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1.
Neurobiol Aging ; 140: 116-121, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38763076

RESUMEN

Synaptic dysfunction is highly correlated with cognitive impairments in Alzheimer's disease (AD), the most common dementia syndrome in the elderly. Long-term potentiation (LTP) and long-term depression (LTD) are two primary forms of synaptic plasticity with opposite direction of synaptic efficiency change. Both LTD and LTD are considered to mediate the cellular process of learning and memory. Substantial studies demonstrate AD-associated deficiency of both LTP and LTD. Meanwhile, the molecular signaling mechanisms underlying impairment of synaptic plasticity, particularly LTD, are poorly understood. By taking advantage of the novel transgenic mouse models recently developed in our lab, here we aimed to investigate the roles of AMP-activated protein kinase (AMPK), a central molecular senor that plays a critical role in maintaining cellular energy homeostasis, in regulation of LTD phenotypes in AD. We found that brain-specific suppression of the AMPKα1 isoform (but not AMPKα2 isoform) was able to alleviate mGluR-LTD deficits in APP/PS1 AD mouse model. Moreover, suppression of either AMPKα isoform failed to alleviate AD-related NMDAR-dependent LTD deficits. Taken together with our recent studies on roles of AMPK signaling in AD pathophysiology, the data indicate isoform-specific roles of AMPK in mediating AD-associated synaptic and cognitive impairments.

2.
J Oral Pathol Med ; 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38763759

RESUMEN

BACKGROUND: Angiopoietin-like 4 is a molecular hallmark that correlates with the growth and metastasis of head and neck squamous cell carcinoma, one of the most prevalent cancers worldwide. However, the molecular mechanisms by which angiopoietin-like 4 promotes head and neck squamous cell carcinoma tumorigenesis are unclear. METHODS: Using well-characterized cell lines of head and neck squamous cell carcinoma development, including human normal oral keratinocytes, dysplastic oral keratinocytes, oral leukoplakia-derived oral keratinocytes, and head and neck squamous cell carcinoma cell lines, HN13, HN6, HN4, HN12, and CAL27, we investigated the signaling pathways upstream and downstream of angiopoietin-like 4-induced head and neck squamous cell carcinoma tumorigenesis. RESULTS: We found that both epidermal growth factor receptor ligands, epithelial growth factor, and amphiregulin led to angiopoietin-like 4 upregulation in normal oral keratinocytes and dysplastic oral keratinocytes and cooperated with the activation of hypoxia-inducible factor-1 in this effect. Interestingly, amphiregulin and angiopoietin-like 4 were increased in dysplastic oral keratinocytes and head and neck squamous cell carcinoma cell lines, and amphiregulin-induced activation of cell proliferation was dependent on angiopoietin-like 4. Although both p38 mitogen-activated protein kinases (p38 MAPK) and protein kinase B (AKT) were activated by angiopoietin-like 4, only pharmacological inhibition of p38 MAPK was sufficient to prevent head and neck squamous cell carcinoma cell proliferation and migration. We further observed that angiopoietin-like 4 promoted the secretion of interleukin 11 (IL-11), interleukin 12 (IL-12), interleukin-1 alpha (IL-1α), vascular endothelial growth factor, platelet-derived growth factor (PDGF), and tumour necrosis factor alpha (TNF-α), cytokines and chemokines previously implicated in head and neck squamous cell carcinoma pathogenesis. CONCLUSION: Our results demonstrate that angiopoietin-like 4 is a downstream effector of amphiregulin and promotes head and neck squamous cell carcinoma development both through direct activation of p38 kinase as well as paracrine mechanisms.

3.
bioRxiv ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38766131

RESUMEN

Obesity is an epidemic with myriad health effects, but little is understood regarding individual obese phenotypes and how they may respond to therapy. Epigenetic changes associated with obesity have been detected in blood, liver, pancreas, and adipose tissues. Previous work found that dietary glucose hyperabsorption occurs in some obese subjects, but detailed transcriptional or epigenomic features of the intestine associated with this phenotype are unknown. This study evaluated differentially expressed genes and relative chromatin accessibility in intestinal organoids established from donors classified as lean, obese, or obese hyperabsorptive by body mass index and glucose transport assays. Transcriptomic analysis indicated that obese hyperabsorptive subjects have significantly upregulated dietary nutrient absorption proteins and downregulated type I interferon targets. Chromatin accessibility and transcription factor footprinting suggested that enhanced binding of HNF4G promotes the obese hyperabsorption phenotype. Quantitative PCR assessment in a larger subject cohort suggested that intestinal epithelial expression of CUBN, GIP, and SLC2A5 have high correlation with hyperabsorption. The obese hyperabsorption phenotype is characterized by transcriptional changes that support increased nutrient uptake and may be driven by differentially accessible chromatin. Recognizing unique intestinal phenotypes in obesity provides new perspective in considering therapeutic targets and options to manage the disease.

4.
BMC Cancer ; 24(1): 620, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38773564

RESUMEN

BACKGROUND: The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC. METHODS: Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM). RESULTS: Of the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6-16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn't. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC. CONCLUSION: Adjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Hepatectomía , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Puntaje de Propensión , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Quimioembolización Terapéutica/métodos , Masculino , Femenino , Persona de Mediana Edad , Hepatectomía/métodos , Anciano , Ablación por Radiofrecuencia/métodos , Estudios Retrospectivos , Terapia Combinada , Resultado del Tratamiento , Quimioterapia Adyuvante/métodos
5.
Front Plant Sci ; 15: 1328834, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774220

RESUMEN

Introduction: Unmanned aerial vehicles (UAVs) equipped with visible and multispectral cameras provide reliable and efficient methods for remote crop monitoring and above-ground biomass (AGB) estimation in rice fields. However, existing research predominantly focuses on AGB estimation based on canopy spectral features or by incorporating plant height (PH) as a parameter. Insufficient consideration has been given to the spatial structure and the phenological stages of rice in these studies. In this study, a novel method was introduced by fully considering the three-dimensional growth dynamics of rice, integrating both horizontal (canopy cover, CC) and vertical (PH) aspects of canopy development, and accounting for the growing days of rice. Methods: To investigate the synergistic effects of combining spectral, spatial and temporal parameters, both small-scale plot experiments and large-scale field testing were conducted in Jiangsu Province, China from 2021 to 2022. Twenty vegetation indices (VIs) were used as spectral features, PH and CC as spatial parameters, and days after transplanting (DAT) as a temporal parameter. AGB estimation models were built with five regression methods (MSR, ENet, PLSR, RF and SVR), using the derived data from six feature combinations (VIs, PH+CC, PH+CC+DAT, VIs+PH +CC, VIs+DAT, VIs+PH+CC+DAT). Results: The results showed a strong correlation between extracted and ground-measured PH (R2 = 0.89, RMSE=5.08 cm). Furthermore, VIs, PH and CC exhibit strong correlations with AGB during the mid-tillering to flowering stages. The optimal AGB estimation results during the mid-tillering to flowering stages on plot data were from the PLSR model with VIs and DAT as inputs (R 2 = 0.88, RMSE=1111kg/ha, NRMSE=9.76%), and with VIs, PH, CC, and DAT all as inputs (R 2 = 0.88, RMSE=1131 kg/ha, NRMSE=9.94%). For the field sampling data, the ENet model combined with different feature inputs had the best estimation results (%error=0.6%-13.5%), demonstrating excellent practical applicability. Discussion: Model evaluation and feature importance ranking demonstrated that augmenting VIs with temporal and spatial parameters significantly enhanced the AGB estimation accuracy. In summary, the fusion of spectral and spatio-temporal features enhanced the actual physical significance of the AGB estimation models and showed great potential for accurate rice AGB estimation during the main phenological stages.

6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(5): 593-597, 2024 May 15.
Artículo en Chino | MEDLINE | ID: mdl-38752247

RESUMEN

Objective: To investigate the accuracy of positioning perforator of medial sural artery with three-dimensional ultrasound technique guided by a wide band linear matrix array volume transducer probe before operation, and the effectiveness of the flap design based on this in repairing the dorsal foot wounds. Methods: Between January 2019 and December 2022, 30 patients with skin and soft tissue defects of the dorsal foot were treated. There were 19 males and 11 females, with an average age of 43.9 years (range, 22-63 years). There were 12 cases of traffic accident injury, 15 cases of heavy crushing injury, and 3 cases of machine injury. The time from injury to hospitalization was 1-8 hours (mean, 3.5 hours). The wounds in size of 5 cm×3 cm to 17 cm×5 cm were thorough debrided and covered with vacuum sealing drainage dressing. Then the wounds were repaired with the medial sural artery perforator flaps after no obvious infection observed. To obtain the complete three-dimensional image, the number and position of the medial sural artery perforator branches and the position of the main blood vessels in the muscle were detected and recorded by wide band linear matrix array volume transducer probe before operation. Suitable perforating branches were selected to design the flap and guide the flap incision on this basis. The size of the perforating flap ranged from 6 cm×4 cm to 18 cm×6 cm. The sensitivity and positive predictive value were calculated by comparing preoperative exploration with intraoperative observation of perforating branches, so as to evaluate the positioning accuracy of three-dimensional ultrasound technique. The donor sites were sutured directly in 25 cases and repaired with free skin grafting in 5 cases. Results: The 60 perforating branches of medial sural artery were found before operation and 58 during operation in 30 patients. Among them, pre- and intra-operative perforations were consistent with 56. The sensitivity was 93.3% and positive predictive value was 96.6%. The intramuscular position and route of the main blood vessels were basically consistent with the pre- and intra-operative observation. All flaps survived and wounds healed by first intention. All incisions at the donor sites healed by first intention, and all skin grafts survived. All patients were follow up 9-24 months (mean, 14.7 months). The appearance, color, and texture of the flaps were good, and no obvious effect on wearing shoes and walking. At last follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind score ranged from 80 to 92, with an average of 87.5. The patient satisfaction was excellent in 29 cases and good in 1 case. Conclusion: The three-dimensional ultrasound technique guided by the wide band linear matrix array volume transducer probe can accurately locate the perforating branch of the medial sural artery, and the three-dimensional imaging is more intuitive, which can be used to guide the design and incision of the medial sural artery perforator flap.


Asunto(s)
Traumatismos de los Pies , Imagenología Tridimensional , Colgajo Perforante , Traumatismos de los Tejidos Blandos , Ultrasonografía , Humanos , Masculino , Adulto , Femenino , Colgajo Perforante/irrigación sanguínea , Persona de Mediana Edad , Traumatismos de los Pies/cirugía , Ultrasonografía/métodos , Traumatismos de los Tejidos Blandos/cirugía , Traumatismos de los Tejidos Blandos/diagnóstico por imagen , Adulto Joven , Procedimientos de Cirugía Plástica/métodos , Peroné/irrigación sanguínea , Arterias , Cicatrización de Heridas , Trasplante de Piel/métodos
7.
J Exp Med ; 221(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38695876

RESUMEN

Platinum-based chemotherapy drugs can lead to the development of anorexia, a detrimental effect on the overall health of cancer patients. However, managing chemotherapy-induced anorexia and subsequent weight loss remains challenging due to limited effective therapeutic strategies. Growth differentiation factor 15 (GDF15) has recently gained significant attention in the context of chemotherapy-induced anorexia. Here, we report that hepatic GDF15 plays a crucial role in regulating body weight in response to chemo drugs cisplatin and doxorubicin. Cisplatin and doxorubicin treatments induce hepatic Gdf15 expression and elevate circulating GDF15 levels, leading to hunger suppression and subsequent weight loss. Mechanistically, selective activation by chemotherapy of hepatic IRE1α-XBP1 pathway of the unfolded protein response (UPR) upregulates Gdf15 expression. Genetic and pharmacological inactivation of IRE1α is sufficient to ameliorate chemotherapy-induced anorexia and body weight loss. These results identify hepatic IRE1α as a molecular driver of GDF15-mediated anorexia and suggest that blocking IRE1α RNase activity offers a therapeutic strategy to alleviate the adverse anorexia effects in chemotherapy.


Asunto(s)
Anorexia , Doxorrubicina , Endorribonucleasas , Factor 15 de Diferenciación de Crecimiento , Hígado , Proteínas Serina-Treonina Quinasas , Pérdida de Peso , Proteína 1 de Unión a la X-Box , Animales , Humanos , Ratones , Anorexia/inducido químicamente , Anorexia/metabolismo , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Doxorrubicina/efectos adversos , Endorribonucleasas/metabolismo , Endorribonucleasas/genética , Factor 15 de Diferenciación de Crecimiento/efectos adversos , Factor 15 de Diferenciación de Crecimiento/genética , Factor 15 de Diferenciación de Crecimiento/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Ratones Endogámicos C57BL , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal/efectos de los fármacos , Respuesta de Proteína Desplegada/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos , Proteína 1 de Unión a la X-Box/metabolismo , Proteína 1 de Unión a la X-Box/genética
8.
Aesthetic Plast Surg ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760536

RESUMEN

BACKGROUND: Autologous fat grafting is a common treatment for tear trough deformities. This procedure involves a potential complication of fat nodule formation, leading to abnormal bulging of the lower eyelid. However, limited information exists about this complication, and an effective treatment is lacking. The present study aimed to present a novel surgical approach for the removal of fat nodules caused by autologous fat grafting in the tear trough. METHODS: This retrospective study included 33 patients who underwent surgery for the removal of fat nodules formed after autologous fat grafting. The procedure was performed using a conjunctival approach, allowing exposure and removal of all fat nodules in the anterior septal space, with the method adapted according to the severity of the deformity. RESULTS: A total of 66 eyelids were treated surgically, including 30 (45.45%) with mild nodular deformity, 23 (34.85%) with moderate nodular deformity, and 13 (10.70%) with severe nodular deformity. A second surgical procedure was required on 3 eyelids (4.56%). The main complications of the surgery were conjunctival congestion (21.21%), and localized depression (18.18%), bruising (12.12%). Among the patients, 29 (87.88%) were satisfied and 4 (12.12%) were dissatisfied with the treatment results. CONCLUSION: Conjunctival approach surgery is an effective method of removing fat nodules formed after autologous fat grafting in the tear trough, with good results and high levels of patient satisfaction. This approach enables the effective management of a common complication of autologous fat grafting and may enable the wider application of autologous fat grafting in the periorbital region. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

9.
Anal Chem ; 96(19): 7669-7678, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38708542

RESUMEN

Protein tyrosine kinase-7 (PTK7) has been reported as a vital participant in the Wnt signaling pathway, influencing tumorigenesis and metastasis. However, their specific roles in the mechanisms underlying cancer development and progression remain elusive. Here, using direct stochastic optical reconstruction microscopy (dSTORM) with aptamer-probe labeling, we first revealed that a weakening clustering distribution of PTK7 on the basal membranes happened as cellular migration increased during cancer progression. This correspondence was further supported by a diminished aggregated state of PTK7 caused by direct enhancement of cell migration. By comparing the alterations in PTK7 distribution with activation or inhibition of specific Wnt signaling pathway, we speculated that PTK7 could modulate cell migration by participating in the interplay between canonical Wnt (in MCF7 cells) and noncanonical Wnt signals (in MDA-MB-231 cells). Furthermore, we discovered that the spatial distribution morphology of PTK7 was also subject to the hydrolysis ability and activation state of the related hydrolase Matrix metallopeptidase14 (MMP14). This function-related specific assembly of PTK7 reveals a clear relationship between PTK7 and cancer. Meanwhile, potential molecular interactions predicted by the apparent assembly morphology can promote a deep understanding of the functional mechanism of PTK7 in cancer progress.


Asunto(s)
Proteínas Tirosina Quinasas Receptoras , Humanos , Proteínas Tirosina Quinasas Receptoras/metabolismo , Movimiento Celular , Moléculas de Adhesión Celular/metabolismo , Vía de Señalización Wnt , Línea Celular Tumoral , Neoplasias/metabolismo , Neoplasias/patología , Metaloproteinasa 14 de la Matriz/metabolismo
10.
JMIR Public Health Surveill ; 10: e47626, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748469

RESUMEN

BACKGROUND: Beyond the direct effect of COVID-19 infection on young people, the wider impact of the pandemic on other infectious diseases remains unknown. OBJECTIVE: This study aims to assess changes in the incidence and mortality of 42 notifiable infectious diseases during the pandemic among children and adolescents in China, compared with prepandemic levels. METHODS: The Notifiable Infectious Disease Surveillance System of China was used to detect new cases and fatalities among individuals aged 5-22 years across 42 notifiable infectious diseases spanning from 2018 to 2021. These infectious diseases were categorized into 5 groups: respiratory, gastrointestinal and enterovirus, sexually transmitted and blood-borne, zoonotic, and vector-borne diseases. Each year (2018-2021) was segmented into 4 phases: phase 1 (January 1-22), phase 2 (January 23-April 7), phase 3 (April 8-August 31), and phase 4 (September 1-December 31) according to the varying intensities of pandemic restrictive measures in 2020. Generalized linear models were applied to assess the change in the incidence and mortality within each disease category, using 2018 and 2019 as the reference. RESULTS: A total of 4,898,260 incident cases and 3701 deaths were included. The overall incidence of notifiable infectious diseases decreased sharply during the first year of the COVID-19 pandemic (2020) compared with prepandemic levels (2018 and 2019), and then rebounded in 2021, particularly in South China. Across the past 4 years, the number of deaths steadily decreased. The incidence of diseases rebounded differentially by the pandemic phase. For instance, although seasonal influenza dominated respiratory diseases in 2019, it showed a substantial decline during the pandemic (percent change in phase 2 2020: 0.21, 95% CI 0.09-0.50), which persisted until 2021 (percent change in phase 4 2021: 1.02, 95% CI 0.74-1.41). The incidence of gastrointestinal and enterovirus diseases decreased by 33.6% during 2020 but rebounded by 56.9% in 2021, mainly driven by hand, foot, and mouth disease (percent change in phase 3 2021: 1.28, 95% CI 1.17-1.41) and infectious diarrhea (percent change in phase 3 2020: 1.22, 95% CI 1.17-1.28). Sexually transmitted and blood-borne diseases were restrained during the first year of 2021 but rebounded quickly in 2021, mainly driven by syphilis (percent change in phase 3 2020: 1.31, 95% CI 1.23-1.40) and gonorrhea (percent change in phase 3 2020: 1.10, 95% CI 1.05-1.16). Zoonotic diseases were not dampened by the pandemic but continued to increase across the study period, mainly due to brucellosis (percent change in phase 2 2020: 0.94, 95% CI 0.75-1.16). Vector-borne diseases showed a continuous decline during 2020, dominated by hemorrhagic fever (percent change in phase 2 2020: 0.68, 95% CI 0.53-0.87), but rebounded in 2021. CONCLUSIONS: The COVID-19 pandemic was associated with a marked decline in notifiable infectious diseases in Chinese children and adolescents. These effects were not sustained, with evidence of a rebound to prepandemic levels by late 2021. To effectively address the postpandemic resurgence of infectious diseases in children and adolescents, it will be essential to maintain disease surveillance and strengthen the implementation of various initiatives. These include extending immunization programs, prioritizing the management of sexually transmitted infections, continuing feasible nonpharmaceutical intervention projects, and effectively managing imported infections.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , China/epidemiología , Adolescente , Niño , Preescolar , Adulto Joven , Incidencia , Masculino , Enfermedades Transmisibles/epidemiología , Femenino , Pandemias , Notificación de Enfermedades/estadística & datos numéricos
11.
Appl Opt ; 63(9): 2132-2139, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38568564

RESUMEN

A terahertz (THz) L i N b O 3-polymer hybrid metamaterial (LPHM) consisting of three-layer Au patterns and two medium interval layers is demonstrated, and the bulk refractive index (RI) sensing performance is also studied. The parameter optimizations and sensing performances of the LPHM are simulated by the finite-element method (FEM). The results show that the reflection or absorption spectrum of the LPHM has four peaks in the 1-10 THz band, and the peaks move toward the lower frequency when the period (P) of the LPHM or the side length (a) of the notched square frame increases but shift to the higher frequency when w 1 or w 2 increases. Moreover, the LPHM has a wide angular stability and good structural stability. The sensing performance shows that the LPHM can achieve an RI sensitivity of 11.5 µm/RIU with a detection limit (DL) of 2.9×10-4 R I U. The LPHM has potential applications in pharmacological biodevices, THz immunosensing, modern medical and clinical practices, and detection of thin films and biochemical substances, and it can be expected to realize multiphysical parameter measurements.

12.
Nat Commun ; 15(1): 2894, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570494

RESUMEN

Steroidal glycoalkaloids (SGAs) are major plant defense metabolites against pests, while they are considered poisonous in food. The genetic basis that guides negative selection of SGAs production during tomato domestication remains poorly understood. Here, we identify a distal enhancer, GAME Enhancer 1 (GE1), as the key regulator of SGAs metabolism in tomato. GE1 recruits MYC2-GAME9 transcriptional complex to regulate the expression of GAME cluster genes via the formation of chromatin loops located in the neighboring DNA region. A naturally occurring GE176 allelic variant is found to be more active in stimulating GAME expression. We show that the weaker GE1 allele has been the main driver for selecting reduced SGAs levels during tomato domestication. Unravelling the "TFs-Enhancer-Promoter" regulatory mechanism operating in SGAs metabolism opens unprecedented prospects for SGAs manipulation in Solanaceae via precision breeding strategies.


Asunto(s)
Solanaceae , Solanum lycopersicum , Solanum lycopersicum/genética , Domesticación , Fitomejoramiento , Esteroides
14.
Acta Pharmacol Sin ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589685

RESUMEN

Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.

15.
J Pharm Anal ; 14(3): 348-370, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38618251

RESUMEN

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aß42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aß42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

16.
J Hazard Mater ; 470: 134154, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38581871

RESUMEN

In this work, a multiplexed colorimetric strategy was initiated for simultaneous and fast visualization of dyes using low-cost and easy-to-prepare indicator papers as sorbents. Response surface methodology (RSM) was employed to model statistically and optimize the process variables for dyes extraction and colorimetric assays. Multiplexed colorimetry was realized by virtue of synchronous color alignments from different dimensions of multiple dyes co-stained colorimetric cards under RSM-optimized conditions, and smartphone-based image analysis was subsequently performed from different modes to double-check the credibility of colorimetric assays. As concept-to-proof trials, simultaneous visualization of dyes in both beverages and simulated dye effluents was experimentally proved with results highly matched to HPLC or spiked amounts at RSM-predicted staining time as short as 50 s ∼3 min, giving LODs as low as 0.97 ± 0.22/0.18 ± 0.08 µg/mL (tartrazine/brilliant blue) for multiplexed colorimetry, which much lower than those obtained by single colorimetry. Since this is the first case to propose such a RSM-guided multiplexed colorimetric concept, it will provide a reference for engineering of other all-in-one devices which can realize synchronous visualization applications within limited experimental steps.


Asunto(s)
Colorimetría , Colorantes , Teléfono Inteligente , Colorimetría/métodos , Colorantes/química , Colorantes/análisis , Contaminación de Alimentos/análisis , Tartrazina/análisis , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Procesamiento de Imagen Asistido por Computador/métodos , Bencenosulfonatos/química , Bebidas/análisis
17.
J Colloid Interface Sci ; 667: 291-302, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38640649

RESUMEN

Single atom metal-nitrogen-carbon materials have emerged as remarkably potent catalysts, demonstrating unprecedented potential for the photo-driven reduction of CO2. Herein, a unique Cu@g-C3N5 catalyst obtained by cooperation of single atom Cu and nitrogen-rich g-C3N5 is proposed. The particular CuN diatomic active sites (DAS) in Cu@g-C3N5 contribute to the formation of highly stable CuOCN adsorption, a key configuration for CO2 activation and CC coupling. The synergistic diatomic active sites interaction is found responsible for the efficient photoreduction of CO2 to C2H4 which has been demonstrated in our Gibbs free energy calculation and COHP analysis. The CO2 activation mechanism was studied, the charge density difference and DOS analysis show that the low oxidation state Cu atom significantly affects the electronic structure of g-C3N5 and then enhance the catalytic activity of CO2 hydrogenation.

18.
Chemistry ; : e202401008, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38624085

RESUMEN

Here we report B(C6F5)3/CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.

19.
ACS Appl Nano Mater ; 7(7): 7395-7407, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38633297

RESUMEN

We utilize plasma-enhanced atomic layer deposition to synthesize two-dimensional Nb-doped WS2 and NbxW1-xSy alloys to expand the range of properties and improve the performance of 2D transition metal dichalcogenides for electronics and catalysis. Using a supercycle deposition process, films are prepared with compositions spanning the range from WS2 to NbS3. While the W-rich films form crystalline disulfides, the Nb-rich films form amorphous trisulfides. Through tuning the composition of the films, the electrical resistivity is reduced by 4 orders of magnitude compared to pure ALD-grown WS2. To produce Nb-doped WS2 films, we developed a separate ABC-type supercycle process in which a W precursor pulse precedes the Nb precursor pulse, thereby reducing the minimum Nb content of the film by a factor of 3 while maintaining a uniform distribution of the Nb dopant. Initial results are presented on the electrical and electrocatalytic performances of the films. Promisingly, the NbxW1-xSy films of 10 nm thickness and composition x ≈ 0.08 are p-type semiconductors and have a low contact resistivity of (8 ± 1) × 102 Ω cm to Pd/Au contacts, demonstrating their potential use in contact engineering of 2D TMD transistors.

20.
ISME Commun ; 4(1): ycae044, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38650709

RESUMEN

Perturbations and modulations during early life are vital to affect gut microbiome assembly and establishment. In this study, we assessed how microbial communities shifted during calf diarrhea and with probiotic yeast supplementation (Saccharomyces cerevisiae var. boulardii, SCB) and determined the key bacterial taxa contributing to the microbial assembly shifts using a total of 393 fecal samples collected from 84 preweaned calves during an 8-week trial. Our results revealed that the microbial assembly patterns differed between healthy and diarrheic calves at 6- and 8-week of the trial, with healthy calves being stochastic-driven and diarrheic calves being deterministic-driven. The two-state Markov model revealed that SCB supplementation had a higher possibility to shift microbial assembly from deterministic- to stochastic-driven in diarrheic calves. Furthermore, a total of 23 and 21 genera were specific ecotypes to assembly patterns in SCB-responsive (SCB-fed calves did not exhibit diarrhea) and nonresponsive (SCB-fed calves occurred diarrhea) calves, respectively. Among these ecotypes, the area under a receiver operating characteristic curve revealed that Blautia and Ruminococcaceae UCG 014, two unidentified genera from the Ruminococcaceae family, had the highest predictiveness for microbial assembly patterns in SCB-responsive calves, while Prevotellaceae, Blautia, and Escherichia-Shigella were the most predictive bacterial taxa for microbial assembly patterns in SCB-nonresponsive calves. Our study suggests that microbiome perturbations and probiotic yeast supplementation serving as deterministic factors influenced assembly patterns during early life with critical genera being predictive for assembly patterns, which sheds light on mechanisms of microbial community establishment in the gut of neonatal calves during early life.

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