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The osteoporotic bone defect caused by excessive activity of osteoclasts has posed a challenge for public healthcare. However, most existing bioinert bone cement fails to effectively regulate the pathological bone microenvironment and reconstruct bone homeostasis in the presence of osteoclast overactivity and osteoblast suppression. Herein, inspired by natural bone tissue, an in-situ modulation system for osteoporotic bone regeneration is developed by fabricating an injectable double-crosslinked PEGylated poly(glycerol sebacate) (PEGS)/calcium phosphate cement (CPC) loaded with sodium alendronate (ALN) (PEGS/CPC@ALN) adhesive bone cement. By incorporating ALN, the organic-inorganic interconnection within PEGS/CPC@ALN results in a 100 % increase in compression modulus and energy dissipation efficiency. Additionally, PEGS/CPC@ALN effectively adheres to the bone by bonding with amine and calcium ions present on the bone surface. Moreover, this in-situ regulation system comprehensively mitigates excessive bone resorption through the buffering effect of CPC to improve the acidic microenvironment of osteoporotic bone and the release of ALN to inhibit hyperactive osteoclasts, and facilitates stem cell proliferation and differentiation into osteoblasts through calcium ion release. Overall, the PEGS/CPC@ALN effectively regulates the pathological microenvironment of osteoporosis while promoting bone regeneration through synergistic effects of drugs and materials, thereby improving bone homeostasis and enabling minimally invasive treatment for osteoporotic defects.
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The quality of meat in prepared dishes deteriorates due to excessive protein denaturation resulting from precooking, freezing, and recooking. This study aimed to link the precooked state with chicken breast's recooked quality. Cooked Value (CV), based on protein denaturation kinetics, was established to indicate the doneness of meat during pre-heating. The effects of CVs after pre-heating on recooked qualities were investigated compared to fully pre-heated samples (control). Mild pre-heating reduced water migration and loss. While full pre-heating inhibited protein oxidation during freezing, intense oxidation during pre-heating led to higher oxidation levels. Surface hydrophobicity analysis revealed that mild pre-heating suppressed aggregation during recooking. These factors contributed to a better texture and microstructure of prepared meat with mild pre-heating. Finally, a potential mechanism of how pre-heating affects final qualities was depicted. This study underlines the need for finely controlling the industrial precooking process to regulate the quality of prepared meat.
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Galinhas , Culinária , Temperatura Alta , Carne , Oxirredução , Desnaturação Proteica , Água , Animais , Cinética , Carne/análise , Água/química , Interações Hidrofóbicas e HidrofílicasRESUMO
Background: Bronchoscopy is widely used in clinical diagnosis and treatment of respiratory diseases. Although it is generally safe, cardiac complications such as acute myocardial ischemia and arrhythmia can also occur in patients especially with comorbidities and in elderly ones. Acute malignant coronary vasospasm as a severe cardiac complication can occur during bronchoscopy. It is essential to observe the occurrence of complications and provide early curing. Case Description: We presented a case of a 52-year-old man who experienced chest pain, dyspnea and even shock during bronchoscopy. Electrocardiogram (ECG) showed an acute muti-leads ST-segment elevation and declined to baseline soon after emergent medication treatment including antithrombotic, expansion of coronary artery and fluid replenishment myocardial infarction. Coronary artery spasm was considered according to the clinical symptom and ECG characteristics. Subsequent coronary angiogram which showed normal coronary artery also supported the diagnosis of coronary artery spasm. The symptom of the patient was discovered timely and was treated successfully with good prognosis. Conclusions: Bronchoscopy is the main and important method of diagnosis and treatment for respiratory diseases. Coronary artery spasm as a serious cardiac complication should be paid more attention during bronchoscopy. Timely and appropriate treatment may lead to better clinical results. Multidisciplinary cooperation plays a key role in the whole therapy. The potential triggers of coronary artery spasm during bronchoscopy mainly include low oxygen, hypersensitivity reactions and chronic inflammatory.
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Novel inflammatory bowel disease (IBD) therapeutic drugs, mainly biologics that neutralize pro-inflammatory factors and janus kinase inhibitors that inhibit cytokine-mediated signal transduction, face problems including low efficacy rates, limited therapeutic benefits, and infection risks. It is an important task to find proteins that broadly regulate a variety of cytokines and to develop corresponding drugs. Cathepsin C (CTSC) mediates neutrophil-related inflammatory, participates in the recruitment and activation of inflammatory cells, and regulates cytokines levels, and is considered an ideal target for IBD treatment. In this study, starting from the in-house molecule, through medicinal chemistry and target-based design, a novel CTSC inhibitor B22 with IBD therapeutic efficacy was discovered. In vitro target verification and mechanism study indicated that B22 inhibit CTSC activity by binding to S2 pocket and S1 site, further inhibiting downstream serine protease activity. In addition, B22 exhibited anti-inflammatory activity and regulated various cytokines levels. In vivo studies highlighted B22 bears acceptable toxicity and suitable pharmacokinetic properties, and displays anti-inflammatory activity in IBD model. In conclusion, B22 is a potential anti-inflammatory molecule for IBD by targeting CTSC and deserves further research.
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Hantaan virus (HTNV) infection in humans can cause hemorrhagic fever and renal syndrome (HFRS). Understanding host responses to HTNV infection is crucial for developing effective disease intervention strategies. Previous RNA-sequencing studies have investigated the role of microRNAs (miRNAs) in the post-transcriptional regulation of host genes in response to HTNV infection. In this study, we demonstrated that HTNV infection induces let-7a expression in human umbilical vein endothelial cells (HUVEC) and that HTNV G protein upregulates the expression of let-7a. miRNA let-7a mimics and inhibitors validated the predicted targets, including cell apoptosis genes (FAS, caspase-8, and caspase-3) and inflammatory factors (IL-6 and its related factors). Modulation of miRNA let-7a levels by miRNA mimics and inhibitors affected HTNV replication, indicating that HTNV modulates host miRNA expression to affect the outcome of the antiviral host response.
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The family Erinaceidae encompasses 27 extant species in two subfamilies: Erinaceinae, which includes spiny hedgehogs, and Galericinae, which comprises silky-furred gymnures and moonrats. Although they are commonly recognized by the general public, their phylogenetic history remains incompletely understood, and several species have never been included in any molecular analyses. Additionally, previous research suggested that the species diversity of Erinaceidae might be underestimated. In this study, we sequenced the mitochondrial genomes of 29 individuals representing 18 erinaceid species using 18 freshly collected tissue and 11 historical museum specimens. We also integrated previously published data for a concatenated analysis. We aimed to elucidate the evolutionary relationships within Erinaceidae, estimate divergence times, and uncover potential underestimated species diversity. Our data finely resolved intergeneric and interspecific relationships and presented the first molecular evidence for the phylogenetic position of Mesechinus wangi, Paraechinus micropus, and P. nudiventris. Our results revealed a sister relationship between Neotetracus and Neohylomys gymnures, as well as a sister relationship between Hemiechinus and Mesechinus, supporting previous hypotheses. Additionally, our findings provided a novel phylogenetic position for Paraechinus aethiopicus, placing it in a basal position within the genus. Furthermore, our study uncovered cryptic species diversity within Hylomys suillus as well as in Neotetracus sinensis, Atelerix albiventris, P. aethiopicus, and Hemiechinus auratus, most of which have been previously overlooked.
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INTRODUCTION: The aim of this study is to investigate whether the testing time for unstimulated whole salivary flow (UWSF) can be shortened to 5 min in patients with suspected Sjögren's syndrome (SjS); and which SjS patients can use UWSF to evaluate salivary gland (SG) secretory function. METHOD: A diagnostic cohort comprising suspected SjS patients was conducted to investigate the correlation between UWSF measurements taken at 10 min (UWSF_10 min) and those taken at 5 min (UWSF_5 min). A group of SjS patients was enrolled for a comparison between UWSF and stimulated whole salivary flow (SWSF). RESULTS: In 734 suspected SjS patients, there was a remarkably high concordance between UWSF_10 min and UWSF_5 min (ICC 0.970, P < 0.001; r 0.973, P < 0.001). Reducing the testing time for UWSF to 5 min resulted in a high PPV of 83.8% and an exceptionally high NPV of 98.7%. In 408 SjS patients, the cut-off values of UWSF_10 min were investigated to classify SG secretory function. Using a threshold of > 0.2 mL/min (36.8%, 150/408) instead of SWSF > 0.7 mL/min (indicating mild secretory hypofunction), the specificity and PPV were found to be 94.2% and 94.0%, respectively; and using a threshold of < 0.05 mL/min (16.9%, 69/408) instead of SWSF ≤ 0.7 mL/min (indicating moderate to severe secretory hypofunction), the specificity was remarkably high at 97.6%, accompanied by a high PPV of 91.3%. CONCLUSIONS: This study supports the possibility of reducing UWSF testing time to 5 min; and the SWSF test may be skipped for SjS patients with USWF > 0.2 mL/min, indicating mild secretory hypofunction, or < 0.05 mL/min, indicating moderate to severe secretory hypofunction. Key Points â¢A diagnostic cohort of 734 patients with clinical suspicion of SjS provides compelling evidence for the potential to reduce the testing time for UWSF from 10 to 5 min. â¢Our finding challenges the 2019 treatment recommendation for SjS, which does not require SWSF measurement in SjS patients with UWSF ≥ 0.1 mL/min. â¢We propose that it may be feasible to consider utilizing UWSF instead of SWSF test for objective classification of SG secretory function in over half of SjS patients.
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Efficient exciton dissociation at low energy offsets is key to overcoming voltage losses in organic solar cells. In this work, we developed two dimeric acceptors, i-YT and o-YT, by precisely controlling the position of an asymmetric electron-donating linker. It induced the foldamer conformation of i-YT with a para linkage (relative to the dicyano groups), while retaining the unfold conformation for o-YT. This subtle structural modification influenced the molecular assembly properties, enabled near-zero energy offset exciton dissociation and power conversion efficiencies exceeding 18% for i-YT based organic solar cells. Detailed excitonic dynamics further revealed that the linker position critically influences three processes: the formation of delocalized singlet excited states, ultrafast charge transfer (~5 ps) in solid blends, and the suppression of exciton recombination. Additionally, devices based on i-YT demonstrated outstanding long-term stability, retaining over 85% of their initial efficiency after 1,400 hours of continuous illumination. These findings introduce a new class of dimeric acceptors that combine high efficiency with exceptional stability, offering a promising pathway toward low-energy-loss organic photovoltaics.
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To optimize the brittle failure of reinforced conerete (RC) over-reinforeed beams and enhance their flexural performance, a novel structural form is proposed. To be specific, the Engineered Cementitious Composite (ECC) layer is installed on top of the RC over-reinforced beam (ERCOB). A total of six test beams are prepared, comprising one unreinforced beam and five reinforced beams. The variables comprised the depth of the ECC, reinforcement ratio, and whether the ECC is configured at the bottom. The test findings are subsequently compared with simulation outcomes to validate the model's precision. Next, the influence of various variables on ERCOB flexural performance, such as load-deflection response, bearing capacity, etc., is deeply analyzed. The research indicates that the ECC applied to both the top and bottom of the specimen exhibits enhanced bearing capacity and ductility. In comparison to CB-1, the maximum load and deflection ductility coefficient of EB-2 increased from 45.73 kN to 2.63-48.52 kN and 3.85, representing increases of 6.1 % and 29.6 %, respectively. It reveals that ECC layer improves the defects caused by excessive reinforcement of over-reinforced beams, and optimizes the tensile capacity of the steel bars, thus improving the bending capacity and ductility of the specimens. Finally, the prediction model of ERCOB flexural capacity is proposed to further verify the effectiveness of ERCOB. This study not only verifies the effectiveness of ECC reinforcement, but also helps to delay the failure process of structures, provide reference for future engineering application design.
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Meta-analyses have reported conflicting data on the whole blood cell count (WBCC) derived indexes (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and lymphocyte-to-monocyte ratio [LMR]) and cancer prognosis. However, the strength and quality of this evidence has not been quantified in aggregate. To grade the evidence from published meta-analyses of cohort studies that investigated the associations between NLR, PLR, and LMR and cancer prognosis. A total of 694 associations from 224 articles were included. And 219 (97.8%) articles rated as moderate-to-high quality according to AMSTAR. There were four associations supported by convincing evidence. Meanwhile, 165 and 164 associations were supported by highly suggestive and suggestive evidence, respectively. In this umbrella review, we summarized the existing evidence on the WBCC-derived indexes and cancer prognosis. Due to the direction of effect sizes is not completely consistent between studies, further research is needed to assess causality and provide firm evidence.
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Spatiotemporal Graph (STG) forecasting is an essential task within the realm of spatiotemporal data mining and urban computing. Over the past few years, Spatiotemporal Graph Neural Networks (STGNNs) have gained significant attention as promising solutions for STG forecasting. However, existing methods often overlook two issues: the dynamic spatial dependencies of urban networks and the heterogeneity of urban spatiotemporal data. In this paper, we propose a novel framework for STG learning called Dynamic Meta-Graph Convolutional Recurrent Network (DMetaGCRN), which effectively tackles both challenges. Specifically, we first build a meta-graph generator to dynamically generate graph structures, which integrates various dynamic features, including input sensor signals and their historical trends, periodic information (timestamp embeddings), and meta-node embeddings. Among them, a memory network is used to guide the learning of meta-node embeddings. The meta-graph generation process enables the model to simulate the dynamic spatial dependencies of urban networks and capture data heterogeneity. Then, we design a Dynamic Meta-Graph Convolutional Recurrent Unit (DMetaGCRU) to simultaneously model spatial and temporal dependencies. Finally, we formulate the proposed DMetaGCRN in an encoder-decoder architecture built upon DMetaGCRU and meta-graph generator components. Extensive experiments on four real-world urban spatiotemporal datasets validate that the proposed DMetaGCRN framework outperforms state-of-the-art approaches.
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This study aimed to develop microcapsules with wheat gluten-coated oil droplets to enhance the oxidation stability and control the digestibility of flaxseed oil. The microcapsules were fabricated using a three-step procedure: (i) flaxseed oil was homogenized with an alkaline gluten solution to form oil-in-water emulsions containing small gluten-coated oil droplets (320-400 nm); (ii) the pH of these emulsions was then neutralized to facilitate the deposition of gluten around the oil droplets, thereby forming a thick layer; (iii) a flaxseed oil microcapsule powder was then prepared by spray drying. During the microcapsule formation, intermolecular interactions, including hydrophobic interactions and hydrogen bonds, were involved in the coacervation of gluten at the emulsion surface. The resultant microcapsules with a multiple-core structure had external diameters of 4-26 µm and encapsulation efficiencies of 90%-94%. The microencapsulated oil powders contained a relatively high flaxseed oil content (60%-80%). Among them, the sample with 60% oil content demonstrated the best stability in resisting oil droplet coalescence; thus, it exhibited a higher lipolysis rate and extent during simulated gastrointestinal digestion. A 30-day accelerated storage study showed that encapsulation of the flaxseed oil improved its resistance to oxidation. These findings suggest that the pH-deposition method can successfully produce microencapsulated polyunsaturated lipids using all plant-derived ingredients, which may facilitate their use in new plant-based foods through a green and sustainable approach.
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Purpose: To explore whether tumor-associated lymphatic vessel density (LVD) could be a biomarker for the prognosis of patients with esophageal cancer after radical resection. Methods: A systematic literature search was performed through PubMed, EMBASE, Wanfang Data, and Cochrane Library from the inception of databases until March 19, 2024. The selected studies investigated overall survival (OS) and/or recurrence-free survival (RFS) of patients with esophageal cancer with different levels of LVD after radical resection. The OS and RFS data were pooled as hazard ratios (HR) and 95% confidential interval (CI). Furthermore, the standardized mean differences (SMDs) and 95% CI were aggregated to evaluate the correlation between LVD and clinicopathological features. Results: A total of 10 retrospective studies of 1,201 patients were finally included for the meta-analysis. Patients with esophageal cancer with a high level of LVD exhibited worse OS (HR 1.65, 95% CI 1.18 to 2.31) and RFS (HR 1.57, 95% CI 1.09 to 2.26) than those with a low level of LVD. Subgroup analysis of different pathological subtypes revealed that patients with esophageal adenocarcinoma with a high level of LVD had significantly worse RFS (HR 2.84, 95% CI 1.61 to 5.02) than those with a low level of LVD; while patients with esophageal squamous cell carcinoma with a high level of LVD had similar OS (HR 1.52, 95% CI 0.93 to 2.47) and RFS (HR 1.03, 95% CI 0.72 to 1.48) to those with a low level of LVD. Furthermore, tumors with lymph node metastasis had significantly higher levels of LVD than those without lymph node metastasis (SMD = 1.11, 95% CI 0.54 to 1.67). Tumors at the stages III-IV had significantly higher levels of LVD than those at the stages I-II (SMD = 1.62, 95% CI 0.90 to 2.34). Conclusion: A high level of LVD in tumor was associated with worse survival of patients with esophageal cancer after radical resection, especially in patients with esophageal adenocarcinoma. Tumor-associated LVD is a new parameter that should be measured in postoperative pathology for predicting the prognosis of patients with esophageal cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42024553766.
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Neoplasias Esofágicas , Vasos Linfáticos , Humanos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Esofagectomia , Metástase Linfática , Vasos Linfáticos/patologia , PrognósticoRESUMO
ABSTRACT: A 70-year-old woman presented with left ovarian mass and thickened peritoneum. 18F-FDG PET/CT showed no significant FDG-avid in the whole body. 68Ga-FAPI-04 demonstrated abnormally high FAPI uptake in the ileocecal region, left ovarian lesion, and thickened peritoneum. The postoperative pathology confirmed the appendiceal goblet cell adenocarcinoma. This case highlights the superior and innovative diagnostic role of 68Ga-FAPI-04 in appendiceal goblet cell adenocarcinoma and its metastases.
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ABSTRACT: A 57-year-old man with primary aldosteronism exhibited multiple nodules in the left adrenal, pancreatic tail, and splenic region. The left adrenal nodule showed positive 68Ga-pentixafor and negative 68Ga-FAPI-04 uptake, suggesting an aldosterone-producing adrenal adenoma. The nodule in the pancreatic tail exhibited high 68Ga-pentixafor and low 68Ga-FAPI-04 uptake, similarity with the nodule in splenic region, indicating accessory splenic nodule. Postoperative pathology confirmed an adrenal cortical adenoma and an accessory splenic nodule in the pancreas. This case underscores the complementary role of 68Ga-pentixafor and 68Ga-FAPI-04 PET/MR in diagnosing complex adrenal and pancreatic pathologies.
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OBJECTIVE: To explore the intricate interplay among cytokines, cognitive functioning, and conversion to psychosis in individuals at clinical high-risk (CHR) for psychosis. METHOD: We initially enrolled 385 individuals at CHR and 95 healthy controls (HCs). Subsequently, 102 participants at CHR completed the 1-year follow-up assessments, and 47 participants transitioned to psychosis. We assessed the levels of interleukins (IL-1ß, IL-2, IL-6, IL-8, IL-10), tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF). We comprehensively evaluated cognitive performance across six domains, including speed of processing (SP), attention/vigilance (AV), working memory (WM), verbal learning (VeL), visual learning (ViL), and reasoning and problem-solving (RPS). RESULTS: Higher baseline cognitive domain scores were associated with elevated GM-CSF and reduced VEGF levels. In the follow-up analysis, significant time effects were observed for IL-1ß and IL-2. We also observed significant interaction effects between specific cognitive domains (AV, WM, VeL, and OCS) and levels of cytokine (GM-CSF, IL-1ß, IL-6, and TNF-α). Changes in WM were negatively correlated with changes in TNF-α levels and positively correlated with changes in VEGF levels. Variations in VeL were inversely correlated with changes in GM-CSF and IL-10 levels, whereas changes in RPS were positively associated with changes in GM-CSF and IL-8 levels. CONCLUSIONS: Our results revealed intricate associations among cytokine levels, cognitive performance, and psychosis progression.
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Xenogeneic decellularized heart valves (DHVs) have become one of the most commonly used scaffolds for tissue engineered heart valves (TEHVs) due to extensive resources and possessing the distinct three-layer structure similar to native heart valves. However, DHVs as scaffolds face the shortages such as poor mechanical properties, proneness to thrombosis and calcification, difficulty in endothelialization and chronic inflammatory responses etc., which limit their applications in clinic. In this work, we constructed a novel TEHV with immunomodulatory functions by loading folic acid modified silver nanoparticles (FS NPs) on DHVs to overcome these issues. The FS NPs preferentially targeted M1 macrophages and reduced their intracellular H2O2 level, resulting in polarizing them into M2 phenotype. The increased M2 macrophages facilitated to eliminate inflammation, recruit endothelial cells, and promote their proliferation and endothelialization by secreting relative factors. We founded that FS NPs with the size of 80 nm modified DHVs (FSD-80) performed optimally on cytocompatibility and regulating macrophage phenotype ability in vitro. In addition, the FSD-80 had excellent mechanical properties, hemocompatibility and anti-bacteria property. The results of the subcutaneous implantation in rats revealed that the FSD-80 also had good performance in regulating macrophage phenotype, promoting endothelialization, remolding the extracellular matrix and anti-calcification in vivo. Therefore, FS NPs-loaded DHVs possess immunomodulatory functions, which is a feasible and promising strategy for constructing TEHVs with excellent comprehensive performance.
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Engineered extracellular vesicles (EVs) have been recognized as important therapeutics for gene and cell therapy. To achieve clinically desired therapy, technologies for EV engineering have high demands on the efficacy in producing EVs and their qualities, which, however, remain challenging to conventional routes due to their limited control on therapeutic payload delivery, EV secretion, and extracellular microenvironments. Here, we report a nanoplatform (denoted as PURE) that enables efficient electro-transfection while stimulating cells to produce high-quality EVs carrying functional RNAs. PURE further employs an ammonium removal zone to maintain the physiological conditions of the extracellular microenvironment and an EV uptake zone that efficiently (87.1%) captures EVs in situ with porous hydrogels. The platform achieved about a 12-fold higher yield of engineered EVs and a 146-fold abundance of desired therapeutics compared to those naturally secreted from cells. The PURE-engineered miR-130a-EVs were validated for effectively upregulating the mTOR signaling pathway in both in vitro and in vivo. Their therapeutic capability was then verified by enhancing the in vitro activation of primordial follicles. In vivo applications further highlighted the therapeutic effects of miR-130a-EVs in restoring ovary function in aged mice. The PURE platform represents a strategy for the clinical translation of EV-mediated therapy.
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In this study, Fe, N co-doped biochar (Fe@N co-doped BC) was synthesized by the carbonization-pyrolysis method and used as a carbocatalyst to activate peroxymonosulfate (PMS) for sulfamethoxazole (SMX) removal. In the Fe@N co-doped BC/PMS system, the degradation efficiency of SMX (10.0 mg·L-1) was 90.2% within 40 min under optimal conditions. Radical quenching experiments and electron spin resonance (ESR) analysis suggested that sulfate radicals (SO4â¢-), hydroxyl radicals (â¢OH), and singlet oxygen (1O2) participated in the degradation process. After the reaction, the proportion of pyrrolic N decreased from 57.9% to 27.1%. Pyrrolic N served as an active site to break the inert carbon network structure and promote the generation of reactive oxygen species (ROS). In addition, pyrrolic N showed a stronger interaction with PMS and significantly reduced the activation energy required for the reaction (∆G = 23.54 kcal/mol). The utilization potentiality of Fe@N co-doped BC was systematically evaluated in terms of its reusability and selectivity to organics. Finally, the intermediates of SMX were also detected.