RESUMO

Chemotherapy-induced cellular senescence leads to an increased proportion of cancer stem cells (CSCs) in breast cancer (BC), contributing to recurrence and metastasis, while effective means to clear them are currently lacking. Herein, we aim to develop new approaches for selectively killing senescent-escape CSCs. High CD276 (95.60%) expression in multidrug-resistant BC cells, facilitates immune evasion by low-immunogenic senescent escape CSCs. CALD1, upregulated in ADR-resistant BC, promoting senescent-escape of CSCs with an anti-apoptosis state and upregulating CD276, PD-L1 to promote chemoresistance and immune escape. We have developed a controlled-released thermosensitive hydrogel containing pH- responsive anti-CD276 scFV engineered biomimetic nanovesicles to overcome BC in primary, recurrent, metastatic and abscopal humanized mice models. Nanovesicles coated anti-CD276 scFV selectively fuses with cell membrane of senescent-escape CSCs, then sequentially delivers siCALD1 and ADR due to pH-responsive MnP shell. siCALD1 together with ADR effectively induce apoptosis of CSCs, decrease expression of CD276 and PD-L1, and upregulate MHC I combined with Mn2+ to overcome chemoresistance and promote CD8+T cells infiltration. This combined therapeutic approach reveals insights into immune surveillance evasion by senescent-escape CSCs, offering a promising strategy to immunotherapy effectiveness in cancer therapy.

Assuntos

Neoplasias da Mama , Senescência Celular , Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas , Humanos , Animais , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Senescência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Engenharia Genética/métodos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Nanopartículas/química , Anticorpos de Cadeia Única/química , Evasão Tumoral/efeitos dos fármacos , Antígeno B7-H1/metabolismo , Apoptose/efeitos dos fármacos , Biomimética/métodos , Antígenos B7

RESUMO

JOURNAL/nrgr/04.03/01300535-202507000-00025/figure1/v/2024-09-09T124005Z/r/image-tiff To investigate the mechanisms underlying the onset and progression of ischemic stroke, some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex. However, these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied, although ischemic stroke is strongly age-related. In this study, we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser. We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation. Moreover, we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke. Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages, thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

RESUMO

Infrared birefringent crystals that hold significant importance for optoelectronic application have been rarely reported. Traditional tetrahedral PS4, ethane-like P2S6, and octahedral InS6 units in thiophosphates typically manifest near isotropy, often resulting in extremely small birefringence. However, this study prepares α-Rb2InP2S7 (1), ß-Rb2InP2S7 (2), and Cs2InP2S7 (3), consisting of the aforementioned microstructures, notably exhibiting the highest refractive index difference or birefringence values (0.247, 0.298, and 0.250 at 546 nm, respectively) among thiophosphates, the middle one being larger than that of commercial birefringent materials. This unusual increase in birefringence can be primarily attributed to two key factors: (1) simultaneous stretching and compressing of the P-S and In-S covalent bond interactions, generating high polarizability anisotropy of InS6, PS4, and P2S6 polyhedral units; (2) the additional incorporation of alkali metals that further reduces the dimensionality of the crystal structure, creating one-dimensional [InP2S7]2- structures with increasing polarizability anisotropy. This study presents an alternative approach to enhance birefringent materials by reconstructing covalent bond interactions and specific spatial arrangements.

RESUMO

Nigrospora oryzae, a newly identified pathogen, is responsible for poplar leaf blight, causing significant harm to poplar growth. Here, we describe, for the first time, a biological control method for the control of poplar leaf blight via the applications of 3 dominant Trichoderma strains/species. In this study, dominant Trichoderma species/strains with the potential for biocontrol were identified and then further characterised via dual culture assays, volatile organic compounds (VOCs), and culture filtrates. The biocontrol efficacy of these strains against N. oryzae was found to exceed 60%. Furthermore, the reactive oxygen species (ROS) content in Populus davidiana × P. alba var. pyramidalis (PdPap) leaves pretreated with these Trichoderma strains significantly decreased. Furthermore, pretreatment of PdPap with a combination of these Trichoderma (Tcom) resulted in 9.71-fold and 1.95-fold increases in peroxidase (POD) and superoxide dismutase (SOD) activity, respectively, and 3.87-fold decrease in the MDA content compared to controls. Moreover, Tcom pretreatment activated the salicylic acid (SA) and jasmonic acid (JA) pathway-dependent defence responses of poplar, upregulating pathogenesis-related protein (PR) and MYC proto-oncogene (MYC-R) by more than 12-fold and 17.32-fold, respectively. In addition, Trichoderma treatments significantly increased the number of lateral roots, aboveground biomass, and stomata number and density of PdPap, and Tcom was superior to the single pretreatments. The soil pH also became weakly acidic in these pretreatments, which is beneficial for the growth of PdPap seedlings. These findings indicate that these dominant Trichoderma strains can effectively increase biocontrol and poplar growth promotion.

Assuntos

Ascomicetos , Doenças das Plantas , Folhas de Planta , Populus , Populus/microbiologia , Populus/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Ascomicetos/fisiologia , Folhas de Planta/microbiologia , Folhas de Planta/metabolismo , Trichoderma/fisiologia , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/metabolismo , Compostos Orgânicos Voláteis/metabolismo , Agentes de Controle Biológico

RESUMO

Transition metal alloys can exhibit synergistic intermetallic effects to obtain high activities for oxygen reduction/evolution reactions (ORR/OER). However, due to the insufficient stability of active sites in alkaline electrolytes, conventional alloy catalysts still do not meet practical needs. Herein, by using polypyrrole tubes and cobalt-iron (CoFe) Prussian blue analogs as precursors, CoFe sulfides is in-situ formed on CoFe alloys to construct (CoFe)(S2)2/CoFe heterostructure in sulfur (S) and nitrogen (N) co-doped carbon nanotubes (CoFe@NCNTs-nS) via a low-temperature sulfidation strategy. The as-marked CoFe@NCNTs-12.5S exhibits a comparable ORR activity (half-wave potential of 0.901 V) to Pt/C (0.903 V) and a superior OER activity (overpotential of 272 mV at 10 mA cm-2) to RuO2 (299 mV). CoFe@NCNTs-12.5S also exhibits ultralow charge transfer resistances (ORR-6.36 Ω and OER-0.21 Ω) and an excellent potential difference of 0.617 V. The sulfidation-induced (CoFe)(S2)2/CoFe heterojunctions can accelerate interfacial charge transfer process. Tubular structure not only disperses the (CoFe)(S2)2/CoFe heterostructure, but also reduces the corrosion of active-sites to enhance catalysis stability. Zinc-air battery with CoFe@NCNTs-12.5S achieves a high specific capacity (718.1 mAh g-1), maintaining a voltage gap of 0.957 V after 400 h. This work reveals the potential of interface engineering for boosting ORR/OER activities of alloys via in-situ heterogenization.

RESUMO

Background: Kidney injuries often carry a grim prognosis, marked by fibrosis development, renal function loss, and macrophage involvement. Despite extensive research on macrophage polarization and its effects on other cells, like fibroblasts, limited attention has been paid to the influence of non-immune cells on macrophages. This study aims to address this gap by shedding light on the intricate dynamics and diversity of macrophages during renal injury and repair. Methods: During the initial research phase, the complexity of intercellular communication in the context of kidney injury was revealed using a publicly available single-cell RNA sequencing library of the unilateral ureteral obstruction (UUO) model. Subsequently, we confirmed our findings using an independent dataset from a renal ischemia-reperfusion injury (IRI) model. We treated two different types of endothelial cells with TGF-ß and co-cultured their supernatants with macrophages, establishing an endothelial cell and macrophage co-culture system. We also established a UUO and an IRI mouse model. Western blot analysis, flow cytometry, immunohistochemistry and immunofluorescence staining were used to validate our results at multiple levels. Results: Our analysis revealed significant changes in the heterogeneity of macrophage subsets during both injury processes. Amyloid ß precursor protein (APP)-CD74 axis mediated endothelial-macrophage intercellular communication plays a dominant role. In the in vitro co-culture system, TGF-ß triggers endothelial APP expression, which subsequently enhances CD74 expression in macrophages. Flow cytometry corroborated these findings. Additionally, APP and CD74 expression were significantly increased in the UUO and IRI mouse models. Immunofluorescence techniques demonstrated the co-localization of F4/80 and CD74 in vivo. Conclusion: Our study unravels a compelling molecular mechanism, elucidating how endothelium-mediated regulation shapes macrophage function during renal repair. The identified APP-CD74 signaling axis emerges as a promising target for optimizing renal recovery post-injury and preventing the progression of chronic kidney disease.

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Solar-driven carbon dioxide (CO2) reduction into C2+ products such as ethylene represents an enticing route toward achieving carbon neutrality. However, due to sluggish electron transfer and intricate C-C coupling, it remains challenging to achieve highly efficient and selective ethylene production from CO2 and H2O beyond capitalizing on Cu-based catalysts. Herein, we report a judicious design to attain asymmetric C-C coupling through interfacial defect-rendered tandem catalytic centers within a sulfur-vacancy-rich MoSx/Fe2O3 photocatalyst sheet, enabling a robust CO2 photoreduction to ethylene without the need for copper, noble metals, and sacrificial agents. Specifically, interfacial S vacancies induce adjacent under-coordinated S atoms to form Fe-S bonds as a rapid electron-transfer pathway for yielding a Z-scheme band alignment. Moreover, these S vacancies further modulate the strong coupling interaction to generate a nitrogenase-analogous Mo-Fe heteronuclear unit and induce the upward shift of the d-band center. This bioinspired interface structure effectively suppresses electrostatic repulsion between neighboring *CO and *COH intermediates via d-p hybridization, ultimately facilitating an asymmetric C-C coupling to achieve a remarkable solar-to-chemical efficiency of 0.565% with a superior selectivity of 84.9% for ethylene production. Further strengthened by MoSx/WO3, our design unveils a promising platform for optimizing interfacial electron transfer and offers a new option for C2+ synthesis from CO2 and H2O using copper-free and noble metal-free catalysts.

RESUMO

Low molecular weight polysaccharides had higher bio-activity and bioavailability compared to ultra-high molecular weight polysaccharides, this study aimed to obtain low molecular weight polysaccharides from Tremella fuciformis (TFLP) by using high-temperature and high-pressure assisted hydrochloric acid method to degrade Tremella fuciformis polysaccharides (TFP), and the structural characteristics, in vivo antioxidant and immune enhancing activities of TFP and TFLP was explored through Caenorhabditis elegans (C. elegans) and mice model. It was found that TFP and TFLP were acidic polysaccharides with molecular weights of 2238 kDa and 3 kDa, respectively. The glycosidic bonding of TFP and TFLP was mainly composed of different configurations of mannopyranose. TFP and TFLP had excellent in vivo antioxidant activity and stress resistance by regulating the mRNA transcription level and metabolites in C. elegans. Results also showed that TFP and TFLP could enhance the antioxidant capacity and immunity of serum, spleen and small intestine tissues in normal mice and cyclophosphamide-induced immunosuppressive mice through regulating the relative transcription and expression levels of anti-inflammatory related signaling factors, and it has found that TFLP showed better immune enhancement and antioxidant activity than TFP. In addition, Akkermansia, Bacteroides and Alloprevotella were characteristic bacteria at the genus level in immunosuppressed mice intervened with TFLP, with a significant increase in relative abundance. The content of SCFAs significantly increased in immunosuppressed mice by TFLP. These results indicated that TFP and TFLP had potential in vivo antioxidant and immune enhancing activities.

RESUMO

This study aims to understand the repercussions of the COVID-19 pandemic on hospitalized patients with peripheral arterial disease (PAD) in China, who did not contract SARS-CoV-2. We conducted a multicenter cross-sectional analysis comparing the characteristics and outcomes of hospitalized PAD patients across two distinct periods: Pre-pandemic (P1, from January 2018 to December 2019) and during the pandemic (P2, from January 2020 to December 2021). During P1, 762 hospitalized patients were treated, with an average age of 72.3 years, while 478 patients were treated in P2, with an average age of 65.1 years. Notably, hospitalized patients admitted during the pandemic (P2) exhibited a significantly higher incidence of chronic limb-threatening ischemia (CLTI, 70% vs 54%), diabetic foot infection (47% vs 29%), and infra-popliteal lesions (28% vs 22%). Furthermore, these patients demonstrated a marked deterioration in their Rutherford category and an increased mean score in the Wound, Ischemia, and foot Infection classification system (WIfI). Treatment during the pandemic emerged as a predictor of reduced procedural success and increased major adverse limb events. Factors such as the presence of diabetic foot infection, renal impairment, and deteriorating WIfI scores were identified as independent risk indicators for major adverse limb events. Our results demonstrate that intensive care was provided to severe cases of PAD even during the challenging circumstances of the COVID-19 pandemic. Despite the unprecedented pressures on healthcare systems, patients with severe PAD, particularly those with CLTI, continued to receive necessary in-patient care. The findings underscore the importance of timely medical interventions and extended follow-up for patients exhibiting high-risk factors.

Assuntos

COVID-19 , Doença Arterial Periférica , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Idoso , Doença Arterial Periférica/epidemiologia , Estudos Transversais , Feminino , Masculino , China/epidemiologia , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Pé Diabético/epidemiologia , Hospitalização , Pandemias , Fatores de Risco , Idoso de 80 Anos ou mais

RESUMO

Hence, N,S-CDs with photoluminescent property were simply synthesized via a one-step hydrothermal method. Combined with the commercial reagent Ce4+, a ratiometric fluorescence assay for ascorbic acid (AA) detection was established. Ce4+, possessing oxidization, could directly oxidize o-phenylenediamine (OPD) to form the yellow fluorescent product oxOPD. Under the excitation wavelength of 370 nm, oxOPD had a maximum fluorescence emission at 562 nm. Meanwhile, due to the occurrence of the inner filter effect (IFE), oxOPD quenched the fluorescence of N,S-CDs. However, ascorbic acid (AA) inhibited the oxidation of Ce4+, causing the fluorescence of oxOPD at 562 nm to decrease, accompanied by an increase in the fluorescence belonging to N,S-CDs at 450 nm. Thus, a Ce4+-assisted ratiometric fluorescence method was established for AA detection. The two fluorescence output signals in this method had opposite changing trends, which could reduce system errors and improve the accuracy. This method was successfully applied to the determination of AA in drugs and fruits.

Assuntos

Ácido Ascórbico , Carbono , Pontos Quânticos , Espectrometria de Fluorescência , Ácido Ascórbico/análise , Ácido Ascórbico/química , Carbono/química , Pontos Quânticos/química , Cério/química , Fluorescência , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química

RESUMO

Access cavity preparation represents the initial step in root canal treatment. Minimally invasive approaches have gained increasing attention and involve advancements in the traditional access cavity preparation. Simultaneously, the development of three-dimensional finite element analysis (3D-FEA) has provided a theoretical foundation for evaluating the merits and drawbacks of various access cavity preparations. Studies using static loading 3D-FEA have suggested that conservative access cavity preparation reduces the concentration of stress in the cervical region, thereby strengthening fracture resistance. However, the lack of support from clinical data raises concerns about the validity of this suggestion. Conversely, studies involving cyclic loading 3D-FEA and dynamic loading 3D-FEA have challenged the prevailing perspectives by taking into account additional factors such as filling materials, thus providing a more comprehensive understanding of the impact of access cavity preparation on fracture resistance. Existing research lacks a comprehensive comparison of the different 3D-FEA methods, and this review fills this gap by providing a systematic assessment of different 3D-FEA methods and their applications in access cavity preparation.

RESUMO

This review provides a comprehensive overview of the recent advancements in research on ATF4 (Activating Transcription Factor 4) within the field of oncology. As a crucial transcription factor, ATF4 has garnered increasing attention for its role in cancer research. The review begins with an exploration of the regulatory mechanisms of ATF4, including its transcriptional control, post-translational modifications, and interactions with other transcription factors. It then highlights key research findings on ATF4's involvement in various aspects of tumor biology, such as cell proliferation, differentiation, apoptosis and survival, invasion and metastasis, and the tumor microenvironment. Furthermore, the review discusses the potential of targeting ATF4 as a novel therapeutic strategy for cancer treatment. It also explores how ATF4's interactions with existing anticancer drugs could inform the development of more effective therapeutic agents. By elucidating the role of ATF4 in tumor biology and its potential clinical applications, this review aims to provide new insights and strategies for cancer treatment.

RESUMO

OBJECTIVE: To evaluate the performance of a semi-automated artificial intelligence (AI) software program (CerebralDoc® system) in aneurysm detection and morphological measurement. METHODS: In this study, 354 cases of computed tomographic angiography (CTA) were retrospectively collected in our hospital. Among them, 280 cases were diagnosed with aneurysms by either digital subtraction angiography (DSA) and CTA (DSA group, n = 102), or CTA-only (non-DSA group, n = 178). The presence or absence of aneurysms, as well as their location and related morphological features determined by AI were evaluated using DSA and radiologist findings. Besides, post-processing image quality from AI and radiologists were also rated and compared. RESULTS: In the DSA group, AI achieved a sensitivity of 88.24% and an accuracy of 81.97%, whereas radiologists achieved a sensitivity of 95.10% and an accuracy of 84.43%, using DSA results as the gold standard. The AI in the non-DSA group achieved 81.46% sensitivity and 76.29% accuracy, as per the radiologists' findings. The comparison of position consistency results showed better performance under loose criteria than strict criteria. In terms of morphological characteristics, both the DSA and the non-DSA groups agreed well with the diagnostic results for neck width and maximum diameter, demonstrating excellent ICC reliability exceeding 0.80. The AI-generated images exhibited superior quality compared to the standard software for post-processing, while also demonstrating a significantly reduced processing time. CONCLUSIONS: The AI-based aneurysm detection rate demonstrates a commendable performance, while the extracted morphological parameters exhibit a remarkable consistency with those assessed by radiologists, thereby showcasing significant potential for clinical application.

Assuntos

Angiografia Digital , Inteligência Artificial , Angiografia por Tomografia Computadorizada , Aneurisma Intracraniano , Sensibilidade e Especificidade , Humanos , Estudos Retrospectivos , Angiografia Digital/métodos , Feminino , Masculino , Angiografia por Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Aneurisma Intracraniano/diagnóstico por imagem , Idoso , Adulto , Software , Idoso de 80 Anos ou mais , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Angiografia Cerebral/métodos

RESUMO

Single atom catalysts (SACs) are promising non-precious catalysts for oxygen reduction reaction (ORR). Unfortunately, the ORR SACs usually suffer from unsatisfactory activity and in particular poor stability. Herein, we report atomically dispersed manganese (Mn) embedded on nitrogen and sulfur co-doped graphene as an efficient and robust electrocatalyst for ORR in alkaline electrolyte, realizing a half-wave potential (E1/2) of 0.883 V vs. reversible hydrogen electrode (RHE) with negligible activity degradation after 40,000 cyclic voltammetry (CV) cycles in 0.1 M KOH. Introducing sulfur (S) to form Mn-S coordination changes the spin state of single Mn atom from high-spin to low-spin, which effectively optimizes the oxygen intermediates adsorption over the single Mn atomic sites and thus greatly improves the ORR activity.

RESUMO

BACKGROUND: Non-endometrioid endometrial carcinomas (NEEC) are characterized by their rarity and adverse prognoses. This study evaluates the outcomes of open versus minimally invasive surgery (MIS) in NEEC patients stratified by prognostic risks according to the 2020 ESGO-ESTRO-ESP risk classification guidelines. METHODS: A retrospective analysis was performed on 99 NEEC patients who underwent initial surgery at Fujian University Cancer Hospital. Patients were categorized into two groups: those undergoing MIS and those undergoing open surgery. We compared disease-free survival (DFS) and overall survival (OS) between these groups. Cox regression analysis was employed to identify risk factors for DFS, which were further validated via bootstrap statistical methods. RESULTS: The study included 31 patients in the MIS group and 68 in the open surgery group. The demographics and clinical characteristics such as age, body mass index, comorbidities, histological subtypes, and FIGO stage were similar between groups (P > 0.05). The MIS group experienced ten recurrences (1 vaginal, 2 lymph nodes, 7 distant metastases), whereas the open surgery group had seven recurrences (1 vaginal, 3 lymph nodes, 1 pelvis, 2 distant metastases), yielding recurrence rates of 10.3% versus 25.6% (P = 0.007). Besides lymphovascular space invasion (LVSI), surgical approach was also identified as an independent prognostic factor for DFS in high-risk patients (P = 0.037, 95% CI: 1.062-7.409). The constructed nomogram demonstrated a robust predictive capability with an area under the curve (AUC) of 0.767. Survival analysis for high- and intermediate-risk patients showed no significant differences in OS between the two groups (Phigh risk = 0.275; Pintermediate-risk = 0.201). However, high-risk patients in the MIS group exhibited significantly worse DFS (P = 0.001). CONCLUSION: This investigation is the inaugural study to assess the impact of surgical approaches on NEEC patients within the framework of the latest ESGO-ESTRO-ESP risk classifications. Although MIS may offer clinical advantages, it should be approached with caution in high-risk NEEC patients due to associated poorer DFS outcomes.

Assuntos

Neoplasias do Endométrio , Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Feminino , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Guias de Prática Clínica como Assunto , Resultado do Tratamento , Medição de Risco/métodos , Fatores de Risco , Intervalo Livre de Doença

RESUMO

Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.

Assuntos

Proteínas de Bactérias , Biofilmes , Regulação Bacteriana da Expressão Gênica , Fator Proteico 1 do Hospedeiro , Pseudomonas aeruginosa , Quinolonas , Percepção de Quorum , RNA Bacteriano , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/metabolismo , Virulência , Biofilmes/crescimento & desenvolvimento , Fator Proteico 1 do Hospedeiro/genética , Fator Proteico 1 do Hospedeiro/metabolismo , RNA Bacteriano/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Quinolonas/metabolismo , Quinolonas/farmacologia , Endorribonucleases/metabolismo , Endorribonucleases/genética , Animais , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo , Infecções por Pseudomonas/microbiologia , Humanos , Camundongos , Glicolipídeos/metabolismo

RESUMO

OBJECTIVE: To analyze the risk factors of percutaneous coronary intervention (PCI) no-reflow in patients with coronary heart disease (CHD) and construct a predictive nomogram model. METHODS: This retrospective study included 260 patients with CHD who underwent PCI in the Third Affiliated Hospital of Chongqing Medical University from January 2022 to December 2023. The subjects were divided into a PCI no-reflow group (n = 86) and normal reflow group (n = 174) based on thrombolysis in myocardial infarction (TIMI) blood flow grading. General data, PCI related data and laboratory indexes of patients were collected. Logistic regression was used to analyze the risk factors of no-reflow after PCI in CHD patients. Based on the significant variables from regression analysis, a nomogram prediction model was constructed by using R language. The accuracy of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve, and the decision curve was drawn to clarify the clinical utility of the model. Model performance metrics included area under the curve (AUC), accuracy, sensitivity and specificity. RESULTS: Multivariate logistic regression analysis showed that hypertension, cystatin C (Cys-C), hypersensitive c-reactive protein (hs-CRP) and platelet-to-lymphocyte ratio (PLR) were risk factors for no-reflow after PCI in CHD patients (OR > 1, P < 0.001), while ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS-13) and lymphocyte (LYM) were protective factors (OR < 1, P < 0.001). The nomogram prediction model based on the above risk factors showed good predictive value. The AUC of the nomogram prediction model in the training set was 0.967 (95% CI: 0.946-0.989), with a specificity of 0.923 and a sensitivity of 0.908. In the validation set, the AUC was 0.894 (95% CI: 0.817-0.971), with a specificity of 0.807 and a sensitivity of 0.857. The calibration curve indicated good agreement between the predicted and actual probabilities, and the decision curve showed clinical benefit across a range of threshold probabilities in both the training and validation sets (0.0-0.99). CONCLUSION: The risk factors affecting the occurrence of no-reflow after PCI in patients with CHD include hypertension, serum Cys-C, hs-CRP, PLR, ADAMTS-13 and LYM levels. The nomogram risk prediction model based on the above factors is valuable for identifying patients with high risk of no-reflow after PCI.

RESUMO

Background and Objective: Lung cancer remains a leading cause of cancer-related mortality globally, with drug resistance posing a significant challenge to effective treatment. The advent of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR-Cas9) technology offers a novel and precise gene-editing technology for targeting and negating drug resistance mechanisms in lung cancer. This review summarizes the research progress in the use of CRISPR-Cas9 technology for investigating and managing drug resistance in lung cancer treatment. Methods: A literature search was conducted using the Web of Science and PubMed databases, with the following keywords: [CRISPR-Cas9], [lung cancer], [drug resistance], [gene editing], and [gene therapy]. The search was limited to articles published in English from 2002 to September 2023. From the search results, studies that utilized CRISPR-Cas9 technology in the context of lung cancer drug resistance were selected for further analysis and summarize. Key Content and Findings: CRISPR-Cas9 technology enables precise DNA-sequence editing, allowing for the targeted addition, deletion, or modification of genes. It has been applied to investigate drug resistance in lung cancer by focusing on key genes such as epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), tumor protein 53 (TP53), and B-cell lymphoma/leukemia-2 (BCL2), among others. The technology has shown potential in inhibiting tumor growth, repairing mutations, and enhancing the sensitivity of cancer cells to chemotherapy. Additionally, CRISPR-Cas9 has been used to identify novel key genes and molecular mechanisms contributing to drug resistance, offering new avenues for therapeutic intervention. The review also highlights the use of CRISPR-Cas9 in targeting immune escape mechanisms and the development of strategies to improve drug sensitivity. Conclusions: The CRISPR-Cas9 technology holds great promise for advancing lung cancer treatment, particularly in addressing drug resistance. The ability to precisely target and edit genes involved in resistance pathways offers a powerful tool for developing more effective and personalized therapies. While challenges remain in terms of delivery, safety, and ethical considerations, ongoing research and technological refinements are expected to further enhance the role of CRISPR-Cas9 in improving patient outcomes in lung cancer treatment.

RESUMO

This study investigated a sustainable approach through dielectric barrier discharge (DBD) enhanced Fenton technology coupling nanofiltration (NF) process for landfill leachate treatment. The DBD/Fe(II)/H2O2 system exhibited significant synergistic effects, removing 55.07 % of TOC and 53.79 % of UV254 within 60 min, respectively. Additionally, the DBD/Fe(II)/H2O2 system demonstrated exceptional performance in removing fluorescent substances and large molecular organic compounds, thereby reducing the formation of cake layer on the nanofiltration membrane. Moreover, membrane flux increased by 2.34 times, with reversible and irreversible resistances decreasing by 75.79 % and 81.55 %, respectively. Quenching experiments revealed ·OH as the primary active species for perfluorooctanoic acid (PFOA) degradation in the DBD/Fe(II)/H2O2 process. The degradation pathway of PFOA was also elucidated via capillary electrophoresis-quadrupole time-of-flight mass spectrometry analysis. Correlation analysis indicated that TOC and EEM were the primary fouling factors. Lastly, through an assessment of energy consumption, economic costs, and carbon dioxide emissions, the advantages and practical application potential of the DBD/Fe(II)/H2O2 system were demonstrated. In summary, the DBD/Fe(II)/H2O2 system emerges as a feasible strategy for NF pretreatment, holding immense potential for treating landfill leachate.

RESUMO

This study investigates the effect of twinning on the corrosion behavior of AZ31B magnesium alloy using solid solution heat treatment (SHT) and laser shock peening (LSP) techniques. The corrosion characteristics are assessed by scanning electron microscopy (SEM), scanning Kelvin probe force microscopy (SKPFM), zero resistance ammeter (ZRA), scanning vibrating electrode technique (SVET), and electrochemical tests. Results indicate that the twinning region in AZ31B magnesium alloy, enriched with { 10 1 ¯ 2 } tensile twins induced by laser shock, demonstrates increased corrosion susceptibility. This region exhibits higher electrochemical activity and an accelerated corrosion rate compared to the matrix region. Micro-galvanic coupling between the twinned and matrix regions promotes faster dissolution of the alloy. Additionally, the corrosion product film on the surface is extensively cracked and propagates to the matrix corrosion surface, confirming that { 10 1 ¯ 2 } tensile twins provide inadequate protection against corrosion in AZ31B alloy.