RESUMO
Adolescents exposed to childhood trauma are at an elevated risk for social anxiety. However, the physiological mechanisms linking childhood trauma and adolescents' social anxiety remain poorly understood. This study examined whether cardiovascular reactivity to acute social stress was a mechanism underlying this association. Participants were Chinese adolescents (N = 172; Mage = 12.95). They first reported their childhood trauma and social anxiety using the Childhood Trauma Questionnaire and the Social Interaction Anxiety Scale. They then participated in a social stress task, during which their cardiovascular data [heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP)] were monitored. The results showed that high levels of childhood trauma were associated with blunted HR, SBP, and DBP reactivity, which in turn were associated with high levels of social anxiety. Mediation analysis indicated that childhood trauma was indirectly associated with social anxiety via blunted cardiovascular reactivity. The findings suggest that blunted cardiovascular reactivity may serve as a physiological pathway linking childhood trauma and adolescents' social anxiety.
RESUMO
BACKGROUND: In recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population. METHODS: This study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS. RESULTS: A total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 - 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OSâ¦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44-13.61), 7.5 months (95% CI 7.33-8.17), and 4.01 months (95% CI 3.94-4.08), respectively, with a log-rank test p-value < 0.001. CONCLUSION: This study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.
Assuntos
Cetuximab , Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Cetuximab/uso terapêutico , Cetuximab/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Idoso , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Medição de Risco/métodos , Taiwan/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Adulto , Fatores de RiscoRESUMO
Squalene (C30H50) is an acyclic triterpenoid compound renowned for its myriad physiological functions, such as anticancer and antioxidative properties, rendering it invaluable in both the food and pharmaceutical sectors. Due to the natural resource constraints, microbial fermentation has emerged as a prominent trend. Schizochytrium sp., known to harbor the intact mevalonate acid (MVA) pathway, possesses the inherent capability to biosynthesize squalene. However, there is a dearth of reported key genes in both the MVA and the squalene synthesis pathways, along with the associated promoter elements for their modification. This study commenced by cloning and characterizing 13 endogenous promoters derived from transcriptome sequencing data. Subsequently, five promoters exhibiting varying expression intensities were chosen from the aforementioned pool to facilitate the overexpression of the squalene synthase gene squalene synthetase (SQS), pivotal in the MVA pathway. Ultimately, a transformed strain designated as SQS-3626, exhibiting squalene production 2.8 times greater than that of the wild-type strain, was identified. Finally, the optimization of nitrogen source concentrations and trace element contents in the fermentation medium was conducted. Following 120 h of fed-batch fermentation, the accumulated final squalene yield in the transformed strain SQS-3626 reached 2.2 g/L.
Assuntos
Farnesil-Difosfato Farnesiltransferase , Fermentação , Ácido Mevalônico , Regiões Promotoras Genéticas , Esqualeno , Estramenópilas , Esqualeno/metabolismo , Estramenópilas/genética , Estramenópilas/metabolismo , Ácido Mevalônico/metabolismo , Farnesil-Difosfato Farnesiltransferase/genética , Farnesil-Difosfato Farnesiltransferase/metabolismo , Engenharia Metabólica/métodos , Clonagem Molecular/métodosRESUMO
Background: Investigation into the immune heterogeneity linked with atherosclerosis remains understudied. This knowledge gap hinders the creation of a robust theoretical framework essential for devising personalized immunotherapies aimed at combating this disease. Methods: Single-cell RNA sequencing (scRNA-seq) analysis was employed to delineate the immune cell-type landscape within atherosclerotic plaques, followed by assessments of cell-cell interactions and phenotype characteristics using scRNA-seq datasets. Subsequently, pseudotime trajectory analysis was utilized to elucidate the heterogeneity in cell fate and differentiation among macrophages. Through integrated approaches, including single-cell sequencing, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning techniques, we identified hallmark genes. A risk score model and a corresponding nomogram were developed and validated using these genes, confirmed through Receiver Operating Characteristic (ROC) curve analysis. Additionally, enrichment and immune characteristic analyses were conducted based on the risk score model. The model's applicability was further corroborated by in vitro and in vivo validation of specific genes implicated in atherosclerosis. Result: This comprehensive scRNA-seq analysis has shed new light on the intricate immune landscape and the role of macrophages in atherosclerotic plaques. The presence of diverse immune cell populations, with a particularly enriched macrophage population, was highlighted by the results. Macrophage heterogeneity was intricately characterized, revealing four distinct subtypes with varying functional attributes that underscore their complex roles in atherosclerotic pathology. Intercellular communication analysis revealed robust macrophage interactions with multiple cell types and detailed pathways differing between proximal adjacent and atherosclerotic core groups. Furthermore, pseudotime trajectories charted the developmental course of macrophage subpopulations, offering insights into their differentiation fates within the plaque microenvironment. The use of machine learning identified potential diagnostic markers, culminating in the identification of RNASE1 and CD14. The risk score model based on these biomarkers exhibited high accuracy in diagnosing atherosclerosis. Immune characteristic analysis validated the risk score model's efficacy in defining patient profiles, distinguishing high-risk individuals with pronounced immune cell activities. Finally, experimental validation affirmed RNASE1's involvement in atherosclerotic progression, suggesting its potential as a therapeutic target. Conclusion: Our findings have advanced our understanding of atherosclerosis immunopathology and paved the way for novel diagnostic and therapeutic strategies.
Assuntos
Aterosclerose , Perfilação da Expressão Gênica , Macrófagos , Análise de Célula Única , Transcriptoma , Aterosclerose/genética , Aterosclerose/imunologia , Animais , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Placa Aterosclerótica/genética , Placa Aterosclerótica/imunologia , Inflamação/genética , Inflamação/imunologia , Medição de Risco , Aprendizado de MáquinaRESUMO
Alcohol is the most consumed and abused psychoactive drug globally, but the molecular mechanisms driving alcohol action and its associated behaviors in the brain remain enigmatic. Here, we have discovered a transmembrane protein TMEM132B that is a GABAA receptor (GABAAR) auxiliary subunit. Functionally, TMEM132B promotes GABAAR expression at the cell surface, slows receptor deactivation, and enhances the allosteric effects of alcohol on the receptor. In TMEM132B knockout (KO) mice or TMEM132B I499A knockin (KI) mice in which the TMEM132B-GABAAR interaction is specifically abolished, GABAergic transmission is decreased and alcohol-induced potentiation of GABAAR-mediated currents is diminished in hippocampal neurons. Behaviorally, the anxiolytic and sedative/hypnotic effects of alcohol are markedly reduced, and compulsive, binge-like alcohol consumption is significantly increased. Taken together, these data reveal a GABAAR auxiliary subunit, identify the TMEM132B-GABAAR complex as a major alcohol target in the brain, and provide mechanistic insights into alcohol-related behaviors.
RESUMO
3D hierarchical superstructures (3DHSs) are key products of nature's evolution and have raised wide interest. However, the preparation of 3DHSs composed of building blocks with different structures is rarely reported, and regulating their structural parameters is challenging. Herein, a simple lecithin-mediated biomineralization approach is reported for the first time to prepare gold 3DHSs composed of 0D nucleus and 1D protruding dendritic spikes. It is demonstrated that a hydrophobic complex by coordination of disulfiram (DSF) with a share of chloroauric acid is the key to forming the 3DHSs. Under the lecithin mediation, chloroauric acid is first reduced to form the 0D nucleus, followed by the spike growth through the reduction of the hydrophobic complex. The prepared 3DHSs possess well-defined morphology with a spike length of ≈95 nm. Notably, the hierarchical spike density is systematically manipulated from 38.9% to 74.3% by controlling DSF concentrations. Moreover, the spike diameter is regulated from 9.2 to 12.9 nm by selecting different lecithin concentrations to tune the biomineralization process. Finite-difference time-domain (FDTD) simulations reveal that the spikes form "hot spots". The dense spike structure endows the 3DHSs with sound performance in surface-enhanced Raman scattering (SERS) applications.
RESUMO
Background: Previous studies have suggested that the Pro-Kin visual feedback balance system can promote the recovery of balance function in stroke patients. Objectives: However, this system has not been used effectively in the early stages of stroke rehabilitation. This study aimed to investigate the effect of Pro-Kin system combined with weight loss system for the early recovery of balance and walking ability following a stroke. Methods: A total of 62 patients who underwent radiological diagnosis of stroke were randomly divided into two groups: a control group (n = 31) and a treatment group (n = 31). Both groups received conventional balance training. The treatment group also received training on the Pro-Kin system in conjunction with a weight loss system. Balance was measured using the Berg Balance Scale (BBS), Timed 'Up & Go' (TUG) test and Pro-Kin system. Walking ability was assessed using the Functional Ambulation Classification (FAC). The tests were performed before the start of treatment and on the 4th week following the training. There was no statistically significant difference between the groups before training. Results: After 4 weeks of training in both groups, there were significant improvements in balance and walking ability. BBS values and FAC were significantly higher (p < 0.01), TUG times, ellipse area and motion trajectory length were significantly reduced (p < 0.01, p < 0.05) after training. The treatment group outperformed the control group (p < 0.05). In addition, there was a positive correlation between balance function and walking ability (p < 0.01). Conclusion: The Pro-Kin system combined with weight loss system is a viable method that promotes early reconstruction of balance and walking ability following a stroke. Trial registration: Clinical trial number ChiCTR1900026370. https://www.chictr.org.cn/showprojEN.html?proj=43736.
RESUMO
The development and quality of tea plants (Camellia sinensis (L.) O. Ktze.) are greatly hampered by drought stress (DS), which affects them in a number of ways, including by interfering with their metabolism of nitrogen (N). Arbuscular mycorrhizal fungi (AMF) are known to enhance water and nutrient absorption in plants, but their specific effects on tea plant N metabolism under DS and the associated regulatory mechanisms remain unclear. This study aimed to evaluate the impact of Claroideoglomus etunicatum inoculation on N assimilation in tea plants (C. sinensis cv. Fuding Dabaicha) under well-watered (WW) and DS conditions, and to explore potential molecular mechanisms. After 8 weeks of DS treatment, root mycorrhizal colonization was significantly inhibited, and the biomass of tea shoots and roots, as well as the contents of various amino acids (AAs) were reduced. However, AMF inoculation significantly increased the contents of tea polyphenols and catechins in leaves by 13.74%-36.90% under both WW and DS conditions. Additionally, mycorrhizal colonization notably increased N content by 12.65%-35.70%, various AAs by 11.88%-325.42%, and enzymatic activities associated with N metabolism by 3.80%-147.62% in both leaves and roots. Gene expression analysis revealed a universal upregulation of N assimilation-related genes (CsAMT1;2, CsAMT3;1, CsGS1, CsNADH-GOGAT, CsTS2, CsGGT1, and CsADC) in AMF-colonized tea roots, regardless of water status. Under DS condition, AMF inoculation significantly upregulated the expressions of CsNRT1;2, CsNRT1;5, CsNRT2;5, CsNR, CsGS1, CsGDH1, CsGDH2, CsTS2, CsGGT1, CsGGT3, and CsSAMDC in tea leaves. These findings suggest that AMF improved tea plant adaptability to DS by enhancing N absorption and assimilation, accompanied by the synthesis and accumulation of various AAs, such as Glu, Gln, Asp, Lys, Arg, GABA and Pro. This is achieved through the upregulation of N metabolism-related genes and the activation of related enzymes in tea plants under DS condition. These findings provide valuable insights into the role of AMF in regulating tea plant N metabolism and enhancing stress tolerance.
RESUMO
Introduction: Infantile Hemangioma (IH) is a prevalent benign vascular tumor affecting approximately 5-10% of infants. Its underlying pathogenesis remains enigmatic, and current therapeutic approaches show limited effectiveness. Our study aimed to discover potential IH-associated therapeutics through a transcriptomic, computational drug repurposing methodology. Methods: Utilizing the IH-specific dataset GSE127487 from the Gene Expression Omnibus, we identified differentially expressed genes (DEGs) and conducted weighted gene coexpression network analysis (WGCNA). Subsequently, a protein-protein interaction (PPI) network was constructed to obtain the top 100 hub genes. Drug candidates were sourced from the Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD). Results: Our analysis revealed 1203 DEGs and a significant module of 1780 mRNAs strongly correlated with IH. These genes were primarily enriched in the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathway. After creating a PPI network of overlapping genes, we filtered out the top 100 hub genes. Ultimately, 44 non-toxic drugs were identified through the CMap and CTD databases. Twelve molecular-targeting agents (belinostat, chir 99021, dasatinib, entinostat, panobinostat, sirolimus, sorafenib, sunitinib, thalidomide, U 0126, vorinostat, and wortmannin) may be potential candidates for IH therapy. Moreover, in vitro experiments demonstrated that entinostat, sorafenib, dasatinib, and sirolimus restricted the proliferation and migration and initiated apoptosis in HemEC cells, thereby underscoring their potential therapeutic value. Conclusion: Our investigation revealed that the pathogenic mechanism underlying IH might be closely associated with the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathways. Furthermore, we identified twelve molecular-targeting agents among the predicted drugs that show promise as therapeutic candidates for IH.
Transcriptomic analysis used to discover potential therapeutics for Infantile Hemangioma (IH). Key IH-related pathways: PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling identified. Identified 44 non-toxic drugs as potential IH therapies via CMap and CTD. Twelve molecular agents show potential as IH therapy candidates. In vitro studies confirmed entinostat, sorafenib, dasatinib, and sirolimus inhibit HemEC cell proliferation and induce apoptosis.
Assuntos
Antineoplásicos , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Hemangioma , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Hemangioma/tratamento farmacológico , Hemangioma/patologia , Hemangioma/genética , Proliferação de Células/efeitos dos fármacos , Lactente , Simulação por Computador , Apoptose/efeitos dos fármacos , Mapas de Interação de Proteínas/efeitos dos fármacos , Reposicionamento de Medicamentos , Relação Dose-Resposta a DrogaRESUMO
Soybean plants form symbiotic nitrogen-fixing nodules with specific rhizobia bacteria. The root hair is the initial infection site for the symbiotic process before the nodules. Since roots and nodules grow in soil and are hard to perceive, little knowledge is available on the process of soybean root hair deformation and nodule development over time. In this study, adaptive microrhizotrons were used to observe root hairs and to investigate detailed root hair deformation and nodule formation subjected to different rhizobia densities. The result showed that the root hair curling angle increased with the increase of rhizobia density. The largest curling angle reached 268° on the 8th day after inoculation. Root hairs were not always straight, even in the uninfected group with a relatively small angle (<45°). The nodule is an organ developed after root hair curling. It was inoculated from curling root hairs and swelled in the root axis on the 15th day after inoculation, with the color changing from light (15th day) to a little dark brown (35th day). There was an error between observing the diameter and the real diameter; thus, a diameter over 1 mm was converted to the real diameter according to the relationship between the perceived diameter and the real diameter. The diameter of the nodule reached 5 mm on the 45th day. Nodule number and curling number were strongly related to rhizobia density with a correlation coefficient of determination of 0.92 and 0.93, respectively. Thus, root hair curling development could be quantified, and nodule number could be estimated through derived formulation.
Assuntos
Glycine max , Raízes de Plantas , Nódulos Radiculares de Plantas , Simbiose , Glycine max/microbiologia , Glycine max/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Simbiose/fisiologia , Nódulos Radiculares de Plantas/microbiologia , Rhizobium/fisiologia , Fixação de NitrogênioRESUMO
Facile non-radiative decay of low-lying metal-centered (MC) d-d excited states has been well documented to pose a significant obstacle to the development of phosphorescent NiII complexes due to substantial structural distortions between the d-d excited state and the ground state. Herein, we prepared a series of dinuclear Ni2II,II complexes by using strong σ-donors, carbene-phenyl-carbene (CNHC^Cphenyl^CNHC) pincer ligands, and prepared their dinuclear Pt2II,II and Pd2II,II analogues. Dinuclear Ni2II,II complexes bridged by formamidinate/α-carbolinato ligand exhibit short Ni-Ni distances of 2.947-3.054 Å and singlet metal-metal-to-ligand charge transfer (1MMLCT) transitions at 500-550 nm. Their 1MMLCT absorption energies are red-shifted relative to the Pt2II,II and Pd2II,II analogues at ~450 nm and ≤420 nm respectively. One-electron oxidation of these Ni2II,II complexes produces valence-trapped dinuclear Ni2II,III species, which are characterized by EPR spectroscopy. Upon photoexcitation, these Ni2II,II complexes display phosphorescence (τ=2.6-8.6 µs) in the NIR (800-1400nm) spectral region in 2-MeTHF and in solid state at 77 K, which is insensitive to π-conjugation of the coordinated [CNHC^Cphenyl^CNHC] ligand. Combined with DFT calculations, the NIR emission is assigned to originate from the 3dd excited state. Studies have found that the dinuclear Ni2II,II complex can sensitize the formation of singlet oxygen and catalyze the oxidation of cyclo-dienes under light irradiation.
RESUMO
We engineered a two-dimensional Pt/WSe2/Ni avalanche photodetector (APD) optimized for ultraweak signal detection at room temperature. By fine-tuning the work functions, we achieved an ultralow dark current of 10-14 A under small bias, with a noise equivalent power (NEP) of 8.09 fW/Hz1/2. This performance is driven by effective dark barrier blocking and a record-long electron mean free path (123 nm) in intrinsic WSe2, minimizing dark carrier replenishment and suppressing noise under an ultralow electric field. Our APD exhibits a high gain of 5 × 105 at a modulation frequency of 20 kHz, effectively balancing gain and bandwidth, a common challenge in traditional photovoltaic-based APDs. By addressing the typical challenges of high noise and low gain and minimizing dependence on high electric fields, this work highlights the potential of 2D materials in developing efficient, low-power, and ultrasensitive photodetections.
RESUMO
As an emerging tumor therapeutic strategy, antibody-drug conjugates (ADCs) overcome the high toxicity of traditional small molecule chemotherapy and improve the targeting of treatment. In this study, we successfully constructed a novel ADC, Tras-16b, for the first time using homocamptothecin 16b as the payload. Tras-16b, at a dose of 3 mg/kg, exhibited comparable anti-tumor activity to Enhertu and demonstrated an enhanced safety profile in the NCI-N87 xenograft model. Notably, this is the first ADC developed based on homocamptothecin, marking a significant advancement with promising prospects for the structural modification of camptothecin ADCs.
RESUMO
In this study, the process of catalytic oxidation of methane considering radiative heat transfer was simulated using FLUENT computational software to study the effect of thermal radiation on the oxidation performance of the simulated device, and to investigate the extent to which radiative heat transfer affects the oxidation performance of the device under different operating conditions. The results show that the extent to which thermal radiation affects the oxidative performance of the equipment increases with increasing inlet temperature. When the intake temperature reaches 900K, its proportion is close to 45 %. At the same time, as the inlet gas temperature increases, the maximum reaction temperature of the oxidation unit is 1154 K, and the methane conversion rate reaches up to 89 %. The main factor affecting the oxidation performance of the unit at this time is radiation heat transfer. The extent to which thermal radiation affects the oxidative performance of the device diminishes with increasing inlet velocity. When the wind speed reaches 2 m/s, the proportion of radiative heat transfer is only 10 %, the maximum reaction temperature of the plant falls to 993 K, and the methane conversion rate drops to 68 %. At this time, the main factor affecting the oxidation performance of the plant is convective heat transfer. The influence of thermal radiation on oxidation performance gradually diminishes with an increase in intake velocity, and the proportion of radiative heat transfer decreases continuously. At methane concentrations above 1 %, the proportion of radiative heat transfer is less than 25 per cent, the maximum reaction temperature of the unit increases to 1087 K, and the methane conversion rises to 88 %. At this point, the main factor affecting the oxidation performance of the plant is convective heat transfer.
RESUMO
Background: To investigate the correlation between retinal vascular changes and ICA stenosis by measuring retinal vessels using full-width-at-half-maximum (FWHM) and intelligent image recognition. Methods: This research selected patients who were admitted to the Vascular Surgery Department of Quzhou People's Hospital from January 2018 to December 2020 and were preparing for Carotid Artery Stenting (CAS). Participants were divided into two groups: without ICA stenosis (Group 0) and with ICA stenosis (Group 1). A total of 109 cases were included in the study, with 50 cases in Group 1 and 59 cases in Group 0. Vascular images of superior temporal zone B of the retina were obtained by spectral domain optical coherence tomography (SD-OCT). The edges of retinal vessels were identified by FWHM. Each vessel of all subjects was measured three times with the FWHM, and the average value was taken to obtain the retinal arteriolar lumen diameter (RALD), retinal arteriolar outer diameter (RAOD), retinal venular lumen diameter (RVLD), and retinal venular outer diameter (RVOD),Arterial Wall Thickness (AWT),Venular Wall Thickness (VWT)=(RVOD-RVLD)/2,Arteriovenous Ratio (AVR) = RAOD/RVOD. Results: We found that compared to Group 0, Group 1 had smaller RALD (P < 0.001) and RAOD (P < 0.001), and wider RVOD (P < 0.001), with thicker VWT (P < 0.001). When compared with the contralateral eye in Group 1, the ipsilateral eye exhibited even smaller RALD,RAOD and AVR (P < 0.001, P < 0.001, P < 0.001). After CAS, the RALD,RAOD and AVR in Group 1 increased (P < 0.001, P < 0.001, P < 0.001),while the RVLD and RVOD decreased (P < 0.05, P < 0.001). Our research reveals a significant correlation between retinal vascular changes and internal ICA stenosis. Conclusion: Utilizing SD-OCT in conjunction with the FWHM,we achieved a non-invasive, intelligent, stable, and precise acquisition of data pertaining to retinal vessels. These findings underscore a significant correlation between alterations in retinal vascular structure and the presence of ICA stenosis, as demonstrated by our research.
RESUMO
The rapid development and clinical application of sequencing technologies enable the genetic diagnosis of inherited deafness. P2RX2, as the gene responsible for autosomal dominant non-syndromic deafness-41 (DFNA41), has been proven to be essential for life-long normal hearing and for the protection of noise-induced hearing loss (NIHL). Our present study reports a missense variant in the P2RX2 gene (c.178G > T (p.V60L)), for the second time worldwide, in a five-generation kindred living in Henan, China. Despite carrying the same variant, the affected members in this family appear to present with earlier-onset hearing loss and poorer hearing compared to the original DFNA41 families. In addition, this study supplements some content that was not covered in previous reports. We quantitatively evaluated the pain perception ability of some members using the Pain Vision PS-2100 system, and further found an interesting clinical manifestation, that is, hyperalgesia, in heterozygotes for P2RX2 p.V60L. The cochlear implant (CI) was also provided for the proband of profound deafness, resulting in satisfactory clinical outcomes. Finally, we carried out a systematic review of recently published articles on the P2RX2 gene, which is beneficial for better understanding the role of the P2RX2 gene in the auditory system and the pathogenic mechanisms in sensorineural hearing loss (SNHL).
RESUMO
Metal selenides have received extensive research attention as anode materials for batteries due to their high theoretical capacity. However, their significant volume expansion and slow ion migration rate result in poor cycling stability and suboptimal rate performance. To address these issues, the present work utilized multivalent iron ions to construct fast pathways similar to superionic conductors (Fe-SSC) and introduced corresponding selenium vacancies to enhance its performance. Based on first-principles calculations and molecular dynamics simulations, it is demonstrated that the addition of iron ions and the presence of selenium vacancies reduced the material's work function and adsorption energy, lowered migration barriers, and enhances the migration rate of Li+ and Na+. In Li-ion half batteries, this composite material exhibites reversible capacity of 1048.3 mAh g-1 at 0.1 A g-1 after 100 cycles and 483.6 mAh g-1 at 5.0 A g-1 after 1000 cycles. In Na-ion half batteries, it is 687.7 mAh g-1 at 0.1 A g-1 after 200 cycles and 325.9 mAh g-1 at 5.0 A g-1 after 1000 cycles. It is proven that materials based on Fe-SSC and selenium vacancies have great applications in both Li-ion batteries and Na-ion batteries.
RESUMO
PURPOSE: Deformable image registration (DIR) has been increasingly used in radiation therapy (RT). The accuracy of DIR algorithms and how it impacts on the RT plan dosimetrically were examined in our study for abdominal sites using biomechanically modeled deformations. METHODS: Five pancreatic cancer patients were enrolled in this study. Following the guidelines of AAPM TG-132, a patient-specific quality assurance (QA) workflow was developed to evaluate DIR for the abdomen using the TG-132 recommended virtual simulation software ImSimQA (Shrewsbury, UK). First, the planning CT was deformed to simulate respiratory motion using the embedded biomechanical model in ImSimQA. Additionally, 5 mm translational motion was added to the stomach, duodenum, and small bowel. The original planning CT and the deformed CT were then imported into Eclipse and MIM to perform DIR. The output displacement vector fields (DVFs) were compared with the ground truth from ImSimQA. Furthermore, the original treatment plan was recalculated on the ground-truth deformed CT and the deformed CT (with Eclipse and MIM DVF). The dose errors were calculated on a voxel-to-voxel basis. RESULTS: Data analysis comparing DVF from Eclipse versus MIM show the average mean DVF magnitude errors of 2.8 ± 1.0 versus 1.1 ± 0.7 mm for stomach and duodenum, 5.2 ± 4.0 versus 2.5 ± 1.0 mm for small bowel, and 4.8 ± 4.1 versus 2.7 ± 1.1 mm for the gross tumor volume (GTV), respectively, across all patients. The mean dose error on stomach+duodenum and small bowel were 2.3 ± 0.6% for Eclipse, and 1.0 ± 0.3% for MIM. As the DIR magnitude error increases, the dose error range increase, for both Eclipse and MIM. CONCLUSION: In our study, an initial assessment was conducted to evaluate the accuracy of DIR and its dosimetric impact on radiotherapy. A patient-specific DIR QA workflow was developed for pancreatic cancer patients. This workflow exhibits promising potential for future implementation as a clinical workflow.
RESUMO
Potassium citrate (KC) and potassium lactate (KL) are considered as salt replacers due to their saltiness, processing advantages, and health benefits. However, the obvious bitter taste associated with these compounds has limited their use in salt substitutes. Despite this challenge, little attention has been paid to improving their sensory properties. This study provided evidence that dietary polysaccharide carrageenan can effectively mask the bitterness of KC and KL by specifically binding K+ and forming double helix chains. A highly accurate prediction model was then established for the saltiness and bitterness of low-sodium salts using mixture design principles. Three low-sodium salt formulas containing different potassium salts (KC, KL, KCl), NaCl, and carrageenan were created based on the prediction model. These formulas exhibited favorable saltiness potencies (>0.85) without any noticeable odor, preserving the sensory characteristics of high-sodium food products like seasoning powder while significantly reducing their sodium content. This research provides a promising approach for the food industry to formulate alternative low-sodium products with substantially reduced sodium content, potentially contributing to decreased salt intake.