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1.
Bioresour Technol ; : 131548, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39343174

RESUMEN

A novel molecularly imprinted biomass carbon (MIP@BC) catalyst functionalized with the virtual template of phthalates was designed as the cathode material which possesses excellent 2-electron oxygen reduction ability and H2O2 production capacity, which is suitable for targeted degradation of phthalates in the electro-Fenton system. Following molecularly imprinted modification, the adsorption capacity of MIP@BC for Dimethyl phthalate (DMP) increased by 40 %, reached 9.26 mg/g. Compared with non-imprinted biomass carbon (NIP@BC), the MIP@BC-mediated electro-Fenton process enhanced the degradation rate of DMP by 72 %. Additionally, the degradation rate of DMP rises by 51 % and 104 % respectively on the basis of river water and domestic sewage. The reactive oxygen species that induced DMP degradation were OH and O2- and targeted adsorption and catalysis exert a synergistic effect. This study provides a new insight into targeted degradation for high-toxicity of emerging contaminants from complex aqueous environment.

2.
Alzheimers Res Ther ; 16(1): 206, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294787

RESUMEN

BACKGROUND: Previous research on the risk of dementia associated with education attainment, smoking status, and alcohol use disorder (AUD) has yielded inconsistent results, indicating potential heterogeneous treatment effects (HTEs) of these factors on dementia risk. Thus, this study aimed to identify the important variables that may contribute to HTEs of these factors in older adults. METHODS: Using 2005-2021 data from the National Alzheimer's Coordinating Center (NACC), we included older adults (≥ 65 years) with normal cognition at the first visit. The exposure of interest included college education or above, current smoking, and AUD and the outcome was all-cause dementia. We applied doubly robust learning to estimate risk differences (RD) and 95% confidence intervals (CI) between exposed and unexposed groups in the overall cohort and subgroups identified through a decision tree model. RESULTS: Of 10,062 participants included, 929 developed all-cause dementia over a median 4.4-year follow-up. College education or above was associated with a lower risk of all-cause dementia in the overall population (RD, -1.5%; 95%CI, -2.8 to -0.3), especially among the subpopulations without hypertension, regardless of the APOE4 status. Current smoking was not related to increased dementia risk overall (2.8%; -1.5 to 7.2) but was significantly associated with increased dementia risk among men with (21.1%, 3.1 to 39.1) and without (8.4%, 0.9 to 15.8) cerebrovascular disease. AUD was not related to increased dementia risk overall (2.0%; -7.7 to 11.7) but was significantly associated with increased dementia risk among men with neuropsychiatric disorders (31.5%; 7.4 to 55.7). CONCLUSIONS: Our studies identified important factors contributing to HTEs of education, smoking, and AUD on risk of all-cause dementia, suggesting an individualized approach is needed to address dementia disparities.


Asunto(s)
Alcoholismo , Demencia , Escolaridad , Fumar , Humanos , Masculino , Anciano , Femenino , Demencia/epidemiología , Estudios Longitudinales , Fumar/epidemiología , Factores de Riesgo , Alcoholismo/epidemiología , Anciano de 80 o más Años
3.
Artículo en Inglés | MEDLINE | ID: mdl-39173811

RESUMEN

Antimony (Sb) and its compounds can be harmful to people and are known to cause cancer, so they are a key pollutant to control. This study investigated the influence of antimony on non-enzymatic antioxidants and the blood-brain barrier (BBB) in zebrafish(Danio rerio), a model organism that shares a high degree of genetic similarity with humans. Zebrafish were exposed to different doses of antimony in water for 7, 18, and 30 days. The results indicated that antimony accumulated most in the liver, followed by the gills, flesh, and brain, with the accumulation increasing as the exposure duration extends. Additionally, under identical antimony concentrations, the buildup in the four tissues was positively correlated with the duration of exposure. After 18 days of exposure, the total antioxidant capacity (T-AOC) and endogenous non-enzymatic antioxidants vitamin C (VC) and vitamin E (VE) decreased as a result of antimony ingestion in zebrafish, although cysteine secretion was increased in the liver, gills, and brain. The structural integrity of the BBB was compromised by the elevation of ApoE4 and MMP-9 levels as a result of antimony exposure, which led to the breakdown of the basal lamina, tight junctions, and nerve fibers in the brain. At this injured region, 5-HT and MBP were also able to easily enter and leave the BBB, albeit at variable rates. Additionally, when the antimony exposure level reached 16.58 mg·L-1, antimony penetrated the BBB and bound to erythrocytes, causing their lysis.


Asunto(s)
Antimonio , Antioxidantes , Barrera Hematoencefálica , Contaminantes Químicos del Agua , Pez Cebra , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Antimonio/toxicidad , Antioxidantes/metabolismo , Contaminantes Químicos del Agua/toxicidad , Branquias/efectos de los fármacos , Branquias/metabolismo , Branquias/ultraestructura , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Estrés Oxidativo/efectos de los fármacos
4.
Int J Mol Sci ; 25(16)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39201243

RESUMEN

MaltAtt-1 is an antimicrobial peptide isolated from Monochamus alternatus with nematocidal activity against pine wood nematode. In this study, a eukaryotic expression system based on Komagataella phaffii GS115 was established, and its secretory expression of MaltAtt-1 was realized. The basic properties and secondary and tertiary structures of the antimicrobial peptide MaltAtt-1 were identified by bioinformatics analysis. MaltAtt-1 is a hydrophilic stable protein, mainly composed of an α-helix (Hh), ß-folds (Ee), and irregular curls (Cc). The optimal fermentation conditions for MaltAtt-1 were determined by a single-factor test and the Box-Behnken response surface method, including an induction time of 72 h, induction temperature of 30 °C, culture medium of pH 7.6, methanol volume fraction of 2.0%, and an initial glycerol concentration of 1%. The stability of MaltAtt-1 indicated its resistant to UV irradiation and repeated freezing and thawing, but the antibacterial activity decreased significantly under the influence of high temperature and a strong acid and base, and it decreased significantly to 1.1 cm and 0.83 cm at pH 2.0 and pH 10.0, respectively. The corrected mortality of B. xylophilus achieved 71.94% in 3 h at a concentration of 300 mg·L-1 MaltAtt-1 exposure. The results provide a theoretical basis for the antimicrobial peptide MaltAtt-1 to become a new green and efficient nematicide.


Asunto(s)
Péptidos Antimicrobianos , Animales , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Nematodos/efectos de los fármacos , Pinus/parasitología , Pinus/química , Saccharomycetales/metabolismo , Concentración de Iones de Hidrógeno , Fermentación , Estabilidad Proteica , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/farmacología
5.
Alzheimers Dement ; 20(8): 5528-5539, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38958394

RESUMEN

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain. METHODS: Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016-2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all-cause dementia. RESULTS: Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all-cause dementia over a 3.2-year follow-up, yielding a lower risk for SGLT2 inhibitors (RD, -2.5%; 95% CI, -3.0% to -2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from -4.3% (-5.5 to -3.2) to -0.9% (-1.9 to 0.2). DISCUSSION: Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all-cause dementia, but the association varied among different subgroups. HIGHLIGHTS: New users of sodium-glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all-cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.


Asunto(s)
Demencia , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Femenino , Demencia/epidemiología , Anciano , Estudios de Cohortes , Compuestos de Sulfonilurea/uso terapéutico , Persona de Mediana Edad , Factores de Riesgo , Hipoglucemiantes/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Heterogeneidad del Efecto del Tratamiento
6.
Surg Endosc ; 38(9): 4956-4964, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38977497

RESUMEN

OBJECTIVE: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). METHODS: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. RESULTS: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I-IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. CONCLUSION: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD.


Asunto(s)
Reflujo Gastroesofágico , Manometría , Humanos , Reflujo Gastroesofágico/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Manometría/métodos , Adulto , Anciano , Gastroscopía/métodos , Unión Esofagogástrica/fisiopatología , Unión Esofagogástrica/patología , Unión Esofagogástrica/cirugía , Monitorización del pH Esofágico , Hernia Hiatal/cirugía , Hernia Hiatal/complicaciones , Esfínter Esofágico Inferior/fisiopatología
7.
Nat Catal ; 7(6): 655-665, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947227

RESUMEN

The development of novel strategies to rapidly construct complex chiral molecules from readily available feedstocks is a long-term pursuit in the chemistry community. Radical-mediated alkene difunctionalizations represent an excellent platform towards this goal. However, asymmetric versions remain highly challenging, and more importantly, examples featuring simple hydrocarbons as reaction partners are elusive. Here we report an asymmetric three-component alkene dicarbofunctionalization capitalizing on the direct activation of C(sp 3)-H bonds through the combination of photocatalysed hydrogen atom transfer and nickel catalysis. This protocol provides an efficient platform for installing two vicinal carbon-carbon bonds across alkenes in an atom-economic fashion, providing a wide array of high-value chiral α-aryl/alkenyl carbonyls and phosphonates, as well as 1,1-diarylalkanes from ubiquitous alkane, ether and alcohol feedstocks. This method exhibits operational simplicity, broad substrate scope and excellent regioselectivity, chemoselectivity and enantioselectivity. The compatibility with bioactive motifs and expedient synthesis of pharmaceutically relevant molecules highlight the synthetic potential of this protocol.

8.
Technol Health Care ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39031415

RESUMEN

BACKGROUND: The Stepped Care Model (SCM) is an evidence-based treatment approach that tailors treatment intensity based on patients' health status, aiming to achieve the most positive treatment outcomes with the least intensive and cost-effective interventions. Currently, the effectiveness of the Stepped Care Model in postoperative rehabilitation for TKA (Total Knee Arthroplasty) patients has not been reported. OBJECTIVE: The present study aimed to investigate whether the stepped care model could improve early-stage self-report quality of life and knee function after total knee arthroplasty via a prospective randomized controlled design. METHODS: It was a mono-center, parallel-group, open-label, prospective randomized controlled study. Patients who aging from 60-75 years old as well as underwent unilateral primary total knee arthroplasty due to end-stage knee osteoarthritis between 2020.06 to 2022.02 were enrolled. Participants were randomized and arranged into two groups in a 1:1 allocation. The control group was given traditional rehabilitation guidance, while the stepped care model group was given continued stepped care. Hospital for special surgery knee score, daily living ability (ADL), knee flexion range, and adverse events at 1, 3, and 6 months after total knee arthroplasty were recorded. RESULTS: 88 patients proceeded to the final analysis. There was no significant difference of age, gender, length of stay, BMI, and educational level between the two groups at the baseline. After specific stepped care model interventions, patients showed significant improvements in HHS in 1 month (85.00 (82.25, 86.00) vs. 80.00 (75.00, 83.00), p< 0.001), 3 months (88.00 (86.00, 92.00) vs. 83.00 (76.75, 85.00), p< 0.001), and 6 months (93.00 (90.25, 98.00) vs. 88.00 (84.25, 91.75), p< 0.001) when compared with the control group. Similar results were also found in both daily living ability and knee flexion angle measurements. No adverse event was observed during the follow-up. CONCLUSION: The present study found that the stepped care model intervention significantly improved early-stage knee function and self-reported life quality after total knee arthroplasty due to knee osteoarthritis. Female patients and those less than 70 years old benefit more from the stepped care model intervention after total knee arthroplasty.

9.
Genes (Basel) ; 15(6)2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38927666

RESUMEN

Fritillaria cirrhosa and its relatives have been utilized in traditional Chinese medicine for many years and are under priority protection in China. Despite their medicinal and protective value, research on their phylogeny, genetic diversity, and divergence remains limited. Here, we investigate the chloroplast genome variation architecture of 46 samples of F. cirrhosa and its relatives collected from various regions, encompassing the majority of wild populations across diverse geographical areas. The results indicate abundant variations in 46 accessions including 1659 single-nucleotide polymorphisms and 440 indels. Six variable markers (psbJ, ndhD, ycf1, ndhG, trnT-trnL, and rpl32-trnL) were identified. Phylogenetic and network analysis, population structure analysis, and principal component analysis showed that the 46 accessions formed five clades with significant divergence, which were related to their geographical distribution. The regions spanning from the southern Hengduan Mountains to the Qinghai-Tibet Plateau exhibited the highest levels of genetic diversity. F. cirrhosa and its relatives may have suffered a genetic bottleneck and have a relatively low genetic diversity level. Moreover, geographical barriers and discrete patches may have accelerated population divergence. The study offers novel perspectives on the phylogeny, genetic diversity, and population structure of F. cirrhosa and its relatives, information that can inform conservation and utilization strategies in the future.


Asunto(s)
Fritillaria , Genoma del Cloroplasto , Filogenia , Polimorfismo de Nucleótido Simple , Fritillaria/genética , Fritillaria/clasificación , Variación Genética , China , Genética de Población
10.
Nat Commun ; 15(1): 5408, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926355

RESUMEN

Anion-intercalation lithium metal batteries (AILMBs) are appealing due to their low cost and fast intercalation/de-intercalation kinetics of graphite cathodes. However, the safety and cycliability of existing AILMBs are constrained by the scarcity of compatible electrolytes. Herein, we showcase that a difluoroester can be applied as electrolyte solvent to realize high-performance AILMBs, which not only endows high oxidation resistance, but also efficiently tunes the solvation shell to enable highly reversible and kinetically fast cathode reaction beyond the trifluoro counterpart. The difluoroester-based electrolyte demonstrates nonflammability, high ionic conductivity, and electrochemical stability, along with excellent electrode compatibility. The Li| |graphite AILMBs reach a high durability of 10000 cycles with only a 0.00128% capacity loss per cycle under fast-cycling of 1 A g-1, and retain ~63% of room-temperature capacity when discharging at -65 °C, meanwhile supply stable power output under deformation and overcharge conditions. The electrolyte design paves a promising path toward fast-rate, low-temperature, durable, and safe AILMBs.

11.
J Biomed Inform ; 156: 104671, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38876452

RESUMEN

Electronic phenotyping is a fundamental task that identifies the special group of patients, which plays an important role in precision medicine in the era of digital health. Phenotyping provides real-world evidence for other related biomedical research and clinical tasks, e.g., disease diagnosis, drug development, and clinical trials, etc. With the development of electronic health records, the performance of electronic phenotyping has been significantly boosted by advanced machine learning techniques. In the healthcare domain, precision and fairness are both essential aspects that should be taken into consideration. However, most related efforts are put into designing phenotyping models with higher accuracy. Few attention is put on the fairness perspective of phenotyping. The neglection of bias in phenotyping leads to subgroups of patients being underrepresented which will further affect the following healthcare activities such as patient recruitment in clinical trials. In this work, we are motivated to bridge this gap through a comprehensive experimental study to identify the bias existing in electronic phenotyping models and evaluate the widely-used debiasing methods' performance on these models. We choose pneumonia and sepsis as our phenotyping target diseases. We benchmark 9 kinds of electronic phenotyping methods spanning from rule-based to data-driven methods. Meanwhile, we evaluate the performance of the 5 bias mitigation strategies covering pre-processing, in-processing, and post-processing. Through the extensive experiments, we summarize several insightful findings from the bias identified in the phenotyping and key points of the bias mitigation strategies in phenotyping.


Asunto(s)
Registros Electrónicos de Salud , Aprendizaje Automático , Fenotipo , Humanos , Medicina de Precisión/métodos , Sepsis/diagnóstico , Sesgo , Neumonía/diagnóstico , Biología Computacional/métodos , Algoritmos
12.
Food Chem ; 452: 139567, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38718456

RESUMEN

In this study, a hydroxyl radical oxidation system was established to simulate the oxidation process in fermented meat products. This system was employed to examine the structural changes in myofibrillar proteins (MPs) resulting from tryptic hydrolysis after a hydroxyl radical oxidative regime. The effect of these changes on the ability of MPs to bind selected aldehydes (3-methyl butanal, pentanal, hexanal, and heptanal) was also investigated. Moderate oxidation (H2O2 ≤ 1.0 mM) unfolded the structure of MPs, facilitating trypsin-mediated hydrolysis and increasing their binding capacity for the four selected aldehydes. However, excessive oxidation (H2O2 ≥ 2.5 mM) led to cross-linking and aggregation of MPs, inhibiting trypsin-mediated hydrolysis. The oxidised MPs had the best binding capacity for heptanal. The interaction of the oxidised trypsin-hydrolysed MPs with heptanal was driven by hydrophobic interactions. The binding of heptanal affected the structure of the oxidised trypsin-hydrolysed MPs and reduced their α-helix content.


Asunto(s)
Aldehídos , Radical Hidroxilo , Estrés Oxidativo , Radical Hidroxilo/química , Radical Hidroxilo/metabolismo , Aldehídos/química , Aldehídos/metabolismo , Hidrólisis , Animales , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Oxidación-Reducción , Miofibrillas/química , Miofibrillas/metabolismo , Tripsina/química , Tripsina/metabolismo , Porcinos , Unión Proteica , Productos de la Carne/análisis
13.
Mol Cell Biol ; 44(5): 178-193, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38767243

RESUMEN

Transcription factor 12 (TCF12) is a known oncogene in many cancers. However, whether TCF12 can regulate malignant phenotypes and angiogenesis in osteosarcoma is not elucidated. In this study, we demonstrated increased expression of TCF12 in osteosarcoma tissues and cell lines. High TCF12 expression was associated with metastasis and poor survival rate of osteosarcoma patients. Knockdown of TCF12 reduced the proliferation, migration, and invasion of osteosarcoma cells. TCF12 was found to bind to the promoter region of sphingosine kinase 1 (SPHK1) to induce transcriptional activation of SPHK1 expression and enhance the secretion of sphingosine-1-phosphate (S1P), which eventually resulted in the malignant phenotypes of osteosarcoma cells. In addition, S1P secreted by osteosarcoma cells promoted the angiogenesis of HUVECs by targeting S1PR4 on the cell membrane to activate the STAT3 signaling pathway. These findings suggest that TCF12 may induce transcriptional activation of SPHK1 to promote the synthesis and secretion of S1P. This process likely enhances the malignant phenotypes of osteosarcoma cells and induces angiogenesis via the S1PR4/STAT3 signaling pathway.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Lisofosfolípidos , Neovascularización Patológica , Osteosarcoma , Fosfotransferasas (Aceptor de Grupo Alcohol) , Factor de Transcripción STAT3 , Transducción de Señal , Esfingosina , Humanos , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Lisofosfolípidos/metabolismo , Neovascularización Patológica/metabolismo , Neovascularización Patológica/genética , Línea Celular Tumoral , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neoplasias Óseas/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Activación Transcripcional/genética , Receptores de Esfingosina-1-Fosfato/metabolismo , Receptores de Esfingosina-1-Fosfato/genética , Receptores de Lisoesfingolípidos/metabolismo , Receptores de Lisoesfingolípidos/genética , Movimiento Celular/genética , Masculino , Animales , Femenino , Angiogénesis
14.
Ecotoxicol Environ Saf ; 277: 116351, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38653027

RESUMEN

The increasing concentration of Antimony (Sb) in ecological environments has raised serious concerns about its potential biotoxicological impact. This study investigated the toxicokinetics, Global DNA Methylation (GDM), biomarker expression, and Integrated Biological Response (IBR) of Sb at different concentrations in zebrafish. The toxic mechanism of Sb exposure was simulated using molecular dynamics (MD). The results showed that significant differences effect existed (BCFk: liver > ovary > gut > brain) and uptake saturation phenomenon of Sb among zebrafish tissues. Over a 54-day exposure period, the liver emerged as the main target site for Sb-induced GDM, and the restoration was slower than in other tissues during the 54-day recovery period. Moreover, the concentration of Sb had a significant impact on the normally expression of biomarkers, with GSTM1 inhibited and MTF2, MT1, TET3, and p53 showing varying degrees of activation at different Sb concentrations. This could be attributed to Sb3+ potentially occupying the active site or tightly binding to the deep cavity of these genes. The IBR and MD results highlighted DNMT1 as the most sensitive biomarker among those assessed. This heightened sensitivity can be attributed to the stable binding of Sb3+ to DNMT1, resulting in alterations in the conformation of DNMT1's catalytic domain and inhibition of its activity. Consequently, this disruption leads to damage to the integrity of GDM. The study suggests that DNA methylation could serve as a valuable biomarker for assessing the ecotoxicological impact of Sb exposure. It contributes to a better understanding of the toxicity mechanisms in aquatic environments caused potential pollutants.


Asunto(s)
Antimonio , Bioacumulación , Metilación de ADN , Contaminantes Químicos del Agua , Pez Cebra , Animales , Antimonio/toxicidad , Metilación de ADN/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Biomarcadores/metabolismo , Femenino , Toxicocinética , Simulación de Dinámica Molecular , Hígado/efectos de los fármacos , Hígado/metabolismo
15.
CNS Neurosci Ther ; 30(3): e14682, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38499993

RESUMEN

BACKGROUND: Accumulating evidence supports the involvement of adaptive immunity in the development of radiation-induced brain injury (RIBI). Our previous work has emphasized the cytotoxic function of CD8+ T cells in RIBI. In this study, we aimed to investigate the presence and potential roles of cytotoxic CD4+ T cells (CD4+ CTLs) in RIBI to gain a more comprehensive understanding of adaptive immunity in this context. MAIN TEXT: Utilizing single-cell RNA sequencing (scRNA-seq), we analyzed 3934 CD4+ T cells from the brain lesions of four RIBI patients and identified six subclusters within this population. A notable subset, the cytotoxic CD4+ T cells (CD4+ CTLs), was marked with high expression of cytotoxicity-related genes (NKG7, GZMH, GNLY, FGFBP2, and GZMB) and several chemokine and chemokine receptors (CCL5, CX3CR1, and CCL4L2). Through in-depth pseudotime analysis, which simulates the development of CD4+ T cells, we observed that the CD4+ CTLs exhibited signatures of terminal differentiation. Their functions were enriched in protein serine/threonine kinase activity, GTPase regulator activity, phosphoprotein phosphatase activity, and cysteine-type endopeptidase activity involved in the apoptotic signaling pathway. Correspondingly, mice subjected to gamma knife irradiation on the brain showed a time-dependent infiltration of CD4+ T cells, an increase of MHCII+ cells, and the existence of CD4+ CTLs in lesions, along with an elevation of apoptotic-related proteins. Finally, and most crucially, single-cell T-cell receptor sequencing (scTCR-seq) analysis at the patient level determined a large clonal expansion of CD4+ CTLs in lesion tissues of RIBI. Transcriptional factor-encoding genes TBX21, RORB, and EOMES showed positive correlations with the cytotoxic functions of CD4+ T cells, suggesting their potential to distinguish RIBI-related CD4+ CTLs from other subsets. CONCLUSION: The present study enriches the understanding of the transcriptional landscape of adaptive immune cells in RIBI patients. It provides the first description of a clonally expanded CD4+ CTL subset in RIBI lesions, which may illuminate new mechanisms in the development of RIBI and offer potential biomarkers or therapeutic targets for the disease.


Asunto(s)
Antineoplásicos , Lesiones Encefálicas , Humanos , Ratones , Animales , Linfocitos T CD8-positivos , Linfocitos T CD4-Positivos , Linfocitos T Citotóxicos , Encéfalo , Lesiones Encefálicas/metabolismo
16.
Chem Rev ; 124(6): 3494-3589, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38478597

RESUMEN

The renewable energy industry demands rechargeable batteries that can be manufactured at low cost using abundant resources while offering high energy density, good safety, wide operating temperature windows, and long lifespans. Utilizing fluorine chemistry to redesign battery configurations/components is considered a critical strategy to fulfill these requirements due to the natural abundance, robust bond strength, and extraordinary electronegativity of fluorine and the high free energy of fluoride formation, which enables the fluorinated components with cost effectiveness, nonflammability, and intrinsic stability. In particular, fluorinated materials and electrode|electrolyte interphases have been demonstrated to significantly affect reaction reversibility/kinetics, safety, and temperature tolerance of rechargeable batteries. However, the underlining principles governing material design and the mechanistic insights of interphases at the atomic level have been largely overlooked. This review covers a wide range of topics from the exploration of fluorine-containing electrodes, fluorinated electrolyte constituents, and other fluorinated battery components for metal-ion shuttle batteries to constructing fluoride-ion batteries, dual-ion batteries, and other new chemistries. In doing so, this review aims to provide a comprehensive understanding of the structure-property interactions, the features of fluorinated interphases, and cutting-edge techniques for elucidating the role of fluorine chemistry in rechargeable batteries. Further, we present current challenges and promising strategies for employing fluorine chemistry, aiming to advance the electrochemical performance, wide temperature operation, and safety attributes of rechargeable batteries.

17.
Photodiagnosis Photodyn Ther ; 46: 104008, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38340885

RESUMEN

BACKGROUND: Condyloma acuminatum (CA) of the vagina is a sexually transmitted disease due to infection by human papilloma virus (HPV). The treatment efficacy of the conventional methods for vaginal CA is often unsatisfactory with a high recurrence rate. Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) combined with CO2 laser pretreatment is a feasible approach for vaginal CA, but the effectiveness and safety need further evaluation. METHODS: This study enrolled 15 patients with vaginal CA. All patients underwent CO2 laser ablation and then ALA-PDT for two or three cycles. The clinical efficacy and side effects were evaluated and analyzed during the treatment and 6 months after the treatment. RESULTS: The wart lesions in 4 cases (26.7 %) disappeared after the first treatment. The wart lesions in 5 cases (33.3 %) disappeared after the second treatment. And 6 cases (40 %) needed three treatment cycles before the lesions disappeared completely. The complete response (CR) rate was 93.3 % (14/15) at 2 weeks after three treatment cycles. There were 5 cases (83.3 %) which have complete remission after 2 treatments in warts diameter <1 cm group. There were only 4 cases (44.4 %) which have complete remission after 2 treatments in diameter>1 cm group. All patients had CR without reoccurrence at 6 months after treatment. The side effects mainly included a mild or moderate burning or stinging sensation (26.7 %). There were no infection, ulcers and scars after treatment. CONCLUSION: Topical 5-aminolevulinic acid-mediated photodynamic therapy combined with CO2 laser pretreatment is a safe and effective treatment for vaginal CA.


Asunto(s)
Ácido Aminolevulínico , Condiloma Acuminado , Láseres de Gas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Femenino , Ácido Aminolevulínico/uso terapéutico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Condiloma Acuminado/tratamiento farmacológico , Condiloma Acuminado/terapia , Adulto , Láseres de Gas/uso terapéutico , Persona de Mediana Edad , Enfermedades Vaginales/tratamiento farmacológico , Enfermedades Vaginales/terapia , Adulto Joven , Terapia Combinada , Administración Tópica
18.
J Biomed Inform ; 151: 104606, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38325698

RESUMEN

Electronic health records (EHRs) store an extensive array of patient information, encompassing medical histories, diagnoses, treatments, and test outcomes. These records are crucial for enabling healthcare providers to make well-informed decisions regarding patient care. Summarizing clinical notes further assists healthcare professionals in pinpointing potential health risks and making better-informed decisions. This process contributes to reducing errors and enhancing patient outcomes by ensuring providers have access to the most pertinent and current patient data. Recent research has shown that incorporating instruction prompts with large language models (LLMs) substantially boosts the efficacy of summarization tasks. However, we show that this approach also leads to increased performance variance, resulting in significantly distinct summaries even when instruction prompts share similar meanings. To tackle this challenge, we introduce a model-agnostic Soft Prompt-BasedCalibration (SPeC) pipeline that employs soft prompts to lower variance while preserving the advantages of prompt-based summarization. Experimental findings on multiple clinical note tasks and LLMs indicate that our method not only bolsters performance but also effectively regulates variance across different LLMs, providing a more consistent and reliable approach to summarizing critical medical information.


Asunto(s)
Registros Electrónicos de Salud , Procesamiento de Lenguaje Natural , Humanos , Calibración , Lenguaje , Personal de Salud
19.
medRxiv ; 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38405723

RESUMEN

A comprehensive view of factors associated with AD/ADRD will significantly aid in studies to develop new treatments for AD/ADRD and identify high-risk populations and patients for prevention efforts. In our study, we summarized the risk factors for AD/ADRD by reviewing existing meta-analyses and review articles on risk and preventive factors for AD/ADRD. In total, we extracted 477 risk factors in 10 categories from 537 studies. We constructed an interactive knowledge map to disseminate our study results. Most of the risk factors are accessible from structured Electronic Health Records (EHRs), and clinical narratives show promise as information sources. However, evaluating genomic risk factors using RWD remains a challenge, as genetic testing for AD/ADRD is still not a common practice and is poorly documented in both structured and unstructured EHRs. Considering the constantly evolving research on AD/ADRD risk factors, literature mining via NLP methods offers a solution to automatically update our knowledge map.

20.
Sci Total Environ ; 914: 169906, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38185163

RESUMEN

The continuous spread of Bursaphelenchus xylophilus (Steiner and Buhrer) Nickle, commonly known as the organism that causes pine wilt disease (PWD), has become a notable threat to forest security in East Asia and southern Europe, and an assessment of the carbon loss caused by PWD damage is important to achieving carbon neutrality. This study used satellite remote sensing and 15-year ground monitoring data to measure the impact of PWD on the carbon storage of Pinus massoniana Lamb. (P. massoniana), the conifer with the largest planted area in southern China. This study showed that the occurrence of PWD had an impact on the increase in carbon storage of P. massoniana. The infected and dead P. massoniana trees accounted for only 1.46 % of the total number of trees but caused a carbon storage loss of 1.99 t/ha, which accounted for 6.23 % of the total carbon sink in healthy P. massoniana forests over the last 15 years. The most pronounced decline in carbon storage occurred in the first five years of PWD invasion. After 10 years of clearcutting and replanting of Schima superba Gardn. et Champ., the increase in carbon storage of the reformed forest far exceeded that of the healthy forest during the same period, which was 2.04 times (10 years) and 1.56 times (15 years) that of the healthy P. massoniana forest. In addition, our study found that during the 15-year period (from the forest age of 22 to the forest age of 37), the average carbon storage of P. massoniana forest was 31.9 t/ha. This study helps to evaluate the impact of PWD on the carbon sink of pine forests and provides methodological references for analyzing the impact of biological disturbances on the carbon cycle.


Asunto(s)
Pinus , Carbono , Tecnología de Sensores Remotos , Bosques , Árboles
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