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1.
J Inflamm Res ; 17: 2811-2823, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737113

RESUMO

Background: Inflammatory Bowel Disease (IBD) patients may experience cognitive impairments in Visuospatial Working Memory (VSWM), significantly impacting their quality of life. However, the mechanisms underlying these impairments remain poorly understood. Methods: We studied functional MRI and graph theory analysis to investigate changes in functional connectivity networks during the Mental Rotation Task (MRT) in IBD patients. Twenty IBD patients (13 males, 7 females; mean age = 34.95 ± 13.80 years; mean disease duration = 2.43 ± 2.37 years) participated in the study. Exclusion criteria encompassed recent use of analgesics, 5-Aminosalicylate, corticosteroids, or immunosuppressants within the past three months. Additionally, we recruited 20 age-, gender-, and education-matched healthy controls for comparison. Results: Compared to a control group, IBD patients exhibited significantly longer reaction times and reduced accuracy during the MRT. Our analysis revealed abnormalities in multiple nodal attributes within the functional connectivity network, particularly in regions such as the bilateral orbitofrontal cortex, right supplementary motor area, bilateral parahippocampal gyrus, and bilateral anterior temporal lobe. We observed that the nodal efficiency in the left temporal pole is negatively correlated with Red Blood Cell Distribution Width (RDW) and positively correlated with response time of MRT. Conclusion: Our findings revealed notable abnormalities in multiple node attributes among IBD patients during MRT, providing evidence of cognitive impairments in VSWM in IBD patients. This study found RDW maybe can serve as a clinical indicator for predicting early VSWM impairment in patients with IBD.

2.
Angew Chem Int Ed Engl ; : e202407491, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735853

RESUMO

Ion-selective nanochannel membranes assembled from two-dimensional (2D) nanosheets hold immense promise for power conversion using salinity gradient. However, they face challenges stemming from insufficient surface charge density, which impairs both permselectivity and durability. Herein, we present a novel vacancy-engineered, oxygen-deficient NiCo layered double hydroxide (NiCoLDH)/cellulose nanofibers-wrapped carbon nanotubes (VOLDH/CNF-CNT) composite membrane. This membrane, featuring abundant angstrom-scale, cation-selective nanochannels, is designed and fabricated through a synergistic combination of vacancy engineering and interfacial super-assembly. The membrane shows interlayer free-spacing of ~3.62 Å, which validates the membrane size exclusion selectivity.This strategy, validated by DFT calculations and experimental data, improves hydrophilicity and surface charge density, leading to the strong interaction with K+ ions to benefit the low ion transport resistance and exceptional charge selectivity. When employed in an artificial river water|seawater salinity gradient power generator, it delivers a high-power density of 5.35 W/m2 with long-term durability (20,000s), which is almost 400% higher than that of the pristine NiCoLDH membrane. Furthermore, it displays both pH- and temperature-sensitive ion transport behavior, offering additional opportunities for optimization. This work establishes a basis for high-performance salinity gradient power conversion and underscores the potential of vacancy engineering and super-assembly in customizing 2D nanomaterials for diverse advanced nanofluidic energy devices.

3.
Comput Struct Biotechnol J ; 23: 1824-1832, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38707538

RESUMO

Estimation of model accuracy plays a crucial role in protein structure prediction, aiming to evaluate the quality of predicted protein structure models accurately and objectively. This process is not only key to screening candidate models that are close to the real structure, but also provides guidance for further optimization of protein structures. With the significant advancements made by AlphaFold2 in monomer structure, the problem of single-domain protein structure prediction has been widely solved. Correspondingly, the importance of assessing the quality of single-domain protein models decreased, and the research focus has shifted to estimation of model accuracy of protein complexes. In this review, our goal is to provide a comprehensive overview of the reference and statistical metrics, as well as representative methods, and the current challenges within four distinct facets (Topology Global Score, Interface Total Score, Interface Residue-Wise Score, and Tertiary Residue-Wise Score) in the field of complex EMA.

4.
Eur J Clin Invest ; : e14211, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726889

RESUMO

BACKGROUND: Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. RESULTS: A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). CONCLUSIONS: MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

5.
J Colloid Interface Sci ; 666: 393-402, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38603881

RESUMO

Humic acids (HA) are ubiquitous in surface waters, leading to significant fouling challenges. While zwitterion-like and zwitterionic surfaces have emerged as promising candidates for antifouling, a quantitative understanding of molecular interaction mechanism, particularly at the nanoscale, still remains elusive. In this work, the intermolecular forces between HA and charged, zwitterion-like or zwitterionic monolayers in aqueous environments were quantified using atomic force microscope. Compared to cationic MTAC ([2-(methacryloyloxy)ethyl]trimethylammonium chloride), which exhibited an adhesion energy of âˆ¼1.342 mJ/m2 with HA due to the synergistic effect of electrostatic attraction and possible cation-π interaction, anionic SPMA (3-sulfopropyl methacrylate) showed a weaker adhesion energy (∼0.258 mJ/m2) attributed to the electrostatic repulsion. Zwitterion-like MTAC/SPMA mixture, driven by electrostatic attraction between opposite charges, formed a hydration layer that prevented the interaction with HA, thereby considerably reducing adhesion energy to âˆ¼0.123 mJ/m2. In contrast, zwitterionic MPC (2-methacryloyloxyethyl phosphorylcholine) and DMAPS ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide) displayed ultralow adhesion energy (0.06-0.07 mJ/m2) with HA, arising from their strong dipole moments which could induce a tight hydration layer that effectively inhibited HA fouling. The pH-mediated electrostatic interaction resulted in the increased adhesion energy for MTAC but decreased adhesion energy for SPMA with elevated pH, while the adhesion energy for zwitterion-like and zwitterionic surfaces was independent of environmental pH. Density functional theory (DFT) simulation confirmed the strong binding capability of MPC and DMAPS with water molecules (∼-12 kcal mol-1). This work provides valuable insights into the molecular interaction mechanisms underlying humic-substance-fouling resistance of charged, zwitterion-like and zwitterionic materials at the nanoscale, shedding light on developing more effective strategy for HA antifouling in water treatment.

6.
BMC Womens Health ; 24(1): 238, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38614969

RESUMO

BACKGROUND: As fertility rates continue to decline and negative population growth emerges, China has sequentially introduced encouraging fertility policies to raise fertility levels. The impact of fertility on women's health remains inconclusive. It is essential to explore further the correlation between fertility and the health status of 113 million migrant women of childbearing age in China. OBJECTIVE: To investigate how fertility affects the health status of migrant women of childbearing age and determine if migrant women's socioeconomic status plays a moderating role in this process. METHODS: Using a nationally representative dataset from the 2018 China Migrants Dynamic Survey (CMDS), we examined the effects of fertility on the self-rated health of migrant women of childbearing age. An ordinary least squares regression model with moderating effects was used for the empirical study, and robustness tests were conducted based on the ordered probit model and propensity score matching to address endogeneity. RESULTS: The empirical results indicated that a rise in the number of children born significantly reduces the self-rated health of migrant women of childbearing age. An increase in years of schooling and household income can significantly mitigate the negative impact of childbearing on the health of migrant women. The robustness of the above results was validated through alternative models and propensity score matching (PSM) methods. The heterogeneity analysis revealed that fertility exerts a negative impact on the health status of migrant women with rural household registration and on the health status of inter-provincial and inter-city migrant women. Further investigation found that the occurrence of childbirth during migration and an increase in the number of girls significantly negatively impacted the health status of migrant women. In contrast, the increase in the number of boys did not show a significant effect. Improving the health of migrant women of childbearing age significantly positively impacted their future childbearing intentions. CONCLUSIONS: Migrant women of childbearing age bear the dual burden of migration and childbirth. Our findings showed the rise in the number of children born and the occurrence of childbirth during migration posed greater challenges to the health status of female migrants, particularly among those with lower socioeconomic status. Government and community efforts for enhancing health among migrant women of childbearing age are recommended.


Assuntos
Migrantes , Masculino , Criança , Gravidez , Feminino , Humanos , Fertilidade , Coeficiente de Natalidade , Parto , Parto Obstétrico
7.
Sci Total Environ ; 927: 172191, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38588738

RESUMO

Although the formation, turnover, and accumulation of soil organic carbon (SOC) are driven by different fertilizer inputs and their subsequent microbial-mediated transformation, the relationship between changes in plant-derived and microbial-derived components and soil microbial life history strategies under different fertilization regimes has not been well explored. In this study, the changes in microbial necromass carbon (MNC), lignin phenols, and glomalin-related soil protein (GRSP), as well as soil microbial life history strategy were determined in a 16-year field experiment in response to different fertilization regimes, including a no-fertilizer control (C), conventional chemical NPK fertilization (NPK), and partial substitutions of the NPK in chemical fertilizers with a low (30 %) or high (60 %) level of straw (0.3S and 0.6S) or cattle manure (0.3M and 0.6M). The results showed that total lignin phenol content and its contribution to SOC were significantly increased by 88.7 % and 74.2 %, respectively, in high-level straw substitution treatment as compared to chemical fertilization. Both high-level straw and cattle manure substitution increased MNC and total GRSP contents, but did not alter their contributions to SOC compared to chemical fertilization. In fertilized treatments, the high-level cattle manure substitution had the lowest and highest bacterial and fungal K/r ratio, respectively. Bacterial K/r ratio was an important factor in predicting bacterial necromass carbon content and there was a significant negative correlation between them. The ratio of ectomycorrhizal to saprotrophic fungi and fungal diversity were important factors for predicting lignin phenol and GRSP contents, respectively. In addition, the SEMs modeling indicated that straw substitution directly affected lignin phenol and MNC accumulation, whereas cattle manure substitution indirectly affected MNC accumulation by affecting microbial life history strategies. In conclusions, agricultural residues inputs support the formation of a multiple carbon pool of SOC compared to chemical fertilization; and microbial life history strategy is an important driver of SOC formation and affects SOC accumulation and stability in agroecosystems.


Assuntos
Agricultura , Carbono , Fertilizantes , Microbiologia do Solo , Solo , Carbono/metabolismo , Solo/química , Agricultura/métodos , Esterco
8.
Biomolecules ; 14(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38672404

RESUMO

Mitosis mediates the accurate separation of daughter cells, and abnormalities are closely related to cancer progression. KIF11, a member of the kinesin family, plays a vital role in the formation and maintenance of the mitotic spindle. Recently, an increasing quantity of data have demonstrated the upregulated expression of KIF11 in various cancers, promoting the emergence and progression of cancers. This suggests the great potential of KIF11 as a prognostic biomarker and therapeutic target. However, the molecular mechanisms of KIF11 in cancers have not been systematically summarized. Therefore, we first discuss the functions of the protein encoded by KIF11 during mitosis and connect the abnormal expression of KIF11 with its clinical significance. Then, we elucidate the mechanism of KIF11 to promote various hallmarks of cancers. Finally, we provide an overview of KIF11 inhibitors and outline areas for future work.


Assuntos
Cinesinas , Mitose , Neoplasias , Cinesinas/metabolismo , Cinesinas/genética , Humanos , Mitose/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Regulação Neoplásica da Expressão Gênica , Fuso Acromático/metabolismo , Fuso Acromático/genética
9.
J Org Chem ; 89(10): 7169-7174, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38679873

RESUMO

α-succinimide-substituted allenoates were employed as phosphine acceptors in phosphine-catalyzed (4 + 2) annulation with 1,1-dicyanoalkenes. They served as C4 synthons in the annulation reaction under mild reaction conditions and produced hexahydroisoindole derivatives in moderate to high yields with good to excellent diastereoselectivities.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38661542

RESUMO

In the field of sustainable chemistry, it is still a significant challenge to realize efficient light-powered space-confined catalysis and propulsion due to the limited solar absorption efficiency and the low mass and heat transfer efficiency. Here, novel semiconductor TiO2 nanorockets with asymmetric, hollow, mesoporous, and double-layer structures are successfully constructed through a facile interfacial superassembly strategy. The high concentration of defects and unique topological features improve light scattering and reduce the distance for charge migration and directed charge separation, resulting in enhanced light harvesting in the confined nanospace and resulting in enhanced catalysis and self-propulsion. The movement velocity of double-layered nanorockets can reach up to 10.5 µm s-1 under visible light, which is approximately 57 and 119% higher than that of asymmetric single-layered TiO2 and isotropic hollow TiO2 nanospheres, respectively. In addition, the double-layered nanorockets improve the degradation rate of the common pollutant methylene blue under sustainable visible light with a 247% rise of first-order rate constant compared to isotropic hollow TiO2 nanospheres. Furthermore, FEA simulations reveal and confirm the double-layered confined-space enhanced catalysis and self-propulsion mechanism.

11.
Front Endocrinol (Lausanne) ; 15: 1359621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577570

RESUMO

Purpose: To assess tumor growth using tumor doubling rate (TDR) during active surveillance (AS) in China. Methods: Between January 2016 and June 2020, a total of 219 patients with low-risk papillary thyroid microcarcinoma (PTMC) (aged 23-75 years) were consecutively enrolled in the AS program. Results: Four sections of TDR, >0.5, 0.1~0.5, -0.1~0.1 and <-0.1, corresponded with four categories of tumor volume kinetics: rapid growth, slow growth, stable, and decreased size. We found that 10.5% of PTMCs exhibited rapid growth, 33.33% exhibited slow growth, 26.48% were stable, and 29.68% decreased in size. Tumor growth was associated with two factors: age and volume of PTMC at diagnosis. 85.72% of elderly patients (≥ 61 years old) had tumors that remained stable or even shrank and rapidly growing tumors were not found in them. When the volume was small (≤14.13 mm3), the proportion of rapid growth was high (41.67%), whereas when the volume was large (> 179.5 mm3), the proportion of non-growth was 68.75%. Conclusion: TDR may be a better metric for evaluating tumor growth in observational PTMCs. A certain proportion of PTMCs grow during the period of AS and tumor growth was associated with age and volume of PTMC at initial diagnosis. Therefore, how to block tumor growth during the AS period, especially for young patients and patients with early-stage PTMC (size ≤ 5 mm), will be a new challenge.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Idoso , Humanos , Pessoa de Meia-Idade , Conduta Expectante , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/epidemiologia , Carcinoma Papilar/patologia , Risco
12.
Mol Pharm ; 21(5): 2327-2339, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38576375

RESUMO

In the present study, we investigated the role of lipid composition of camptothecin (CPT)-loaded liposomes (CPT-Lips) to adjust their residence time, drug distribution, and therefore the toxicities and antitumor activity. The CPT was loaded into liposomes using a click drug loading method, which utilized liposomes preloaded with GSH and then exposed to CPT-maleimide. The method produced CPT-Lips with a high encapsulation efficiency (>95%) and sustained drug release. It is shown that the residence times of CPT-Lips in the body were highly dependent on lipid compositions with an order of non-PEGylated liposomes of unsaturated lipids < non-PEGylated liposomes of saturated lipids < PEGylated liposomes of saturated lipids. Interestingly, the fast clearance of CPT-Lips resulted in significantly decreased toxicities but did not cause a significant decrease in their in vivo antitumor activity. These results suggested that the lipid composition could effectively adjust the residence time of CPT-Lips in the body and further optimize their therapeutic index, which would guide the development of a liposomal formulation of CPT.


Assuntos
Camptotecina , Lipídeos , Lipossomos , Camptotecina/química , Camptotecina/administração & dosagem , Camptotecina/farmacocinética , Camptotecina/farmacologia , Lipossomos/química , Animais , Camundongos , Lipídeos/química , Humanos , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Polietilenoglicóis/química , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Feminino , Química Click/métodos , Camundongos Endogâmicos BALB C
13.
Gigascience ; 132024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38649301

RESUMO

BACKGROUND: Phage therapy, reemerging as a promising approach to counter antimicrobial-resistant infections, relies on a comprehensive understanding of the specificity of individual phages. Yet the significant diversity within phage populations presents a considerable challenge. Currently, there is a notable lack of tools designed for large-scale characterization of phage receptor-binding proteins, which are crucial in determining the phage host range. RESULTS: In this study, we present SpikeHunter, a deep learning method based on the ESM-2 protein language model. With SpikeHunter, we identified 231,965 diverse phage-encoded tailspike proteins, a crucial determinant of phage specificity that targets bacterial polysaccharide receptors, across 787,566 bacterial genomes from 5 virulent, antibiotic-resistant pathogens. Notably, 86.60% (143,200) of these proteins exhibited strong associations with specific bacterial polysaccharides. We discovered that phages with identical tailspike proteins can infect different bacterial species with similar polysaccharide receptors, underscoring the pivotal role of tailspike proteins in determining host range. The specificity is mainly attributed to the protein's C-terminal domain, which strictly correlates with host specificity during domain swapping in tailspike proteins. Importantly, our dataset-driven predictions of phage-host specificity closely match the phage-host pairs observed in real-world phage therapy cases we studied. CONCLUSIONS: Our research provides a rich resource, including both the method and a database derived from a large-scale genomics survey. This substantially enhances understanding of phage specificity determinants at the strain level and offers a valuable framework for guiding phage selection in therapeutic applications.


Assuntos
Bacteriófagos , Aprendizado Profundo , Especificidade de Hospedeiro , Bacteriófagos/genética , Especificidade de Hospedeiro/genética , Genômica/métodos , Genoma Bacteriano , Proteínas da Cauda Viral/genética , Genoma Viral , Bactérias/virologia , Bactérias/genética , Glicosídeo Hidrolases/genética
14.
Biomed Pharmacother ; 174: 116521, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38593700

RESUMO

AIM: American ginseng berries, grown in the aerial parts and harvested in August, are a potentially valuable material. The aim of the study was to analyze the specific polysaccharides in American ginseng berries, and to demonstrate the anti-inflammation effect through in vitro and in vivo experiments and molecular docking. METHODS: After deproteinization and dialysis, the extracted crude polysaccharide was separated and purified. The structure of the specific isolated polysaccharide was investigated by Fourier Transform infrared spectroscopy (FT-IR), GC-MS and nuclear magnetic resonance (NMR), and anti-inflammatory activity was evaluated using in vitro and in vivo models (Raw 264.7 cells and zebrafish). Molecular docking was used to analyze the binding capacity and interaction with cyclooxygenase-2 (COX-2). RESULTS: A novel neutral polysaccharide fraction (AGBP-A) was isolated from American ginseng berries. The structural analysis demonstrated that AGBP-A had a weight-average molecular weight (Mw) of 122,988 Da with a dispersity index (Mw/Mn) value of 1.59 and was composed of arabinose and galactose with a core structure containing →6)-Gal-(1→ residues as the backbone and a branching substitution at the C3 position. The side-chains comprised of α-L-Ara-(1→, α-L-Ara-(1→, →5)-α-L-Ara-(1→, ß-D-Gal-(1→. The results showed that it significantly decreased pro-inflammatory cytokines in the cell model. In a zebrafish model, AGBP-A reduced the massive recruitment of neutrophils to the caudal lateral line neuromast, suggesting the relief of inflammation. Molecular docking was used to analyze the combined capacity and interaction with COX-2. CONCLUSION: Our study indicated the potential efficacy of AGBP-A as a safe and valid natural anti-inflammatory component.


Assuntos
Anti-Inflamatórios , Frutas , Simulação de Acoplamento Molecular , Panax , Polissacarídeos , Peixe-Zebra , Animais , Panax/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Polissacarídeos/química , Camundongos , Frutas/química , Células RAW 264.7 , Ciclo-Oxigenase 2/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
15.
J Org Chem ; 89(9): 6405-6415, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38603543

RESUMO

An oxidative cascade iodocyclization of 1,7- or 1,8-dienes has been realized under mild conditions. By employing I2 as an iodine source, this protocol provides a concise and efficient approach to a great deal of biologically significant iodinated benzo[b]azepine and benzo[b]azocine derivatives in moderate to good yields. The gram-scale synthesis and further transformation of products render the approach practical and attractive. Radical trapping and deuterium-labeling experiments help to understand the mechanism.

16.
Cancer Lett ; 589: 216834, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38537773

RESUMO

Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4+ and CD8+ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Vírus Oncolíticos/genética , Glioblastoma/genética , Glioblastoma/terapia , Linfócitos T CD8-Positivos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia
17.
Chem Commun (Camb) ; 60(31): 4206-4209, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38523529

RESUMO

A novel silyl radical-induced cascade silylation/cyclization of 1,7-dienes has been realized employing readily available hydrosilanes as a silicon source and Cu(I) salt as a catalyst. This protocol introduces diverse silicon fragments into a challenging 7-membered ring structure and provides an efficient approach to a wide array of biologically important silyl-substituted benzo[b]azepin-2-ones. Several control experiments suggest that the reaction undergoes a free radical process. The gram-scale synthesis and late-stage transformations further demonstrate the scalability and applicability of the reaction in organic synthesis.

18.
RMD Open ; 10(1)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38428977

RESUMO

OBJECTIVE: This study explored the dynamic functional connective (DFC) alterations in patients with rheumatoid arthritis (RA) and investigated the correlation between the neuropsychiatric symptoms, peripheral inflammation and DFC alterations. METHOD: Using resting-state functional MRI, we investigated the DFC based on spatial independent component analysis and sliding window method for 30 patients with RA and 30 healthy controls (HCs). The Spearman correlation was calculated between aberrant DFC alterations, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HAD), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Diagnostic efficacy of indicators was assessed using receiver operating characteristic analysis (ROC). RESULTS: Three dynamic functional states were identified. Compared with HC, patients with RA showed reduced FC variabilities between sensorimotor network (SMN) and insula, SMN and orbitofrontal cortex, which were the crucial regions of sensory processing network. The above FC variabilities were correlated with the MoCA, HAD, CRP and ESR in patients with RA. Additionally, the CRP and ESR were negatively correlated to MoCA and positively related to HAD in patients with RA. The ROC analysis results showed that MoCA, HAD and FC variabilities of the sensory processing network could distinguish patients with RA from HC and also identify patients with RA with high ESR. CONCLUSION: Our findings demonstrated that abnormal DFC patterns in sensory processing networks in patients with RA were closely associated with peripheral inflammation and neuropsychiatric symptoms. This indicates that the dynamic temporal characteristics of the brain functional network may be potential neuroimaging biomarkers for revealing the pathological mechanism of RA.


Assuntos
Artrite Reumatoide , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Inflamação , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Encéfalo/diagnóstico por imagem , Proteína C-Reativa
19.
Cell Rep ; 43(4): 113699, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38517891

RESUMO

Over the past decade, the rapid development of DNA synthesis and sequencing technologies has enabled preliminary use of DNA molecules for digital data storage, overcoming the capacity and persistence bottlenecks of silicon-based storage media. DNA storage has now been fully accomplished in the laboratory through existing biotechnology, which again demonstrates the viability of carbon-based storage media. However, the high cost and latency of data reconstruction pose challenges that hinder the practical implementation of DNA storage beyond the laboratory. In this article, we review existing advanced DNA storage methods, analyze the characteristics and performance of biotechnological approaches at various stages of data writing and reading, and discuss potential factors influencing DNA storage from the perspective of data reconstruction.


Assuntos
DNA , DNA/metabolismo , Armazenamento e Recuperação da Informação/métodos , Humanos
20.
Animals (Basel) ; 14(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38539930

RESUMO

During the transition period, dairy cows exhibit heightened energy requirements to sustain fetal growth and lactogenesis. The mammary gland and the growing fetus increase their demand for glucose, leading to the mobilization of lipids to support the function of tissues that can use fatty acids as energy substrates. These physiological adaptations lead to negative energy balance, metabolic inflammation, and transient insulin resistance (IR), processes that are part of the normal homeorhetic adaptations related to parturition and subsequent lactation. Insulin resistance is characterized by a reduced biological response of insulin-sensitive tissues to normal physiological concentrations of insulin. Metabolic inflammation is characterized by a chronic, low-level inflammatory state that is strongly associated with metabolic disorders. The relationship between IR and metabolic inflammation in transitioning cows is intricate and mutually influential. On one hand, IR may play a role in the initiation of metabolic inflammation by promoting lipolysis in adipose tissue and increasing the release of free fatty acids. Metabolic inflammation, conversely, triggers inflammatory signaling pathways by pro-inflammatory cytokines, thereby leading to impaired insulin signaling. The interaction of these factors results in a harmful cycle in which IR and metabolic inflammation mutually reinforce each other. This article offers a comprehensive review of recent advancements in the research on IR, metabolic inflammation, and their intricate interrelationship. The text delves into multiple facets of physiological regulation, pathogenesis, and their consequent impacts.

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