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1.
Food Chem ; 462: 141063, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39226640

RESUMEN

In this research, the TT-COF(Fe)@NH2-CNTs was innovatively prepared through a post-modification synthetic process functionalized TT-COF@NH2-CNTs with active site (Fe), where TT-COF@NH2-CNTs was prepared via a one-pot strategy using 5,10,15,20-tetrakis (para-aminophenyl) porphyrin (TTAP), 2,3,6,7-tetra (4-formylphenyl) tetrathiafulvalene (TTF) and aminated carbon nanotubes (NH2-CNTs) as raw materials. The complex TT-COF(Fe)@NH2-CNTs material possessed porous structures, outstanding conductivity and rich catalytic sites. Thus, it can be adopted to construct electrochemical sensor with glassy carbon electrode (GCE). The TT-COF(Fe)@NH2-CNTs/GCE can selectively detect luteolin (Lu) with a wide linear plot ranging from 0.005 to 3 µM and a low limit of detection (LOD) of 1.45 nM (S/N = 3). The Lu residues in carrot samples were determined using TT-COF(Fe)@NH2-CNTs sensor and UV-visible (UV-Vis) approach. This TT-COF(Fe)@NH2-CNTs/GCE sensor paves the way for the quantification of Lu through a cost-efficient and sensitive electrochemical approach, which can make a significant step in the sensing field based on crystalline COFs.


Asunto(s)
Técnicas Electroquímicas , Luteolina , Nanotubos de Carbono , Nanotubos de Carbono/química , Luteolina/química , Luteolina/análisis , Técnicas Electroquímicas/instrumentación , Límite de Detección , Estructuras Metalorgánicas/química , Contaminación de Alimentos/análisis , Dominio Catalítico
2.
Artículo en Inglés | MEDLINE | ID: mdl-39241493

RESUMEN

The aim of this study was to investigate the effects of immersion on immune enzyme activity, haemolymph index, intestinal microbiome and metabolome of E. sinensis after low temperature air exposure. The results showed that low temperature air exposure induced stress response, which led to hepatopancreas injury and increased membrane permeability, but this situation was reversible and alleviated after immersion. In addition, after exposure to low temperature air, haemolymph metabolism-related substances such as glucose and total cholesterol were significantly different from the initial value (P < 0.05), and gradually returned to the initial level after immersion. The changes of intestinal flora and hepatopancreas metabolism caused by low temperature air exposure did not fully recover after immersion, and its negative effects did not completely disappear. The sequencing results showed that the species composition and diversity of intestinal microorganisms of Chinese mitten crabs were changed after low temperature air exposure and immersion treatment. The relative abundance of Bacteroidetes and Proteobacteria were increased, while the relative abundance of Firmicutes was decreased (P < 0.05). Metabolomics analysis showed that lysine levels increased significantly, taurocholic acid levels decreased significantly, and amino acid metabolism and lipid metabolism balance were disturbed in hepatopancreas of E. sinensis after exposure to low temperature air and immersion (P < 0.05). This study will provide new insights into the recovery mechanism of water immersion on Chinese mitten crabs after exposure to air.

3.
Int J Biol Macromol ; : 135286, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39245100

RESUMEN

Benefiting from the good electromechanical performance, ionic conductive hydrogel can easily convert the deformation into electrical signals, showing great potential in wearable electronic devices. However, due to the high water content, icing and water evaporation problems seriously limit their development. Although additives can ease these disadvantages, the accompanying performance degradation and complex preparation processes couldn't meet application needs. In this work, a convenient method was provided to prepare ionic conductive hydrogels with sensitive electromechanical performance, harsh environmental tolerance, and long-term stability without additives. Based on the hydratability between metal ions and water molecules resulting in spatial condensation of the hydrogel framework, the hydrogel exhibits good flexibility and ionic conductivity (70.3 mS/cm). Furthermore, the metal salt can bind with water molecules to reduce the vapor pressure, thus endowing the hydrogel with good freezing resistance (-40 °C) and long-term stability over a wide temperature range (-20 °C-50 °C). Based on these unique advantages, the hydrogel shows good sensitivity. Even in a harsh environment, it still maintained excellent stability (-20 °C-50 °C, GF = 2.2, R2 > 0.99). Assembled with a Wi-Fi device, the hydrogel sensor demonstrates good health activity and physiological state detection performance, demonstrating great potential for wearable medical devices.

4.
Angew Chem Int Ed Engl ; : e202414366, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245853

RESUMEN

The existing electronic waste (e-waste) and leaching solutions generated by industries accumulate significant amounts of gold (Au), even in excess of those in natural minerals. Therefore, the recycling of Au is extremely significant for the potential sustainability of chemical industry. By designing ionic covalent organic frameworks (COFs), here we synthesize a series of Ionic-COF-X (X=Cl-, Br-, AcO-, and SO42-) by anion regulation strategy. All these ionic COFs exhibit ultrahigh gold adsorption efficiency and excellent regeneration. Moreover, anion regulation could indeed affect the Au capture performance. In particular, when Cl- ions serve as counter ions, the Au capacity of Ionic-COF-Cl could reach 1270.8 mg g-1. Moreover, in the actual CPU leaching solution test, the selectivity of Ionic-COF-Cl towards Au3+ ion hits 39000 and 4600 times higher than that of Cu2+ and Ni2+ ions, respectively, suggesting that the Ionic-COF-Cl is a promising material for highly selective recovering gold from actual e-waste. DFT calculations further reveal that counter ions can regulate the adsorption affinity of ionic COF framework toward Au. In short, this work provides a useful anion regulation strategy to design ionic COFs as a promising platform for gold selective recovery from actual e-waste.

7.
Orthop Surg ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235036

RESUMEN

OBJECTIVES: Calcaneus defect remains challenging with limited strategies for reconstruction. Current methods, including graft transplantation, substitution, and distraction osteogenesis, showed limited advantages with certain shortcomings. Current calcaneus lengthening for partial calcaneus loss reconstruction requires bone loss of less than 35%. We introduced our combination of tarsal bone fusion and gradual lengthening method in treating massive calcaneus loss. METHODS: From January 2015 to December 2021, tarsal bone fusion and calcaneus gradual lengthening were performed in six patients with unilateral massive traumatic loss of the calcaneal tuberosity. A retrospective study was held to evaluate the outcomes of this novel technique. Clinical outcomes were assessed based on the American Orthopedic Foot and Ankle Score (AOFAS). Radiological data were assessed, which included tibio-calcaneal angle (TCA), calcaneal interface angle (CIA), metatarsal declination angle (MDA), angle of longitudinal arch (ALA), and the amount of calcaneus axial lengthening (CAL). RESULTS: The mean calcaneal axial lengthening was 43.8 ± 3.1 mm (range, 39-49.5 mm), and the mean proportion of the lengthened calcaneus was 47.8% ± 3.7% (range, 42.8-55.3%). The mean external fixation time was 104.8 ± 67.5 days (range, 69 to 242 days), and the mean external fixation index was 2.4 ± 1.6 days/cm. All patients stuck to the postoperative follow-up plan with an average follow-up time (FT) of 35.0 ± 6.7 months (range, 26-40 months). Deformities of the injured limbs were all corrected according to radiography. Based on the AOFAS, three excellent and three good results were achieved. CONCLUSION: The Ilizarov technique remains an option for calcaneus reconstruction with a great amount of loss once combined with tarsal bone fusion. The function of the injured foot and ankle can be satisfactorily restored using these techniques in our study. Apart from calcaneus elongation, tarsal bone fusion is somehow necessary to reinforce the proximal segment of the distracted calcaneus for creating a larger distraction callus, correcting concomitant foot deformities, and enhancing hindfoot stability. It is necessary to choose flexibly when tarsal bones should be fused.

8.
Proc Natl Acad Sci U S A ; 121(37): e2314337121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39226363

RESUMEN

Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer's disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane-dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.


Asunto(s)
Enfermedad de Alzheimer , Neoplasias Colorrectales , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Animales , Enfermedad de Alzheimer/microbiología , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Ratones , Humanos , Masculino , Inflamación , Disfunción Cognitiva , Femenino , Prevotella , Modelos Animales de Enfermedad , Lipopolisacáridos , Carcinogénesis , Sulfato de Dextran
9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(7): 717-722, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39223886

RESUMEN

OBJECTIVE: To investigate the protective effects of an anti-inflammatory mixture on acute lung injury (ALI) induced by sepsis in rats, as well as its possible mechanisms. METHODS: A total of 40 Sprague-Dawley (SD) rats were randomly divided into the sham group, septic ALI model group (model group), 3-methyladenine (3-MA) control group, and anti-inflammatory mixture pretreatment group, with 10 rats in each group. Cecal ligation and perforation (CLP) was performed to reproduce a septic ALI model. The rats in the sham group only underwent opening and closing the abdomen without perforation and ligation. Both groups were given saline gavage and intraperitoneal injection for 3 consecutive days before surgery. The 3-MA control group was given intraperitoneal injection of saline and autophagy inhibitor 3-MA 15 mg/kg for 3 consecutive days before modeling. The anti-inflammatory mixture pretreatment group was given 8.8 mL/kg of anti-inflammatory mixture by gavage [the composition of anti-inflammatory mixture: rhubarb 15 g (after the next), coptis chinensis 15 g, baical skullcap root 12 g, magnoliae cortex 12 g, dahurian patrinia herb 30 g] and saline intraperitoneal injection for 3 consecutive days before modeling. The rats in each group were anesthetized 24 hours after surgery and died due to abdominal aortic blood collection. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum inflammatory cytokines interleukins (IL-1ß and IL-6). Lung tissue was taken and then the bronchoalveolar lavage fluid (BALF) was collected, and the levels of IL-1ß and IL-6 were detected by ELISA. Lung wet/dry weight (W/D) ratio was measured. After hematoxylin-eosin (HE) staining, the histopathological changes of the lungs were observed under light microscopy. Western blotting was used to detect the expression of autophagy markers microtubule-associated protein 1 light chain 3- II/I (LC3- II/I) and Beclin-1 protein in lung tissue. Autophagosomes in lung tissue were observed with transmission electron microscopy. RESULTS: Compared with the sham group, the rats in the model group exhibited severe destruction of lung tissue structure, with significant infiltration of inflammatory cells, the lung W/D ratio and the levels of IL-1ß and IL-6 in serum and BALF were significantly increased, the expressions of LC3- II/I and Beclin-1 protein were down-regulated, the autophagosomes were more. The rats in the 3-MA control group exhibited more severe lung tissue injury as compared with the model group, the lung W/D ratio and the levels of inflammatory cytokines in serum and BALF were further increased, the expressions of LC3- II/I and Beclin-1 protein still showed a decrease tendency as compared with the sham group, and the autophagosomes were less than that in the model group. Compared with the model group, the anti-inflammatory mixture pretreatment group showed milder lung tissue injury with a minimal amount of inflammatory cell infiltration, the lung W/D ratio was significantly reduced (7.07±1.02 vs. 11.33±1.85, P < 0.05), the levels of IL-1ß and IL-6 in both serum and BALF were significantly decreased [IL-1ß (ng/L): 26.04±3.86 vs. 40.83±5.46 in serum, 17.75±2.02 vs. 26.86±4.32 in BALF; IL-6 (ng/L): 91.28±10.15 vs. 129.44±13.05 in serum, 76.06±7.51 vs. 120.91±7.47 in BALF, all P < 0.05], and the ratio of LC3- II/I and Beclin-1 protein expression were significantly increased [LC3- II/I ratio: 1.23±0.02 vs. 0.60±0.02, Beclin-1 protein (Beclin-1/GAPDH): 2.37±0.33 vs. 0.62±0.05, both P < 0.05]. Furthermore, an increase in the number of autophagosomes was observed. CONCLUSIONS: The anti-inflammatory mixture improves lung injury in rats with sepsis induced by CLP and reduce inflammation levels, potentially through upregulation of Beclin-1-mediated autophagy.


Asunto(s)
Lesión Pulmonar Aguda , Autofagia , Beclina-1 , Ratas Sprague-Dawley , Sepsis , Animales , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/metabolismo , Ratas , Sepsis/complicaciones , Sepsis/metabolismo , Sepsis/tratamiento farmacológico , Autofagia/efectos de los fármacos , Masculino , Beclina-1/metabolismo , Antiinflamatorios/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Interleucina-1beta/metabolismo , Pulmón/patología , Pulmón/metabolismo , Interleucina-6/metabolismo , Modelos Animales de Enfermedad
10.
J Control Release ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39284525

RESUMEN

Methicillin-Resistant Staphylococcus aureus forming into biofilms can trigger chronic inflammation and disrupt skin wound healing processes. Prolonged and excessive use of antibiotics can expedite the development of resistance, primarily because of their limited ability to penetrate microbial membranes and biofilms, especially antibiotics with intracellular drug targets. Herein, we devise a strategy in which virus-inspired nanoparticles control the release of antibiotics through rapid penetration into both bacterial cells and biofilms, thereby combating antimicrobial-resistant infections and promoting skin wound healing. Lipid-based nanoparticles based on stearamine and cholesterol were designed to mimic viral highly ordered nanostructures. To mimic the arginine-rich fragments in viral protein transduction domains, the primary amines on the surface of the lipid-based nanoparticles were exchanged by guanidine segments. Levofloxacin, an antibiotic that inhibits DNA replication, was chosen as the model drug to be incorporated into nanoparticles. Hyaluronic acid was coated on the surface of nanoparticles acting as a capping agent to achieve bacterial-specific degradation and guanidine explosion in the bacterial microenvironment. Our virus-inspired nanoparticles displayed long-acting antibacterial effects and powerful biofilm elimination to overcome antimicrobial-resistant infections and promote skin wound healing. This work demonstrates the ability of virus-inspired nanoparticles to achieve a dual penetration of microbial cell membranes and biofilm structures to address antimicrobial-resistant infections and trigger skin wound healing.

11.
Am J Transl Res ; 16(8): 3702-3712, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39262764

RESUMEN

OBJECTIVE: To assess the efficacy and safety of combining Programmed Death-1/Programmed Death-Ligand 1 (PD-1/L1) inhibitors with platinum-containing chemotherapy for treating late-stage Non-Small Cell Lung Cancer (NSCLC) patients who have developed resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs). METHODS: A retrospective analysis was conducted at Baoji Traditional Chinese Medicine Hospital involving 133 patients with advanced NSCLC who had shown resistance to EGFR-TKIs and were treated from October 2018 to May 2021. The cohort was categorized into two groups: one treated with immune checkpoint inhibitors (ICIs) plus chemotherapy and antiangiogenic agents (ICIs+BCP group), and the other treated with ICIs alone (ICIs group). Baseline data collected included demographic factors, smoking status, PD-L1 Tumor Proportion Score (TPS), EGFR mutation, Eastern Cooperative Oncology Group (ECOG) score, and routine blood markers prior to second-line therapy. Computed Tomography (CT) scans were performed every two treatment courses to evaluate the treatment efficacy. RESULTS: The ICIs+BCP group exhibited a statistically significant improvement in Overall Survival (OS) compared to the ICIs group (P=0.001). Cox survival analysis uncovered age (P=0.012), PD-L1 TPS expression (P<0.001), treatment regimen (P=0.006), Neutrophil-to-Lymphocyte Ratio (NLR) (P=0.024), and Platelet-to-Lymphocyte Ratio (PLR) (P=0.005) as independent factors influencing OS in patients with advanced NSCLC resistant to primary-line EGFR-TKI therapy. The nomogram model, based on these prognostic factors, exhibited Area Under the Curve (AUC) values of 0.823 and 0.769, indicating its predictive accuracy for 1-year and 2-year survival, respectively. CONCLUSION: Combining ICIs with BCP prolongs OS in patients with NSCLC resistant to EGFR-TKIs. This study underscores the importance of personalized treatment plans and biomarker evaluations to improve outcomes in drug-resistant cases.

12.
Antiviral Res ; 231: 106004, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39265655

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV), recently named as Dabie bandavirus, belongs to the family Phenuiviridae of the order Bunyavirales, is a newly-identified bunyavirus with a case fatality rate of up to 30%, posing a serious threat to public health. Lipid rafts on plasm membranes are important for the entry of enveloped viruses; however, the role of lipid rafts in bunyavirus entry remains unclear. In this study, we found that methyl-beta-cyclodextrin (MßCD), a drug that disrupts cholesterol in lipid rafts of cell membranes, inhibits SFTSV infection. Additionally, there is a back-complementary effect of SFTSV infection upon the addition of cholesterol. Moreover, the concentration of SFTSV particles in lipid rafts during entry directly indicated the role of lipid rafts as a gateway, whereas MßCD could inhibit SFTSV entry by affecting the structure of lipid rafts. In an in vivo study, MßCD also reduced the susceptibility of mice to SFTSV infection. Our results suggest that SFTSV can interact with Talin1 proteins on lipid rafts to enter host cells by endocytosis of lipid rafts and reveal the potential therapeutic value of MßCD for SFTSV infection.

14.
Bioresour Technol ; 413: 131434, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39236905

RESUMEN

This study assessed the characteristics and toxicity of aqueous pyrolytic liquid (APL) derived from digested sewage sludge on anaerobic digestion (AD) and determined its rate-limiting step. Digested sewage sludge was pyrolyzed at multiple temperatures (350-650 °C) and moisture levels (0-40.4 %), resulting in APLs with varying AD toxicities. APL 350 °C-0 % showed the least toxicity, whereas APL 650 °C-40.4 % exhibited the greatest toxicity. Glucose (GL) and sodium acetate (SA) were introduced to elucidate the rate-limiting steps. SA, but not GL, enhanced APL conversion to CH4. And volatile fatty acid lack was observed in treatments without SA addition. This suggested that acidification was the primary rate-limiting step. This finding was confirmed using the modified Gompertz model: SA considerably improved the maximum methane production rate, whereas GL did not. Insights gained from this research clarified the feasibility and potential of AD for APL utilization and conversion.

15.
Reproduction ; 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39231094

RESUMEN

Biallelic variants in the NSUN2 gene cause a rare intellectual disability and female infertility in humans. However, the function and mechanism of NSUN2 during mouse oocyte meiotic maturation and early embryonic development are unknown. Here, we show that NSUN2 is important for mouse oocyte meiotic maturation and early embryonic development. Specifically, NSUN2 is required for ovarian development and oocyte meiosis, and deletion of Nsun2 reduces oocyte maturation and increases the rates of misaligned chromosomes and aberrant spindles. In addition, Nsun2 deficiency results in a low blastocyst rate and impaired blastocyst quality. Strikingly, loss of Nsun2 leads to approximately 35% of embryos being blocked at the 2-cell stage, and Nsun2 knockdown impairs zygotic genome activation at the 2-cell stage. Taken together, these findings suggest that NSUN2 plays a critical role in mouse oocyte meiotic maturation and early embryonic development, and provide key resources for elucidating female infertility with NSUN2 mutations.

16.
Proc Natl Acad Sci U S A ; 121(37): e2402395121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39231202

RESUMEN

Entanglement in a soft condensed matter system is enabled in the form of entangled disclination lines by using colloidal particles in nematic liquid crystals. These topological excitations are manifested as colloidal entanglement at equilibrium. How to further utilize nonequilibrium disclination lines to manipulate colloidal entanglement remains a nontrivial and challenging task. In this work, we use experiments and simulations to demonstrate the reconfigurations of nematic colloidal entanglement in light-driven spatiotemporal evolutions of disclination lines. Colloidal entanglement can sense subtle changes in the topological structures of disclination lines and realize chirality conversion. This conversion is manifested as the "domino effect" of the collective rotation of colloids in the disclination lines. By programming the topological patterns and the geometry of the disclination lines, colloidal entanglement can be assembled and split. More remarkably, a double-helix entangled structure can be formed by controlling the changes in the morphology of the disclination lines. Thus, this work will provide opportunities to program colloidal composites for smart materials and micromachines.

17.
Food Funct ; 15(18): 9552-9562, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39225754

RESUMEN

Tea consumption is avoided by some due to concerns about its potential to cause anemia. To clarify this impact, we assessed the association between tea intake and anemia in a Chinese prospective cohort study and by Mendelian randomization (MR). We analyzed associations of tea intake with anemia using data from the baseline (N = 30 085) and three subsequent follow-ups (the first: N = 17 898; the second: N = 10 435; the third: N = 5311) in the Guangzhou Biobank Cohort Study (GBCS). We also assessed the causal effect of tea intake on anemia, hemoglobin (Hgb) and hematocrit (Hct) using two-sample MR with summary statistics from relevant genome-wide association studies and the UK Biobank (N = 447 485). At the baseline, compared with never-drinkers, regular tea drinkers had higher levels of Hgb and Hct and a lower risk of anemia after adjustment for confounders (all P < 0.05; all P for trend ≤0.006). Prospectively, compared with never-drinkers, regular tea drinkers had higher Hgb (g L-1) (ß = 0.69; 95% CI, 0.28 to 1.10; P for trend <0.001) and Hct (%) (ß = 0.30; 95% CI, 0.19 to 0.41; P for trend <0.001), but no significant difference in anemia risk (OR = 0.91; 95% CI, 0.82 to 1.02; P for trend = 0.071). MR analyses showed no association between tea intake and anemia, Hgb and Hct. Through triangulation of evidence using a Chinese cohort and genetics, tea consumption appears unlikely to impact anemia risk.


Asunto(s)
Anemia , Hemoglobinas , Análisis de la Aleatorización Mendeliana , , Humanos , Persona de Mediana Edad , Femenino , Masculino , Estudios Prospectivos , Anemia/epidemiología , Anciano , Hemoglobinas/metabolismo , Hemoglobinas/análisis , China/epidemiología , Adulto , Factores de Riesgo , Estudio de Asociación del Genoma Completo , Estudios de Cohortes
18.
JAMA Neurol ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250132

RESUMEN

Importance: The X chromosome has remained enigmatic in Alzheimer disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD. Objectives: To perform the first large-scale X chromosome-wide association study (XWAS) of AD. Design, Setting, and Participants: This was a meta-analysis of genetic association studies in case-control, family-based, population-based, and longitudinal AD-related cohorts from the US Alzheimer's Disease Genetics Consortium, the Alzheimer's Disease Sequencing Project, the UK Biobank, the Finnish health registry, and the US Million Veterans Program. Risk of AD was evaluated through case-control logistic regression analyses. Data were analyzed between January 2023 and March 2024. Genetic data available from high-density single-nucleotide variant microarrays and whole-genome sequencing and summary statistics for multitissue expression and protein quantitative trait loci available from published studies were included, enabling follow-up genetic colocalization analyses. A total of 1 629 863 eligible participants were selected from referred and volunteer samples, 477 596 of whom were excluded for analysis exclusion criteria. The number of participants who declined to participate in original studies was not available. Main Outcome and Measures: Risk of AD, reported as odds ratios (ORs) with 95% CIs. Associations were considered at X chromosome-wide (P < 1 × 10-5) and genome-wide (P < 5 × 10-8) significance. Primary analyses are nonstratified, while secondary analyses evaluate sex-stratified effects. Results: Analyses included 1 152 284 participants of non-Hispanic White, European ancestry (664 403 [57.7%] female and 487 881 [42.3%] male), including 138 558 individuals with AD. Six independent genetic loci passed X chromosome-wide significance, with 4 showing support for links between the genetic signal for AD and expression of nearby genes in brain and nonbrain tissues. One of these 4 loci passed conservative genome-wide significance, with its lead variant centered on an intron of SLC9A7 (OR, 1.03; 95% CI, 1.02-1.04) and colocalization analyses prioritizing both the SLC9A7 and nearby CHST7 genes. Of these 6 loci, 4 displayed evidence for escape from X chromosome inactivation with regard to AD risk. Conclusion and Relevance: This large-scale XWAS of AD identified the novel SLC9A7 locus. SLC9A7 regulates pH homeostasis in Golgi secretory compartments and is anticipated to have downstream effects on amyloid ß accumulation. Overall, this study advances our knowledge of AD genetics and may provide novel biological drug targets. The results further provide initial insights into elucidating the role of the X chromosome in sex-based differences in AD.

19.
Clin Respir J ; 18(9): e70000, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39275901

RESUMEN

INTRODUCTION: Immunotherapy has revolutionized the management of lung cancer and improved lung cancer survival in trials, but its real-world impact at the population level remains unclear. METHODS: Using data obtained from eight Surveillance, Epidemiology, and End Results (SEER) registries from 2004 through 2019, we addressed the long-term trends in the incidence, incidence-based mortality (IBM), and survival of lung cancer patients in the United States. RESULTS: The incidence and IBM of both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) all significantly decreased steadily from 2004 to 2019. The 1-year survival (1-YS) of both NSCLC and SCLC improved over time, with the best improvement observed for Stage 4 NSCLC. Two significant turning points of Stage 4 NSCLC 1-YS were observed over the years: 0.63% (95% confidence interval [CI]: 0.33%-0.93%) from 2004 to 2010, 0.81% (95% CI: 0.41%-1.21%) from 2010 to 2014 and a striking 2.09% (95% CI: 1.70%-2.47%) from 2014 to 2019. The same two turning points in 1-YS were pronounced for Stage 4 NSCLC in women, which were coincident with the introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immunotherapy. However, for Stage 4 NSCLC in men, only one significant turning point in the 1-YS starting in 2014 was found, which might only correspond to immunotherapy. Significant period effects in reduced IBM were also observed for both Stage 4 AD and Stage 4 SQCC during the period. CONCLUSION: This SEER analysis found that immunotherapy improved the survival of Stage 4 NSCLC patients at the population level in the United States. This real-world evidence confirms that immunotherapy has truly revolutionized the management of lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Estadificación de Neoplasias , Programa de VERF , Humanos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Masculino , Femenino , Estados Unidos/epidemiología , Inmunoterapia/métodos , Anciano , Persona de Mediana Edad , Tasa de Supervivencia/tendencias , Incidencia
20.
Food Chem ; 463(Pt 2): 141194, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39278074

RESUMEN

Protein deterioration caused by ice crystals is an important factors affecting the frozen storage of fish. In this study, antifreeze peptides extracted from hydrolysates of sea cucumber intestinal protein with inhibition of protein denaturation were screened and characterized. The peptide Leu-Pro-Glu-Phe-Thr-Glu-Glu-Glu-Lys (LPEFTEEEK), derived from neutral protease hydrolysates of sea cucumber intestinal protein, was investigated for its potential to enhance the quality of salmon fillets during three freeze-thaw cycles. The results showed that the application of LPEFTEEEK effectively maintained the texture of fish fillets, as well as the oxidative and conformation stability of myofibrillar protein during the freezing process. Additionally, molecular dynamics simulations verified that LPEFTEEEK could bind to ice crystals and inhibit their recrystallization, thus preventing organisms from being damaged by freezing. This suggests that LPEFTEEEK holds significant promise as a novel cryoprotective agent for marine-derived antifreeze peptides.

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