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OBJECTIVE: Diet-derived circulating antioxidants have been associated with functional outcome after ischemic stroke (IS), but the causality remains unclear. The aim of our study is to explore the potential causal effect of diet-derived circulating antioxidants on long-term functional outcome (at 3 months) following IS through the utilization of the Mendelian randomization (MR) approach. MATERIALS AND METHODS: For this two-sample MR analysis, genetic variants associated with the diet-derived circulating antioxidants, including selenium, zinc, vitamin A (retinol), vitamin C, and vitamin E (α-tocopherol and γ-tocopherol), were identified in a large-scale Genome-Wide Association Studies (GWAS) database and utilized as instrumental variables (IVs). Summary data for long-term functional outcome after IS were obtained from the Genetics of Ischemic Stroke Functional Outcome (GISCOME) network of 6021 patients. Our study used the Inverse-variance weighting method as our primary MR method and also performed a series of sensitivity analyses for pleiotropy and heterogeneity. RESULTS: We observed that selenium (odds ratio (OR)=0.81; 95 % confidence interval (CI): 0.68-0.97; p=0.02) was significantly associated with poor functional outcome (modified Rankin Scale score≥3) after IS. Genetic liabilities to other diet-derived circulating antioxidants were not strongly associated with functional outcome after IS (all p>0.05). Sensitivity analyses confirmed the reliability of these results. CONCLUSION: This MR study suggested the positive effect of selenium on the long-term functional outcome after IS. Giving a longer period of selenium exposure can be used as a potential treatment to improve recovery after IS.

RESUMO

Modulating the immunosuppressive tumor immune microenvironment (TIME) is considered a promising strategy for cancer treatment. However, effectively modulating the immunosuppressive TIME within hypoxic zones remains a significant challenge. In this work, we developed a hypoxia-responsive amphiphilic drug carrier using boron-dipyrromethene (BODIPY) dye-modified chitosan (CsB), and then fabricated a hypoxia-targeted nanotheranostic system, named CsBPNs, through self-assembly of CsB and pexidartinib (5-((5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl), PLX3397), an immunotherapeutic drug targeting tumor-associated macrophages (TAMs), for synergistic photothermal/immunotherapy and hypoxia imaging. CsBPNs demonstrated uniform size, good stability, and hypoxia-switchable fluorescence and photothermal effects, enabling deep penetration and hypoxia imaging capacities in three-dimensional tumor cell spheres and tumor tissues. In vitro and in vivo experiments showed that CsBPNs under laser irradiation promoted TAMs repolarization, reversed the immunosuppressive TIME, and enhanced the therapeutic outcome of PLX3397 in solid tumors by facilitating deep delivery into hypoxic regions and synergistic photothermal therapy. This work provides a new strategy for detecting and modulating the immunosuppressive TIME in hypoxic zones, potentially enabling more precise and effective photo-immunotherapy in the future.

RESUMO

The oxygen level in the tumor microenvironment (TME) plays a critical role in regulating cell fates such as proliferation, migration, apoptosis, and so forth. To better elucidate how hypoxia affects tumor cell behaviors, a series of microfluidic strategies have been utilized to generate an oxygen gradient covering both hypoxia and normoxia conditions. However, in most studies, some chemicals are introduced into microfluidic chips, causing the potential of their poor biocompatibility. The common oxygen gradient with linear variation does not allow the effects of specific oxygen concentrations on tumor cells to be analyzed accurately. In this paper, based on the physical method of gas diffusion, a microfluidic device integrated with an oxygen gradient generator is proposed for investigating effects of different hypoxia levels on responses of tumor cells. This device consists of three layers, i.e., upper layer, thin film layer, and bottom layer. The upper layer is used for introducing the initial gas and generating an oxygen gradient in the form of gas. The bottom layer is used for introducing cells and culture medium. The thin film layer separates the former two layers, allowing the gas to diffuse from the top to the bottom through it. The oxygen gradient in the bottom layer is finally generated in the form of dissolved oxygen. The device is fabricated using microfabrication technology. The effects of structural and working parameters of the device on the oxygen gradient are evaluated by finite element simulation. The oxygen gradient in cell culture channels is characterized by using oxygen-sensitive fluorescence materials. The proliferation and morphology of HeLa cells under specific oxygen levels are compared after culturing for 48 h. The oxygen gradient with a ladder-like distribution demonstrates that this microfluidic device can provide a prospective experimental platform for in vitro cell studies and revelation of the mechanism of tumor metastasis associated with a specific hypoxic microenvironment.

Assuntos

Oxigênio , Humanos , Oxigênio/química , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/instrumentação , Células HeLa , Microambiente Tumoral , Hipóxia Celular

RESUMO

Soluble guanylate cyclase (sGC) serves as a receptor of nitric oxide (NO) and is the core metalloenzyme in the NO signal transduction pathway. sGC plays a key role in the NO-cGMP signal transduction pathway and participates in various physiological processes, including cell differentiation, neuron transmission, and internal environment homeostasis. sGC consists of two subunits, α and ß, each subunit containing multiple isoforms. In this study, we cloned and analyzed the sGC-α1 gene in the silkworm Bombyx mori (BmsGC-α1). The BmsGC-α1 gene was expressed highest at the pupal stages. The highest BmsGC-α1 mRNA expression was observed in the head of fifth instar larvae and in fat body during the wandering stage of B. mori. Furthermore, we observed that feeding fifth instar larvae with thyroid hormone and nitroglycerin induced the expression of the BmsGC-α1 gene. Injection of BmsGC-α1 siRNA into silkworms at the prepupal stage resulted in a significant decrease in BmsGC-α1 expression levels at 48 and 72 h postinjection. After silencing BmsGC-α1, both the egg-laying amount and hatching rate of silkworm eggs were significantly reduced compared to the control group. These results suggest that BmsGC-α1 plays an important role in regulating the reproductive system of silkworms. This finding enhances our understanding of the functional diversity of sGC in insects.

Assuntos

Bombyx , Proteínas de Insetos , Larva , Guanilil Ciclase Solúvel , Animais , Bombyx/genética , Bombyx/crescimento & desenvolvimento , Bombyx/enzimologia , Guanilil Ciclase Solúvel/metabolismo , Guanilil Ciclase Solúvel/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Larva/crescimento & desenvolvimento , Larva/genética , Larva/metabolismo , Oviposição/genética , Filogenia , Sequência de Aminoácidos , Pupa/crescimento & desenvolvimento , Pupa/genética , Pupa/metabolismo , Feminino

RESUMO

The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy. Thereafter, M1NVs can induce M1 repolarization of TAMs, resulting in increased infiltration of cytotoxic T lymphocytes within the tumor to promote tumor regression. This study investigated the effect of phototherapy on the immune environment of liver cancer using single-cell RNA sequencing (scRNA-seq) by comparing HCC tissues before and after MPDA/ICG@M1NVs + NIR treatment. The results showed significant shifts in cell composition and gene expression, with decreases in epithelial cells, B cells, and macrophages and increases in neutrophils and myeloid cells. Additionally, gene analysis indicated a reduction in pro-inflammatory signals and immunosuppressive functions, along with enhanced B-cell function and anti-tumor immunity, downregulation of the Gtsf1 gene in the epithelial cells of the MPDA/ICG @M1NVs + NIR group, and decreased expression of the lars2 gene in immune subpopulations. Eno3 expression is reduced in M1 macrophages, whereas Clec4a3 expression is downregulated in M2 macrophages. Notably, the B cell population decreased, whereas Pou2f2 expression increased. These genes regulate cell growth, death, metabolism, and tumor environment, indicating their key role in HCC progression. This study highlights the potential for understanding cellular and molecular dynamics to improve immunotherapy.

RESUMO

Multiphase Pickering emulsions, including two or more active agents, are of great importance to effectively manage complicated wounds. However, current strategies based on Pickering emulsions are still unsatisfying since they involve only stabilization by inactive particles and encapsulation of the hydrophobic drugs in the oil phase. Herein, thyme essential oil (TEO) was encapsulated in the shell of functional tea polyphenol (TP)-curcumin (Cur) nanoparticles (TC NPs) to exemplarily develop a novel Pickering emulsion (TEO/TC PE). Hydrophobic Cur was loaded with hydrophilic TP to obtain TC NPs, and under homogenization, these TC NPs adsorbed on the surface of TEO droplets to form a stable core-shell structure. Owing to such an oil-in-water (O/W) structure, the sequential release of the first Cur from pH-responsive disintegrated TC NPs and then the leaked TEO from the emulsion yielded synergetic functions of TEO/TC PE, leading to enhanced antibacterial, biofilm elimination, antioxidant, and anti-inflammatory activities. This injectable TEO/TC PE was applied to treat the infected full-thickness skin defects, and satisfactory wound healing effects were achieved with rapid angiogenesis, collagen deposition, and skin regeneration. The present TEO/TC PE constituted entirely of plant-sourced active products is biosafe and expected to spearhead the future development of novel wound dressings.

Assuntos

Antibacterianos , Anti-Inflamatórios , Antioxidantes , Curcumina , Emulsões , Polifenóis , Chá , Cicatrização , Curcumina/química , Curcumina/farmacologia , Cicatrização/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Emulsões/química , Antibacterianos/química , Antibacterianos/farmacologia , Animais , Polifenóis/química , Polifenóis/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Chá/química , Camundongos , Nanopartículas/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Humanos , Thymus (Planta)/química , Staphylococcus aureus/efeitos dos fármacos

RESUMO

Nobiletin has been reported to protect against obesity-related metabolic disorders by enhancing the circadian rhythm; however its effects on lipid metabolism in adipose tissue are unclear. In this study, mice were fed with high-fat diet (HFD) for four weeks firstly and gavaged with 50 or 200 mg/kg bodyweight/day nobiletin at Zeitgeber time (ZT) 4 for another four weeks while still receiving HFD. At the end of the 8-week experimental period, the mice were sacrificed at ZT4 or ZT8 on the same day. Mature 3T3-L1 adipocytes were treated with nobiletin in the presence or absence of siBmal1, siRora, siRorc, SR8278 or SR9009. Nobiletin reduced the weight of white adipose tissue (WAT) and the size of adipocytes in WAT. At ZT4, nobiletin decreased the TG, TC and LDL-c levels and increased serum FFA level and glucose tolerance. Nobiletin triggered the lipolysis of mesenteric and epididymal WAT at both ZT4 and ZT16. Nobiletin increased the level of RORγ at ZT16, that of BMAL1 and PPARγ at ZT4, and that of ATGL at both ZT4 and ZT16. Nobiletin increased lipolysis and ATGL levels in 3T3-L1 adipocytes in Bmal1- or Rora/c- dependent manner. Dual luciferase assay indicated that nobiletin enhanced the transcriptional activation of RORα/γ on Atgl promoter and decreased the repression of RORα/γ on PPARγ-binding PPRE. Promoter deletion analysis indicated that nobiletin inhibited the suppression of PPARγ-mediated Atgl transcription by RORα/γ. Taken together, nobiletin elevated lipolysis in WAT by increasing ATGL levels through activating the transcriptional activity of RORα/γ and decreasing the repression of RORα/γ on PPARγ-binding PPRE.

Assuntos

Células 3T3-L1 , Tecido Adiposo Branco , Relógios Circadianos , Flavonas , Lipólise , Camundongos Endogâmicos C57BL , Animais , Flavonas/farmacologia , Lipólise/efeitos dos fármacos , Camundongos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Masculino , Relógios Circadianos/efeitos dos fármacos , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/genética , Dieta Hiperlipídica/efeitos adversos , PPAR gama/metabolismo , PPAR gama/genética , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Lipase/metabolismo , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Aciltransferases , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares

RESUMO

With increasing land resource constraints, wetlands, as ecological hotspots, are expected to enhance biogeochemical processes to mitigate nitrogen (N) pollution, particularly nitrate-nitrogen (NO3--N). However, the interactions among bacteria, algae, and macrophytes in wetlands, which are crucial for N removal, remain largely unknown. This study explored how macrophyte coverage influences bacterial-algal interactions, shifting from mutualism to inhibition, thereby affecting N removal. Moderate coverage enhanced NO3--N and total nitrogen (TN) removal (P < 0.05), which was correlated with increased microbial abundance (P < 0.05). This may have resulted from moderate algal photosynthesis, reduced physiological stress, and the expansion of ecological niches for microbes. Insufficient coverage promoted algal growth (chlorophyll-a > 31.8 µg·L-1), leading to increased competition for substrates and elevated pH, which further inhibited bacterial activity. Excessive coverage also inhibited bacterial activity by reducing illumination and oxidation-reduction potential. Consequently, insufficient and excessive coverage decreased N removal efficiencies by 2.7-15.7 % (NO3--N) and 3.7-11.1 % (TN) while increasing methane emission potential by 1.4-6.9 times compared with moderate coverage. These findings offer insights into solving NO3--N contamination using near-natural methods and balancing the ecological and practical considerations for small wetlands.

Assuntos

Bactérias , Nitratos , Simbiose , Áreas Alagadas , Nitratos/metabolismo , Bactérias/metabolismo , Poluentes Químicos da Água/metabolismo , Nitrogênio/metabolismo , Biodegradação Ambiental

RESUMO

OBJECTIVE: To analyze the relational factors influencing the formation of cauda equina redundant nerve roots (RNRs) of the lumbar spinal stenosis. METHODS: Clinical data of 116 patients with lumbar spinal stenosis treated from January 2016 to June 2019 were retrospectively analyzed. The patients were divided into redundant nerve roots(RNRs) group and non-RNRs group based on the presence or absence of RNRs on sagittal T2-weighted MRI. In the non-RNRs group, there were 74 patients, including 38 males and 36 females with an average age of (62.00±10.41) years old, the body mass index (BMI) was (23.09±2.22) kg·m-2;the maximum stenosis segment was L2-L3 in 12 cases, L3-L4 in 38, L4-L5 in 20, and L5S1 in 4, respectively. In the RNRs group, there were 42 patients, including 18 males and 24 females with an average age of (63.36±8.73) years old, the BMI was (22.63±2.60) kg·m-2;the maximum stenosis segment was L2-L3 in 3 cases, L3-L4 in 9, L4-L5 in 27 and L5S1 in 3, respectively. MRI was performed in the supine position to observe the conshape and morphology of the redundant nerve in the sagittal position. The preoperative low back and leg pain visual analogue scale(VAS), and preoperative Oswestry disability index(ODI) were analyzed, and the rate of spondylolisthesis and ligamentum flavum hypertrophy were compared. Simultaneously, the inter-vertebral height, intervertebral foramen height, inter-vertebral height+vertebral height, median sagittal diameter at the inter-vertebral space level(DIW-MSD), median sagittal diameter at the pedicel level(DV-MSD), range of motion(ROM) of the stenotic segment were measured and analyzed. RESULTS: Among the 116 patients with lumbar spinal stenosis, 42 patients developed RNRs, with an incidence of 36.2%. There were no significant differences in gender, age, BMI, preoperative VAS for lumbar and leg pain and ODI between two groups(P>0.05). There were statistically significant differences regard to the duration of symptoms and the rate of spondylolisthesis and ligamentum flavum hypertrophy (P<0.05);the inter-vertebral height, intervertebral foramen height, inter-vertebral height+vertebral height, DIW-MSD, ROM of the stenotic segment were also significantly different between two groups(P<0.05). However, there was no significant difference in DV-MSD between two groups(P>0.05). CONCLUSION: The inter-vertebral height, inter-vertebral foramen height, inter-vertebral height+vertebral height, DIW-MSD and ROM of the stenotic segment were the crucial factors related to RNRs in lumbar spinal stenosis.

Assuntos

Cauda Equina , Vértebras Lombares , Estenose Espinal , Humanos , Estenose Espinal/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Vértebras Lombares/diagnóstico por imagem , Cauda Equina/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Imageamento por Ressonância Magnética

RESUMO

BACKGROUND: The administration of tranexamic acid (TXA) during spinal surgery has been shown to reduce blood loss. However, the efficacy and safety of intravenous TXA (ivTXA) and topical TXA (tTXA) are poorly documented. The present meta-analysis aimed to compare the efficacy and safety of ivTXA and tTXA administration in spinal surgery. METHODS: Potentially relevant academic articles were identified from PubMed, Ovid, Cochrane Library, CNKI database, and Wanfang Data from the date of inception until March 1, 2024. Randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) were included in our meta-analysis if they compared the efficacy and safety of ivTXA versus tTXA administration during spinal surgery. Secondary sources were identified from the references of the included literature. The meta-analysis was performed in accordance with the guidelines of the Cochrane Reviewer's Handbook and the PRISMA statement. Data were summarized using RevMan 5.3 software from Denmark. RESULTS: Four RCTs and one non-RCT met our inclusion criteria. The pooled outcomes demonstrated that ivTXA groups compared with tTXA groups had significantly less amount of total blood loss [weighted mean difference (WMD)=-159.55, 95% CI (-181.91,-137.19), P < 0.00001], hidden blood loss [WMD=-132.27, 95% CI (-159.81, -104.72), P < 0.00001], intraoperative blood loss [WMD=-86.22, 95% CI (-99.13, -73.31), P < 0.00001, I2 = 96%], and more high postoperative hemoglobin level [WMD = 8.96, 95% CI (5.18, 12.75), P < 0.00001, I2 = 29%], and less transfusion rate [risk ratio (RR) = 1.11, 95% CI (0.81,1.52), P = 0.50, I2 = 94%]. The pooled results showed no significant difference in thromboembolic events (deep venous thrombosis and pulmonary embolism) between the two groups. CONCLUSION: Our meta-analysis demonstrated that ivTXA was more effective than tTXA in inducing hemostatic effect during spinal surgery. However, the risk of a thrombotic event was not different between the two administration methods of TXA. More high quality RCTs are needed to further confirm our conclusions.

Assuntos

Administração Intravenosa , Administração Tópica , Antifibrinolíticos , Perda Sanguínea Cirúrgica , Ácido Tranexâmico , Humanos , Administração Intravenosa/efeitos adversos , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Coluna Vertebral/cirurgia , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/efeitos adversos , Resultado do Tratamento

RESUMO

Innovation competence is an essential core literacy skill for 21st century students. While some research exists on innovation competence in college students, there has been relatively little examination of the factors influencing this competence in children and adolescents aged 10 to 15. This study evaluated innovation competence among students from Suzhou, China, focusing on four key social and emotional skills: creativity, curiosity, cooperation, and responsibility. Data from the Organization for Economic Cooperation and Development were utilized for this analysis. Hierarchical linear modelling was applied to analyze potential factors at both individual and school levels influencing innovation competence across family and school environments. We calculated a t-test statistic to compare factors between the two cohorts. Factors significantly influencing children and adolescents' innovation competence included socio-economic status, time spent engaging in online gaming, time spent browsing the Internet for information, and the perceived cooperative climate atschool. Gender significantly influenced only adolescents' innovation competence, while teachers' disruptive behaviors had an impact solely on children's innovation competence. Apart from time spent engaging in online gaming and browsing the Internet for information, the effects of other variables showed significant differences between the groups. The findings highlight the need for targeted support from families, schools, and society to foster students' innovation competence.

RESUMO

The COVID-19 outbreak led to widespread school closures and the shift to remote teaching, potentially resulting in lasting negative impacts on teachers' psychological well-being due to increased workloads and a perceived lack of administrative support. Despite the significance of these challenges, few studies have delved into the long-term effects of perceived instructional leadership on teachers' psychological health. To bridge this research gap, we utilized longitudinal data from 927 primary and secondary school teachers surveyed in two phases: Time 1 in mid-November 2021 and Time 2 in early January 2022. Using hierarchical linear modeling (HLM), our findings revealed that perceptions of instructional leadership, especially the "perceived school neglect of teaching autonomy" at Time 1 were positively correlated with burnout levels at Time 2. Additionally, burnout at Time 2 was positively associated with psychological distress and acted as a mediator between the "perceived school neglect of teaching autonomy" and psychological distress. In light of these findings, we recommend that schools prioritize teachers' teaching autonomy and take proactive measures to mitigate burnout and psychological distress, aiming for the sustainable well-being of both teachers and students in the post-pandemic era.

Assuntos

Esgotamento Profissional , COVID-19 , Liderança , Bem-Estar Psicológico , Professores Escolares , Humanos , Esgotamento Profissional/psicologia , Esgotamento Profissional/prevenção & controle , COVID-19/psicologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Longitudinais , Saúde Mental , Pandemias , Angústia Psicológica , SARS-CoV-2 , Professores Escolares/psicologia , Instituições Acadêmicas , Inquéritos e Questionários

RESUMO

O3-type NaNi0.5Mn0.5O2 (NNM) is very competitive for sodium-ion batteries (SIBs) due to its high capacity and easy production. Nevertheless, the intricate phase transitions during the charging-discharging significantly impede its practical application. This paper proposes a strategy for successfully synthesizing NaNi0.5Mn0.3Ti0.2O2 (NNMT) by combining coprecipitation and a high-temperature solid-state method. This method introduces Ti elements while retaining the electrochemically active Ni2+ content, thus, the NNMT has a high initial specific capacity of 151.4 mAh g-1 at 1 C. It is demonstrated that introducing Ti4+ leads to the transition metal layers becoming disordered by ex situ XRD, thus mitigating the irreversible phase transition of the material. In addition, Ti4+ does not have an outer electron, which can reduce electron delocalization in the transition metal layer and improve the material's cyclic stability. The NNMT possesses a capacity retention rate of 60.66% after 150 cycles, much higher than the initial NNM's 18.96%. It also exhibits an excellent discharge capacity of 86.8 mAh g-1 at 5 C. In conclusion, the cycling and rate performance of the Ti-substituted NNMT are greatly improved without capacity loss, which offers innovative concepts for the modification means of the SIBs layered oxide cathode materials.

RESUMO

Background: Breast cancer is the most widespread malignant tumor worldwide. Single-cell sequencing technology offers novel insights and methods to understand the onset, progression, and treatment of tumors. Nevertheless, there is currently an absence of a thorough and unbiased report on the comprehensive research status of single-cell sequencing in breast cancer. This study seeks to summarize and quantify the dynamics and trends of research on breast cancer single-cell sequencing by bibliometric analysis. Methods: Research articles and reviews related to breast cancer single-cell sequencing were selected from the WoSCC database. Visualization of data regarding countries, institutions, authors, references, and keywords was performed by CiteSpace and VOSviewer software. Results: 583 articles and reviews were analyzed in this study. The quantity of publications related to breast cancer single-cell sequencing has been increasing annually. These studies originate from 302 institutions in 46 countries, with YMAX S WICHA producing the most publications and WANG Y being the most cited author. Nature Communications is the most researched journal, while Nature holds the highest number of citations. These journals predominantly cover topics in the molecular/biological/immunological fields. Moreover, an analysis of reference and keyword bursts revealed that current research trends in this area are primarily centered on "clonal evolution," "tumor microenvironment," and "immunotherapy." Conclusion: Breast cancer single-cell sequencing is a rapidly growing area of scientific interest. Future research requires more frequent and in-depth collaborations among countries, institutions, and authors. Furthermore, "clonal evolution," "tumor microenvironment," and "immunotherapy" are likely to become major focal points in upcoming research on breast cancer single-cell sequencing.

RESUMO

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance. Now, the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs. However, data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance mutations. Therefore, finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system (UPS) has emerged as a focus. The UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological processes. In recent years, the study of UPS in hematological malignant tumors has resulted in effective treatments, such as bortezomib in the treatment of multiple myeloma and mantle cell lymphoma. In CML, the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL, interfering with CML-related signaling pathways, and negatively or positively affecting leukemia stem cells. Some of these molecules may help overcome TKI resistance and treat CML. In this review, the mechanism of TKI resistance is briefly described, the components of UPS are introduced, existing studies on UPS participating in TKI resistance are listed, and UPS as the therapeutic target and strategies are discussed.

RESUMO

In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin-eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia-reperfusion injury.

Assuntos

Cobre , Dissulfiram , Homeostase , Inflamação , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Dissulfiram/farmacologia , Camundongos , Cobre/metabolismo , Homeostase/efeitos dos fármacos , Masculino , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Regulação para Baixo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Modelos Animais de Doenças , Proteínas Ferro-Enxofre/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Apoptose/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Receptor 4 Toll-Like/metabolismo

RESUMO

Therapy-induced modulation of the tumor microenvironment (TME) to overcome the immunosuppressive TME is considered to be an opportunity for cancer treatment. However, monitoring of TME modulation during the therapeutic process to accurately determine immune responses and adjust treatment plans in a timely manner remains to be challenging. Herein, we report a carrier-free nanotheranostic system (CANPs) assembled by two boron dipyrromethene (BODIPY) dyes, a sonophotosensitizer C-BDP, and a nitric oxide (NO) probe amino-BODIPY (A-BDP). CANPs can exert combined sonophototherapeutic effects of C-BDP under ultrasound and light irradiation and simultaneously induce inflammatory TME, as well as emit bright fluorescence via A-BDP by monitoring tumor-associated macrophages (TAMs) repolarization through the released NO in vitro and in vivo. Of note, transforming growth factor-ß (TGF-ß) could be the key cytokine involved in the sonophototherapy-induced TME reprogramming. By virtue of high physiological stability, good biocompatibility, and effective tumor targetability, CANPs could be a potential nanotheranostic system for the simultaneous induction and detection of TME reprogramming triggered by sonophototherapy.

Assuntos

Nanomedicina Teranóstica , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Animais , Camundongos , Porfobilinogênio/análogos & derivados , Porfobilinogênio/química , Porfobilinogênio/farmacologia , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Compostos de Boro/química , Compostos de Boro/farmacologia , Óxido Nítrico/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Feminino , Nanopartículas/química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Células RAW 264.7

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Patients with IBD are at an increased risk for postoperative complications following surgery. The goal of this study is to investigate if inflammatory bowel disease (IBD) is a risk factor for complications following lumbar discectomy. METHODS: We identified IBD patients who underwent lumbar discectomy for lumbar disc herniation (LDH) and matched to them with controls without IBD in a1:5 ratio. We excluded patients with a history of spinal injury, cancer, infection, trauma, or surgery to remove the digestive tract. We used multivariate logistic regression analyses to compare postoperative outcomes, including 90-day complications, 90-day emergency department visits, and 90-day readmissions. In addition, 2-year re-discectomy rates and a 3-year lumbar fusion rate were compared between the cohorts. RESULTS: After applying the study criteria, we identified 6134 IBD patients with LDH for further analysis. With the exception of dura tears, patients with IBD had significantly higher rates of medical complications, incision-related complications, ED visits, and readmission rates compared to patients without IBD, especially for the 2-year and 3-year rates of disc recurrence and revision surgery. CONCLUSIONS: Patients with IBD who underwent lumbar discectomy are at a significantly higher rate of complications. Therefore, spine surgeons and other health care providers should be aware of this higher risk associated with IBD patients and properly treat the patients' IBD before surgery to lower these risks.

RESUMO

Extraintestinal Pathogenic Escherichia coli (ExPEC) pose a significant threat to human and animal health. However, the diversity and antibiotic resistance of animal ExPEC, and their connection to human infections, remain largely unexplored. The study performs large-scale genome sequencing and antibiotic resistance testing of 499 swine-derived ExPEC isolates from China. Results show swine ExPEC are phylogenetically diverse, with over 80% belonging to phylogroups B1 and A. Importantly, 15 swine ExPEC isolates exhibit genetic relatedness to human-origin E. coli strains. Additionally, 49 strains harbor toxins typical of enteric E. coli pathotypes, implying hybrid pathotypes. Notably, 97% of the total strains are multidrug resistant, including resistance to critical human drugs like third- and fourth-generation cephalosporins. Correspondingly, genomic analysis unveils prevalent antibiotic resistance genes (ARGs), often associated with co-transfer mechanisms. Furthermore, analysis of 20 complete genomes illuminates the transmission pathways of ARGs within swine ExPEC and to human pathogens. For example, the transmission of plasmids co-harboring fosA3, blaCTX-M-14, and mcr-1 genes between swine ExPEC and human-origin Salmonella enterica is observed. These findings underscore the importance of monitoring and controlling ExPEC infections in animals, as they can serve as a reservoir of ARGs with the potential to affect human health or even be the origin of pathogens infecting humans.

Assuntos

Antibacterianos , Infecções por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli Extraintestinal Patogênica , Filogenia , Doenças dos Suínos , Animais , Suínos , China/epidemiologia , Escherichia coli Extraintestinal Patogênica/genética , Escherichia coli Extraintestinal Patogênica/efeitos dos fármacos , Escherichia coli Extraintestinal Patogênica/isolamento & purificação , Escherichia coli Extraintestinal Patogênica/patogenicidade , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Doenças dos Suínos/microbiologia , Proteínas de Escherichia coli/genética , Antibacterianos/farmacologia , Humanos , Farmacorresistência Bacteriana Múltipla/genética , Plasmídeos/genética , Genoma Bacteriano/genética , Sequenciamento Completo do Genoma , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genética , beta-Lactamases/genética

RESUMO

In this research, a range of Pt/CeO2 catalysts featuring varying Pt-O-Ce bond contents were developed by modulating the oxygen vacancies of the CeO2 support for toluene abatement. The Pt/CeO2-HA catalyst generated a maximum quantity of Pt-O-Ce bonds (possessed the strongest metal-support interaction), as evidenced by the visible Raman results, which demonstrated outstanding toluene catalytic performance. Additionally, the UV Raman results revealed that the strong metal-support interaction stimulated a substantial increase in oxygen vacancies, which could facilitate the activation of gaseous oxygen to generate abundant reactive oxygen species accumulated on the Pt/CeO2-HA catalyst surface, a conclusion supported by the H2-TPR, XPS, and toluene-TPSR results. Furthermore, the results from quasi-in situ XPS, in situ DRIFTS, and DFT indicated that the Pt/CeO2-HA catalyst with a strong metal-support interaction led to improved mobility of reactive oxygen species and lower oxygen activation energies, which could transfer a large number of activated reactive oxygen species to the reaction interface to participate in the toluene oxidation, resulting in the relatively superior catalytic performance. The approach of tuning the metal-support interaction of catalysts offers a promising avenue to develop highly active catalysts for toluene degradation.