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Previous studies have shown that the heterogeneity of tumor-associated fibroblasts (CAFs) in the tumor microenvironment may play a critical role in tumorigenesis; however, the biological function of CAFs in pancreatic cancer is still controversial. In this study, we found that CD105-positive (CD105+) CAF-derived exosomes significantly promoted the proliferative and invasive metastatic abilities of pancreatic cancer cells. Furthermore, RNA-seq and qRTâPCR experiments revealed circAMPK1 as a key molecule in exosomes from CD105+ CAFs that mediates the malignant progression of pancreatic cancer. Furthermore, we demonstrated that circAMPK1 encodes a novel protein (AMPK1-360aa) in pancreatic cancer cells. This protein competes with AMPK1 to bind to the ubiquitination ligase NEDD4, which inhibits AMPK1 protein degradation and ubiquitination and thereby increases AMPK1 levels. Finally, we demonstrated that AMPK1-360aa induces cellular autophagy via NEDD4/AMPK1 to promote the proliferation and invasion of pancreatic cancer cells. In summary, circAMPK1 in CD105+ CAF-derived exosomes may mediate pancreatic cancer cell proliferation and invasive metastasis by inducing autophagy in target cells. Moreover, circAMPK1 may competitively bind to ubiquitinating enzymes through the encoded protein AMPK1-360aa, which in turn inhibits the ubiquitination-mediated degradation of AMPK1 and contributes to the upregulation of AMPK1 expression, thus inducing cellular autophagy to mediate the malignant progression of pancreatic cancer.
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Background: This study aimed to investigate the effect of different doses of dexmedetomidine combined with sufentanil on postoperative analgesia in developmental hip dislocation in children after Salter osteotomy. Methods: The clinical data of 98 children with developmental hip dislocation, who underwent Salter osteotomy in our center between January 2020 and February 2023, were selected. The children were randomly divided into four groups based on the application of patient-controlled intravenous analgesia (sufentanil + granisetron ± dexmedetomidine). All children received 1â µg/kg/day of sufentanil and 3â mg of granisetron. Group A did not receive dexmedetomidine, and Groups B, C, and D received 0.5, 0.75, and 1.0â µg/kg/day of dexmedetomidine, respectively. The pain indicators and immune factor levels of children in each group were compared. Results: The heart rate (HR) and respiratory rate (RR) 2â h after operation in Groups C and D were significantly lower than those in Groups A and B (P < 0.05). The pain scores decreased over time after treatment in all groups. When compared at the same time point, children in Group D had the lowest pain scores, which were significantly lower than the other three groups (P < 0.05). The total consumption of sufentanil in Groups C and D was significantly lower than that in Group A (P < 0.05). On the first day after surgery, the children in Group D had lower levels of serum adrenocorticotropic hormone, interleukin-6, and corticosterone than those in Group A (P < 0.05). Conclusion: Administration of 1.0â µg/kg/day of dexmedetomidine combined with sufentanil in intravenous controlled analgesia after Salter osteotomy for developmental hip dislocation in children has a better analgesic effect, less consumption of sufentanil, and low incidence of opioid adverse reactions.
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Catalytic conversion of carbon dioxide (CO2) into value-added chemicals is of pivotal importance, well the cost of capturing CO2 from dilute atmosphere is super challenge. One promising strategy is combining the adsorption and transformation at one step, such as applying alkali solution that could selectively reduce carbonate (CO3 2-) as consequences of CO2 adsorption. Due to complexity of this system, the mechanistic details on controlling the hydrogenation have not been investigated in depth. Herein, Ru/TiO2 catalyst was applied as a probe to elucidate the mechanism of CO3 2- activation, in which with thermodynamic and kinetic investigations, a compact Langmuir-Hinshelwood reaction model was established which suggests that the overall rate of CO3 2- hydrogenation was controlled by a specific C-O bond rupture elementary step within HCOO- and the Ru surface was mainly covered by CO3 2- or HCOO- at independent conditions. This assumption was further supported by negligible kinetic isotope effects (kH/kD≈1), similarity on reaction barriers of CO3 2- and HCOO- hydrogenation (ΔH≠ hydr,Na2CO3 and ΔH≠ hydr,HCOONa) and a non-variation of entropy (ΔS≠ hydr≈0). More interestingly, the alkalinity of the solution is certainly like a two sides in a sword and could facilitate the adsorption of CO2 while hold back catalysis during CO3 2- hydrogenation.
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Background: Fungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest. Objectives: This study aimed to provide evidence for the early warning and management of fungal infections. Methods: We analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed. Results: A total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053-1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015-1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855-0.970) were an independent risk factor for empirical antifungal therapy. Conclusion: The most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.
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Objective: Unresectable hepatocellular carcinoma (uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization (TACE) for the treatment of uHCC. Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival (PFS), objective response rate (ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while survival analysis was conducted through Kaplan-Meier curve analysis for overall survival (OS) and PFS. Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval (95% CI), 5.3-14.6] months, and the median PFS (mPFS) was 15.5 (95% CI, 5.4-NA) months. Median OS (mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate (DCR) was 70.6%. AEs were reported in 27 (79.4%) patients. The most frequently reported AEs (with an incidence rate >10%) included abnormal liver function (52.9%), abdominal pain (44.1%), abdominal distension and constipation (29.4%), hypertension (20.6%), leukopenia (17.6%), constipation (17.6%), ascites (14.7%), and insomnia (14.7%). Abnormal liver function (14.7%) had the most common grade 3 or higher AEs. Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for uHCC, showcasing a promising therapeutic strategy for managing uHCC.
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The treatment of infected tibial bone defects can be challenging for the orthopedic surgeon. Therefore, the aim of the present study was to compare the fixation endurance, bone union time, lower limb joint function and complications associated with different fixation methods in the treatment of bone defects caused by debridement in the treatment of post-traumatic osteomyelitis. The clinical data of 55 patients with infected bone defects of the lower extremities following traumatic injury, who had undergone radical debridement between January 2017 and September 2020, were retrospectively analyzed. The patients were divided into three groups according to the type of fixation during reconstruction, namely the external fixation (EX), internal fixation (IX) and non-contact locking plate (LP) groups. The demographic data, time to bone union, bacterial culture results, complications and Self-Rating Anxiety Scale (SAS) scores of the patients were compared among the three groups. The results indicated that the differences in time to bone union and recurrence rates of osteomyelitis among the three groups were not statistically significant. By contrast, functional status after surgery was significantly higher in the LP group compared with the EX group. In total, 8/22 patients (36.4%) in the EX group, 4/13 patients (30.8%) in the IX group and 4/20 patients (20.0%) in the non-contact LP group had shortened limbs and deformed tibia. The SAS assessment results revealed that patients in the non-contact LP group had the lowest rates of moderate and severe anxiety. In conclusion, the results of the present study demonstrate that the non-contact locking plate technique provided stable fixation without any contact between the implant and bone tissues. Therefore, this technique may be viable for use during the reconstruction stage of post-traumatic tibial osteomyelitis.
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Background: Diallyl trisulfide (DATS), a compound derived from garlic, has been demonstrated its anti-cancer properties. While it has been shown to inhibit the expression of epidermal growth factor receptor (EGFR) in various cancers, its effects on osteosarcoma (OS) cells remain unclear. This study aimed to investigate the impacts of DATS on OS cells growth, migration, invasion, epithelial-mesenchymal transition (EMT) and autophagy, as well as its underlying mechanisms which was involving in the EGFR/PI3K/AKT/mTOR pathway. Methods: In this study, human osteosarcoma cells (143B) were treated with different concentrations of DATS (10, 50, 100 and 200 µM) for 24 and 48 h, respectively. Cell viability was measured using CCK8, the half lethal concentration was selected for the following experiments. Wound healing and transwell assays were performed to evaluate migration and invasion abilities, while flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and confocal imaging were employed to analyze the related mRNA and protein expression levels of epithelial-mesenchymal transition (EMT), EGFR/Phosphoinositide 3 kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related markers. Results: DATS significantly inhibited proliferation, migration and EMT in osteosarcoma cells. Additionally, DATS promoted cell apoptosis and induced autophagy, which could be rescued by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, DATS treatment led to the inactivation of the EGFR/PI3K/AKT/mTOR pathway in osteosarcoma cells. Conclusions: This study demonstrated that DATS inhibited osteosarcoma cell growth, migration and EMT, but inducing apoptosis and autophagy. These effects were mediated by the inactivation of the EGFR/PI3K/AKT/mTOR signaling pathway. These findings suggested that DATS could serve as a potential therapeutic agent for osteosarcoma treatment.
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Frequent oil spills and the discharge of oily wastewaters have caused a serious threat to the environment, ecosystems, and human beings. Herein, a photothermal and superhydrophobic melamine sponge (MS) decorated with MXene and lignin particles has been prepared for the separation of oil/water mixtures, the recovery of crude oils, and active deicing. The obtained superhydrophobic melamine sponge shows a water contact angle (WCA) of 152.3° and an oil contact angle of â¼0° and possesses good chemical stability, thermal stability, and mechanical durability in terms of being immersed in various liquids (i.e., corrosive solutions, organic solvents, and boiling water) and being abrased by sandpapers. This superhydrophobic MS displays a high oil adsorption capacity of CCl4, up to 91.6 times its own weight and a high separation efficiency of 99.4%. Furthermore, the maximum surface temperature of the superhydrophobic MS reaches 57.5 °C under sunlight irradiation (1.0 kW/m2) due to the excellent photothermal heating conversion performance of MXene and lignin particles. When exposed to sunlight, the superhydrophobic MS can quickly absorb viscous crude oils up to 72 times its own weight. Also, the WCA of the superhydrophobic MS remains above 146° after 50 icing/deicing cycles, showing excellent photothermal anti-icing properties. Thus, this study presents an easy and low-cost method for designing photothermal superhydrophobic melamine sponges and opens a new avenue to the applications of efficient oil/water separation, fast crude oil recovery, and active deicing.
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Tumor organoids, especially patient-derived organoids (PDOs) exhibit marked similarities in histopathological morphology, genomic alterations, and specific marker expression profiles to those of primary tumour tissues. They are applied in various fields including drug screening, gene editing, and identification of oncogenes. However, CAR-T therapy in the treatment of solid tumours is still at an exploratory stage. Tumour organoids offer unique advantages over other preclinical models commonly used for CAR-T therapy research, which the preservation of the biological characteristics of primary tumour tissue is critical for the study of early-stage solid tumour CAR-T therapies. Although some investigators have used this co-culture model to validate newly targeted CAR-T cells, optimise existing CAR-T cells and explore combination therapy strategies, there is still untapped potential in the co-culture models used today. This review introduces the current status of the application of tumour organoid and CAR-T cell co-culture models in recent years and commented on the limitations of the current co-cultivation model. Meanwhile, we compared the tumour organoid model with two pre-clinical models commonly used in CAR-T therapy research. Eventually, combined with the new progress of organoid technologies, optimization suggestions were proposed for the co-culture model from five perspectives: preserving or reconstructing the tumor microenvironment, systematization, vascularization, standardized culture procedures, and expanding the tumor organoids resource library, aimed at assisting related researchers to better utilize co-culture models.
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BACKGROUND: Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis. Postoperative adjuvant external radiation therapy (RT) has been shown to effectively prevent recurrence after liver cancer resection. However, there are multiple RT techniques available, and the differential effects of these techniques in preventing postoperative liver cancer recurrence require further investigation. AIM: To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival (OS) and disease-free survival (DFS) and to determine the optimal strategy. METHODS: This study involved network meta-analyses and followed the PRISMA guidelines. The data of qualified studies published before July 10, 2023, were collected from PubMed, Embase, the Web of Science, and the Cochrane Library. We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints. The magnitudes of the effects were determined using risk ratios with 95% confidential intervals. The results were analyzed using R software and STATA software. RESULTS: A total of 12 studies, including 1265 patients with hepatocellular carcinoma (HCC) after liver resection, were included in this study. There was no significant heterogeneity in the direct paired comparisons, and there were no significant differences in the inclusion or exclusion criteria, intervention measures, or outcome indicators, meeting the assumptions of heterogeneity and transitivity. OS analysis revealed that patients who underwent stereotactic body radiotherapy (SBRT) after resection had longer OS than those who underwent intensity modulated radiotherapy (IMRT) or 3-dimensional conformal RT (3D-CRT). DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS. Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT. CONCLUSION: HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT. IMRT, a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT, may be a preferred option.
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BACKGROUND: Recent studies have highlighted a connection between gut microbiota and hypertension, yet the precise nature of this relationship remains unclear. OBJECTIVE: This research aims to analyze the causal link between gut microbiota and hypertension, along with associated complications, utilizing two-sample bidirectional Mendelian randomization (MR). MATERIALS AND METHODS: Summary data from genome-wide association studies (GWAS) meta-analyses, including gut microbiota GWAS data from 24 cohorts, and the latest GWAS data for hypertension-related conditions were acquired. Employing various MR methods, including Inverse-variance weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode, we investigated the association between gut microbiota and hypertension-related conditions. Sensitivity analyses were conducted for result stability, and reverse MR analysis assessed the potential for reverse causality. RESULTS: The Mendelian randomization analysis involving 199 microbial taxa and four phenotypes identified 46 microbial taxa with potential causal links to hypertension and its complications. Following Bonferroni correction, genus.Victivallis showed a robust causal relationship with hypertension (OR = 1.08, 95% CI = 1.04-1.12, P = 9.82e-5). This suggests an 8% increased risk of hypertension with each unit rise in genus.Victivallis abundance. CONCLUSION: In conclusion, this study establishes a causal connection between gut microbiota and hypertension, along with common associated complications. The findings unveil potential targets and evidence for future hypertension and complication treatment through gut microbiota interventions, offering a novel avenue for therapeutic exploration.
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Lumbar disc degeneration (LDD) is a prevalent clinical spinal disease characterized by the calcification and degeneration of the cartilage endplate (CEP), which significantly reduces nutrient supply to the intervertebral disc. Traditional Chinese medicine offers a conservative and effective approach for treating LDD. We aimed to investigate the molecular mechanisms underlying the therapeutic effects of Sesamin in LDD treatment. Transcriptome sequencing was used to analyze the effect of Sesamin on LPS-induced ATDC5. We explored the role of BECN2, a target gene of Sesamin, in attenuating LPS-induced degeneration of ATDC5 cells. Our results revealed the identification of 117 differentially expressed genes (DEGs), with 54 up-regulated and 63 down-regulated genes. Notably, Sesamin significantly increased the expression of BECN2 in LPS-induced ATDC5 cell degeneration. Overexpressed BECN2 enhanced cell viability and inhibited cell apoptosis in LPS-induced ATDC5 cells, while BECN2 knockdown reduced cell viability and increased apoptosis. Furthermore, BECN2 played a crucial role in attenuating chondrocyte degeneration by modulating autophagy and inflammation. Specifically, BECN2 suppressed autophagy by reducing the expression of ATG14, VPS34, and GASP1, and alleviated the inflammatory response by decreasing the expression of inflammasome proteins NLRP3, NLRC4, NLRP1, and AIM2. In vivo experiments further supported the beneficial effects of Sesamin in mitigating LDD. This study provides novel insights into the potential molecular mechanism of Sesamin in treating LDD, highlighting its ability to mediate autophagy and inflammation inhibition via targeting the BECN2. This study provides a new therapeutic strategy for the treatment of LDD, as well as a potential molecular target for LDD.
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Dioxóis , Degeneração do Disco Intervertebral , Peptídeos e Proteínas de Sinalização Intracelular , Lignanas , Autofagia , Cartilagem/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lipopolissacarídeos/farmacologia , Animais , CamundongosRESUMO
The major liver cancer subtype is hepatocellular carcinoma (HCC). Studies have indicated that a better prognosis is related to the presence of tumor-infiltrating lymphocytes (TILs) in HCC. However, the molecular pathways that drive immune cell variation in the tumor microenvironment (TME) remain poorly understood. Glycosylation (GLY)-related genes have a vital function in the pathogenesis of numerous tumors, including HCC. This study aimed to develop a GLY/TME classifier based on glycosylation-related gene scores and tumor microenvironment scores to provide a novel prognostic model to improve the prediction of clinical outcomes. The reliability of the signatures was assessed using receiver operating characteristic (ROC) and survival analyses and was verified with external datasets. Furthermore, the correlation between glycosylation-related genes and other cells in the immune environment, the immune signature of the GLY/TME classifier, and the efficacy of immunotherapy were also investigated. The GLY score low/TME score high subgroup showed a favorable prognosis and therapeutic response based on significant differences in immune-related molecules and cancer cell signaling mechanisms. We evaluated the prognostic role of the GLY/TME classifier that demonstrated overall prognostic significance for prognosis and therapeutic response before treatment, which may provide new options for creating the best possible therapeutic approaches for patients.
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The intracellular pathway of Janus kinase/signal transducer and activator of transcription (JAK/STAT) and modification of nucleosome histone marks regulate the expression of proinflammatory mediators, playing an essential role in carcinogenesis, antiviral immunity and the interaction of host proteins with Herpesviral particles. The pathway has also been suggested to play a vital role in the clinical course of the acute infection caused by severe acute respiratory syndrome coronavirus type 2 (SARSCoV2; known as coronavirus infection2019), a novel human coronavirus initially identified in the central Chinese city Wuhan towards the end of 2019, which evolved into a pandemic affecting nearly two million people worldwide. The infection mainly manifests as fever, cough, myalgia and pulmonary involvement, while it also attacks multiple viscera, such as the liver. The pathogenesis is characterized by a cytokine storm, with an overproduction of proinflammatory mediators. Innate and adaptive host immunity against the viral pathogen is exerted by various effectors and is regulated by different signaling pathways notably the JAK/STAT. The elucidation of the underlying mechanism of the regulation of mediating factors expressed in the viral infection would assist diagnosis and antiviral targeting therapy, which will help overcome the infection caused by SARSCoV2.
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COVID-19 , Herpesviridae , Humanos , Carcinogênese , Herpesviridae/metabolismo , Janus Quinases/metabolismo , SARS-CoV-2/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição STAT/metabolismoRESUMO
Frequent oceanic oil spill incidents and the discharge of industrial oily wastewaters have caused serious threats to environments, food chains and human beings. Lignin wastes with many reactive groups exist as the byproducts from bioethanol and pulping processing industries, and they are either discarded as wastes or directly consumed as a fuel. To make full use of lignin wastes and simultaneously deal with oily wastewaters, porous lignin-based composites have been rationally designed and prepared. In this review, recent advances in the preparation of porous lignin-based composites are summarized in terms of aerogels, sponges, foams, papers, and membranes, respectively. Then, the mechanisms and the application of porous lignin-based adsorbents and filtration materials for oil/water separation are discussed. Finally, the challenges and perspectives of porous lignin-based composites are proposed in the field of oil/water separation. The utilization of abundant lignin wastes can replace fossil resources, and meanwhile porous lignin-based composites can be used to efficiently treat with oily wastewaters. The above utilization strategy opens an avenue to the rational design and preparation of lignin wastes with high-added value, and gives a possible solution to use lignin wastes in a sustainable and environmentally friendly way.
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Líquidos Corporais , Lignina , Humanos , Porosidade , Águas Residuárias , FiltraçãoRESUMO
The interfacial compatibility between cathodes and sulfide solid-electrolytes (SEs) is a critical limiting factor of electrochemical performance in all-solid-state lithium-ion batteries (ASSLBs). This work presents a gas-solid interface reduction reaction (GSIRR), aiming to mitigate the reactivity of surface oxygen by inducing a surface reconstruction layer (SRL) . The application of a SRL, CoO/Li2 CO3 , onto LiCoO2 (LCO) cathode results in impressive outcomes, including high capacity (149.7 mAh g-1 ), remarkable cyclability (retention of 84.63% over 400 cycles at 0.2 C), outstanding rate capability (86.1 mAh g-1 at 2 C), and exceptional stability in high-loading cathode (28.97 and 23.45 mg cm-2 ) within ASSLBs. Furthermore, the SRL CoO/Li2 CO3 enhances the interfacial stability between LCO and Li10 GeP2 S12 as well as Li3 PS4 SEs. Significantly, the experiments suggest that the GSIRR mechanism can be broadly applied, not only to LCO cathodes but also to LiNi0.8 Co0.1 Mn0.1 O2 cathodes and other reducing gases such as H2 S and CO, indicating its practical universality. This study highlights the significant influence of the surface chemistry of the oxide cathode on interfacial compatibility, and introduces a surface reconstruction strategy based on the GSIRR process as a promising avenue for designing enhanced ASSLBs.
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Starvation therapy is an innovative approach in cancer treatment aimed at depriving cancer cells of necessary resources by impeding tumor angiogenesis or blocking the energy supply. In addition to the commonly observed anaerobic glycolysis energy supply mode, adipocyte-rich tumor tissue triggers the fatty acid energy supply pathway, which fuels the proliferation and metastasis of cancer cells. To completely disrupt these dual-energy-supply pathways, we developed an exceptional nanoreactor. This nanoreactor consisted of yolk-shell mesoporous organosilica nanoparticles (YSMONs) loaded with a fatty acid transport inhibitor (Dox), conjugated with a luminal breast-cancer-specific targeting aptamer, and integrated with a glucose oxidation catalyst (GOx). Upon reaching cancer cells with the assistance of the aptamer, the nanoreactor underwent a structural collapse of the shell triggered by the high concentration of glutathione within cancer cells. This collapse led to the release of GOx and Dox, achieving targeted delivery and exhibiting significant efficacy in starving therapy. Additionally, the byproducts of glucose metabolism, gluconic acid and H2O2, enhanced the acidity and reactive oxygen species levels of the intracellular microenvironment, inducing oxidative damage to cancer cells. Simultaneously, released Dox acted as a potent broad-spectrum anticancer drug, inhibiting the activity of carnitine palmitoyltransferase 1A and exerting marked effects. Combining these effects ensures high anticancer efficiency, and the "dual-starvation" nanoreactor has the potential to establish a novel synergistic therapy paradigm with considerable clinical significance. Furthermore, this approach minimizes damage to normal organs, making it highly valuable in the field of cancer treatment.
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Antineoplásicos , Neoplasias da Mama , Nanopartículas , Neoplasias , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Peróxido de Hidrogênio/química , Antineoplásicos/farmacologia , Glutationa , Ácidos Graxos , Nanopartículas/química , Neoplasias/patologia , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Background: Research on diabetes remission has garnered prominence in recent years. However, to date, no pertinent bibliometric study has been published. This study sought to elucidate the current landscape and pinpoint potential new research directions through a bibliometric analysis of diabetes remission. Methods: We perused relevant articles on diabetes remission from January 1, 2000, to April 16, 2023, in the Web of Science. We utilized CiteSpace software and VOSviewer software to construct knowledge maps and undertake analysis of countries, institutional affiliations, author contributions, journals, and keywords. This analysis facilitated the identification of current research foci and forecasting future trends. Results: A total of 970 English articles were procured, and the annual publication volume manifested a steady growth trend. Most of the articles originated from America (n=342, 35.26%), succeeded by China and England. Pertaining to institutions, the University of Newcastle in England proliferated the most articles (n=36, 3.71%). Taylor R authored the most articles (n=35, 3.61%), and his articles were also the most co-cited (n=1756 times). Obesity Surgery dominated in terms of published articles (n=81, 8.35%). "Bariatric surgery" was the most prevalently used keyword. The keyword-clustering map revealed that the research predominantly centered on diabetes remission, type 1 diabetes, bariatric surgery, and lifestyle interventions. The keyword emergence and keyword time-zone maps depicted hotspots and shifts in the domain of diabetes remission. Initially, the hotspots were primarily fundamental experiments probing the feasibilities and mechanisms of diabetes remission, such as transplantation. Over the course, the research trajectory transitioned from basic to clinical concerning diabetes remission through bariatric surgery, lifestyle interventions, and alternative strategies. Conclusion: Over the preceding 20 years, the domain of diabetes remission has flourished globally. Bariatric surgery and lifestyle interventions bestow unique advantages for diabetes remission. Via the maps, the developmental milieu, research foci, and avant-garde trends in this domain are cogently portrayed, offering guidance for scholars.
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Cirurgia Bariátrica , Vacinas Anticâncer , Diabetes Mellitus Tipo 1 , Humanos , Bibliometria , ChinaRESUMO
Nematophagous fungi constitute a category of fungi that exhibit parasitic behavior by capturing, colonizing, and poisoning nematodes, which are critical factors in controlling nematode populations in nature, and provide important research materials for biological control. Arthrobotrys oligospora serves as a model strain among nematophagous fungi, which begins its life as conidia, and then its hyphae produce traps to capture nematodes, completing its lifestyle switch from saprophytic to parasitic. There have been many descriptions of the morphological characteristics of A. oligospora lifestyle changes, but there have been no reports on the nuclear dynamics in this species. In this work, we constructed A. oligospora strains labeled with histone H2B-EGFP and observed the nuclear dynamics from conidia germination and hyphal extension to trap formation. We conducted real-time imaging observations on live cells of germinating and extending hyphae and found that the nucleus was located near the tip. It is interesting that the migration rate of this type of cell nucleus is very fast, and we speculate that this may be related to the morphological changes involved in the transformation to a predatory lifestyle. We suggest that alterations in nuclear shape and fixation imply the immediate disruption of the interaction with cytoskeletal mechanisms during nuclear migration. In conclusion, these findings suggest that the signal initiating nuclear migration into fungal traps is generated at the onset of nucleus entry into a trap cell. Our work provides a reference for analysis of the dynamics of nucleus distribution and a means to visualize protein localization and interactions in A. oligospora.
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With the increasing power density of electronic devices, solder joints are prone to electromigration under high currents, which results in a significant threat to reliability. In this study, the molecular dynamics method is used to study the diffusion mechanism of the Cu3Sn/Cu interface under the action of electrothermal coupling. The results show that the diffusion activation energy decreases with an increase in electric field intensity, accelerating the diffusion of the Cu3Sn/Cu interface. Furthermore, it is noted that the abrupt change in the vacancy-time curve lags behind that of the mean square displacement curve, which depicts that the responses of the vacancies are driven by the electric field. The vacancy-responsive diffusion mechanism of the Cu3Sn/Cu interface is proposed. The atoms around the interface in the electric field get rid of the shackles of the neighboring atoms easily. The vacancy concentration increases as the atoms leave the equilibrium position, which accelerates the movement of vacancies and enhances the diffusion of the Cu3Sn/Cu interface.