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1.
J Multidiscip Healthc ; 17: 2105-2120, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736544

RESUMEN

Purpose: With the rapid development of immunotherapy, cancer treatment has entered a new phase. Medical imaging, as a primary diagnostic method, is closely related to cancer immunotherapy. However, until now, there has been no systematic bibliometric analysis of the state of this field. Therefore, the main purpose of this article is to clarify the past research trajectory, summarize current research hotspots, reveal dynamic scientific developments, and explore future research directions. Patients and Methods: A comprehensive search was conducted on the Web of Science Core Collection (WoSCC) database to identify publications related to immunotherapy specifically for the medical imaging of carcinoma. The search spanned the period from the year 2003 to 2023. Several analytical tools were employed. These included CiteSpace (6.2.4), and the Microsoft Office Excel (2016). Results: By searching the database, a total of 704 English articles published between 2003 and 2023 were obtained. We have observed a rapid increase in the number of publications since 2018. The two most active countries are the United States (n=265) and China (n=170). Pittock, Sean J and Abu-sbeih, Hamzah are very concerned about the relationship between cancer immunotherapy and medical images and have published more academic papers (n = 5; n = 4). Among the top 10 co-cited authors, Topalian Sl (n=43) cited ranked first, followed by Graus F (n=40) cited. According to clustering, timeline, and burst word analysis, the results show that the current research focus is on "MRI", "deep learning", "tumor microenvironment" and so on. Conclusion: Medical imaging and cancer immunotherapy are hot topics. The United States is the country with the most publications and the greatest influence in this field, followed by China. "MRI", "PET/PET-CT", "deep learning", "immune-related adverse events" and "tumor microenvironment" are currently hot research topics and potential targets.

2.
Exp Hematol Oncol ; 13(1): 48, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38725070

RESUMEN

BACKGROUND: Cancer is the leading cause of death among older adults. Although the integration of immunotherapy has revolutionized the therapeutic landscape of cancer, the complex interactions between age and immunotherapy efficacy remain incompletely defined. Here, we aimed to elucidate the relationship between aging and immunotherapy resistance. METHODS: Flow cytometry was performed to evaluate the infiltration of immune cells in the tumor microenvironment (TME). In vivo T cell proliferation, cytotoxicity and migration assays were performed to evaluate the antitumor capacity of tumor antigen-specific CD8+ T cells in mice. Real-time quantitative PCR (qPCR) was used to investigate the expression of IFN-γ-associated gene and natural killer (NK)-associated chemokine. Adoptive NK cell transfer was adopted to evaluate the effects of NK cells from young mice in overcoming the immunotherapy resistance of aged mice. RESULTS: We found that elderly patients with advanced non-small cell lung cancer (aNSCLC) aged ≥ 75 years exhibited poorer progression-free survival (PFS), overall survival (OS) and a lower clinical response rate after immunotherapy. Mechanistically, we showed that the infiltration of NK cells was significantly reduced in aged mice compared to younger mice. Furthermore, the aged NK cells could also suppress the activation of tumor antigen-specific CD8+ T cells by inhibiting the recruitment and activation of CD103+ dendritic cells (DCs). Adoptive transfer of NK cells from young mice to aged mice promoted TME remodeling, and reversed immunotherapy resistance. CONCLUSION: Our findings revealed the decreased sensitivity of elderly patients to immunotherapy, as well as in aged mice. This may be attributed to the reduction of NK cells in aged mice, which inhibits CD103+ DCs recruitment and its CD86 expression and ultimately leads to immunotherapy resistance.

3.
Materials (Basel) ; 17(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38730827

RESUMEN

In order to address the challenges of resource utilization posed by construction waste, the substitution of natural aggregate (NA) with public fill (PF) contents was investigated for load reclamation and road grassroots applications. A comprehensive assessment of road performance for the recycled mixture was conducted, focusing on parameters such as unconfined compressive strength, splitting strength, compressive resilience modulus, dry shrinkage, and frost resistance. Additionally, the impact of incorporating PF at various types and replacement ratios on the microstructure of cement-stabilized aggregate (CSA) was analyzed. The results indicated that the unconfined compressive strength of cement-stabilized recycled mixture with varying PF contents meets the base strength requirements for heavy, medium, and light traffic pavement on secondary and sub-secondary roads in China. Notably, the unconfined compressive strength and resilience modulus follow a similar pattern, reaching their peak at a 25% PF content. Microscopic examination reveals that an appropriate PF content leads to the predominant formation of C(N)-A-S-H, hydrotalcite, Ca(OH)2, and CaCO3 as paste reaction products. As the replacement of public fill increases from 0% to 25%, there is a gradual stacking of gel products, which enhances the compactness of the microstructure by cementing together unreacted particles. Consequently, this process reduces dry shrinkage strain and effectively mitigates the formation of reflection cracks. Applying large quantities of public fill to road construction can effectively deal with various waste accumulation problems and produce a novel road material with significant social, economic, and environmental benefits.

4.
Ther Apher Dial ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38751182

RESUMEN

INTRODUCTION: Therapeutic plasma exchange (TPE), an effective method to eliminate harmful soluble mediators associated with tissue injury, serves as a crucial intervention for systemic rheumatologic diseases (SRDs). However, its value in critically ill SRDs remains uncertain. This retrospective study aims to evaluate the efficacy of TPE in SRDs. METHODS: Critically ill SRD patients admitted to the department of intensive care unit of a large tertiary hospital receiving TPE from January 2011 to December 2019 were included. RESULTS: A total of 91 critically ill SRD patients received TPE were enrolled. Their mean age was 47.67 ± 16.35 years with a female predominance (n = 68). Significant decrease in SOFA score post-TPE treatment was observed (p < 0.05). There were no TPE-related fatalities. Improvement was observed in 64 (70.32%) patients. CONCLUSION: This study shows favorable clinical outcomes. TPE may be an acceptable treatment option for critically ill SRD patients.

5.
Bioorg Chem ; 148: 107434, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38744168

RESUMEN

Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H2O2-induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway.

6.
bioRxiv ; 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38746129

RESUMEN

The actin filament (F-actin) bundling protein fascin-1 is highly enriched in many metastatic cancers. Fascin's contribution to metastasis have been ascribed to its enhancement of cell migration and invasion. However, mouse genetic studies clearly point to functions also in tumorigenesis, yet without mechanistic underpinnings. Here, we show that fascin expression promotes the formation of a non-canonical signaling complex that enables anchorage-independent proliferation. This complex shares similarities to focal adhesions and we refer to them as pseudo-adhesion signaling scaffolds (PASS). PASS are enriched with tyrosine phosphorylated proteins and require fascin's F-actin-bundling activity for its assembly. PASS serve as hubs for the Rac1/PAK/JNK proliferation signaling axis, driven by PASS-associated Rac-specific GEFs. Experimental disruption of either fascin or RacGEF function abrogates sustained proliferation of aggressive cancers in vitro and in vivo . These results add a new molecular element to the growing arsenal of metabolic and oncogenic signaling programs regulated by the cytoskeleton architecture.

7.
Heliyon ; 10(10): e30986, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38778944

RESUMEN

Gastric cancer (GC) with high morbidity and mortality is one major cause of tumor-related death. Mechanisms underlying GC invasion and metastasis remain unclear. IGFBP7 exerted variable effects in different cancers and its role in GC is controversial. Here, IGFBP7 was found to be upregulated and elevated IGFBP7 expression represented a poorer overall survival in GC using bioinformatics analysis. Moreover, IGFBP7 was up-regulated in human GC specimens and promoted tumor growth in xenograft tumor animals. For GC cell lines, we found that IGFBP7 was also upregulated and facilitated the cell malignant behavior and EMT of GC cells, which may involve NF-κB and ERK signaling pathways. This research may provide new avenues for GC therapy.

8.
Chem Sci ; 15(20): 7586-7595, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38784730

RESUMEN

Fabricating three dimensional (3D) supramolecular frameworks (SMFs) into stable crystalline nanosheets remains a great challenge due to the homogeneous and weak inter-building block interactions along 3D directions. Herein, crystalline nanosheets of a 3D SMF with a uniform thickness of 4.8 ± 0.1 nm immobilized with Pt nanocrystals on the surface (Q[8]/Pt NSs) were fabricated via the solid-liquid reaction between cucurbit[8]uril/H2PtCl6 single crystals and hydrazine hydrate with the help of gas and heat yielded during the reaction process. A series of experiments and theoretical calculations reveal the ultrahigh stability of Q[8]/Pt NSs due to the high density hydrogen bonding interaction among neighboring Q[8] molecules. This in turn endows Q[8]/Pt NSs with excellent photocatalytic and continuous thermocatalytic CO oxidation performance, representing the thus-far reported best Pt nano-material-based catalysts.

9.
PLoS Pathog ; 20(5): e1012228, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38739679

RESUMEN

The arthropod exoskeleton provides protection and support and is vital for survival and adaption. The integrity and mechanical properties of the exoskeleton are often impaired after pathogenic infection; however, the detailed mechanism by which infection affects the exoskeleton remains largely unknown. Here, we report that the damage to the shrimp exoskeleton is caused by modulation of host lipid profiles after infection with white spot syndrome virus (WSSV). WSSV infection disrupts the mechanical performance of the exoskeleton by inducing the expression of a chitinase (Chi2) in the sub-cuticle epidermis and decreasing the cuticle chitin content. The induction of Chi2 expression is mediated by a nuclear receptor that can be activated by certain enriched long-chain saturated fatty acids after infection. The damage to the exoskeleton, an aftereffect of the induction of host lipogenesis by WSSV, significantly impairs the motor ability of shrimp. Blocking the WSSV-caused lipogenesis restored the mechanical performance of the cuticle and improved the motor ability of infected shrimp. Therefore, this study reveals a mechanism by which WSSV infection modulates shrimp internal metabolism resulting in phenotypic impairment, and provides new insights into the interactions between the arthropod host and virus.


Asunto(s)
Exoesqueleto , Metabolismo de los Lípidos , Penaeidae , Virus del Síndrome de la Mancha Blanca 1 , Animales , Penaeidae/virología , Penaeidae/metabolismo , Exoesqueleto/metabolismo , Exoesqueleto/virología , Virus del Síndrome de la Mancha Blanca 1/fisiología , Metabolismo de los Lípidos/fisiología , Interacciones Huésped-Patógeno , Lipogénesis/fisiología
11.
ACS Appl Mater Interfaces ; 16(20): 26234-26244, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38711193

RESUMEN

The huge volume expansion/contraction of silicon (Si) during the lithium (Li) insertion/extraction process, which can lead to cracking and pulverization, poses a substantial impediment to its practical implementation in lithium-ion batteries (LIBs). The development of low-strain Si-based composite materials is imperative to address the challenges associated with Si anodes. In this study, we have engineered a TiSi2 interface on the surface of Si particles via a high-temperature calcination process, followed by the introduction of an outermost carbon (C) shell, leading to the construction of a low-strain and highly stable Si@TiSi2@NC composite. The robust TiSi2 interface not only enhances electrical and ionic transport but also, more critically, significantly mitigates particle cracking by restraining the stress/strain induced by volumetric variations, thus alleviating pulverization during the lithiation/delithiation process. As a result, the as-fabricated Si@TiSi2@NC electrode exhibits a high initial reversible capacity (2172.7 mAh g-1 at 0.2 A g-1), superior rate performance (1198.4 mAh g-1 at 2.0 A g-1), and excellent long-term cycling stability (847.0 mAh g-1 after 1000 cycles at 2.0 A g-1). Upon pairing with LiNi0.6Co0.2Mn0.2O2 (NCM622), the assembled Si@TiSi2@NC||NCM622 pouch-type full cell exhibits exceptional cycling stability, retaining 90.1% of its capacity after 160 cycles at 0.5 C.

12.
Sci Total Environ ; 934: 173095, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38729370

RESUMEN

Deep dewatering of Waste Activated Sludge (WAS) through mechanical processes remains inefficient, primarily due to the formation of a stable hydrogen bonding network between the biopolymers and water, which consequently leads to significant water trapped by Extracellular Polymeric Substances (EPS). In this study, a novel and recyclable treatment for WAS based on Ionic Liquids (ILs) was established, named IL-biphasic aqueous system (IL-ABS) treatment. Specifically, the IL-ABS formed in WAS facilitated rapid and efficient in-situ deep dewatering while concurrently recovering hydroxyapatite. The water content decreased from an initial 98.27 % to 65.35 % with IL-ABS, formed by 1-Butyl-3-methylimidazolium bromide (BmimBr) and K3PO4 synthesized from waste H3PO4. Moreover, the recycled BmimBr maintaining the water content of the dewatered sludge consistently between 65.61 % and 67.25 % across five cycles, exhibited remarkable reproducibility. Through three-dimensional excitation-emission matrix, lactate dehydrogenase analyses and confocal laser scanning microscopy, the high concentration of BmimBr in the upper phase effectively disrupted the cells and EPS, which exposed protein and polysaccharide on the EPS surface. Subsequently, the K3PO4 in the lower phase led to an enhanced salting-out effect in WAS. Furthermore, FT-IR analysis revealed that K3PO4 disrupted the original hydrogen bonds between EPS and water. Then, BmimBr formed numerous hydrogen bonds with the sludge flocs, leading to deep dewatering and agglomeration of the sludge flocs during the unique phase separation process of IL-ABS. Notably, sludge-derived hydroxyapatite product exhibited remarkable adsorption capacity for prevalent heavy metal contaminants such as Pb2+, Cd2+ and Cu2+, with efficiencies comparable to those of commercial hydroxyapatite, thereby achieving the resource utilization of waste H3PO4. Moreover, economic calculations demonstrated the suitability of this novel treatment. This innovative treatment exhibits potential for practical applications in the non-mechanical deep dewatering of WAS.

13.
Phytochemistry ; 223: 114122, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38710376

RESUMEN

Quantitative analysis of Rumex nepalensis var. remotiflorus revealed that its roots contain rich anthraquinones, which has emodin, chrysophanol, and physcion contents of up to 0.30, 0.67, and 0.98 mg/g, respectively. Further phytochemical study led to the isolation and purification of seven undescribed phenolic constituents, including one flavan derivative with a 13-membered ring, polygorumin A (1), two dianthrone glucosides, polygonumnolides F and G (2, 3), two diphenylmethanones, rumepalens A and B (4, 5), and a pair of epimeric oxanthrone C-glucosides, rumejaposides K and L (6a, 6b) from the roots of R. nepalensis var. remotiflorus. Furthermore, 1 undescribed natural product, 1-ß-D-glucoside-6'-[(2E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate]-3-hydroxy-5-methylphenyl (19), and 21 known phenolic compounds were obtained from the aforementioned plant for the first time. Their structures were elucidated through extensive spectroscopic data analysis. Notably, compounds 1, 4-5, and 7-9 exhibited inhibitory activity on α-glucosidase with IC50 values ranging from 1.61 ± 0.17 to 32.41 ± 0.87 µM. In addition, the isolated dianthrone, chrysophanol bianthrone (14), showed obvious cytotoxicity against four human cancer cell lines (HL-60, SMMC-7721, A-549, and MDA-MB-231) with IC50 values ranging from 3.81 ± 0.17 to 35.15 ± 2.24 µM. In silico target prediction and molecular docking studies demonstrated that the mechanism of the anticancer activity of 14 may be related to the interaction with protein kinase CK2.


Asunto(s)
Antineoplásicos Fitogénicos , Inhibidores de Glicósido Hidrolasas , Fenoles , Rumex , alfa-Glucosidasas , Humanos , Fenoles/farmacología , Fenoles/química , Fenoles/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Rumex/química , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Línea Celular Tumoral , Raíces de Plantas/química , Relación Dosis-Respuesta a Droga , Proliferación Celular/efectos de los fármacos
14.
RSC Med Chem ; 15(4): 1198-1209, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38665835

RESUMEN

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

15.
J Toxicol Environ Health A ; 87(11): 471-479, 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38590254

RESUMEN

Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aß). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.


Asunto(s)
Enfermedad de Alzheimer , Cannabidiol , Disfunción Cognitiva , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Eje Cerebro-Intestino , Cognición , Disfunción Cognitiva/tratamiento farmacológico , Modelos Animales de Enfermedad
16.
J Gastrointest Surg ; 28(4): 458-466, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38583896

RESUMEN

Computed tomography (CT) imaging has the potential to assist in predicting the prognosis and treatment strategies for pancreatic cancer (PC). This study aimed to develop and validate a radio-clinical model based on preoperative multiphase CT assessments to predict the overall survival (OS) of PC and identify differentially expressed genes associated with OS. METHODS: Patients with PC who had undergone radical pancreatectomy (R0 resection) were divided into development and external validation sets. Independent predictors of OS were identified using Cox regression analyses and included in the nomogram, which was externally validated. The area under the curve was used to measure the model's accuracy in estimating OS probability. RNA sequencing data from The Cancer Genome Atlas were used for gene expression analysis. RESULTS: In the development and external validation sets, survival was estimated respectively for 132 and 27 patients. Multivariate Cox regression analysis identified 5 independent OS predictors: age (P = .049), sex (P = .001), bilirubin level (P = .005), tumor size (P = .020), and venous invasion (P = .041). These variables were incorporated into the nomogram. Patients were divided into high- and low-risk groups for OS and survival curves showed that all patients in the low-risk group had better OS than that of those in the high-risk group (P < .001). Differentially expressed genes in patients with a poor prognosis were involved in neuroactive ligand-receptor interaction. CONCLUSION: The radio-clinical model may be clinically useful for successfully predicting PC prognosis.


Asunto(s)
Productos Biológicos , Neoplasias Pancreáticas , Humanos , Pronóstico , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirugía , Tomografía Computarizada por Rayos X , Nomogramas
17.
Drug Des Devel Ther ; 18: 1339-1347, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38681205

RESUMEN

Purpose: Post-induction hypotension (PIH) is a common clinical phenomenon linked to increased morbidity and mortality in various non-cardiac surgeries. Patients with surgery in the afternoon may have preoperative hypovolemia caused by prolonged fasting and dehydration, which increases the risk of hypotension during the induction period. However, studies on the fluid therapy in early morning combating PIH remain inadequate. Therefore, we aimed to investigate the influence of prophylactic high-volume fluid in the early morning of the operation day on the incidence of PIH during non-cardiac surgery after noon. Patients and Methods: We reviewed the medical records of patients who underwent non-cardiac surgery after noon between October 2021 and October 2022. The patients were divided into two groups based on whether they received a substantial volume of intravenous fluid (high-volume group) or not (low-volume group) in the early morning of the surgery day. We investigated the incidence of PIH and intraoperative hypotension (IOH) as well as the accumulated duration of PIH in the first 15 minutes. In total, 550 patients were included in the analysis. Results: After propensity score matching, the incidence of PIH was 39.7% in the high-volume group and 54.1% in the low-volume group. Multivariate logistic regression analysis showed that patients in the high-volume group had lower incidence of hypotension after induction compared with the low-volume group (odds ratio, 0.55; 95% CI, 0.34-0.89; p = 0.016). The high-volume fluid infusion in the preoperative morning was significantly correlated with the decreased duration of PIH (p = 0.013), but no statistical difference was observed for the occurrence of IOH between the two groups (p = 0.075). Conclusion: The fluid therapy of more than or equal to 1000 mL in the early morning of the surgery day was associated with a decreased incidence of PIH compared with the low-volume group in patients undergoing non-cardiac surgery after noon.


Asunto(s)
Fluidoterapia , Hipotensión , Humanos , Estudios Retrospectivos , Hipotensión/prevención & control , Hipotensión/etiología , Hipotensión/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Incidencia , Anciano , Factores de Tiempo , Procedimientos Quirúrgicos Operativos/efectos adversos
18.
bioRxiv ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38617314

RESUMEN

How genetic lesions drive cell transformation and whether they can be circumvented without compromising function of non-transformed cells are enduring questions in oncology. Here we show that in mature T cells-in which physiologic clonal proliferation is a cardinal feature- constitutive MYC transcription and Tsc1 loss in mice modeled aggressive human malignancy by reinforcing each other's oncogenic programs. This cooperation was supported by MYC-induced large neutral amino acid transporter chaperone SLC3A2 and dietary leucine, which in synergy with Tsc1 deletion overstimulated mTORC1 to promote mitochondrial fitness and MYC protein overexpression in a positive feedback circuit. A low leucine diet was therapeutic even in late-stage disease but did not hinder T cell immunity to infectious challenge, nor impede T cell transformation driven by constitutive nutrient mTORC1 signaling via Depdc5 loss. Thus, mTORC1 signaling hypersensitivity to leucine as an onco-nutrient enables an onco-circuit, decoupling pathologic from physiologic utilization of nutrient acquisition pathways.

19.
Small ; : e2312067, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563596

RESUMEN

The open circuit voltage (VOC) losses at multiple interfaces within perovskite solar cells (PSCs) limit the improvements in power conversion efficiency (PCE). Herein, a tailored strategy is proposed to reduce the energy offset at both hetero-interfaces within PSCs to decrease the VOC losses. For the interface of perovskite and electron transport layer where exists a mass of defects, it uses the pyromellitic acid to serve as a molecular bridge, which reduces non-radiative recombination and energy level offset. For the interface of perovskite and hole transport layer, which includes a passivator of PEAI, the detrimental effect (negative shift of work function) of PEAI passivation and optimizing the interface energy level alignment are neutralized by incorporating (2-(4-(bis(4-methoxyphenyl)amino)phenyl)-1-cyanovinyl)phosphonic acid. Owing to synergistically reduced hetero-interface energy offset, the PSCs achieve a PCE of 25.13%, and the VOC is increased from 1.134 to 1.174 V. In addition, the resulting PSCs possess enhanced stability, the unencapsulated PSCs can maintain ≈96% and ≈97% of their initial PCE after 2000 h of aging under ambient conditions and 210 h under operation conditions.

20.
J Toxicol Environ Health A ; 87(10): 436-447, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38557424

RESUMEN

One of the main pathological features noted in Alzheimer's disease (AD) is the presence of plagues of aggregated ß-amyloid (Aß1-42)-peptides. Excess deposition of amyloid-ß oligomers (AßO) are known to promote neuroinflammation. Sequentially, following neuroinflammation astrocytes become activated with cellular characteristics to initiate activated astrocytes. The purpose of this study was to determine whether total flavonoids derived from Dracocephalum moldavica L. (TFDM) inhibited Aß1-42-induced damage attributed to activated C8-D1A astrocytes. Western blotting and ELISA were used to determine the expression of glial fibrillary acidic protein (GFAP), and complement C3 to establish the activation status of astrocytes following induction from exposure to Aß1-42. Data demonstrated that stimulation of C8-D1A astrocytes by treatment with 40 µM Aß1-42 for 24 hr produced significant elevation in protein expression and protein levels of acidic protein (GFAP) and complement C3 accompanied by increased expression and levels of inflammatory cytokines. Treatment with TFDM or the clinically employed drug donepezil in AD therapy reduced production of inflammatory cytokines, and toxicity initiated following activation of C8-D1A astrocytes following exposure to Aß1-42. Therefore, TFDM similar to donepezil inhibited inflammatory secretion in reactive astrocytes, suggesting that TFDM may be considered as a potential compound to be utilized in AD therapy.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Lamiaceae , Humanos , Péptidos beta-Amiloides/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Flavonoides/farmacología , Complemento C3/metabolismo , Complemento C3/farmacología , Complemento C3/uso terapéutico , Enfermedades Neuroinflamatorias , Astrocitos/metabolismo , Donepezilo/metabolismo , Donepezilo/farmacología , Donepezilo/uso terapéutico , Citocinas/metabolismo , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/toxicidad
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