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1.
Plants (Basel) ; 13(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38999624

RESUMO

Light, as a critical environmental factor, plays a pivotal role in photosynthesis, ultimately influencing the timing of bud flush in tea plants. However, the synergistic effects of different photoperiods and light qualities on the timing of bud flush in the albino tea cultivar 'HuangKui' (later germination variety) remain unknown. Thus, the objective of this study was to investigate the effects of different photoperiods (12L/12D, 14L/10D, 16L/8D, and 18L/6D, where L = the number of daylight hours and D = the number of hours of darkness) and ratios of red (R) to blue (B) light (R/B 1:1, R/B 1:2, R/B 1:3, and R/B 2:1) on the germination and growth of the albino tea variety 'HuangKui'. In our study, we examined how different photoperiods and red light and blue light affected tea germination and growth by investigating the timing of bud flush, photosynthesis, chlorophyll content, and growth indicators. First, our study showed that 'HuangKui' germinated 4 days, 2 days, and 1 day earlier under the 16L/8D photoperiod at the one bud and one leaf period compared with plants cultivated under the 12L/12D, 14L/10D, and 18L/6D photoperiods under light simulating the solar spectrum. Also, the growth of 'HuangKui' was maximumly promoted under the 16L/8D photoperiod treatment. Additionally, the earliest germination of 'HuangKui' was observed for the 16L/8D photoperiod under the R/B 2:1 (red/blue) treatment compared with the other treatments. Moreover, the greatest plant height, length of the new shoots, and new leaf areas were detected in the albino tea variety 'HuangKui' under R/B 2:1. Moreover, the contents of auxin (indole acetic acid, IAA) and trans-zeatin (tZ) under R/B 2:1 were significantly higher than those under the R/B 1:1 and control treatments with the 16L/8D photoperiod. Additionally, the auxin-related expression levels of CsIAA13, CsGH3.1, CsAUX1, and CsARF2 under the R/B 2:1 treatment were significantly higher than those in the control. The expression of CsARR-B, a positive regulator of cytokinin-related genes, was significantly higher under the R/B 2:1 treatment than under the control treatment, while the opposite result was found for the expression of the negative regulator CsARR-A. Therefore, the R/B 2:1 treatment with the 16L/8D photoperiod was an appropriate means of timing the bud flush for the albino tea variety 'HuangKui', which may be related to IAA or tZ signal transduction. In conclusion, our research offers a novel lighting strategy that promotes the germination and growth of albino tea cultivars.

2.
Mater Today Bio ; 27: 101120, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38975240

RESUMO

Reactive oxygen species play a vital role in tissue repair, and nonequilibrium of redox homeostasis around bone defect can compromise osteogenesis. However, insufficient antioxidant capacity and weak osteogenic performance remain major obstacles for bone scaffold materials. Herein, integrating the mussel-inspired polydopamine (PDA) coating and 3D printing technologies, we utilized the merits of both osteogenic bredigite and antioxidative fullerol to construct 3D-printed porous, biodegradable acid-buffering, reactive oxygen species (ROS) -scavenging and robust osteogenic bio-scaffold (denoted "FPBS") for in situ bone defect restoration under oxidative stress microenvironment. Initially, fullerol nanoparticles were attached to the surface of the bredigite scaffold via covalently inter-crosslinking with PDA. Upon injury, extracellular ROS capturing triggered the oxidative degradation of PDA, releasing fullerol nanoparticles to enter into cells for further intracellular ROS scavenging. In vitro, FPBS had good biocompatibility and excellent antioxidative capability. Furthermore, FPBS promoted the osteogenesis of stem cells with significant elevation of osteogenic markers. Finally, in vivo implantation of FPBS remarkably enhanced new bone formation in a rat critical calvarial defect model. Overall, with amelioration of the ROS microenvironment of injured tissue and enhancement of osteogenic differentiation of stem cells simultaneously, FPBS may hold great potential towards bone defect repair.

4.
Appl Microbiol Biotechnol ; 108(1): 360, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836914

RESUMO

In the fight against hospital-acquired infections, the challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) necessitates the development of novel treatment methods. This study focused on undermining the virulence of S. aureus, especially by targeting surface proteins crucial for bacterial adherence and evasion of the immune system. A primary aspect of our approach involves inhibiting sortase A (SrtA), a vital enzyme for attaching microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) to the bacterial cell wall, thereby reducing the pathogenicity of S. aureus. Verbascoside, a phenylethanoid glycoside, was found to be an effective SrtA inhibitor in our research. Advanced fluorescence quenching and molecular docking studies revealed a specific interaction between verbascoside and SrtA, pinpointing the critical active sites involved in this interaction. This molecular interaction significantly impedes the SrtA-mediated attachment of MSCRAMMs, resulting in a substantial reduction in bacterial adhesion, invasion, and biofilm formation. The effectiveness of verbascoside has also been demonstrated in vivo, as shown by its considerable protective effects on pneumonia and Galleria mellonella (wax moth) infection models. These findings underscore the potential of verbascoside as a promising component in new antivirulence therapies for S. aureus infections. By targeting crucial virulence factors such as SrtA, agents such as verbascoside constitute a strategic and potent approach for tackling antibiotic resistance worldwide. KEY POINTS: • Verbascoside inhibits SrtA, reducing S. aureus adhesion and biofilm formation. • In vivo studies demonstrated the efficacy of verbascoside against S. aureus infections. • Targeting virulence factors such as SrtA offers new avenues against antibiotic resistance.


Assuntos
Aminoaciltransferases , Antibacterianos , Aderência Bacteriana , Proteínas de Bactérias , Biofilmes , Cisteína Endopeptidases , Glucosídeos , Staphylococcus aureus Resistente à Meticilina , Simulação de Acoplamento Molecular , Fenóis , Infecções Estafilocócicas , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Aminoaciltransferases/antagonistas & inibidores , Aminoaciltransferases/metabolismo , Cisteína Endopeptidases/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Glucosídeos/farmacologia , Animais , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Fenóis/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Mariposas/microbiologia , Virulência/efeitos dos fármacos , Modelos Animais de Doenças , Fatores de Virulência/metabolismo , Inibidores Enzimáticos/farmacologia , Polifenóis
5.
ISA Trans ; 150: 15-29, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38755064

RESUMO

Aiming to address the problem of robot path planning in environments containing narrow passages, this paper proposes a novel global path planning method: the DSR (Dual-source Light Continuous Reflection Exploration) algorithm. This algorithm, inspired by the natural reflection of light, employs the concept of continuous reflection for path planning. It can efficiently generate an asymptotically optimal path on the map containing narrow passages. The DSR algorithm has been evaluated on different maps with narrow passages and compared with other algorithms. In comparison with the bidirectional Rapidly-exploring Random Tree algorithm, the DSR algorithm achieves a significant reduction in both path length (by 27.08% and 34.35%) and time consumption (by 98.47% and 91.03%). Numerical simulations and experimental analysis have demonstrated the excellent performance of the DSR algorithm.

6.
Int J Biol Macromol ; 270(Pt 2): 132419, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38759859

RESUMO

Bacterial infection is a serious challenge in the treatment of open bone defects, and reliance on antibiotic therapy may contribute to the emergence of drug-resistant bacteria. To solve this problem, this study developed a mineralized hydrogel (PVA-Ag-PHA) with excellent antibacterial properties and osteogenic capabilities. Silver nanoparticles (CNC/TA@AgNPs) were greenly synthesized using natural macromolecular cellulose nanocrystals (CNC) and plant polyphenolic tannins (TA) as stabilizers and reducing agents respectively, and then introduced into polyvinyl alcohol (PVA) and polydopamine-modified hydroxyapatite (PDA@HAP) hydrogel. The experimental results indicate that the PVA-Ag-PHA hydrogel, benefiting from the excellent antibacterial properties of CNC/TA@AgNPs, can not only eliminate Staphylococcus aureus and Escherichia coli, but also maintain a sustained sterile environment. At the same time, the HAP modified by PDA is uniformly dispersed within the hydrogel, thus releasing and maintaining stable concentrations of Ca2+ and PO43- ions in the local environment. The porous structure of the hydrogel with excellent biocompatibility creates a suitable bioactive environment that facilitates cell adhesion and bone regeneration. The experimental results in the rat critical-sized calvarial defect model indicate that the PVA-Ag-PHA hydrogel can effectively accelerate the bone healing process. Thus, this mussel-inspired hydrogel with antibacterial properties provides a feasible solution for the repair of open bone defects, demonstrating the considerable potential for diverse applications in bone repair.


Assuntos
Regeneração Óssea , Celulose , Hidrogéis , Nanopartículas Metálicas , Prata , Crânio , Taninos , Prata/química , Prata/farmacologia , Animais , Regeneração Óssea/efeitos dos fármacos , Celulose/química , Celulose/farmacologia , Nanopartículas Metálicas/química , Ratos , Hidrogéis/química , Hidrogéis/farmacologia , Crânio/efeitos dos fármacos , Crânio/lesões , Taninos/química , Taninos/farmacologia , Bivalves/química , Antibacterianos/farmacologia , Antibacterianos/química , Álcool de Polivinil/química , Staphylococcus aureus/efeitos dos fármacos , Durapatita/química , Durapatita/farmacologia , Ratos Sprague-Dawley , Escherichia coli/efeitos dos fármacos
7.
ACS Appl Mater Interfaces ; 16(15): 18551-18563, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564314

RESUMO

High levels of reactive oxygen species (ROS) are known to play a critical role in the secondary cascade of spinal cord injury (SCI). The scavenging of ROS has emerged as a promising approach for alleviating acute SCI. Moreover, identifying the precise location of the SCI site remains challenging. Enhancing the visualization of the spinal cord and improving the ability to distinguish the lesion site are crucial for accurate and safe treatment. Therefore, there is an urgent clinical need to develop a biomaterial that integrates diagnosis and treatment for SCI. Herein, ultra-small-sized gold nanodots (AuNDs) were designed for dual-mode imaging-guided precision treatment of SCI. The designed AuNDs demonstrate two important functions. First, they effectively scavenge ROS, inhibit oxidative stress, reduce the infiltration of inflammatory cells, and prevent apoptosis. This leads to a significant improvement in SCI repair and promotes a functional recovery after injury. Second, leveraging their excellent dual-mode imaging capabilities, the AuNDs enable rapid and accurate identification of SCI sites. The high contrast observed between the injured and adjacent uninjured areas highlights the tremendous potential of AuNDs for SCI detection. Overall, by integrating ROS scavenging and dual-mode imaging in a single biomaterial, our work on functionalized AuNDs provides a promising strategy for the clinical diagnosis and treatment of SCI.


Assuntos
Ouro , Traumatismos da Medula Espinal , Humanos , Espécies Reativas de Oxigênio , Ouro/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Estresse Oxidativo , Materiais Biocompatíveis/uso terapêutico
8.
J Transl Med ; 22(1): 127, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308352

RESUMO

BACKGROUND: Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients. METHODS: We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients. RESULTS: Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828-0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05). CONCLUSION: We have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Feminino , Humanos , Hiperplasia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Endométrio/tratamento farmacológico , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/patologia , China
9.
Gut ; 73(7): 1169-1182, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38395437

RESUMO

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Neoplasias Hepáticas , Integração Viral , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/patologia , Vírus da Hepatite B/genética , Humanos , Integração Viral/genética , Animais , Camundongos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Sequenciamento Completo do Genoma , Variações do Número de Cópias de DNA , Idoso
10.
J Gynecol Oncol ; 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38282259

RESUMO

OBJECTIVE: This study aims to assess the impact of the metabolic risk score (MRS) on both the time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early EC patients. METHODS: Univariate and multivariate logistic analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan-Meier analysis was utilized to determine the cumulative CR rate for patients. RESULTS: The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (<6, 6-9, >9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=-2.16; 95% CI=-4.03, -0.28; p=0.025), and histological type (HR=0.36; 95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan-Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. CONCLUSION: MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation.

11.
Cancer Immunol Immunother ; 73(2): 31, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38279998

RESUMO

The small, heavily glycosylated protein CD24 is primarily expressed by many immune cells and is highly expressed mostly in cancer cells. As one of the most crucial biomarkers of cancers, CD24 is frequently highly expressed in solid tumors, while tumor-associated macrophages express Siglec-10 at high levels, Siglec-10 and CD24 can interact on innate immune cells to lessen inflammatory responses to a variety of disorders. Inhibiting inflammation brought on by SHP-1 and/or SHP-2 phosphatases as well as cell phagocytosis by macrophages, the binding of CD24 to Siglec-10 can prevent toll-like receptor-mediated inflammation. Targeted immunotherapy with immune checkpoint inhibitors (ICI) has lately gained popularity as one of the best ways to treat different tumors. CD24 is a prominent innate immune checkpoint that may be a useful target for cancer immunotherapy. In recent years, numerous CD24/Siglec-10-related research studies have made tremendous progress. This study discusses the characteristics and workings of CD24/Siglec-10-targeted immunotherapy and offers a summary of current advances in CD24/Siglec-10-related immunotherapy research for cancer. We then suggested potential directions for CD24-targeted immunotherapy, basing our speculation mostly on the results of recent preclinical and clinical trials.


Assuntos
Macrófagos , Neoplasias , Humanos , Transdução de Sinais , Inflamação , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico , Imunoterapia/métodos , Antígeno CD24/metabolismo
12.
Arch Orthop Trauma Surg ; 144(1): 229-237, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37838982

RESUMO

PURPOSE: To evaluate the outcomes of patients with supination-adduction (SAD) type II (OTA/AO 44A2) fractures who had a lateral ankle ligament rupture repaired compared with patients who did not have a lateral ankle ligament repaired using patients who underwent fibula fracture fixation as a control group. METHODS: A retrospective analysis of all 104 patients diagnosed with SAD type II fractures from January 2011 to December 2020 and managed operatively was performed. The patients were divided into three groups: 32 patients with ruptures of the lateral ligaments that were not repaired (group A), 34 patients with ruptures of the lateral ligaments that were repaired (group B), and 38 patients with fibula fracture fixation acting as the control group (group C). The objective outcomes including radiographic findings, the ankle range of motion, the manual ankle stress tests, and complications were gained from the record of the last time in outpatient clinics. The functional outcomes including the identification of functional ankle instability (IdFAI) scores were collected postoperatively at 12-month intervals to assess clinical outcomes. The Manchester Oxford Foot Questionnaire (MOXFQ) and Karlsson scoring scale were also recorded at the last follow-up. RESULTS: The mean follow-up of the objective and subjective functional outcomes was 23.4 (range, 13-42) and 76.9 (range, 25-134) months, respectively. There was no significant difference in the radiographic findings, the ankle range of motion and complications between the three groups. All ankles were found to be stable using the manual ankle stress test in both group A and group B. The IdFAI scores showed a significant difference between group A and group B (1.12 ± 1.3 vs 0.35 ± 0.69; p < 0.001) in the first year of follow-up and no significant difference after the first year. No differences were noted in MOXFQ scores or Karlsson scores among the groups. CONCLUSION: Directly repairing the lateral ligament could minimize the proportion of the first year of postoperative functional ankle instability, although the final stability of the ankle and clinical outcomes were not significantly different in SAD type II fractures. LEVEL OF EVIDENCE: Level III, retrospective comparative case series.


Assuntos
Fraturas do Tornozelo , Ligamentos Laterais do Tornozelo , Humanos , Fraturas do Tornozelo/cirurgia , Tornozelo , Estudos Retrospectivos , Supinação , Fixação Interna de Fraturas , Resultado do Tratamento , Articulação do Tornozelo/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia
13.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5419-5437, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38114136

RESUMO

Curcuma wenyujin, as one of the eight Daodi-herbs in Zhejiang province, is widely used. It has the effects of eliminating stasis and dissipating mass, moving Qi and activating blood, and clearing heart and relieving depression. Modern studies have shown that it has anti-tumor, anti-inflammatory, anti-oxidation, anti-thrombus and liver-protecting effects and mainly contains sesquiterpenoids, monoterpenoids, diterpenoids, and curcumins. This paper reviews the research progress in the chemical constituents and pharmacological effects of C. wenyujin in the last decade, discusses the modern clinical applications combined with the traditional efficacy, and predicts its quality markers(Q-markers) from plant consanguinity, medicinal properties, efficacy, processing and measurability of chemical components based on the theory of Q-markers, so as to provide a reference for the establishment of a scientific quality evaluation system and the research and application of this herb in the future.


Assuntos
Curcuma , Anti-Inflamatórios , Curcuma/química , Fígado
14.
Sci Rep ; 13(1): 22766, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123581

RESUMO

In the actual decision-making process, there will be situations where decision-makers with hesitant attitudes have difficulties in evaluating alternatives numerically, and hesitant fuzzy linguistic term sets can provide decision-makers with an effective way to describe hesitancy in linguistic terms. In multi-attribute group decision-making, each decision maker typically holds different preferences. If the variation in decision makers' assessment weights across evaluations of each attribute for every alternative is not adequately accounted for, it can result in a problem of coarse-grained calculations, leading to information loss. Additionally, the three-way decision model faces significant challenges in information fusion within the context of the hesitant fuzzy linguistic environment. Therefore, we propose a new three-way decision-making model under the hesitant fuzzy linguistic environment. The model obtains the confidence of different decision makers in attribute evaluations through the fusion of D-S evidence theory, and can perform more fine-grained fusion calculations on the evaluation information of different decision makers. In addition, the model considers the cost function of each alternative in different decision-making actions under hesitant fuzzy linguistic environment, calculates the two thresholds of each alternative in the three-way decision model, and derives the decision rules. The effectiveness of the model is verified through a numerical example and two comparative experiments, therefore, the model can be applied in intelligent classification or recommendation systems of hesitant fuzzy linguistic information systems.

15.
Clin Transl Med ; 13(11): e1483, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37965796

RESUMO

BACKGROUND: Oncogenic PIK3CA mutations (PIK3CAmut ) frequently occur in a higher proportion in luminal breast cancer (LBC), especially in refractory advanced cases, and are associated with changes in tumour cellular metabolism. Nevertheless, its effect on the progression of the immune microenvironment (TIME) within tumours and vital molecular events remains veiled. METHODS: Multiplex immunohistochemistry (mIHC) and single-cell mass cytometry (CyTOF) was used to describe the landscape of TIME in PIK3CAmut LBC. The PIK3CA mutant cell lines were established using CRISPER/Cas9 system. The gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA, immunofluorescence staining or western blotting. GSEA analysis, transwell chemotaxis assay, live cell imaging, flow cytometry metabolite analysis targeting arachidonic acid, Dual-luciferase reporter assay, and Chromatin immunoprecipitation assay were used to investigate the underlying function and mechanism of the PI3K/5-LOX/LTB4 axis. RESULTS: PIK3CAmut LBC cells can induce an immunosuppressive TIME by recruiting myeloid-derived suppressor cells (MDSCs) and excluding cytotoxic T cells via the arachidonic acid (AA) metabolism pathway. Mechanistically, PIK3CAmut activates the transcription of 5-lipoxygenase (5-LOX) in a STAT3-dependent manner, which in turn directly results in high LTB4 production, binding to BLT2 on MDSCs and promoting their infiltration. Since a suppressive TIME is a critical barrier for the success of cancer immunotherapy, the strategies that can convert "cold" tumours into "hot" tumours were compared. Targeted therapy against the PI3K/5-LOX/LTB4 axis synergizing with immune checkpoint blockade (ICB) therapy achieved dramatic shrinkage in vivo. CONCLUSIONS: The results emphasize that PIK3CAmut can induce immune evasion by recruiting MDSCs through the 5-LOX-dependent AA pathway, and combination targeted therapy with ICB may provide a promising treatment option for refractory advanced LBC patients.


Assuntos
Neoplasias da Mama , Células Supressoras Mieloides , Feminino , Humanos , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/metabolismo , Ácido Araquidônico/metabolismo , Neoplasias da Mama/metabolismo , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Imunossupressores , Leucotrieno B4/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Microambiente Tumoral
16.
ACS Cent Sci ; 9(10): 1976-1988, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37901175

RESUMO

Surgery, radiotherapy (RT), and brachytherapy are crucial treatments for localized deep tumors. However, imprecise tumor location often leads to issues such as positive surgical margins, extended radiotherapy target volumes, and radiation damage to healthy tissues. Reducing side effects in healthy tissue and enhancing RT efficacy are critical challenges. To address these issues, we developed a multifunctional theranostic platform using Au/Ag nanodots (Au/AgNDs) that act as a "pilot light" for real-time guided surgery, high-efficiency RT, and brachytherapy, achieving a strategy of killing three birds with one stone. First, dual-mode imaging of Au/AgNDs enabled precision RT, minimizing damage to adjacent normal tissue during X-ray irradiation. Au/AgNDs enhanced ionizing radiation energy deposition, increased intracellular reactive oxygen species (ROS) generation, regulated the cell cycle, promoted DNA damage formation, and inhibited DNA repair in tumor cells, significantly improving RT efficacy. Second, in brachytherapy, precise guidance provided by dual-mode imaging addressed challenges related to non-visualization of existing interstitial brachytherapy and multiple adjustments of insertion needle positions. Meanwhile, the effect of brachytherapy was improved. Third, the excellent fluorescence imaging of Au/AgNDs accurately distinguished tumors from normal tissue, facilitating their use as a powerful tool for assisting surgeons during tumor resection. Taken together, our multifunctional theranostic platform offers real-time guidance for surgery and high-efficiency RT, and improves brachytherapy precision, providing a novel strategy and vision for the clinical diagnosis and treatment of cancer.

17.
Expert Opin Biol Ther ; 23(12): 1193-1195, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37852928

RESUMO

According to recent research, bispecific antibodies (BsAbs) are a promising new immunotherapy method. Various BsAb forms are constantly being developed. In the year 2022 alone, four BsAbs (tebentafusp, faricimab, mosunetuzumab, and teclistamab) were approved for clinical applications. BsAbs including odronextamab, talquetamab, linvoseltamab, and elranatamab are being actively evaluated in different clinical studies. Preliminary results show promising response rates in relapsed/refractory follicular lymphoma (RRFL), relapsed/refractory diffuse large B-cell lymphoma (RRDLBCL), and relapsed/refractory multiple myeloma (RRMM), especially in heavily pretreated patients, including those who have progressed after proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies, and CAR-T therapies. We summarized data published at the 28th European Hematology Association (EHA) annual meeting, which was held in Frankfurt between 8 June 2023 and 11 June 2023 on BsAbs monotherapy or combination therapy for RRFL, RRDLBCL, and RRMM.


Assuntos
Anticorpos Biespecíficos , Antineoplásicos , Neoplasias Hematológicas , Hematologia , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Mieloma Múltiplo , Humanos , Anticorpos Biespecíficos/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Antineoplásicos/uso terapêutico , Mieloma Múltiplo/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico
18.
Chem Commun (Camb) ; 59(79): 11831-11834, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37711078

RESUMO

Novel N,P-fused coronene derivatives have been successfully designed and achieved in one step using a three-fold Bischler-Napieralski cyclization as the key step. The unique structure, and tunable photophysical and electronic properties make them promising candidates for emissive and electron-transport materials.

19.
J Colloid Interface Sci ; 652(Pt A): 770-779, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37619256

RESUMO

HYPOTHESIS: The use of tumor cell membrane-camouflaged nanoparticles, specifically the multifunctional biomimetic core-shell nanosystem MPCONPs, can enhance the targeting ability and immune escape functionality of traditional chemotherapy, leading to more precise drug delivery and improved treatment outcomes. EXPERIMENTS: Preparation of MPCONPs: Autologous tumor cell membrane (CM) fragments are collected and used to create a shell for the nanoparticles. A trypsin-sensitive cationic polylysine framework is synthesized and embedded with oxaliplatin (l-OHP) and Ce6-AuNDs (a singlet oxygen generator). The MPCONPs are formed by assembling these components. FINDINGS: MPCONPs, as nanoparticles camouflaged with tumor CM, have enhanced cellular uptake in cancer cells and improved the efficacy of photodynamic therapy (PDT) and chemotherapy (CT). This offers great potential for their use as individualized therapeutic agents for clinical oncology treatment.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Biomimética , Fotoquimioterapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Membrana Celular , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
20.
Behav Sci (Basel) ; 13(6)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37366759

RESUMO

Intrapersonal emotion dysregulation has been found to be a transdiagnostic predictor in the development of almost all affective disorders. Interpersonal resources are also involved in achieving people's emotion regulation goals. The Interpersonal Regulation Questionnaire (IRQ) has been developed to assess the tendency and efficacy of people using external resources to help manage their emotions. Under the restrictions of the COVID-19 pandemic, the role of interpersonal emotion regulation in individuals' adjustment and well-being remains unclear. This study aimed to investigate the optimal factor structure of the IRQ in Chinese culture using an exploratory structural equation modeling approach and to examine the associations between interpersonal emotion regulation, tested by the IRQ, and young people's intrapersonal emotion dysregulation and social and emotional well-being. The sample consisted of 556 college students aged from 17 to 31 from Mainland China. Factor analyses suggested that the four-factor structure was the optimal model for the current data. Females reported a higher tendency to use external resources to regulate their negative emotions and higher efficacy in regulating negative emotions. The Chinese version of the IRQ (C-IRQ) presented adequate psychometric properties and would be a useful tool for measuring interpersonal emotion regulation behaviors.

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