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To explore air contamination resulting from special biomass combustion and suspended dust in Lhasa, the present study focused on the size distribution and chemical characteristics of particulate matter (PM) emission resulting from 7 types of non-fossil pollution sources. We investigated the concentration and size distribution of trace elements from 7 pollution sources collected in Lhasa. Combining Lhasa's atmospheric particulate matter data, enrichment factors (EFs) have been calculated to examine the potential impact of those pollution sources on the atmosphere quality of Lhasa. The highest mass concentration of total elements of biomass combustion appeared at PM0.4, and the second highest concentration existed in the size fraction 0.4-1 µm; the higher proportion (12 %) of toxic metals was produced by biomass combustion. The elemental composition of suspended dust and atmospheric particulate matter was close (except for As and Cd); the highest concentration of elements was all noted in PM2.5-10 (PM3-10). Potassium was found to be one of the main biomass markers. The proportion of Cu in suspended dust is significantly lower than that of atmospheric particulate matter (0.53 % and 3.75 %), which indicates that there are other anthropogenic sources. The EFs analysis showed that the Cr, Cu, Zn, and Pb produced by biomass combustion were highly enriched (EFs > 100) in all particle sizes. The EFs of most trace elements increased with decreasing particle size, indicating the greater influence of humanfactors on smaller particles.
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Aerosoles , Contaminantes Atmosféricos , Polvo , Monitoreo del Ambiente , Tamaño de la Partícula , Material Particulado , Contaminantes Atmosféricos/análisis , Aerosoles/análisis , Material Particulado/análisis , Polvo/análisis , Oligoelementos/análisis , Contaminación del Aire/estadística & datos numéricos , Contaminación del Aire/análisis , China , Atmósfera/químicaRESUMEN
We aimed to uncover the pathological mechanism of ischemic stroke (IS) using a combined analysis of untargeted metabolomics and proteomics. The serum samples from a discovery set of 44 IS patients and 44 matched controls were analyzed using a specific detection method. The same method was then used to validate metabolites and proteins in the two validation sets: one with 30 IS patients and 30 matched controls, and the other with 50 IS patients and 50 matched controls. A total of 105 and 221 differentially expressed metabolites or proteins were identified, and the association between the two omics was determined in the discovery set. Enrichment analysis of the top 25 metabolites and 25 proteins in the two-way orthogonal partial least-squares with discriminant analysis, which was employed to identify highly correlated biomarkers, highlighted 15 pathways relevant to the pathological process. One metabolite and seven proteins exhibited differences between groups in the validation set. The binary logistic regression model, which included metabolite 2-hydroxyhippuric acid and proteins APOM_O95445, MASP2_O00187, and PRTN3_D6CHE9, achieved an area under the curve of 0.985 (95% CI: 0.966-1) in the discovery set. This study elucidated alterations and potential coregulatory influences of metabolites and proteins in the blood of IS patients.
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Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.
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High perceptual quality and low distortion degree are two important goals in image restoration tasks such as super-resolution (SR). Most of the existing SR methods aim to achieve these goals by minimizing the corresponding yet conflicting losses, such as the l1 loss and the adversarial loss. Unfortunately, the commonly used gradient-based optimizers, such as Adam, are hard to balance these objectives due to the opposite gradient decent directions of the contradictory losses. In this paper, we formulate the perception-distortion trade-off in SR as a multi-objective optimization problem and develop a new optimizer by integrating the gradient-free evolutionary algorithm (EA) with gradient-based Adam, where EA and Adam focus on the divergence and convergence of the optimization directions respectively. As a result, a population of optimal models with different perception-distortion preferences is obtained. We then design a fusion network to merge these models into a single stronger one for an effective perception-distortion trade-off. Experiments demonstrate that with the same backbone network, the perception-distortion balanced SR model trained by our method can achieve better perceptual quality than its competitors while attaining better reconstruction fidelity. Codes and models can be found at https://github.com/csslc/EA-Adam.
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Electrocatalytic H2 production from seawater, recognized as a promising technology utilizing offshore renewables, faces challenges from chloride-induced reactions and corrosion. Here, We introduce a catalytic surface where OH- dominates over Cl- in adsorption and activation, which is crucial for O2 production. Our NiFe-based anode, enhanced by nearby Cr sites, achieves low overpotentials and selective alkaline seawater oxidation. It outperforms the RuO2 counterpart in terms of lifespan in scaled-up stacks, maintaining stability for over 2500 h in three-electrode tests. Ex situ/in situ analyses reveal that Cr(III) sites enrich OH-, while Cl- is repelled by Cr(VI) sites, both of which are well-dispersed and close to NiFe, enhancing charge transfer and overall electrode performance. Such multiple effects fundamentally boost the activity, selectively, and chemical stability of the NiFe-based electrode. This development marks a significant advance in creating durable, noble-metal-free electrodes for alkaline seawater electrolysis, highlighting the importance of well-distributed catalytic sites.
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The influence of epigallocatechin gallate (EGCG) on the physicochemical-rheological properties of silver carp surimi gel was investigated. The gel strength, texture, water-holding capacity (WHC), dynamic distribution of water, and rheological properties of surimi gels added with different levels (0, 0.02, 0.04, 0.06, 0.08, and 0.1%) of EGCG were measured. The results showed that with the increase of EGCG content, the gel strength, hardness, WHC, and immobilized water contents of surimi gels showed a trend of first increasing and then decreasing, and EGCG 0.02% and EGCG 0.04% showed better gel performance as compared with the control. EGCG 0.02% had the highest gel strength (406.62 g·cm), hardness (356.67 g), WHC (64.37%), and immobilized water contents (98.958%). The gel performance decreased significantly when the amounts of EGCG were higher than 0.06%. The viscosity, G', and Gâ³ of the rheological properties also showed the same trends. The chemical interaction of surimi gels, secondary structure of myofibrillar protein (MP), and molecular docking results of EGCG and silver carp myosin showed that EGCG mainly affected the structure and aggregation behavior of silver carp myosin through non-covalent interactions such as those of hydrogen bonds, hydrophobic interactions, and electrostatic interactions. The microstructures of EGCG 0.02% and EGCG 0.04% were compact and homogeneous, and had better gel formation ability. The lower concentrations of EGCG formed a large number of chemical interactions such as those of disulfide bonds and hydrophobic interactions inside the surimi gels by proper cross-linking with MP, and also increased the ordered ß-sheet structure of MP, which facilitated the formation of the compact three-dimensional network gel.
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Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.
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Background: The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer. Methods: Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed. Results: A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19-1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18-1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer. Conclusions: Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466).
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Neoplasias de la Mama , Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/diagnóstico , Persona de Mediana Edad , Insuficiencia Cardíaca/epidemiología , Infarto del Miocardio/epidemiología , Infarto del Miocardio/diagnóstico , Estudios Prospectivos , Anciano , Reino Unido/epidemiología , Adulto , Factores de Edad , Incidencia , Factores de Riesgo , Modelos de Riesgos Proporcionales , Puntaje de PropensiónRESUMEN
Deep learning-based image compression has made great progresses recently. However, some leading schemes use serial context-adaptive entropy model to improve the rate-distortion (R-D) performance, which is very slow. In addition, the complexities of the encoding and decoding networks are quite high and not suitable for many practical applications. In this paper, we propose four techniques to balance the trade-off between the complexity and performance. We first introduce the deformable residual module to remove more redundancies in the input image, thereby enhancing compression performance. Second, we design an improved checkerboard context model with two separate distribution parameter estimation networks and different probability models, which enables parallel decoding without sacrificing the performance compared to the sequential context-adaptive model. Third, we develop a three-pass knowledge distillation scheme to retrain the decoder and entropy coding, and reduce the complexity of the core decoder network, which transfers both the final and intermediate results of the teacher network to the student network to improve its performance. Fourth, we introduce L1 regularization to make the numerical values of the latent representation more sparse, and we only encode non-zero channels in the encoding and decoding process to reduce the bit rate. This also reduces the encoding and decoding time. Experiments show that compared to the state-of-the-art learned image coding scheme, our method can be about 20 times faster in encoding and 70-90 times faster in decoding, and our R-D performance is also 2.3% higher. Our method achieves better rate-distortion performance than classical image codecs including H.266/VVC-intra (4:4:4) and some recent learned methods, as measured by both PSNR and MS-SSIM metrics on the Kodak and Tecnick-40 datasets.
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Background: To investigate whether the novel mutation of PKHD1 could cause polycystic kidney disease by affecting splicing with a recessive inheritance pattern. Methods: A nonconsanguineous Chinese couple with two recurrent pregnancies showed fetal enlarged echogenic polycystic kidney and oligoamnios were recruited. Pedigree WES, minigene splicing assay experiment and following bioinformatics analysis were performed to verify the effects, and inheritance pattern of diseasing-causing mutations. Results: WES revealed that both fetuses were identified as carrying the same novel mutation c.3592_3628 + 45del, p.? and c.11207 T>C, p.(Ile3736Thr) in the PKHD1 gene (NM_138694.4), which inherited from the father and mother respectively. Both bioinformatic method prediction and minigene splicing assay experience results supported the mutation c.3592_3628 + 45del, p.? affects the splicing of the PKHD1 transcript, resulting in exon 31 skipping. Another missense mutation c.11207 T>C, p.(Ile3736Thr) has a low frequency in populations and is predicted to be deleterious by bioinformatic methods. Conclusion: These findings provide a direct clinical and functional evidence that the truncating mutations of the PKHD1 gene could lead to more severe phenotypes, and cause ARPKD as a homozygous or compound heterozygous pattern. Our study broadens the variant spectrum of the PKHD1 gene and provides a basis for genetic counseling and diagnosis of ARPKD.
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The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.
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Salivary collection (SC) following surgery for oral cancer represents an underreported and unrecognized complication. Our study aimed to evaluate the efficacy of parotideomasseteric fascia flap (PFF) in preventing postoperative SC, comparing its effectiveness with other conventional methods. Between November 2019 and January 2023, 221 patients diagnosed with oral squamous cell carcinoma (OSCC) undergoing wide tumor ablation and neck dissection at Xiangya Hospital were included in the study. Patients were randomly allocated into four groups based on different intraoperative techniques to assess the preventive efficacy of PFF against SC. The incidence of SC in the PFF group was only 5.9%, which was significantly lower than the other three groups (p < 0.05). Among the 221 patients, the highest SC incidence occurred in buccal cancer cases (19.6%). However, in the PFF group, the incidence was not significantly different (9.5%; p > 0.05). Univariate analysis revealed a higher SC incidence associated with advanced clinical T stage (p = 0.02), N(+) stage (p = 0.01), low average serum albumin (SA) level (p = 0.00), and a large parotid wound (p = 0.00). In multivariate analysis, only average SA (p = 0.01; odds ratio [OR] 4.104; 95% CI 0.921-11.746) emerged as the most prevalent factor predisposing to SC. The utilization of PFF demonstrated a notable reduction in the incidence of postoperative SC, establishing it as a safe, effective, and convenient method for patients undergoing radical ablation for OSCC.
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BACKGROUND AND AIMS: Whether the natural course of ulcerative colitis (UC) in mainland China is similar or different from that in Western countries is unknown, and data on it is limited. We aimed to provide a comprehensive description of the natural course of UC in China and compare it with Western UC patients. METHODS: Based on a prospective Chinese nationwide registry of consecutive patients with inflammatory bowel diseases, the medical treatments and natural history of UC were described in detail, including disease extension, surgery, and neoplasia. The Cox regression model was used to identify factors associated with poor outcomes. RESULTS: A total of 1081 UC patients were included with a median follow-up duration of 5.3 years. The overall cumulative exposure was 99.1% to 5-aminosalicylic acids, 52.1% to corticosteroids, 25.6% to immunomodulators, and 15.4% to biologics. Disease extent at diagnosis was proctitis in 26.9%, left-sided colitis in 34.8%, and extensive colitis in 38.3%. Of 667 patients with proctitis and left-sided colitis, 380 (57.0%) experienced disease extent progression. A total of 58 (5.4%) UC patients underwent colectomy, demonstrating cumulative proportions of surgery at 1, 5, and 10 years after diagnosis of 0.6%, 3.4%, and 8.2%, respectively. In addition, 23 (2.1%) UC patients were diagnosed with neoplasia, demonstrating cumulative proportions of neoplasia at 1, 5, and 10 years after diagnosis of 0.5%, 1.0%, and 3.5%, respectively. CONCLUSIONS: Chinese UC patients had similar cumulative proportions of exposure to IBD-specific treatments but a lower surgical rate than patients in Western countries, indicating a different natural course, and close monitoring needs for UC in China. However, these results must be confirmed in population-based studies because the hospital-based cohort in our study might lead to selection bias.
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Objective. Eye-tracking research has proven valuable in understanding numerous cognitive functions. Recently, Freyet alprovided an exciting deep learning method for learning eye movements from functional magnetic resonance imaging (fMRI) data. It employed the multi-step co-registration of fMRI into the group template to obtain eyeball signal, and thus required additional templates and was time consuming. To resolve this issue, in this paper, we propose a framework named MRGazer for predicting eye gaze points from fMRI in individual space.Approach. The MRGazer consists of an eyeball extraction module and a residual network-based eye gaze prediction module. Compared to the previous method, the proposed framework skips the fMRI co-registration step, simplifies the processing protocol, and achieves end-to-end eye gaze regression.Main results. The proposed method achieved superior performance in eye fixation regression (Euclidean error, EE = 2.04°) than the co-registration-based method (EE = 2.89°), and delivered objective results within a shorter time (â¼0.02 s volume-1) than prior method (â¼0.3 s volume-1).Significance. The MRGazer is an efficient, simple, and accurate deep learning framework for predicting eye movement from fMRI data, and can be employed during fMRI scans in psychological and cognitive research. The code is available athttps://github.com/ustc-bmec/MRGazer.
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Fijación Ocular , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Fijación Ocular/fisiología , Masculino , Adulto , Femenino , Adulto Joven , Tecnología de Seguimiento Ocular , Movimientos Oculares/fisiología , Aprendizaje Profundo , Encéfalo/fisiología , Encéfalo/diagnóstico por imagenRESUMEN
Litchi chinensis Sonn (Litchi) has been listed in the Chinese Pharmacopeia, and is an economically and medicinally valuable species within the family Sapindaceae. However, the material basis of its pharmacological action and the pharmacodynamic substances associated with its hypoglycemic effect are still unclear. The predominant objective of this study was to establish the fingerprint profile of litchi leaves and to evaluate the relationship between the components of the high-performance liquid chromatography (HPLC) fingerprint of litchi leaves, assess its hypoglycemic effect by measuring α-glucosidase and α-amylase inhibition, and find the spectrum-effect relationship of litchi leaves by bivariate correlation analysis, Grey relational analysis and partial least squares regression analysis. In this study, the fingerprint of litchi leaves was established by HPLC, and a total of 15 common peaks were identified that clearly calibrated eight components, with P1 being gallic acid, P2 being protocatechuic acid, P3 being catechin, P6 being epicatechin, P12 being rutin, P13 being astragalin, P14 being quercetin and P15 being kaempferol. The similarities between the fingerprints of 11 batches of litchi leaves were 0.766-0.979. Simultaneously, the results of the spectrum-effect relationship showed that the chemical constituents represented by peaks P8, P3, P12, P14, P2, P13, and P11 were relevant to the hypoglycemic effect.
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Hipoglucemiantes , Litchi , Extractos Vegetales , Hojas de la Planta , Litchi/química , Hojas de la Planta/química , Cromatografía Líquida de Alta Presión/métodos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/análisisRESUMEN
Gene expression involves transcription, translation, and mRNA and protein degradation. Advanced RNA sequencing measures mRNA levels for cell state assessment, but mRNA level does not fully reflect protein level. Identifying heart cell proteomes and their stress response is crucial. Using a cardiomyocyte-specific mouse model, we tracked protein synthesis after myocardial infarction. Our results showed that myocardial infarction suppresses protein synthesis and unveils a decoupling of translation and transcription regulation in cardiomyocytes.
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Furin primarily localizes to the trans-Golgi network (TGN), where it cleaves and activates a broad range of immature proproteins that play critical roles in cellular homeostasis, disease progression, and infection. Furin is retrieved from endosomes to the TGN after being phosphorylated, but it is still unclear how furin exits the TGN to initiate the post-Golgi trafficking and how its activity is regulated in the TGN. Here three membrane-associated RING-CH finger (MARCHF) proteins (2, 8, 9) are identified as furin E3 ubiquitin ligases, which catalyze furin K33-polyubiquitination. Polyubiquitination prevents furin from maturation by blocking its ectodomain cleavage inside cells but promotes its egress from the TGN and shedding. Further ubiquitin-specific protease 32 (USP32) is identified as the furin deubiquitinase in the TGN that counteracts the MARCHF inhibitory activity on furin. Thus, the furin post-Golgi trafficking is regulated by an interplay between polyubiquitination and phosphorylation. Polyubiquitination is required for furin anterograde transport but inhibits its proprotein convertase activity, and phosphorylation is required for furin retrograde transport to produce fully active furin inside cells.
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BACKGROUND AND OBJECTIVE: Complex acetabular fractures involving quadrilateral areas are more challenging to treat during surgery. To date, there has been no ideal internal fixation for these acetabular fractures. The purpose of this study was to evaluate the biomechanical stability of complex acetabular fractures using a dynamic anterior titanium-plate screw system of the quadrilateral area (DAPSQ) by simulating the standing and sitting positions of pelvic specimens. MATERIALS AND METHODS: Eight formal in-preserved cadaveric pelvises aged 30-50 years were selected as the research objects. First, one hip of the normal pelvises was randomly used as the control model (group B) for measurement, and then one hip of the pelvises was randomly selected to make the fracture model in the 8 intact pelvises as the experimental model (group A) for measurement. In group A, acetabular both-column fractures in the quadrilateral area were established, and the fractures were fixed by DAPSQ. The biomechanical testing machine was used to load (simulated physiological load) from 400 N to 700 N at a 1 mm/min speed for 30 s in the vertical direction when the specimens were measured at random in simulated standing or sitting positions in groups. The horizontal displacement and longitudinal displacement of the acetabular fractures in the quadrilateral area were measured in both the standing and sitting simulations. RESULTS: As the load increased, no dislocation or internal fixation breakage occurred during the measurements. In the standing position, the horizontal displacement of the quadrilateral area fractures in group A and group B appeared to be less than 1 mm with loads ranging from 400 N to 700 N, and there was no significant difference between group A and group B (p > 0.05). The longitudinal displacement appeared to be greater than 1 mm with a load of 700 mm in group A (700 N, 2 cases), and the difference was significant between group A and group B (p < 0.05). In the sitting position, the horizontal and longitudinal displacements of the quadrilateral areas were within 0.5 mm in group A and group B, and there was no significant difference between group A and group B (p > 0.05). CONCLUSION: For complex acetabular fractures in the quadrilateral area, DAPSQ fixation may provide early sitting stability, but it is inappropriate for patients to stand too early.
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Acetábulo , Placas Óseas , Tornillos Óseos , Fijación Interna de Fracturas , Fracturas Óseas , Titanio , Humanos , Acetábulo/cirugía , Acetábulo/lesiones , Fenómenos Biomecánicos , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Adulto , Persona de Mediana Edad , Fracturas Óseas/cirugía , Fracturas Óseas/fisiopatología , Masculino , Femenino , CadáverRESUMEN
The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.
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Anticuerpos Monoclonales , Linfocitos T CD8-positivos , Células Asesinas Naturales , Nanopartículas , Células Asesinas Naturales/inmunología , Animales , Humanos , Ratones , Nanopartículas/química , Anticuerpos Monoclonales/inmunología , Línea Celular Tumoral , Linfocitos T CD8-positivos/inmunología , Inmunoterapia/métodos , Neoplasias/inmunología , Neoplasias/terapia , Antígeno B7-H1/inmunología , Subfamília C de Receptores Similares a Lectina de Células NK/inmunología , Femenino , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Ratones Endogámicos NODRESUMEN
It is vital to explore effective ways for prolonging electrode lifespans under harsh electrolysis conditions, such as high current densities, acid environment, and impure water source. Here we report alternating electrolysis approaches that realize promptly and regularly repair/maintenance and concurrent bubble evolution. Electrode lifespans are improved by co-action of Fe group elemental ions and alkali metal cations, especially a unique Co2+-Na+ combo. A commercial Ni foam sustains ampere-level current densities alternatingly during continuous electrolysis for 93.8 h in an acidic solution, whereas such a Ni foam is completely dissolved in ~2 h for conventional electrolysis conditions. The work not only explores an alternating electrolysis-based system, alkali metal cation-based catalytic systems, and alkali metal cation-based electrodeposition techniques, and beyond, but demonstrates the possibility of prolonged electrolysis by repeated deposition-dissolution processes. With enough adjustable experimental variables, the upper improvement limit in the electrode lifespan would be high.