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Objectives: Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam-like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of l-oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated. Methods: The study adopts a multicenter, randomized, double-blind, parallel-group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: l-oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow-up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments. Discussion: There is no robust evidence to suggest that l-oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question. Trial registration: chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565.
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In thermoelectric, phase interface engineering proves effective in reducing the lattice thermal conductivity via interface scattering and amplifying the density-of-states effective mass by energy filtering. However, the indiscriminate introduction of phase interfaces inevitably leads to diminished carrier mobility. Moreover, relying on a singular energy barrier is insufficient for comprehensive filtration of low-energy carriers throughout the entire temperature range. Addressing these challenges, we advocate the establishment of a composite phase interface using atomic layer deposition (ALD) technology. This design aims to effectively decouple the interrelated thermoelectric parameters in ZrNiSn. The engineered coherent dual-interface energy barriers substantially enhance the density-of-states effective mass across the entire temperature spectrum while preser carrier mobility. Simultaneously, the strong interface scattering on phonons is crucial for curtailing lattice thermal conductivity. Consequently, a 40-cycles TiO2 coating on ZrNi1.03Sn0.99Sb0.01 achieves an unprecedented zT value of 1.3 at 873 K. These findings deepen the understanding of coherent composite-phase interface engineering.
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Texture-modified, multi-nutrient composite foods are essential in clinical treatment for dysphagia individuals. Herein, fibrous whey protein-stabilized emulsion and different crystalline starches (wheat, corn, rice, potato, sweet potato, cassava, mung bean and pea) were used to structure composite emulsion gels (CEGs). These CEGs then underwent 3D printing to explore the feasibility of developing a dysphagia diet. The network of molded CEGs was mainly maintained by hydrophobic interactions and hydrogen bonds. Rice and cassava starches were better suited for structuring soft-textured CEGs. Compared with molded CEGs, 3D printing decreased hydrogen bonds and the compactness of the nano-aggregate structure within the gel system, forming a looser gel network and softening the CEGs. Interestingly, these effects were more pronounced for the CEGs with high initial hardness. This study provided new strategy to fabricate CEGs as dysphagia diet using fibrous whey protein and starch, and to design texture-modified foods for patients using 3D printing.
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Bitter gourd has numerous health-promoting effects on the human body. However, its use has been greatly limited due to its poor acceptance by consumers, resulting from its strong bitterness. This study investigated the effects of five wall materials, namely, soybean protein isolate, gum arabic, maltodextrin, resistant starch, and a soybean lecithin calcium caseinate mixture, on the physicochemical properties of spray-dried bitter gourd powders. The results showed that all five wall materials reduced the moisture content, water activity, browning degree, agglomeration, and bitterness of the spray-dried bitter gourd powder. Maltodextrin was found to be the most effective at reducing water activity, while soybean protein isolate was best at protecting the colour, and the soybean lecithin calcium caseinate mixture was best at reducing hygroscopicity and masking bitterness. Additionally, all five wall materials improved the preservation of flavonoids, saponins, and vitamin C, with soybean protein isolate being the most effective in improving the total flavonoid retention ratio and the soybean lecithin calcium caseinate mixture being the best in improving the retention ratios of total saponins and vitamin C. The spray-dried bitter gourd powder prepared with soybean protein isolate had the highest antioxidant activity and α-glucosidase inhibitory activity. These results are significant for understanding the relationship between wall materials and the physicochemical properties of spray-dried powder. Additionally, these materials provide bitter gourd product manufacturers with useful guidance for producing high-quality products. Furthermore, the results could provide useful insights for processing fruits with similar product characteristics, thus contributing to the enrichment of food processing knowledge.
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Combination therapy proven to be an effective therapeutic approach for estrogen receptor (ER)-positive breast cancer. Currently, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are combined with aromatase inhibitors (AIs) or selective estrogen receptor degraders (SERDs) as first-line therapy for advanced ER-positive breast cancer. Herein, a new family of quinoline scaffold SERDs was synthesized and evaluated in MCF-7 cells. Among them, compounds 18j and 24d exhibited remarkable MCF-7 inhibition, both alone and in combination with ribociclib (CDK4/6 inhibitor), in vitro and in vivo. Meanwhile, compounds 18j and 24d effectively degraded ER and inhibited ER downstream signaling pathways. Interestingly, compounds 18j and 24d induced endoplasmic reticulum stress (ERS) and triggered immunogenic cell death (ICD) via damage-associated molecular patterns (DAMPs) in MCF-7 cells. These findings highlight the immune-related and enhanced antiproliferative effects of oral SERDs in ER positive breast cancer treatment.
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Antineoplásicos , Neoplasias de la Mama , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Quinolinas , Receptores de Estrógenos , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Proliferación Celular/efectos de los fármacos , Quinolinas/farmacología , Quinolinas/química , Quinolinas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Femenino , Receptores de Estrógenos/metabolismo , Relación Estructura-Actividad , Estructura Molecular , Animales , Muerte Celular Inmunogénica/efectos de los fármacos , Descubrimiento de Drogas , Relación Dosis-Respuesta a Droga , Células MCF-7 , Ratones , Estrés del Retículo Endoplásmico/efectos de los fármacosRESUMEN
Purpose: The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF). Patients and Methods: We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor. Results: The levels of IL-1ß, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1ß, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission. Conclusion: Inflammatory markers, including IL-1ß, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.
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A novel ratiometric Molecularly Imprinted Electrochemical sensor for the specific marker of Glycyrrhiza glabra L. was developed in this work. To achieve simultaneous detection of two analytes on one sensor, we constructed a double template molecular imprinted electrochemical sensor with glabridin (GLA) and isoliquiritin (ISL) as templates. Further, Ferrocene/ZIF-8 (Fc/ZIF-8) composites were prepared via a one-pot solvothermal reaction and coated on the surface of a glassy carbon electrode (GCE), and the oxidation of Fc was presented as the internal reference signal. Nitrogen-doped carbon (NOC) with high conductivity was further loaded on the modified GCE. Based on theoretical exploration and computer directional simulation of density functional theory (DFT), the optimal functional monomer and the best ratio of double template molecules to functional monomer were screened. Under optimal conditions, the sensor produced electrochemical curves when exposed to a solution containing GLA and ISL. As the concentration of GLA and ISL increased, the peak current intensity of GLA and ISL (IGLA and IISL) also increased, while the peak current intensity of Fc (as a reference signal) remained relatively constant. The values of IGLA/IFc and IISL/IFc showed excellent linear relationships with GLA and ISL concentrations in the range of 0.1-160 µM and 0.5-150 µM, respectively. The detection limits were 0.052 µM and 0.27 µM (S/N = 3), respectively. Due to the imprinting effect of MIP and the existence of a reference signal, the sensor exhibited excellent selectivity and anti-interference ability and was successfully applied to the quality evaluation of Glycyrrhiza glabra L.
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Técnicas Biosensibles , Carbono , Técnicas Electroquímicas , Impresión Molecular , Nitrógeno , Técnicas Biosensibles/métodos , Carbono/química , Técnicas Electroquímicas/métodos , Nitrógeno/química , Impresión Molecular/métodos , Límite de Detección , Conductividad Eléctrica , Glycyrrhiza/química , ElectrodosRESUMEN
The poor thermal stability and ion tolerance of whey protein hydrolysates (WPH) restrict its application in emulsions, while glycosylation shows potential benefits in improving WPH stability. However, the relationship between saccharides with different Mw and the glycosylation behavior of WPH rich in short peptides is unclear. In response, the effect of different saccharides on glycosylated WPH rich in short peptides and its emulsion stability were investigated. Grafted small Mw saccharides were more beneficial to the emulsion stability of WPH. Specifically, grafting xylose effectively inhibited 121 °C sterilization and 5 mM CaCl2-induced coalescence of WPH emulsion (687.50 nm) by comprehensively enhancing steric hindrance, conformational flexibility and electrostatic repulsion, and dissociating large aggregates into small aggregates. Conversely, grafting maltodextrin (30,590 Da) reduced thermal stability of WPH emulsion (4791.80 nm) by steric shielding and bridging flocculation. These findings provide new sights into glycosylation mechanism for WPH and achieving its application in nutritional emulsions.
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Calcio , Emulsiones , Calor , Hidrolisados de Proteína , Proteína de Suero de Leche , Proteína de Suero de Leche/química , Emulsiones/química , Glicosilación , Hidrolisados de Proteína/química , Calcio/química , Tamaño de la PartículaRESUMEN
Oil bodies (OBs) are naturally occurring pre-emulsified oil droplets that have broad application prospects in emulsions and gels. The main purpose of this research was to examine the impact of the OB content on the structure and functional aspects of acid-mediated soy protein isolate (SPI) gel filled with OBs. The results indicated that the peanut oil body (POBs) content significantly affected the water holding capacity of the gel. The rheological and textural analyses showed that POBs reduced the gel strength and hardness. The scanning electron and confocal laser scanning microscopy analyses revealed that POBs aggregated during gel formation and reduced the gel network density. The Fourier transform infrared spectrum (FTIR) analysis demonstrated that POBs participated in protein gels through hydrogen bonds, steric hindrance and hydrophobic interactions. Therefore, OBs served as inactive filler in the acid-mediated protein gel, replaced traditional oils and provided alternative ingredients for the development of new emulsion-filled gels.
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Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first step in triacylglycerol synthesis. Understanding its substrate recognition mechanism may help to design drugs to regulate the production of glycerol lipids in cells. In this work, we investigate how the native substrate, glycerol-3-phosphate (G3P), and palmitoyl-coenzyme A (CoA) bind to the human GPAT isoform GPAT4 via molecular dynamics simulations (MD). As no experimentally resolved GPAT4 structure is available, the AlphaFold model is employed to construct the GPAT4-substrate complex model. Using another isoform, GPAT1, we demonstrate that once the ligand binding is properly addressed, the AlphaFold complex model can deliver similar results to the experimentally resolved structure in MD simulations. Following the validated protocol of complex construction, we perform MD simulations using the GPAT4-substrate complex. Our simulations reveal that R427 is an important residue in recognizing G3P via a stable salt bridge, but its motion can bring the ligand to different binding hotspots on GPAT4. Such high flexibility can be attributed to the flexible region that exists only on GPAT4 and not on GPAT1. Our study reveals the substrate recognition mechanism of GPAT4 and hence paves the way towards designing GPAT4 inhibitors.
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Glicerol , Glicerofosfatos , Simulación de Dinámica Molecular , Humanos , Ligandos , Glicerol-3-Fosfato O-Aciltransferasa , Isoformas de Proteínas , FosfatosRESUMEN
Antibiotic resistance has garnered significant attention due to the scarcity of new antibiotics in development. Protoporphyrin IX (PpIX)-mediated photodynamic therapy shows promise as a novel antibacterial strategy, serving as an alternative to antibiotics. However, the poor solubility of PpIX and its tendency to aggregate greatly hinder its photodynamic efficacy. In this study, we demonstrate that alkylated EDTA derivatives (aEDTA), particularly C14-EDTA, can enhance the solubility of PpIX by facilitating its dispersion in aqueous solutions. The combination of C14-EDTA and PpIX exhibits potent antibacterial activity against Staphylococcus aureus (S. aureus) when exposed to LED light irradiation. Furthermore, this combination effectively eradicates S. aureus biofilms, which are known to be strongly resistant to antibiotics, and demonstrates high therapeutic efficacy in an animal model of infected ulcers. Mechanistic studies reveal that C14-EDTA can disrupt PpIX crystallization, increase bacterial membrane permeability and sequester divalent cations, thereby improving the accumulation of PpIX in bacteria. This, in turn, enhances reactive oxygen species (ROS) production and the antibacterial photodynamic activity. Overall, this effective strategy holds great promise in combating antibiotic-resistant strains.
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Fotoquimioterapia , Staphylococcus aureus , Animales , Protoporfirinas/farmacología , Ácido Edético/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/químicaRESUMEN
The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.
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Calcio , Retículo Endoplásmico , Mecanotransducción Celular , Optogenética , Canales Catiónicos TRPP , Animales , Retículo Endoplásmico/metabolismo , Chlorocebus aethiops , Células COS , Optogenética/métodos , Calcio/metabolismo , Canales Catiónicos TRPP/metabolismo , Canales Catiónicos TRPP/genética , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Aparato de Golgi/metabolismo , Estrés del Retículo Endoplásmico/fisiología , Chaperón BiP del Retículo Endoplásmico/metabolismoRESUMEN
Feature point matching is one of the fundamental tasks in binocular vision. It directly affects the accuracy and quality of 3D reconstruction. This study proposes a directional region-based feature point matching algorithm based on the SURF algorithm to improve the accuracy of feature point matching. First, same-name points are selected as the matching reference points in the left and right images. Then, the SURF algorithm is used to extract feature points and construct the SURF feature point descriptors. During the matching process, the location relationship between the query feature point and the reference point in the left image is directed to determine the corresponding matching region in the right image. Then, the matching is completed within this region based on Euclidean distance. Finally, the grid-based motion statistics algorithm is used to eliminate mismatches. Experimental results show that the proposed algorithm can substantially improve the matching accuracy and the number of valid matched points, particularly in the presence of a large amount of noise and interference. It also exhibits good robustness and stability.
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Traumatic Brain Injury (TBI) is a prevalent form of neurological damage that may induce varying degrees of cognitive dysfunction in patients, consequently impacting their quality of life and social functioning. This article provides a mini review of the epidemiology in Chinese TBI patients and etiology of cognitive impairment. It analyzes the risk factors of cognitive impairment, discusses current management strategies for cognitive dysfunction in Chinese TBI patients, and summarizes the strengths and limitations of primary testing tools for TBI-related cognitive functions. Furthermore, the article offers a prospective analysis of future challenges and opportunities. Its objective is to contribute as a reference for the prevention and management of cognitive dysfunction in Chinese TBI patients.
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One strategy to reduce CO2 emissions from cement production is to reduce the amount of Portland cement produced by replacing it with supplementary cementitious materials (SCMs). Biochar is a potential SCM that is an eco-friendly and stable porous pyrolytic material. However, the effects of biochar addition on the performances of Portland cement composites are not fully understood. This meta-analysis investigated the impact of biochar addition on the 7- and 28-day compressive strength of Portland cement composites based on 606 paired observations. Biochar feedstock type, pyrolysis conditions, pre-treatments and modifications, biochar dosage, and curing type all influenced the compressive strength of Portland cement composites. Biochars obtained from plant-based feedstocks (except rice and hardwood) improved the 28-day compressive strength of Portland cement composites by 3-13%. Biochars produced at pyrolysis temperatures higher than 450 °C, with a heating rate of around 10 C min-1, increased the 28-day compressive strength more effectively. Furthermore, the addition of biochar with small particle sizes increased the compressive strength of Portland cement composites by 2-7% compared to those without biochar addition. Biochar dosage of < 2.5% of the binder weight enhanced both compressive strengths, and common curing methods maintained the effect of biochar addition. However, when mixing the cement, adding fine and coarse aggregates such as sand and gravel affects the concrete and mortar's compressive strength, diminishing the effect of biochar addition and making the biochar effect nonsignificant. We concluded that appropriate biochar addition could maintain or enhance the mechanical performance of Portland cement composites, and future research should explore the mechanisms of biochar effects on the performance of cement composites. Supplementary Information: The online version contains supplementary material available at 10.1007/s42773-024-00309-2.
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Mitochondria constantly fuse and divide for mitochondrial inheritance and functions. Here, we identified a distinct type of naturally occurring fission, tail-autotomy fission, wherein a tail-like thin tubule protrudes from the mitochondrial body and disconnects, resembling autotomy. Next, utilizing an optogenetic mitochondria-specific mechanostimulator, we revealed that mechanical tensile force drives tail-autotomy fission. This force-induced fission involves DRP1/MFF and endoplasmic reticulum tubule wrapping. It redistributes mitochondrial DNA, producing mitochondrial fragments with or without mitochondrial DNA for different fates. Moreover, tensile force can decouple outer and inner mitochondrial membranes, pulling out matrix-excluded tubule segments. Subsequent tail-autotomy fission separates the matrix-excluded tubule segments into matrix-excluded mitochondrial-derived vesicles (MDVs) which recruit Parkin and LC3B, indicating the unique role of tail-autotomy fission in segregating only outer membrane components for mitophagy. Sustained force promotes fission and MDV biogenesis more effectively than transient one. Our results uncover a mechanistically and functionally distinct type of fission and unveil the role of tensile forces in modulating fission and MDV biogenesis for quality control, underscoring the heterogeneity of fission and mechanoregulation of mitochondrial dynamics.
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Proteínas de la Membrana , Dinámicas Mitocondriales , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genética , Mitocondrias/genética , ADN Mitocondrial , Control de Calidad , Dinaminas/genéticaRESUMEN
Human health and the environment face significant challenges of air pollution, which is predominantly caused by PM2.5 or PM10 particles. Existing control methods often require elevated energy consumption or bulky high-voltage electrical equipment. To overcome these limitations, a self-powered, convenient, and compact direct current high-voltage triboelectric nanogenerator based on triboelectrification and electrostatic breakdown effects is proposed. By optimizing the structure-design of the direct current triboelectric nanogenerator and corresponding output voltage, it can easily achieve an output voltage of over 3 kV with a high charge density of 320 µC m-2. A power management circuit is designed to overcome the influence of third domain self-breakdown, optimize 92.5% amplitude of voltage shake, and raise 5% charge utilization ratio. With a device size as tiny as 2.25 cm3, it can continuously drive carbon nanowires to generate negative ions that settle dust within 300 s. This compact, simple, efficient, and safe high-voltage direct current triboelectric nanogenerator represents a promising sustainable solution. It offers efficient dust mitigation, fostering cleaner environments, and enhancing overall health.
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Background: Gallbladder neuroendocrine neoplasms (GB-NENs) are a rare malignant disease, with most cases diagnosed at advanced stages, often resulting in poor prognosis. However, studies regarding the prognosis of this condition and its comparison with gallbladder adenocarcinomas (GB-ADCs) have yet to yield convincing conclusions. Methods: We extracted cases of GB-NENs and GB-ADCs from the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Firstly, we corrected differences in clinical characteristics between the two groups using propensity score matching (PSM). Subsequently, we visualized and compared the survival outcomes of the two groups using the Kaplan-Meier method. Next, we employed the least absolute shrinkage and selection operator (LASSO) regression and Cox regression to identify prognostic factors for GB-NENs and constructed two nomograms for predicting prognosis. These nomograms were validated with an internal validation dataset from the SEER database and an external validation dataset from a hospital. Finally, we categorized patients into high-risk and low-risk groups based on their overall survival (OS) scores. Results: A total of 7,105 patients were enrolled in the study, comprising 287 GB-NENs patients and, 6,818 GB-ADCs patients. There were substantial differences in clinical characteristics between patients, and GB-NENs exhibited a significantly better prognosis. Even after balancing these differences using PSM, the superior prognosis of GB-NENs remained evident. Independent prognostic factors selected through LASSO and Cox regression were age, histology type, first primary malignancy, tumor size, and surgery. Two nomograms for prognosis were developed based on these factors, and their performance was verified from three perspectives: discrimination, calibration, and clinical applicability using training, internal validation, and external validation datasets, all of which exhibited excellent validation results. Using a cutoff value of 166.5 for the OS nomogram score, patient mortality risk can be identified effectively. Conclusion: Patients with GB-NENs have a better overall prognosis compared to those with GB-ADCs. Nomograms for GB-NENs prognosis have been effectively established and validated, making them a valuable tool for assessing the risk of mortality in clinical practice.
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Adenocarcinoma , Neoplasias de la Vesícula Biliar , Neoplasias Gastrointestinales , Tumores Neuroendocrinos , Humanos , Estados Unidos , Pronóstico , Tumores Neuroendocrinos/diagnóstico , Medición de Riesgo , Adenocarcinoma/diagnóstico , Neoplasias de la Vesícula Biliar/diagnósticoRESUMEN
The damage to the endocrine pancreas among patients with diseases of the exocrine pancreas (DP) leads to reduced glycemic deterioration, ultimately resulting in diabetes of the exocrine pancreas (DEP). The present research aims to investigate the mechanism responsible for glycemic deterioration in DP patients, and to identify useful biomarkers, with the ultimate goal of enhancing clinical practice awareness. Gene expression profiles of patients with DP in this study were acquired from the Gene Expression Omnibus database. The original study defines DP patients to belong in one of three categories: non-diabetic (ND), impaired glucose tolerance (IGT) and DEP, which correspond to normoglycemia, early and late glycemic deterioration, respectively. After ensuring quality control, the discovery cohort included 8 ND, 20 IGT, and 12 DEP, while the validation cohort included 27 ND, 15 IGT, and 20 DEP. Gene set enrichment analysis (GSEA) employed differentially expressed genes (DEGs), while immunocyte infiltration was determined using single sample gene set enrichment analysis (ssGSEA). Additionally, correlation analysis was conducted to establish the link between clinical characteristics and immunocyte infiltration. The least absolute shrinkage and selection operator regression and random forest combined to identify biomarkers indicating glycemic deterioration in DP patients. These biomarkers were further validated through independent cohorts and animal experiments. With glycemic deterioration, biological processes in the pancreatic islets such as nutrient metabolism and complex immune responses are disrupted in DP patients. The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated. Immunocyte infiltration in the islet microenvironment showed a significant positive correlation with the age, body mass index (BMI), HbA1c and glycemia at the 2-h of patients. It was a crucial factor in glycemic deterioration. Additionally, B2M demonstrated a significant positive correlation with immunocyte infiltration and clinical features. Quantitative real-time PCR (qRT-PCR) and western blotting confirmed the upregulation in B2M. Immunofluorescent staining suggested the alteration of B2M was mainly in the alpha cells and beta cells. Overall, the study showed that gradually increased immunocyte infiltration was a significant contributor to glycemic deterioration in patients with DP, and it also highlighted B2M as a biomarker.
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Experimentación Animal , Intolerancia a la Glucosa , Páncreas Exocrino , Animales , Humanos , Complejo Antígeno-Anticuerpo , Biomarcadores , Western BlottingRESUMEN
As bulky pollutants in industrial and agricultural wastewater, nitrate and formaldehyde pose serious threats to the human health and ecosystem. Current purification technologies including chemical and bio-/photo-/electro-chemical methods, are generally high-cost, time-consuming, or energy-intensive. Here, we report a novel formaldehyde-nitrate battery by pairing anodic formaldehyde oxidation with cathodic nitrate reduction, which simultaneously enables wastewater purification, electricity generation, and the production of high-value-added ammonia and formate. As a result, the formaldehyde-nitrate battery remarkably exhibits an open-circuit voltage of 0.75â V, a peak power density of 3.38â mW cm-2 and the yield rates of 32.7â mg h-1 cm-2 for ammonia and 889.4â mg h-1 cm-2 for formate. In a large-scale formaldehyde-nitrate battery (25â cm2 ), 99.9 % of nitrate and 99.8 % of formaldehyde are removed from simulated industrial wastewater and the electricity of 2.03â Wâ h per day is generated. Moreover, the design of such a multi-functional battery is universally applicable to the coupling of NO3 - or NO2 - reduction with various aldehyde oxidization, paving a new avenue for wastewater purification and chemical manufacturing.