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The escalating adoption of laparoscopic surgical techniques has demonstrated their capacity to yield improved clinical outcomes. However, concomitant with the advantages of this minimally invasive approach, certain adverse complications have been reported. In this report, we present a noteworthy case involving a 72-year-old male patient who underwent laparoscopic inguinal hernia repair. The surgical procedure proceeded without noteworthy complications, and the patient maintained hemodynamic stability throughout. However, the post-anesthetic recovery was compromised by the onset of subcutaneous emphysema and bilateral tension pneumothorax. Immediate intervention was imperative, prompting the performance of an emergent needle thoracostomy, subsequently followed by the implementation of a closed drainage system within the thoracic cavity. These interventions proved efficacious in mitigating the patient's distressing symptoms. Although pneumothorax complications in the context of laparoscopic surgery are infrequent, it is imperative for anesthetists to remain vigilant regarding the potential occurrence of subcutaneous emphysema and pneumothorax in the perioperative period. This case underscores the significance of meticulous perioperative monitoring and rapid intervention, particularly in laparoscopic procedures, where the insufflation of carbon dioxide into the abdominal cavity can predispose patients to these rare yet potentially life-threatening complications. Heightened awareness among healthcare providers regarding the possibility of such events is pivotal in ensuring the safety and well-being of surgical patients.
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Cytokinins (CKs) are one of important classes of plant hormones essential for plant growth and development. The TATA-box binding protein-associated factor 12b (TAF12b) is involved in cytokinin (CK) signaling, but its molecular and biochemical mechanisms remain unclear. In this study, TAF12b of Nicotiana benthamiana (NbTAF12b) was found to mediate CK response by directly interacting with type-B response regulators (B-RRs), which are positive regulators of CK signaling, and inhibiting their transcriptional activities. The co-factor specifically facilitated the proteasomal degradation of non-phosphorylated B-RRs by recruiting the KMD family of F-box proteins. Such interactions between TAF12b and B-RRs also occur in other plant species. Genetic transformation experiments further showed that overexpression of NbTAF12b attenuates the CK-hypersensitive phenotype conferred by NbRR1 overexpression. Taken together, these results suggest a conserved mechanism that TAF12b negatively regulates CK responses through promoting 26S proteasome-mediated degradation of B-RRs degradation in multiple plant species, which provides novel insights into the regulatory network of CK signaling in plants.
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Lipid metabolism reprogramming stands as a fundamental hallmark of cancer cells. Unraveling the core regulators of lipid biosynthesis holds the potential to find promising therapeutic targets in pancreatic ductal adenocarcinoma (PDAC). Here, it is demonstrated that platelet-derived growth factor C (PDGFC) orchestrated lipid metabolism, thereby facilitated the malignant progression of PDAC. Expression of PDGFC is upregulated in PDAC cohorts and is corelated with a poor prognosis. Aberrantly high expression of PDGFC promoted proliferation and metastasis of PDAC both in vitro and in vivo. Mechanistically, PDGFC accelerated the malignant progression of PDAC by upregulating fatty acid accumulation through sterol regulatory element-binding protein 1 (SREBP1), a key transcription factor in lipid metabolism. Remarkably, Betulin, an inhibitor of SREBP1, demonstrated the capability to inhibit proliferation and metastasis of PDAC cell lines, along with attenuating the process of liver metastasis in vivo. Overall, the study underscores the pivotal role of PDGFC-mediated lipid metabolism in PDAC progression, suggesting PDGFC as a potential biomarker for PDAC metastasis. Targeting PDGFC-induced lipid metabolism emerges as a promising therapeutic strategy for metastatic PDAC, with the potential to improve clinical outcomes.
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A subfamily of conserved proteins called serpins plays crucial roles in various physiological functions, particularly in the activation pathway of the serine protease cascade, an essential component of insect innate immunity. Here, we found Bombyx mori serpin 3 (BmSerpin3) was most highly expressed in the fat body, and was up-regulated after exposure to bacteria, fungus and virus. Further, the expression of BmSerpin3 in the hemocytes, fat body, midgut of silkworm larvae, and BmN cells was up-regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Through Bac-to-Bac expression system, we obtained the active protein of BmSerpin3, and the enzyme activity assay showed that BmSerpin3 significantly inhibited the activity of both subtilisin and trypsin. In addition, BmSerpin3 could inhibit the activation of prophenoloxidase (PPO) in larvae. The knockdown of BmSerpin3 showed increased phenoloxidase (PO) activity compared to control after BmNPV infection. Ultimately, we confirmed that BmSerpin3 interacts with B. mori Serine Protease 7 (BmSP7). Hence, we hypothesize that BmSerpin3 is involved in innate immunity by interacting with BmSP7 to regulate the PPO activation cascade. Taken together, these results showed that BmSerpin3 play a role in silkworm innate immunity and lay a foundation for studying its functions.
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Ubiquitination is a common post-translational modification of proteins in eukaryotic cells, and it is also a significant method of regulating protein biological function. The use of computational methods for predicting ubiquitination sites can replace costly and time-consuming experimental methods. Existing computational methods often build classifiers based on protein sequence information, physical and chemical properties of amino acids, evolutionary information, and structural parameters. However, structural information about most proteins cannot be found in existing databases directly. The features of proteins differ among species, and some species have small amounts of ubiquitinated proteins. Therefore, it is necessary to develop species-specific models that can be applied to datasets with small sample sizes. To solve these problems, we propose a species-specific model (SSUbi) based on a capsule network, which integrates proteins' sequence and structural information. In this model, the feature extraction module is composed of two sub-modules that extract multi-dimensional features from sequence and structural information respectively. In the submodule, the convolution operation is used to extract encoding dimension features, and the channel attention mechanism is used to extract feature map dimension features. After the multi-dimensional features of the two kinds of information are integrated, the species-specific capsule network further converts the features into capsule vectors and classifies species-specific ubiquitination sites. The experimental results show that SSUbi can effectively improve the prediction performance of species with small sample sizes and outperform other models.
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CONTEXT: Pain is one of the most common symptoms of cancer patients, affecting the patient's physical, psychological, behavioral, social relations and other aspects. Previous studies have demonstrated that exercise is effective for cancer pain, and the optimal exercise is still unknown. OBJECTIVES: This study aimed to compare the effects of different exercise interventions on cancer pain in adults. METHODS: Randomized control trials identified from medical literature databases that reported effects of exercise in adults with cancer pain were included in this study. Literature screening and data extraction were conducted independently by two researchers. Cochrane Bias Assessment 2.0 was used to assess the quality of the literature, and Stata 15.0 software was used for Network meta-analysis. RESULTS: Forty-one studies were included, involving 3537 patients with cancer pain. The types of exercise involved included aerobic exercise, medium intensity continuous training, high-intensity interval training, resistance exercise, mind-body exercise and comprehensive exercise program (CEP). The results suggested that CEP was more effective than the usual care in relieving pain intensity in cancer patients [SMD=-1.96,95%CI (-3.47, -0.44)] (SUCRA=97.9%). Mind-body exercise outperformed usual care in reducing pain interference in cancer patients [SMDâ¯=â¯-0.65, 95% CI (-1.21, -0.09)] (SUCRA=83.8%). CONCLUSION: Current evidence shows that CEP is the best way to relieve the pain intensity of cancer patients, and mind-body exercise is the best way to reduce pain interference of cancer patients. Due to the limited number and quality of the included studies, the above conclusions need to be further verified by more high-quality studies.
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Humans recognize and manipulate objects relying on the multidimensional force features captured by the tactile sense of skin during the manipulation. Since the current sensors integrated in robots cannot support the robots to sense the multiple interaction states between manipulator and objects, achieving human-like perception and analytical capabilities remains a major challenge for service robots. Prompted by the tactile perception involved in robots performing complex tasks, a multimodal tactile sensory system is presented to provide in situ simultaneous sensing for robots when approaching, touching, and manipulating objects. The system comprises a capacitive sensor owning the high sensitivity of 1.11E-2 pF mm-1, a triboelectricity nanogenerator with the fast response speed of 30 ms, and a pressure sensor array capable of 3D force detection. By Combining transfer learning models, which fuses multimodal tactile information to achieve high-precision (up to 95%) recognition of the multi-featured targets such as random hardness and texture information under random sampling conditions, including random grasp force and velocity. This sensory system is expected to enhance the intelligent recognition and behavior-planning capabilities of autonomous robots when performing complex tasks in undefined surrounding environments.
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Membranous nephropathy (MN) is a common pathological type of adult nephrotic syndrome. Up to 20% of patients with MN develop end-stage renal disease (ESRD). Podocytes have an important function in maintaining the glomerular filtration barrier and play a crucial role in the occurrence and development of proteinuria and MN. PI3K/AKT signaling pathway is involved in the entire process of podocyte growth, differentiation, and apoptosis. Kemeng Fang (KMF) is a traditional Chinese medicine formula that has been used to delay kidney injury. However, the therapeutic mechanism of KMF in MN is unclear. Here, the MN rat model was established by axillary, inguinal, and tail vein injections of cationized bovine serum albumin (C-BSA), and then KMF and PI3K inhibitor (LY294002) were administered. The data of liver function, kidney function, blood lipid, renal pathology, podocyte function, expression level of PI3K/AKT signaling pathway, and transcriptomics of rats demonstrated that KMF has a protective effect on the podocytes of MN rats by activating the PI3K/AKT signaling pathway, and it can effectively prevent the progression of MN.
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Apoptosis , Medicamentos Herbarios Chinos , Glomerulonefritis Membranosa , Fosfatidilinositol 3-Quinasas , Podocitos , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/metabolismo , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Podocitos/patología , Ratas , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Medicamentos Herbarios Chinos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Masculino , Ratas Sprague-Dawley , Morfolinas/farmacología , Morfolinas/uso terapéutico , Cromonas/farmacología , Modelos Animales de EnfermedadRESUMEN
A speech intelligibility (SI) prediction model is proposed that includes an auditory preprocessing component based on the physiological anatomy and activity of the human ear, a hierarchical spiking neural network, and a decision back-end processing based on correlation analysis. The auditory preprocessing component effectively captures advanced physiological details of the auditory system, such as retrograde traveling waves, longitudinal coupling, and cochlear nonlinearity. The ability of the model to predict data from normal-hearing listeners under various additive noise conditions was considered. The predictions closely matched the experimental test data under all conditions. Furthermore, we developed a lumped mass model of a McGee stainless-steel piston with the middle-ear to study the recovery of individuals with otosclerosis. We show that the proposed SI model accurately simulates the effect of middle-ear intervention on SI. Consequently, the model establishes a model-based relationship between objective measures of human ear damage, like distortion product otoacoustic emissions, and speech perception. Moreover, the SI model can serve as a robust tool for optimizing parameters and for preoperative assessment of artificial stimuli, providing a valuable reference for clinical treatments of conductive hearing loss.
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Redes Neurales de la Computación , Inteligibilidad del Habla , Percepción del Habla , Humanos , Percepción del Habla/fisiología , Estimulación Acústica , Oído Medio/fisiología , Ruido/efectos adversos , Emisiones Otoacústicas Espontáneas , Otosclerosis/fisiopatología , Otosclerosis/cirugía , Simulación por Computador , Vías Auditivas/fisiología , Cóclea/fisiologíaRESUMEN
Aims: To investigate the therapeutic effect of acupuncture on acute inflammatory nerve root injury by regulating lymphatic function. Main methods: A mouse model of L5 nerve root compression was used to simulate acute nerve root injury. After modeling, acupuncture treatment was given each day for one week. Pain thresholds were assessed before and after modeling and treatment. Immunofluorescence staining was performed to observe the distribution astrocytes and neurons in the lumbar spinal cord, the innervation rate of neuromuscular junctions (NMJs), lymphatic endothelial cells (LECs) of lumbar aortic lymph nodes, and the percentage of M1 macrophages. The number of each type of immune cells in the lumbar aortic lymph nodes (LALNs) was measured by flow cytometry. Key findings: The model group showed a significant decrease in pain threshold in the affected lower limb, while acupuncture treatment was able to significantly increase it. Acupuncture significantly repaired astrocytes and neurons in the lumbar spinal cord of the compressed segment, increased the innervation rate of nerve endings at NMJs, reduced LECs in the LALNs, reduced the proportion of M1 macrophages in the LALNs, and significantly reduced mononuclear neutrophils and monocytic neutrophils. Significance: Acupuncture can reduce pain, promote nerve repair in mice with acute nerve root injury, and suppress immune responses in lumbar aortic lymph nodes.
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Abnormal biosynthesis of spliceosomes and ribosomes can lead to their dysfunction, which in turn disrupts protein synthesis and results in various diseases. While genetic factors have been extensively studied, our understanding of how environmental compounds interfere with spliceosome and ribosome biosynthesis remains limited. In the present study, we employed a Reduced Transcriptome Analysis (RTA) approach, integrating large-scale transcriptome data sets of zebrafish and compiling a specific zebrafish gene panel focusing on the spliceosome and ribosome, to elucidate the potential disruptors targeting their biosynthesis. Transcriptomic data sets for 118 environmental substances and 1400 related gene expression profiles were integrated resulting in 513 exposure signatures. Among these substances, several categories including PCB126, transition metals Lanthanum (La) and praseodymium (Pr), heavy metals Cd2+ and AgNO3 and atrazine were highlighted for inducing the significant transcriptional alterations. Furthermore, we found that the transcriptional patterns were distinct between categories, yet overlapping patterns were generally observed within each group. For instance, over 82 % differentially expressed ribosomal genes were shared between La and Pr within the equivalent concentration range. Additionally, transcriptional complexities were also evident across various organs and developmental stages of zebrafish, with notable differences in the inhibition of the transcription of various spliceosome subunits. Overall, our results provide novel insights into the understanding of the adverse effects of environmental compounds, thereby contributing to their environmental risk assessments.
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Sepsis-induced cardiomyopathy (SIC) is described as a reversible myocardial depression that occurs in patients with septic shock. Increasing evidence shows that microRNA-194-5p (miR-194-5p) participates in the regulation of oxidative stress, mitochondrial dysfunction, and apoptosis and its expression is associated with the occurrence and progression of cardiovascular disease; however, the effects of miR-194-5p in SIC are still unclear. This study explores whether miR-194-5p could modulate SIC by affecting oxidative stress, mitochondrial function, and apoptosis. Experimental septic mice were induced by intraperitoneal injection of lipopolysaccharide (LPS) in C57BL/6J mice. The biological role of miR-194-5p in SIC in vivo was investigated using cardiac echocardiography, ELISA, western blot, qRT-PCR, transmission electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, bioinformatics analysis, and dual-luciferase reporter gene assay. Our major finding is that miR-194-5p antagomir mitigates sepsis-induced cardiac dysfunction, inflammation, oxidative stress, apoptosis and mitochondrial dysfunction in the hearts of septic mice, while miR-194-5p agomir triggers the opposite effects. Furthermore, dual-specificity phosphatase 9 (DUSP9) is a direct target of miR-194-5p and the cardioprotective effects of miR-194-5p antagomir on cardiac dysfunction, inflammation, apoptosis, mitochondrial dysfunction and oxidative stress are abolished through inhibiting DUSP9. Therefore, miR-194-5p inhibition could mitigate SIC via DUSP9 in vivo and the novel miR-194-5p/DUSP9 axis might be the potential treatment targets for SIC patients.
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Apoptosis , Cardiomiopatías , Fosfatasas de Especificidad Dual , Ratones Endogámicos C57BL , MicroARNs , Estrés Oxidativo , Sepsis , Animales , Masculino , Ratones , Antagomirs/farmacología , Antagomirs/metabolismo , Cardiomiopatías/etiología , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Cardiomiopatías/genética , Modelos Animales de Enfermedad , Regulación hacia Abajo , Fosfatasas de Especificidad Dual/metabolismo , Fosfatasas de Especificidad Dual/genética , Lipopolisacáridos , MicroARNs/genética , MicroARNs/metabolismo , Sepsis/complicaciones , Sepsis/metabolismo , Sepsis/genéticaRESUMEN
The surge in advanced imaging techniques has generated vast biomedical image data with diverse dimensions in space, time and spectrum, posing big challenges to conventional compression techniques in image storage, transmission, and sharing. Here, we propose an intelligent image compression approach with the first-proved semantic redundancy of biomedical data in the implicit neural function domain. This Semantic redundancy based Implicit Neural Compression guided with Saliency map (SINCS) can notably improve the compression efficiency for arbitrary-dimensional image data in terms of compression ratio and fidelity. Moreover, with weight transfer and residual entropy coding strategies, it shows improved compression speed while maintaining high quality. SINCS yields high quality compression with over 2000-fold compression ratio on 2D, 2D-T, 3D, 4D biomedical images of diverse targets ranging from single virus to entire human organs, and ensures reliable downstream tasks, such as object segmentation and quantitative analyses, to be conducted at high efficiency.
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Compresión de Datos , Semántica , Compresión de Datos/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , AlgoritmosRESUMEN
Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for immunotherapy. Here, we identify a natural pentacyclic triterpenoid, Pygenic Acid A (PA), as a PD-1 signaling inhibitor. PA exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of T cells to promote immune responses by disrupting the PD-1 signaling transduction. Furthermore, we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling transduction. Subsequently, mechanistic studies suggest that PA binds to a new druggable site in the phosphorylated PD-1 ITSM recognition site of SHP-2, inhibiting the recruitment of SHP-2 by PD-1. Taken together, our findings demonstrate that PA has a potential application in cancer immunotherapy and occupying the phosphorylated ITSM recognition site of SHP-2 may serve as an alternative strategy to develop PD-1 signaling inhibitors. In addition, our success in target recognition provides a paradigm of target identification and confirmation for natural products.
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Petroleum can be generated by thermal cracking of organic matter within sediments, and the organic matter within sediments plays the dominant role in determining oil and gas generation. Organic matter within sediments is characterized by various sources, such as sapropelic organic matter from algal, microbial, and planktonic organisms and humic organic matter from higher plants. Paleo-productivity, terrestrial influx, and depositional environments could obviously influence the enrichment processes of the organic matter within sediments. Organic and elemental geochemical proxies can investigate the sedimentary process and reflect the enrichment characteristics of organic matter. In this study, hydrocarbon source rocks from the Shuixigou Group were collected from the Taibei Sag of the Turpan-Hami Basin, rock-eval pyrolysis was conducted, and stable carbon isotope composition of organic carbon and major and trace element distributions were measured. Based on this, the type and maturation of organic matter, paleo-productivity, terrestrial influx, and depositional paleo-environments were investigated. The results show that the Jurassic hydrocarbon source rocks are characterized by type III kerogen and are in the oil-window stage of maturation. The depositional paleo-environments of hydrocarbon source rocks in different formations are not remarkably different. The water bodies have freshwater oxidizing environments, and the paleo-climatic characteristics are warm and humid. However, the paleo-productivity of samples from the lower Jurassic Sangonghe Formation is higher than samples from other formations. Overall, the organic matter enrichment in Jurassic hydrocarbon source rocks of the Turpan-Hami Basin could be mutually controlled by the paleo-productivity and depositional paleo-environments. The results of this study could provide theoretical insight into deep petroleum exploration and resource evaluation in the Turpan-Hami Basin.
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Phyllosticta citricarpa is an important citrus-pathogen and a quarantine organism in the European Union. Its recently described relative, P. paracitricarpa, is very closely related and not listed as a quarantine organism. P. paracitricarpa is very difficult to distinguish from P. citricarpa, since its morphological features overlap and the barcoding gene sequences that were originally used to delimit them as distinct species have a low number of species-specific polymorphisms that have subsequently been shown to overlap between the two clades. Therefore, we performed extensive genomic analyses to determine whether the genetic variation between P. citricarpa and P. paracitricarpa strains should be considered to represent infraspecific variation within P. citricarpa, or whether it is indicative of distinct species. Using a phylogenomic analysis with 3,000 single copy ortholog genes and whole-genome comparisons, we determined that the variation between P. citricarpa and P. paracitricarpa can be considered as infraspecies variation within P. citricarpa. We also determined the level of variation in mitochondrial assemblies of several Phyllosticta species and concluded there are only minimal differences between the assemblies of P. citricarpa and P. paracitricarpa. Thus, using several orthogonal approaches, we here demonstrate that variation within the nuclear and mitochondrial genomes of other Phyllosticta species is larger than variation between genomes obtained from P. citricarpa and P. paracitricarpa strains. Thus, P. citricarpa and P. paracitricarpa should be considered as conspecific.
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Hand, foot, and mouth disease (HFMD) is a prevalent acute infectious disease caused by enteroviruses, presenting substantial public health challenges in Shanghai, especially among children. The dynamic nature of HFMD's etiology necessitates an ongoing evaluation of its epidemiological and virological trends to inform effective control strategies. This study aims to investigate the epidemiological patterns and viral evolution of HFMD in Fengxian District, Shanghai, China, with a focus on shifts in predominant viral strains over a 14-year period. We conducted a retrospective analysis of HFMD cases reported to the National Notifiable Disease Reporting System in Fengxian District from January 1, 2009 to December 31, 2022. Epidemiological trends, strain prevalence, and demographic impacts were assessed. A total of 27,272 HFMD cases were documented during the study period, with incidence showing pronounced seasonal fluctuations-peaking in spring and summer and a lesser peak in autumn. The disease incidence demonstrated significant positive correlations with several meteorological variables: daily average temperature (r = 0.30, P < 0.05), relative humidity (r = 0.20, P < 0.05), wind speed (r = 0.17, P < 0.05), and precipitation (r = 0.17, P < 0.05). Geographically, Nanqiao Town, Fengcheng Town, and Xidu Subdistrict reported the highest incidence rates. The demographic analysis revealed a male-to-female ratio of 1.60:1, predominantly affecting children aged 1-3 years. Prior to 2017, Enterovirus 71 (EV71) and Coxsackievirus A16 (CoxA16) were the primary detected strains; post-2017, Coxsackievirus A6 (CoxA6) emerged as the dominant strain. Statistical analysis confirmed significant year-to-year variations in virus detection rates, with decreasing trends for EV71 and other enteroviruses and an increasing trend for CoxA6. The findings indicate a distinct seasonal incidence of HFMD in Fengxian District. This study underscores the need for targeted public health education, enhanced surveillance, and proactive measures in childcare facilities to mitigate disease spread during peak seasons. Moreover, the evolving viral landscape warrants accelerated efforts in vaccine development against new strains to reduce HFMD incidence.
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Enfermedad de Boca, Mano y Pie , Estaciones del Año , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/virología , Humanos , China/epidemiología , Masculino , Femenino , Preescolar , Lactante , Incidencia , Estudios Retrospectivos , Niño , Análisis Espacio-Temporal , Enterovirus/aislamiento & purificación , Prevalencia , AdolescenteRESUMEN
The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8+ T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo. Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.
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Alzheimer's disease has escalated into a critical public health concern, marked by its neurodegenerative nature that progressively diminishes cognitive abilities. Recognized as a continuously advancing and presently incurable condition, AD underscores the necessity for early-stage diagnosis and interventions aimed at delaying the decline in mental function. Despite the proven efficacy of cerebrospinal fluid and positron emission tomography in diagnosing AD, their broader utility is constrained by significant costs and the invasive nature of these procedures. Consequently, the innovation of blood biomarkers such as Amyloid-beta, phosphorylated-tau, total-tau et al, distinguished by their high sensitivity, minimal invasiveness, accessibility, and cost-efficiency, emerges as a promising avenue for AD diagnosis. The advent of ultra-sensitive detection methodologies, including single-molecule enzyme-linked immunosorbent assay and immunoprecipitation-mass spectrometry, has revolutionized the detection of AD plasma biomarkers, supplanting previous low-sensitivity techniques. This rapid advancement in detection technology facilitates the more accurate quantification of pathological brain proteins and AD-associated biomarkers in the bloodstream. This manuscript meticulously reviews the landscape of current research on immunological markers for AD, anchored in the National Institute on Aging-Alzheimer's Association AT(N) research framework. It highlights a selection of forefront ultra-sensitive detection technologies now integral to assessing AD blood immunological markers. Additionally, this review examines the crucial pre-analytical processing steps for AD blood samples that significantly impact research outcomes and addresses the practical challenges faced during clinical testing. These discussions are crucial for enhancing our comprehension and refining the diagnostic precision of AD using blood-based biomarkers. The review aims to shed light on potential avenues for innovation and improvement in the techniques employed for detecting and investigating AD, thereby contributing to the broader field of neurodegenerative disease research.