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1.
Geroscience ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822946

RESUMO

Considerable uncertainty remains regarding the associations of multiple factors with brain health. We aimed to conduct an exposome-wide association study on neurodegenerative disease and neuropsychiatry disorders using data of participants from the UK Biobank. Multivariable Cox regression models with the least absolute shrinkage and selection operator technique as well as principal component analyses were used to evaluate the exposures in relation to common disorders of central nervous system (CNS). Restricted cubic splines were conducted to explore potential nonlinear correlations. Then, weighted standardized scores were generated based on the coefficients to calculate the joint effects of risk factors. We also estimated the potential impact of eliminating the unfavorable profiles of risk domains on CNS disorders using population attributable fraction (PAF). Finally, sensitivity analyses were performed to reduce the risk of reverse causality. The current study discovered the significantly associated exposures fell into six primary exposome categories. The joint effects of identified risk factors demonstrated higher risks for common disorders of CNS (HR = 1.278 ~ 3.743, p < 2e-16). The PAF varied by exposome categories, with lifestyle and medical history contributing to majority of disease cases. In total, we estimated that up to 3.7 ~ 64.1% of disease cases could be prevented.This study yielded modifiable variables of different categories and assessed their joint effects on common disorders of CNS. Targeting the identified exposures might help formulate effective strategies for maintaining brain health.

2.
Brain Topogr ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874853

RESUMO

The ability to comprehend the intention conveyed through human body movements is crucial for effective interpersonal interactions. If people can't understand the intention behind other individuals' isolated or interactive actions, their actions will become meaningless. Psychologists have investigated the cognitive processes and neural representations involved in understanding action intention, yet a cohesive theoretical explanation remains elusive. Hence, we mainly review existing literature related to neural correlates of action intention, and primarily propose a putative Three-stage Dynamic Brain-cognitive Model of understanding action intention, which involves body perception, action identification and intention understanding. Specifically, at the first stage, body parts/shapes are processed by those brain regions such as extrastriate and fusiform body areas; During the second stage, differentiating observed actions relies on configuring relationships between body parts, facilitated by the activation of the Mirror Neuron System; The last stage involves identifying various intention categories, utilizing the Mentalizing System for recruitment, and different activation patterns concerning the nature of the intentions participants dealing with. Finally, we delves into the clinical practice, like intervention training based on a theoretical model for individuals with autism spectrum disorders who encounter difficulties in interpersonal communication.

3.
Small ; : e2402676, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847072

RESUMO

Fluorescent lateral flow immunoassays (FLFIA) is a well-established rapid detection technique for quantitative analysis. However, achieving accurate analysis of biomarkers at the pg mL-1 level using FLFIA still poses challenges. Herein, an ultrasensitive FLFIA platform is reported utilizing a kiwi-type magneto-fluorescent silica nanohybrid (designated as MFS) that serves as both a target-enrichment substrate and an optical signal enhancement label. The spatially-layered architecture comprises a Fe3O4 core, an endocarp-fibers like dendritic mesoporous silica, seed-like quantum dots, and a kiwi-flesh like silica matrix. The MFS demonstrates heightened fluorescence brightness, swift magnetic response, excellent size uniformity, and dispersibility in water. Through liquid-phase capturing and fluorescence-enhanced signal amplification, as well as magnetic-enrichment sample amplification and magnetic-separation noise reduction, the MFS-based FLFIA is successfully applied to the detection of cardiac troponin I that achieved a limit of detection at 8.4 pg mL-1, tens of times lower than those of previously published fluorescent and colorimetric lateral flow immunoassays. This work offers insights into the strategic design of magneto-fluorescent synergetic signal amplification on LFIA platform and underscores their prospects in high-sensitive rapid and on-site diagnosis of biomarkers.

4.
J Hazard Mater ; 474: 134846, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38852247

RESUMO

Chromium (Cr) pollution may threaten food safety in China. In this study, the concentration, pollution level, distribution, and non-cancer risk of Cr in wheat grains grown in 186 areas across 28 provinces in China were investigated. Results indicated that mean concentration of Cr was 0.28 ± 2.5 mg/kg, dry mass (dm). Of the samples, 7.5 % were found to be polluted with Cr. The mean concentrations were in the following order: Northwest > Northeast > South > East > North > Southwest > Central China. Based on deterministic models, mean hazard quotient (HQ) values for adult males, adult females, and children were 0.11 ± 3.4, 0.11 ± 3.4, and 0.13 ± 3.5, respectively with < 6 % of HQ values ≥ 1. Eleven sites in northern China were identified as hotspots, whereas Gansu Province and Northwestern China were labeled as priority provinces and regions for risk control. The mean HQ values estimated by probabilistic risk assessment were two times greater than those estimated using deterministic models. The risk probabilities for adult males, adult females, and children were 4.81 %, 3.78 %, and 6.55 %, respectively. This study provides valuable information on Cr pollution in wheat grains and its risks at a national scale in China.

5.
Gastrointest Endosc ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851454

RESUMO

BACKGROUND AND AIMS: This study aims to identify the cause of disinfection failure of multiple flexible gastrointestinal endoscopes and to enhance the cleaning and disinfection procedures. METHODS: Samples from endoscopy devices, surrounding objects, cleaning water, automatic sterilizer, and integrated endoscopic washing workstation in a Digestive Endoscopy Center were collected and analyzed for microbial contamination and DNA/gene contents, between May and July 2021. RESULTS: The sample analysis revealed that the sink irrigation tubing of the washing workstation was contaminated with Burkholderia cepacia. After effective disinfection measures, the B. cepacia detection in the disinfected endoscope dropped from 13.23% to 0% (p=0.041). The presence of B. cepacia was confirmed through homology search and gene sequencing. CONCLUSIONS: The primary reason for endoscope disinfection failure is the contamination of the sink irrigation tubing by the B. cepacia bacteria. These findings emphasize the need for thorough cleaning of irrigation tubings in integrated endoscopic washing workstations, which is generally neglected in routine maintanance.

6.
ANZ J Surg ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38817200

RESUMO

BACKGROUNDS: Liver resection plus lymphadenectomy is essential to ensure precise staging in patients with intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate the influence of the clinical status of lymph nodes on the survival outcomes in ICC patients. METHODS: Between January 2015 and December 2020, consecutive patients diagnosed with ICC who underwent liver resection plus lymphadenectomy were enrolled. Clinical assessment of lymph node status included positron emission tomography/computed tomography examination by radiologists pre-operatively, alongside intraoperative abdominal examination by the surgical team. Retrospective collection and analysis of clinical information alongside survival data were performed to assess outcomes. RESULTS: The study included a total of 359 patients, with 291 (81.0%) and 151 (42.1%) displaying clinically and pathologically positive lymph nodes, respectively. The clinical assessment method had a sensitivity of 81.2% and a specificity of 54.3%. Following a median follow-up period of 32 months, the overall survival (OS) rates at 1, 3, and 5 years were 69.1%, 50.6%, and 41.2%, respectively, while the disease-free survival (DFS) rates were 60.7%, 42.8%, and 40.1%, respectively, across the cohort. Patients who had clinically positive but pathologically negative lymph nodes recorded the highest median OS (52 months) and median DFS (32 months). Conversely, those who were clinically negative but pathologically positive experienced the lowest median OS (16 months) and median DFS (8 months). CONCLUSION: The current approach to clinically assessing lymph node status in ICC has a significant rate of false positives. Patients with clinically positive but pathologically negative lymph nodes exhibit the most favourable survival outcomes.

8.
J Immunother Cancer ; 12(5)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802271

RESUMO

BACKGROUND: Relapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready process developed in China, demonstrated remarkable efficacy and manageable safety in the pivotal RELIANCE study. However, no published data are available on the "real-world" use of relma-cel, especially for patients with CNS involvement. PATIENTS AND METHODS: Retrospective analyses were conducted for commercial relma-cel used in patients with R/R CNSL at 12 clinics. The primary endpoint was to evaluate the proportion of patients who achieved complete response (CR) at 3 months. Secondary endpoints included best complete response (BCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and the incidence of adverse events. RESULTS: Among the 22 CNSL patients (12 primary CNSLs; 10 secondary CNSLs), the best overall response rate was 90.9% and the BCR rate was 68.2%. With median follow-up of 316 days (range, 55-618 days), the estimated 1-year PFS rate, DOR, and OS rate were 64.4%, 71.5%, and 79.2%, respectively. Significant clinical benefits were observed in patients who were in durable CR or partial response to the most recent prior therapy preleukapheresis and received relma-cel as consolidation therapy (n=8), with 1-year PFS rate of 100.0% versus 41.7% (p=0.02). In addition, in terms of primary endpoint, non-CR at 3 months postinfusion seemed to be predictive of a worse prognosis, with an estimated 1-year PFS of 83.3% versus 37.0% (p=0.03), respectively. CRS occurred in 72.9% of patients (grade 3: 4.5%) and immune effector cell-associated neurotoxicity syndrome in 36.4% of patients (grade 3: 4.5%). With the add-on agent PD-1 inhibitor (tislelizumab) to the ongoing BTKi, significant re-expansions of CAR T-cell were detected by quantitative PCR or flow cytometry after a median of 2 weeks (range, 12-32 days). CONCLUSIONS: This study was the first and largest real-world study of commercial relma-cel for R/R CNSL, demonstrating promising efficacy and acceptable safety. We reaffirmed the benefit of immuno-agents such as BTKi or PD-1 inhibitor on CAR T-cell re-expansion and hypothesized a dual-agent CAR-T related combinatorial therapies, which warrants further validation. Most importantly, we highlighted the earlier use of CAR T-cell therapy as a consolidative therapy for patients sensitive to salvage therapy, which provided an impetus and inspired-future strategy.


Assuntos
Neoplasias do Sistema Nervoso Central , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/terapia , China , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Linfoma/terapia , Linfoma/tratamento farmacológico , Receptores de Antígenos Quiméricos/uso terapêutico , Estudos Retrospectivos
9.
Eur J Pharm Biopharm ; 199: 114309, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704102

RESUMO

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.


Assuntos
Alginatos , Quitosana , Colite Ulcerativa , Sistemas de Liberação de Medicamentos , Géis , Microesferas , Saponinas , Colite Ulcerativa/tratamento farmacológico , Animais , Ratos , Alginatos/química , Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Masculino , Saponinas/farmacologia , Saponinas/administração & dosagem , Saponinas/química , Tamanho da Partícula , Humanos , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Ratos Sprague-Dawley , Polímeros/química , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Administração Oral
10.
Sci Immunol ; 9(95): eadj9730, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728414

RESUMO

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.


Assuntos
Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Análise de Célula Única , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Autoimunidade/imunologia , Neuromielite Óptica/imunologia , Neuromielite Óptica/terapia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Sistema Nervoso Central/imunologia
11.
Mol Cancer ; 23(1): 99, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730464

RESUMO

The gut microbiota has been demonstrated to be correlated with the clinical phenotypes of diseases, including cancers. However, there are few studies on clinical subtyping based on the gut microbiota, especially in breast cancer (BC) patients. Here, using machine learning methods, we analysed the gut microbiota of BC, colorectal cancer (CRC), and gastric cancer (GC) patients to identify their shared metabolic pathways and the importance of these pathways in cancer development. Based on the gut microbiota-related metabolic pathways, human gene expression profile and patient prognosis, we established a novel BC subtyping system and identified a subtype called "challenging BC". Tumours with this subtype have more genetic mutations and a more complex immune environment than those of other subtypes. A score index was proposed for in-depth analysis and showed a significant negative correlation with patient prognosis. Notably, activation of the TPK1-FOXP3-mediated Hedgehog signalling pathway and TPK1-ITGAE-mediated mTOR signalling pathway was linked to poor prognosis in "challenging BC" patients with high scores, as validated in a patient-derived xenograft (PDX) model. Furthermore, our subtyping system and score index are effective predictors of the response to current neoadjuvant therapy regimens, with the score index significantly negatively correlated with both treatment efficacy and the number of immune cells. Therefore, our findings provide valuable insights into predicting molecular characteristics and treatment responses in "challenging BC" patients.


Assuntos
Neoplasias da Mama , Microbioma Gastrointestinal , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/microbiologia , Neoplasias da Mama/metabolismo , Feminino , Prognóstico , Animais , Camundongos , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Perfilação da Expressão Gênica , Ensaios Antitumorais Modelo de Xenoenxerto , Multiômica
12.
Cancers (Basel) ; 16(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38730623

RESUMO

BACKGROUND: Chronic periodontitis, an inflammation-related disorder affecting global populations, has been revealed to be linked to diverse cancers. Numerous epidemiological studies have not shown a link between chronic periodontitis and blood cancers in Taiwan. METHODS: This study included 601,628 patients, diagnosed with newly chronic periodontitis by the ICD-9-CM classification, who were enrolled from 2001 to 2021 in the National Health Insurance Research Database (NHIRD) in Taiwan. In this study, we employed comprehensive statistical analyses to investigate the association between chronic periodontitis and hematologic cancers. Initially, we calculated incidence density and used a Poisson regression to analyze relative risk. Subsequently, we compared the cumulative incidence of hematological cancer in both chronic and non-chronic periodontitis groups using the Kaplan-Meier method. RESULTS: The results revealed a significantly lower cumulative incidence of hematologic cancer in individuals with non-chronic periodontitis over a 12-year follow-up period. To further explore the risk factors, a Cox proportional hazard regression analysis was conducted. Being male (adjusted hazard ratio [aHR] = 1.21, 95% CI: 1.04 to 1.42; p = 0.014) and having hypertension (aHR = 1.34, 95% CI: 1.06 to 1.69; p = 0.015) were demonstrated to be associated with an increased risk of hematologic cancers, respectively. In addition, in a subtype multivariate analysis for categorizing hematologic cancers into lymphoma and leukemia, the aHR for leukemia was 1.48 (95% CI: 1.13 to 1.93; p = 0.004) and aHR for lymphoma was 1.15 (95% CI: 0.96 to 1.37; p = 0.140). CONCLUSIONS: This study found that being male and having hypertension were the significant risk factors for hematological malignancies. Moreover, the association between chronic periodontitis and specific subtypes of hematologic cancers was confirmed.

13.
Sci Total Environ ; 931: 172944, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38701919

RESUMO

Air pollution poses a significant threat to public health, while biogenic volatile organic compounds (BVOCs) play a crucial role in both aspects. However, the unclear relationship between BVOCs and air pollutants in the under-canopy space limits the accuracy of air pollution control and the exploitation of forest healthcare functions. To clarify the variation of BVOCs in forest therapy bases, and their impacts on ozone (O3) and fine particulate matter (PM2.5) at nose height, total VOCs (TVOCs) in the forest were collected during typical sunny days, while air pollutants and meteorological factors were observed simultaneously. The results showed that the branch-level emissions of P. tabuliformis were dominated by healthcare-effective monoterpenoids, with only α-pinene having relative air concentrations of over 5 % in forest air samples. The correlation between concentrations of under-canopy TVOCs and emission rates of BVOCs from P. tabuliformis was weak (p > 0.09) in all seasons. However, the correlation between concentrations of TVOCs and the concentrations of O3 and PM2.5 showed clear seasonal differences. In spring, TVOCs only showed a significant negative correlation with PM2.5 in the forest (p < 0.01). In summer and autumn, TVOCs were significantly negatively correlated with both O3 (p < 0.001) and PM2.5 (p < 0.01). Specifically, the negative linear relationships were more pronounced for O3 and oxygenated VOCs in autumn (R2 = 0.40, p < 0.001) than for other relationships. The relationship between air pollutant concentrations inside and outside the forest also showed significant seasonal differences, generally characterized by a weaker correlation between them during seasons of strong emissions. Therefore, BVOCs in coniferous forests are health functions as they can provide healthcare effects and mitigate the concentration of air pollutants in the forest, and the establishment of forest therapy bases in rural areas with low NOx can be a sensible approach to promote good health, well-being, and sustainable development.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Florestas , Ozônio , Material Particulado , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Poluição do Ar/estatística & dados numéricos , Ozônio/análise , Estações do Ano
14.
J Alzheimers Dis ; 99(4): 1273-1283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728186

RESUMO

Background: Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score serves as a credible predictor of an individual's risk of dementia. However, studies on the link of the CAIDE score to Alzheimer's disease (AD) pathology are scarce. Objective: To explore the links of CAIDE score to cerebrospinal fluid (CSF) biomarkers of AD as well as to cognitive performance. Methods: In the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, we recruited 600 cognitively normal participants. Correlations between the CAIDE score and CSF biomarkers of AD as well as cognitive performance were probed through multiple linear regression models. Whether the correlation between CAIDE score and cognitive performance was mediated by AD pathology was researched by means of mediation analyses. Results: Linear regression analyses illustrated that CAIDE score was positively associated with tau-related biomarkers, including pTau (p < 0.001), tTau (p < 0.001), as well as tTau/Aß42 (p = 0.008), while it was in negative association with cognitive scores, consisting of MMSE score (p < 0.001) as well as MoCA score (p < 0.001). The correlation from CAIDE score to cognitive scores was in part mediated by tau pathology, with a mediation rate varying from 3.2% to 13.2%. Conclusions: A higher CAIDE score, as demonstrated in our study, was linked to more severe tau pathology and poorer cognitive performance, and tau pathology mediated the link of CAIDE score to cognitive performance. Increased dementia risk will lead to cognitive decline through aggravating neurodegeneration.


Assuntos
Doença de Alzheimer , Biomarcadores , Cognição , Proteínas tau , Humanos , Masculino , Feminino , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Idoso , Cognição/fisiologia , Biomarcadores/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Pessoa de Meia-Idade , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Envelhecimento/psicologia , Fatores de Risco , Testes Neuropsicológicos/estatística & dados numéricos , Doenças Cardiovasculares , Idoso de 80 Anos ou mais , Fragmentos de Peptídeos/líquido cefalorraquidiano
15.
J Agric Food Chem ; 72(23): 13015-13022, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38807413

RESUMO

The extensive and repeated application of chemical fungicides results in the rapid development of fungicide resistance. Novel antifungal pesticides are urgently required. Natural products have been considered precious sources of pesticides. It is necessary to discover antifungal pesticides by using natural products. Herein, 42 various griseofulvin derivatives were synthesized. Their antifungal activities were evaluated in vitro. Most of them showed good antifungal activity, especially 3d exhibited a very broad antifungal spectrum and the most significant activities against 7 phytopathogenic fungi. In vivo activity results suggested that 3d protected apples and tomatoes from serious infection by phytopathogenic fungi. These proved that 3d had the potential to be a natural product-derived antiphytopathogenic fungi agent. Furthermore, docking analysis suggested that tubulin might be one of the action sites of 3d. It is reasonable to believe that griseofulvin derivatives are worth further development for the discovery of new pesticides.


Assuntos
Fungos , Fungicidas Industriais , Griseofulvina , Doenças das Plantas , Griseofulvina/farmacologia , Griseofulvina/química , Griseofulvina/síntese química , Fungicidas Industriais/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Doenças das Plantas/microbiologia , Relação Estrutura-Atividade , Fungos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Solanum lycopersicum/microbiologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química
16.
Int J Biol Macromol ; 270(Pt 2): 132174, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38750842

RESUMO

Hydrogels containing catechol group have received attention in the biomedical field due to their robust adhesive/cohesive capabilities, biocompatibility, and hemostatic abilities. Catechol-functionalized chitosan holds promise for preparing self-assembly hydrogels. However, issues of inefficient gelation and instability still persist in these hydrogels. In the current study, we synthesized chitosan catechol (CC) of high catechol substitution (∼28 %) and combined CC with tannic acid (TA, which also contains catechol) to form self-healing CC-TA hydrogels. The catechol-enriched CC-TA composite hydrogels showed rapid gelation and mechanical reinforcement (shear modulus ∼110 Pa). In situ coherent small-angle X-ray scattering (SAXS) coupled with rheometry revealed a morphological feature of mesoscale clusters (∼20 nm) within CC-TA hydrogel. The clusters underwent dynamic destruction under large-amplitude oscillatory shear, corresponding with the strain-dependent and self-healing behavior of the CC-TA hydrogel. The composite hydrogel had osmotic-responsive and notable adhesive properties. Meanwhile, CC-TA composite cryogel prepared simply through freeze-thawing procedures exhibited distinctive macroporous structure (∼200 µm), high water swelling ratio (∼7000 %), and favorable compressive modulus (∼8 kPa). The sponge-like cryogel was fabricated into swabs, demonstrating hemostatic capacity. The CC-TA composites, in both hydrogel and cryogel forms, possessed ROS scavenging ability, antimicrobial activity, and cell compatibility with potentials in biological applications.


Assuntos
Catecóis , Quitosana , Criogéis , Hemostáticos , Hidrogéis , Taninos , Quitosana/química , Quitosana/farmacologia , Catecóis/química , Catecóis/farmacologia , Taninos/química , Taninos/farmacologia , Criogéis/química , Hidrogéis/química , Hidrogéis/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Animais , Reologia
17.
Sci Rep ; 14(1): 12384, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811601

RESUMO

Compared with conventional soils, such as sand and clay, little knowledge on the coefficient of lateral earth pressure at-rest (K0) has been established for loess in the current literature. This paper presents an experimental investigation on K0 of compacted loess and the associated impacts on undrained shear behaviour. By adopting a K0 consolidation module in the triaxial system, the K0 stress state for loess samples was achieved through a unique feedback control. During the K0 consolidation, the deviatoric stress (q) increases progressively with the premise that the volumetric strain (εv) of the sample equals to the axial strain (εa). The results show that the K0 value of compacted loess is in a range of 0.28 to 0.53, which is dependent on the packing density and the clay content. A distinguishable decrease of K0 was found in the course of K0 consolidation for the loosely compacted loess sample, whereas a similar trend was not observed in the dense sample. In the undrained shear stage, all loess specimens revealed contractive response in the stress path (q-p') diagram, which can be quantified by a modified collapsibility index (Ic). The index is consistently higher for the K0 consolidated loess samples than for the isotropic ones. The experimental results indicate a strong impact of the initial stress state on the shear behaviour of compacted loess.

18.
medRxiv ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38798420

RESUMO

Background: Initial insights into oncology clinical trial outcomes are often gleaned manually from conference abstracts. We aimed to develop an automated system to extract safety and efficacy information from study abstracts with high precision and fine granularity, transforming them into computable data for timely clinical decision-making. Methods: We collected clinical trial abstracts from key conferences and PubMed (2012-2023). The SEETrials system was developed with four modules: preprocessing, prompt modeling, knowledge ingestion and postprocessing. We evaluated the system's performance qualitatively and quantitatively and assessed its generalizability across different cancer types- multiple myeloma (MM), breast, lung, lymphoma, and leukemia. Furthermore, the efficacy and safety of innovative therapies, including CAR-T, bispecific antibodies, and antibody-drug conjugates (ADC), in MM were analyzed across a large scale of clinical trial studies. Results: SEETrials achieved high precision (0.958), recall (sensitivity) (0.944), and F1 score (0.951) across 70 data elements present in the MM trial studies Generalizability tests on four additional cancers yielded precision, recall, and F1 scores within the 0.966-0.986 range. Variation in the distribution of safety and efficacy-related entities was observed across diverse therapies, with certain adverse events more common in specific treatments. Comparative performance analysis using overall response rate (ORR) and complete response (CR) highlighted differences among therapies: CAR-T (ORR: 88%, 95% CI: 84-92%; CR: 95%, 95% CI: 53-66%), bispecific antibodies (ORR: 64%, 95% CI: 55-73%; CR: 27%, 95% CI: 16-37%), and ADC (ORR: 51%, 95% CI: 37-65%; CR: 26%, 95% CI: 1-51%). Notable study heterogeneity was identified (>75% I 2 heterogeneity index scores) across several outcome entities analyzed within therapy subgroups. Conclusion: SEETrials demonstrated highly accurate data extraction and versatility across different therapeutics and various cancer domains. Its automated processing of large datasets facilitates nuanced data comparisons, promoting the swift and effective dissemination of clinical insights.

19.
Small ; : e2401299, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38746996

RESUMO

The immunosuppressive tumor microenvironment (TME) reduces the chimeric antigen receptor (CAR) T-cell therapy against solid tumors. Here, a CAR T cell membrane-camouflaged nanocatalyst (ACSP@TCM) is prepared to augment CAR T cell therapy efficacy against solid tumors. ACSP@TCM is prepared by encapsulating core/shell Au/Cu2- xSe and 3-bromopyruvate with a CAR T cell membrane. It is demonstrated that the CAR T cell membrane camouflaging has much better-targeting effect than the homologous tumors cell membrane camouflaging. ACSP@TCM has an appealing synergistic chemodynamic/photothermal therapy (CDT/PTT) effect that can induce the immunogenic cell death (ICD) of NALM 6 cells. Moreover, 3-bromopyruvate can inhibit the efflux of lactic acid by inhibiting the glycolysis process, regulating the acidity of TME, and providing a more favorable environment for the survival of CAR T cells. In addition, the photoacoustic (PA) imaging and computed tomography (CT) imaging performance can guide the ACSP@TCM-mediated tumor therapy. The results demonstrated that the ACSP@TCM significantly enhanced the CAR T cell therapy efficacy against NALM 6 solid tumor mass, and completely eliminated tumors. This work provides an effective tumor strategy for CAR T cell therapy in solid tumors.

20.
Sci Rep ; 14(1): 11571, 2024 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773125

RESUMO

This study delves into expressing primary emotions anger, happiness, sadness, and fear through drawings. Moving beyond the well-researched color-emotion link, it explores under-examined aspects like spatial concepts and drawing styles. Employing Python and OpenCV for objective analysis, we make a breakthrough by converting subjective perceptions into measurable data through 728 digital images from 182 university students. For the prominent color chosen for each emotion, the majority of participants chose red for anger (73.11%), yellow for happiness (17.8%), blue for sadness (51.1%), and black for fear (40.7%). Happiness led with the highest saturation (68.52%) and brightness (75.44%) percentages, while fear recorded the lowest in both categories (47.33% saturation, 48.78% brightness). Fear, however, topped in color fill percentage (35.49%), with happiness at the lowest (25.14%). Tangible imagery prevailed (71.43-83.52%), with abstract styles peaking in fear representations (28.57%). Facial expressions were a common element (41.76-49.45%). The study achieved an 81.3% predictive accuracy for anger, higher than the 71.3% overall average. Future research can build on these results by improving technological methods to quantify more aspects of drawing content. Investigating a more comprehensive array of emotions and examining factors influencing emotional drawing styles will further our understanding of visual-emotional communication.


Assuntos
Emoções , Expressão Facial , Humanos , Emoções/fisiologia , Masculino , Feminino , Adulto Jovem , Felicidade , Ira/fisiologia , Adulto , Medo/psicologia , Tristeza
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