Subsequently, the zwitterion radical copolymerization system was introduced in situ to perform double cross-linking to obtain double crosslinked BHVs with biomimetic modification (P(APM/MPC)-OCS-BP). P(APM/MPC)-OCS-BP presented enhanced mechanical properties, collagen stability and enzymatic degradation resistance due to double crosslinking. The ex vivo AV-shunt assay and coagulation factors test suggested that P(APM/MPC)-OCS-BP exhibited excellent anticoagulant and antithrombotic properties due to the introduction of P(APM/MPC). P(APM/MPC)-OCS-BP also showed good HUVEC-cytocompatibility due to the substantial reduction of its residual aldehyde group. The subcutaneous implantation also demonstrated that P(APM/MPC)-OCS-BP showed a weak inflammatory response due to the anti-inflammatory effect of OCS. Finally, in vivo and in vitro results revealed that P(APM/MPC)-OCS-BP exhibited an excellent anti-calcification property. In a word, this simple cooperative crosslinking strategy provides a novel solution to obtain BHVs with good mechanical properties, and HUVEC-cytocompatibility, anti-coagulation, anti-inflammatory and anti-calcification properties. It might be a promising alternative to GA-fixed BP and exhibited good prospects in clinical applications.


Asunto(s)
Calcinosis , Prótesis Valvulares Cardíacas , Humanos , Animales , Bovinos , Anciano , Sulfatos de Condroitina/farmacología , Reactivos de Enlaces Cruzados/farmacología , Válvulas Cardíacas , Glutaral , Antiinflamatorios/farmacología , Pericardio
5.
Genome Biol ; 25(1): 54, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388963

RESUMEN

BACKGROUND: RNA secondary structure (RSS) can influence the regulation of transcription, RNA processing, and protein synthesis, among other processes. 3' untranslated regions (3' UTRs) of mRNA also hold the key for many aspects of gene regulation. However, there are often contradictory results regarding the roles of RSS in 3' UTRs in gene expression in different organisms and/or contexts. RESULTS: Here, we incidentally observe that the primary substrate of miR159a (pri-miR159a), when embedded in a 3' UTR, could promote mRNA accumulation. The enhanced expression is attributed to the earlier polyadenylation of the transcript within the hybrid pri-miR159a-3' UTR and, resultantly, a poorly structured 3' UTR. RNA decay assays indicate that poorly structured 3' UTRs could promote mRNA stability, whereas highly structured 3' UTRs destabilize mRNA in vivo. Genome-wide DMS-MaPseq also reveals the prevailing inverse relationship between 3' UTRs' RSS and transcript accumulation in the transcriptomes of Arabidopsis, rice, and even human. Mechanistically, transcripts with highly structured 3' UTRs are preferentially degraded by 3'-5' exoribonuclease SOV and 5'-3' exoribonuclease XRN4, leading to decreased expression in Arabidopsis. Finally, we engineer different structured 3' UTRs to an endogenous FT gene and alter the FT-regulated flowering time in Arabidopsis. CONCLUSIONS: We conclude that highly structured 3' UTRs typically cause reduced accumulation of the harbored transcripts in Arabidopsis. This pattern extends to rice and even mammals. Furthermore, our study provides a new strategy of engineering the 3' UTRs' RSS to modify plant traits in agricultural production and mRNA stability in biotechnology.


Asunto(s)
Arabidopsis , Exorribonucleasas , Animales , Humanos , Regiones no Traducidas 3' , ARN Mensajero/genética , ARN Mensajero/metabolismo , Exorribonucleasas/genética , Exorribonucleasas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Regulación de la Expresión Génica , Mamíferos/genética
6.
Waste Manag ; 178: 46-56, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38377768

RESUMEN

In a global context, the production of urban solid waste significantly varies with changes in living standards. This trend exhibits diversity across different countries and regions, reflecting shifts in lifestyles as well as varying needs and challenges in waste management strategies. However, current standards of waste recycling are too complex for the general public to follow. In this study, we propose a model called DSYOLO-Trash to identify solid waste by integrating the dual attention mechanisms convolutional block attention module (CBAM) and Contextual Transformer Networks(CotNet), which significantly enhance its ability to mine channel-related and spatial attention features while optimizing the learning process. We apply the deep simple online and realtime tracking (DeepSORT) object tracking algorithm to solid waste detection for the first time in the literature to enable the real-time identification and tracking of waste. We also develop a multi-label dataset of mixed solid waste, called MMTrash, to realistically simulate actual scenarios of waste classification. Our proposed DSYOLO-Trash delivered superior performance to classical detection algorithms on both the MMTrash and the TrashNet datasets. Our system combines the improved you only look once(YOLO) algorithm with DeepSORT technology by using industrial cameras and PLC-controlled robotic arms to intelligently sort waste. The work here constitutes an important contribution to intelligent waste management and the sustainable development of cities.


Asunto(s)
Residuos de Alimentos , Residuos Sólidos , Algoritmos , Ciudades , Suministros de Energía Eléctrica
7.
Psychiatry Res Neuroimaging ; 339: 111787, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38295529

RESUMEN

BACKGROUND: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy for major depressive disorder (MDD) that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. However, there are few neuroimaging studies involving the TECAS for the treatment of MDD. Therefore, this study aimed to investigate the treatment response and neurological effects of TECAS using resting-state functional magnetic resonance imaging (rs-fMRI). METHOD: A total of 34 patients with mild-to-moderate MDD and 34 demographically matched healthy controls (HCs) were recruited. After an eight-week treatment the primary outcome was clinical response, defined as a baseline-to-endpoint ≥ 50 % reduction in the 17-item Hamilton Depression Rating Scale (HAMD-17). The low-frequency fluctuations (ALFF) method were used to investigate the brain abnormalities of MDD patients and HCs, and altered brain networks were analyzed between pre- and post-treatment using seed-based functional connectivity (FC) analysis. RESULTS: We found no significant differences in terms of gender, age, and years of education between the two groups. After treatment, the response rate was 58.82 %. Compared to HCs, MDD patients showed lower ALFF values in the left insula(t = -4.298,P < 0.005), the insula-based FC revealed in the right middle frontal gyrus (MFG)/ right superior frontal gyrus, orbital part (ORBsupmed) (t = -5.29,P < 0.005) and the right anterior cingulate gyrus (ACC)were decreased (t = -6.08,P < 0.005). Furthermore, Compared to pre-treatment, abnormal FC values in the ACC /orbital superior frontal gyrus (SFG) (t = 3.42,P < 0.005) and left superior frontal gyrus (SFG)/ supplement motor area (SMA) were enhanced (t = 3.34,P < 0.005). CONCLUSION: TECAS exhibits antidepressant efficacy, particularly influencing the insula-based functional connections within the Default Mode Network (DMN) related to emotion processing in individuals with MDD.


Asunto(s)
Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Puntos de Acupuntura , Red en Modo Predeterminado , Encéfalo/diagnóstico por imagen , Antidepresivos
8.
Anal Chem ; 96(5): 1852-1860, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38279192

RESUMEN

The self-powered electrochemical sensor (SPES), an analytical sensing device without external power supply, is integrated with the dual function of power supply and detection performance, which lay the foundation for the development of intelligent and portable electrochemical sensing devices. Herein, a novel SPES based on a zinc-air battery was constructed for the detection of hydrogen sulfide (H2S) in the lysate of colon cancer cells. Typically, an Fe/Fe3C@graphene foam with oxygen reduction performance was used to construct SPES based on a zinc-air battery (ZAB-SPES), which brings the open-circuit voltage to 1.30 V. Among them, the poisoning effect of H2S causes the catalytic performance of the oxygen reduction catalyst to decrease, causing a significant decrease in the discharge voltage of ZAB. Based on this principle, ZAB-SPES was constructed for the detection of H2S using a digital multimeter. The proposed ZAB-SPES demonstrated good selectivity and reproducibility for detecting H2S compared to the results of the H2S-specific fluorescence probe. This strategy enriches the idea of constructing a self-powered sensor and a digital multimeter as detection devices, providing technical support for the portability of SPESs.

9.
Nat Commun ; 15(1): 661, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38253617

RESUMEN

Understanding the nature and extent of non-canonical human leukocyte antigen (HLA) presentation in tumour cells is a priority for target antigen discovery for the development of next generation immunotherapies in cancer. We here employ a de novo mass spectrometric sequencing approach with a refined, MHC-centric analysis strategy to detect non-canonical MHC-associated peptides specific to cancer without any prior knowledge of the target sequence from genomic or RNA sequencing data. Our strategy integrates MHC binding rank, Average local confidence scores, and peptide Retention time prediction for improved de novo candidate Selection; culminating in the machine learning model MARS. We benchmark our model on a large synthetic peptide library dataset and reanalysis of a published dataset of high-quality non-canonical MHC-associated peptide identifications in human cancer. We achieve almost 2-fold improvement for high quality spectral assignments in comparison to de novo sequencing alone with an estimated accuracy of above 85.7% when integrated with a stepwise peptide sequence mapping strategy. Finally, we utilize MARS to detect and validate lncRNA-derived peptides in human cervical tumour resections, demonstrating its suitability to discover novel, immunogenic, non-canonical peptide sequences in primary tumour tissue.


Asunto(s)
Péptidos , Neoplasias del Cuello Uterino , Humanos , Femenino , Péptidos/genética , Neoplasias del Cuello Uterino/genética , Secuencia de Aminoácidos , Biblioteca de Péptidos , Benchmarking
10.
World J Gastroenterol ; 30(1): 34-49, 2024 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-38293325

RESUMEN

Crohn's disease (CD) is caused by immune, environmental, and genetic factors. It can involve the entire gastrointestinal tract, and although its prevalence is rapidly increasing its etiology remains unclear. Emerging biological and small-molecule drugs have advanced the treatment of CD; however, a considerable proportion of patients are non-responsive to all known drugs. To achieve a breakthrough in this field, innovations that could guide the further development of effective therapies are of utmost urgency. In this review, we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases, and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data. The supporting evidence is fully summarized, including the existence of lymphatic system dysfunction, recognition of the inside-out model, disorders of immune cells, changes in cell plasticity, partial overlap of the underlying mechanisms, and common gut-derived fatty and bile acid metabolism. Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases, especially CD, as this model is good at presenting and mimicking lymphatic dysfunction. More importantly, the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.


Asunto(s)
Enfermedad de Crohn , Vasos Linfáticos , Humanos , Animales , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Pez Cebra , Sistema Linfático
11.
Cancer Rep (Hoboken) ; 7(2): e1918, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38073600

RESUMEN

OBJECTIVES: To analyze the clinical characteristics and influencing factors of hepatotoxicity in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death protein-1 (PD-1) inhibitors, and to provide a theoretical basis for the treatment of immune-related hepatotoxicity in patients with advanced HCC. METHODS: Retrospective analysis of clinical data of patients with advanced HCC from February 2021 to February 2023, in order to summarize and statistically analyze the influencing factors of immune-related liver adverse reactions. RESULTS: A total of 135 patients met the inclusion criteria, among whom 46 patients experienced varying degrees of immune-related liver adverse reactions, with an incidence rate of 34.1% (46/135). The time range of immune-related liver adverse reactions was 3-26 weeks, with a median time of 4 weeks. The age range of immune-related liver adverse reactions was 34-73 years, with a median age of 62 years. Statistical analysis of the influencing factors and liver adverse reactions showed that age, total bilirubin level, and Child-Pugh (C-P) grading were influencing factors for the occurrence of liver adverse reactions (p < .05), and among these three influencing factors, the proportion of males with ≥2 influencing factors was higher than that of females; liver function C-P B was an independent influencing factor for liver adverse reactions (p < .05). CONCLUSION: For male patients over 60 years old, with bilirubin levels ≥51 µmol/L and liver function C-P B, close observation of the occurrence of immune-related adverse reactions during treatment is recommended.


Asunto(s)
Carcinoma Hepatocelular , Enfermedad Hepática Inducida por Sustancias y Drogas , Neoplasias Hepáticas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto , Anciano , Neoplasias Hepáticas/tratamiento farmacológico , Carcinoma Hepatocelular/tratamiento farmacológico , Estudios Retrospectivos , Inmunoterapia/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Bilirrubina/uso terapéutico
12.
Nano Lett ; 24(2): 607-616, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38095305

RESUMEN

In recent years, live-cell-based drug delivery systems have gained considerable attention. However, shear stress, which accompanies blood flow, may cause cell death and weaken the delivery performance. In this study, we found that reducing cholesterol in macrophage plasma membranes enhanced their tumor targeting ability by more than 2-fold. Our study demonstrates that the reduced cholesterol level deactivated the mammalian target of rapamycin (mTOR) and consequently promoted the nuclear translocation of transcription factor EB (TFEB), which in turn enhanced the expression of superoxide dismutase (SOD) to reduce reactive oxygen species (ROS) induced by shear stress. A proof-of-concept system using low cholesterol macrophages attached to MXene (e.g., l-RX) was fabricated. In a melanoma mouse model, l-RX and laser irradiation treatments eliminated tumors with no recurrences observed in mice. Therefore, cholesterol reduction is a simple and effective way to enhance the targeting performance of macrophage-based drug delivery systems.


Asunto(s)
Macrófagos , Superóxido Dismutasa , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Macrófagos/metabolismo , Sistemas de Liberación de Medicamentos , Colesterol/metabolismo , Mamíferos/metabolismo
13.
ACS Appl Mater Interfaces ; 16(1): 201-216, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38127723

RESUMEN

Conventional strontium-doped calcium polyphosphate (SCPP) ceramics have attracted a lot of attention due to good cytocompatibility and controlled degradation. However, their poor mechanical strength, brittleness, and difficulty in eliminating unavoidable postoperative inflammation and bacterial infections in practical applications limit their further clinical application. In this study, carboxylated molybdenum disulfide nanospheres (MoS2-COOH) were first prepared via a one-step hydrothermal method. The optimal doping concentration of MoS2-COOH was then incorporated into SCPP to overcome its poor mechanical strength. To further enhance the anti-inflammatory properties of scaffolds, metformin (MET) was loaded onto MoS2-COOH through covalent bond cross-linking (MoS2-MET). Then MoS2-MET was doped into SCPP (SCPP/MoS2-MET) according to the previously obtained concentration, resulting in the controlled and sustained release of MET from the SCPP/MoS2-MET scaffolds for 21 days in vitro. The SCPP/MoS2-MET scaffolds were shown to have good biological activity in vitro to promote stem cell proliferation and the potential to promote mineralization in vitro. It also showed good osteoimmunomodulatory activity could reduce the expression of proinflammatory factors and effectively induce the differentiation of BMSCs under inflammatory conditions, upregulating the expression of relevant osteoblastic cytokines. In addition, SCPP/MoS2-MET scaffolds could effectively inhibit Staphylococcus aureus and Escherichia coli. In vivo experiments also demonstrated better osteogenic potential of SCPP/MoS2-MET scaffolds compared with the other scaffold-samples. Thus, the introduction of carboxylated molybdenum disulfide nanospheres is a promising approach to improve the properties of SCPP and may provide a new modification strategy for inert ceramic scaffolds and the construction of multifunctional composite scaffolds for bone tissue engineering.


Asunto(s)
Disulfuros , Nanosferas , Andamios del Tejido , Andamios del Tejido/química , Molibdeno/farmacología , Osteoblastos , Regeneración Ósea
14.
World J Gastrointest Oncol ; 15(11): 1936-1950, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38077650

RESUMEN

BACKGROUND: Dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain. However, recent studies have shown that DARPP-32 is also expressed in other tissues, including colorectal cancer (CRC), where its function is not well understood. AIM: To explore the effect of DARPP-32 on CRC progression. METHODS: The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays. The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, while apoptosis was measured by flow cytometry. The migratory and invasive potential of CRC cell lines were determined using wound healing and transwell chamber assays. In vivo studies involved monitoring the growth rate of xenograft tumors. Finally, the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses. RESULTS: DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer cell proliferation, migration, and invasion and reduce apoptosis. DARPP-32 knockdown resulted in the opposite functional effects. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in order to carry out its biological function. CONCLUSION: DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.

15.
Sci Rep ; 13(1): 22980, 2023 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-38151505

RESUMEN

To investigate the biomechanical properties of posterior cruciate ligament avulsion fractures of the tibia fixed using four different methods, including triple tibial channel net suture fixation. In 40 porcine knees, a standardized bony avulsion of the posterior cruciate ligament was generated. Double tibial bone channel suture fixation was performed in group A, double-head hollow compression screw fixation was performed in group B, triple tibial bone channel net suture fixation was performed in group C, and cortical suspension EndoButton fixation was performed in group D. The constructs were cyclically loaded 500 times (10 to 100 N) to measure the initial displacement and stiffness values. Subsequently, loading to failure was performed, and the yield load and peak load were measured. The results were analysed by one-way ANOVA, with significance set at P < 0.05. The initial displacement in group D (1.00 ± 0.20 mm) was lower than that in group C (1.46 ± 0.33 mm, P = 0.000), group B (1.91 ± 1.71 mm, P = 0.000) and group A (3.91 ± 0.79 mm, P = 0.000), but there was no significant difference between groups B and C (P = 0.055). The initial stiffness in group A (50.59 ± 6.89 N/mm) was lower than that in group C (67.21 ± 12.80 N/mm, P = 0.001), group D (71.18 ± 9.20 N/mm, P = 0.000) and group B (78.67 ± 5.91 N/mm, P = 0.000). However, there was no significant difference between groups B and D or between groups C and D (P = 0.111 and P = 0.391). The yield load in group A (554.86 ± 71.43 N) was lower than that in group C (767.00 ± 34.53 N, P = 0.000), group D (777.62 ± 73.03 N, P = 0.000) and group B (837.50 ± 55.73 N, P = 0.000). There was no significant difference between groups C and D (P = 0.729). The peak load in group A (667.38 ± 61.54 N) was lower than that in group C (842.00 ± 26.20 N, P = 0.000), group D (867.63 ± 63.42 N, P = 0.000) and group B (901.25 ± 54.38 N, P = 0.000). There was no significant difference between groups C and D (P = 0.346). Different failure modes were found among the four groups. The triple tibial bone channel suture fixation group showed better initial stability and fixation strength, which was comparable to that in the cortical suspension EndoButton fixation group and double-head hollow compression screw fixation group and significantly stronger than that in the double tibial bone channel suture fixation group. This study analysed the dynamic and static indexes of posterior cruciate ligament tibial avulsion fractures fixed by four different fixation methods under cyclic loading tests and single failure loading tests, providing a theoretical basis for clinical treatment.


Asunto(s)
Fracturas por Avulsión , Ligamento Cruzado Posterior , Fracturas de la Tibia , Animales , Porcinos , Tibia/cirugía , Ligamento Cruzado Posterior/cirugía , Fracturas por Avulsión/cirugía , Fracturas de la Tibia/cirugía , Suturas , Fenómenos Biomecánicos , Técnicas de Sutura
16.
Cell Host Microbe ; 31(11): 1837-1849.e5, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37909049

RESUMEN

Despite a wide presence of type III clustered regularly interspaced short palindromic repeats, CRISPR-associated (CRISPR-Cas) in archaea and bacteria, very few anti-CRISPR (Acr) proteins inhibiting type III immunity have been identified, and even less is known about their inhibition mechanism. Here, we present the discovery of a type III CRISPR-Cas inhibitor, AcrIIIB2, encoded by Sulfolobus virus S. islandicus rod-shaped virus 3 (SIRV3). AcrIIIB2 inhibits type III-B CRISPR-Cas immune response to protospacers encoded in middle/late-expressed viral genes. Investigation of the interactions between S. islandicus type III-B CRISPR-Cas Cmr-α-related proteins and AcrIIIB2 reveals that the Acr does not bind to Csx1 but rather interacts with the Cmr-α effector complex. Furthermore, in vitro assays demonstrate that AcrIIIB2 can block the dissociation of cleaved target RNA from the Cmr-α complex, thereby inhibiting the Cmr-α turnover, thus preventing host cellular dormancy and further viral genome degradation by the type III-B CRISPR-Cas immunity.


Asunto(s)
Virus de Archaea , Proteínas Asociadas a CRISPR , Virus de Archaea/metabolismo , Proteínas Virales/genética , Sistemas CRISPR-Cas , Archaea/metabolismo , Proteínas Asociadas a CRISPR/genética
17.
Nat Commun ; 14(1): 7484, 2023 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-37980416

RESUMEN

The H3 methyltransferases ATXR5 and ATXR6 deposit H3.1K27me1 to heterochromatin to prevent genomic instability and transposon re-activation. Here, we report that atxr5 atxr6 mutants display robust resistance to Geminivirus. The viral resistance is correlated with activation of DNA repair pathways, but not with transposon re-activation or heterochromatin amplification. We identify RAD51 and RPA1A as partners of virus-encoded Rep protein. The two DNA repair proteins show increased binding to heterochromatic regions and defense-related genes in atxr5 atxr6 vs wild-type plants. Consequently, the proteins have reduced binding to viral DNA in the mutant, thus hampering viral amplification. Additionally, RAD51 recruitment to the host genome arise via BRCA1, HOP2, and CYCB1;1, and this recruitment is essential for viral resistance in atxr5 atxr6. Thus, Geminiviruses adapt to healthy plants by hijacking DNA repair pathways, whereas the unstable genome, triggered by reduced H3.1K27me1, could retain DNA repairing proteins to suppress viral amplification in atxr5 atxr6.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Geminiviridae , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Heterocromatina/metabolismo , Geminiviridae/genética , Histonas/metabolismo , Replicación del ADN , Reparación del ADN/genética , Metiltransferasas/metabolismo
18.
Front Public Health ; 11: 1274080, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38026371

RESUMEN

Objective: This study aimed to investigate the use intention and influencing factors of telerehabilitation in people with rehabilitation needs. Methods: This cross-sectional survey recruited a total of 183 participants with rehabilitation needs from May 2022 to December 2022. Sociodemographic and medical data were collected by a structured questionnaire. The factors influencing the use intention of telerehabilitation were measured by the extended Unified Theory of Acceptance and Use of Technology (UTAUT) model. Multiple hierarchical regression analyses were performed. Results: A total of 150 valid questionnaires were included for analysis. The results indicated that the use intention of telerehabilitation was overall high in people with rehabilitation needs. Health condition (ß = -0.21, p = 0.03), performance expectancy (ß = 0.21, p = 0.01), facilitating conditions (ß = 0.25, p = 0.03), perceived trust (ß = 0.25, p < 0.01), and self-efficacy (ß = 0.19, p = 0.04) were significant factors influencing the use intention of telerehabilitation. Conclusion: Overall, the use intention of telerehabilitation is high in individuals with rehabilitation needs. Health conditions, performance expectancy, facilitating conditions, perceived trust, and self-efficacy are important factors influencing the use intention of telerehabilitation in individuals with rehabilitation needs.


Asunto(s)
Telerrehabilitación , Humanos , Intención , Estudios Transversales , Encuestas y Cuestionarios , Tecnología
19.
J Mater Chem B ; 11(43): 10464-10481, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37901956

RESUMEN

Repairing articular cartilage defects is a great challenge due to the poor self-regenerative capability of cartilage. Inspired by active substances found in the natural cartilage extracellular matrix, we used methacrylated carboxymethyl chitosan (MA-CMCS) and oxidized locust bean gum (OLBG) as the hydrogel backbone, and prepared a photocrosslinked dual network hydrogel containing allicin and decellularized cartilage powder (DCP). The rheological, swelling and water retention capacities of MA-CMCS@OLBG-Allicin/DCP (MCOAC) hydrogels were investigated to confirm the successful preparation of hydrogels suitable for cartilage repair. The MCOAC hydrogels showed good antibacterial ability to kill S. aureus and E. coli and anti-inflammatory properties due to the introduction of allicin. Furthermore, MA-CMCS@OLBG-Allicin/DCP hydrogels presented good cytocompatibility due to the addition of DCP, which could promote chondrocyte proliferation and promote the differentiation of BMSCs to chondrocytes. Further studies in vivo demonstrated that the DCP-contained MCOAC hydrogel exhibited superior performance in promoting cartilage tissue growth and wound healing in articular cartilage defects. Thus, the MCOAC hydrogel is a promising cartilage repair hydrogel with potential for clinical use.


Asunto(s)
Cartílago Articular , Quitosano , Hidrogeles/farmacología , Escherichia coli , Staphylococcus aureus
20.
ACS Appl Mater Interfaces ; 15(41): 47880-47892, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37788009

RESUMEN

Bone regenerative biomaterials are essential in treating bone defects as they serve as extracellular matrix (ECM) mimics, creating a favorable environment for cell attachment, proliferation, and differentiation. However, the currently used bone regenerative biomaterials mostly exhibit high stiffness, which may lead to difficulties in degradation and thus increase the risk of foreign body ingestion. In this study, we prepared soft fibrous scaffolds modified with Zn-MOF-74 nanoparticles via electrostatic spinning. The soft fibers (only 1 kPa) permit remodeling under cellular adhesive force, optimizing the mechanical cues in the microenvironment to support cell adhesion and mechanosensing. In addition, the incorporation of Zn-MOF-74 nanoparticles enables the stable and sustained release of zinc ions, promoting stem cell mechanotransduction and osteogenic differentiation. Therefore, the hybrid soft fibers facilitate the regeneration of new bone in the rat femoral defect model, which provides a promising approach for regenerative medicine.


Asunto(s)
Células Madre Mesenquimatosas , Osteogénesis , Ratas , Animales , Osteogénesis/fisiología , Andamios del Tejido , Ingeniería de Tejidos , Mecanotransducción Celular , Células Madre , Regeneración Ósea , Materiales Biocompatibles/metabolismo , Diferenciación Celular/fisiología , Proliferación Celular
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...