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1.
medRxiv ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38798318

RESUMEN

Understanding the genetic basis of gene expression can help us understand the molecular underpinnings of human traits and disease. Expression quantitative trait locus (eQTL) mapping can help in studying this relationship but have been shown to be very cell-type specific, motivating the use of single-cell RNA sequencing and single-cell eQTLs to obtain a more granular view of genetic regulation. Current methods for single-cell eQTL mapping either rely on the "pseudobulk" approach and traditional pipelines for bulk transcriptomics or do not scale well to large datasets. Here, we propose SAIGE-QTL, a robust and scalable tool that can directly map eQTLs using single-cell profiles without needing aggregation at the pseudobulk level. Additionally, SAIGE-QTL allows for testing the effects of less frequent/rare genetic variation through set-based tests, which is traditionally excluded from eQTL mapping studies. We evaluate the performance of SAIGE-QTL on both real and simulated data and demonstrate the improved power for eQTL mapping over existing pipelines.

2.
Front Endocrinol (Lausanne) ; 15: 1373363, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808107

RESUMEN

Objectives: To explore the correlation between the vessel density (VD) of the retina and choroid vascular plexuses and the thicknesses of their respective retinal layers and choroid membranes in participants with severe non-proliferative diabetic retinopathy (NPDR). Methods: We retrospectively analyzed the data of 42 eyes of 42 participants with diabetes mellitus (DM) and severe NPDR. In addition, 41 eyes of 41 healthy controls were evaluated. Measurements were taken for both groups using optical coherence tomography angiography (OCTA), including the area and perimeter of the foveal vascular zone (FAZ) and the vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choroid capillary (CC). These measurements were compared with the retinal thickness (RT) of the inner/intermediate retinal layers and choroidal thickness (CT). The study evaluated the correlation between RT or CT and VD in the respective vascular networks, namely superficial capillary plexus (SCP), deep capillary plexus (DCP), or CC. Results: The inner RT and VD in all plexuses were significantly lower in the severe NPDR group than in the healthy controls. Furthermore, the FAZ area and perimeter were larger in the severe NPDR group. Inner RT was correlated with VD in the SCP group (r=0.67 and r=0.71 in the healthy control and severe NPDR groups, respectively; p<0.05). CT negatively correlated with VD in the CC (r=-0.697 and r=-0.759 in the healthy control and severe NPDR groups, respectively; p<0.05). Intermediate RT significantly correlated with VD in the DCP of the severe NPDR group (r=-0.55, p<0.05), but not in the healthy control group. Conclusions: Retinal or choroidal thickness strongly correlated with VD. Therefore, patients with severe NPDR must consider the distinct anatomical and functional entities of the various retinal layers and the choroid.


Asunto(s)
Coroides , Retinopatía Diabética , Retina , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Retinopatía Diabética/diagnóstico por imagen , Retinopatía Diabética/patología , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Coroides/patología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Retina/patología , Retina/diagnóstico por imagen , Anciano , Adulto , Densidad Microvascular , Estudios de Casos y Controles , Índice de Severidad de la Enfermedad , Angiografía con Fluoresceína/métodos
3.
Org Lett ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38809099

RESUMEN

A mild copper-catalyzed asymmetric Kinugasa/Michael addition cascade process is developed. The reaction of α, ß-unsaturated ester-tethered propiolamides with nitrones provides an efficient protocol for the construction of functionalized chiral 2,6-diazaspiro[3.4]octane-1,5-dione products in satisfactory yields and with high enantio- and diastereoselectivities.

4.
J Clin Invest ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38781024

RESUMEN

PTEN inactivation is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Herein, we report that PTEN deficiency induces KLF5 acetylation; and interruption of KLF5 acetylation orchestrates intricate interactions between cancer cells and CAFs that enhance FGFR1 signaling and promote tumor growth. Deacetylated KLF5 promotes tumor cells to secrete TNF-α, which stimulates inflammatory CAFs to release FGF9. CX3CR1 inhibition blocks FGFR1 activation triggered by FGF9 and sensitizes PTEN-deficient prostate cancer to AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rational for combined therapies using inhibitors of AKT and CX3CR1.

5.
Biochim Biophys Acta Mol Cell Res ; : 119751, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38776988

RESUMEN

Akkermansia muciniphila (A. muciniphila), a probiotic, has been linked to macrophage phenotypic polarization in different diseases. However, the role and mechanisms of A. muciniphila in regulating macrophage during ulcerative colitis (UC) are not clear. This research aimed to examine the impact of A. muciniphila on dextran sulfate sodium (DSS)-induced acute colitis and elucidate the underlying mechanism related to macrophage phenotypic polarization. A. muciniphila inhibited weight loss, increased disease activity index, and ameliorated inflammatory injury in colonic tissues in mice induced with DSS. Furthermore, A. muciniphila reduced macrophage M1 polarization and ameliorated epithelial barrier damage in colonic tissues of DSS-induced mice through inhibition of histone deacetylase 5 (HDAC5). In contrast, the effect of A. muciniphila was compromised by HDAC5 overexpression. HDAC5 deacetylated H3K9ac modification of the disabled homolog 2 (DAB2) promoter, which led to repressed DAB2 expression. DAB2 overexpression blocked HDAC5-induced pro-inflammatory polarization of macrophages, whereas knockdown of DAB2 resulted in the loss of effects of A. muciniphila against colonic injury in DSS-induced mice. Taken together, A. muciniphila-induced loss of HDAC5 hampered the deacetylation of DAB2 and enhanced the expression of DAB2. Our findings propose that A. muciniphila may be a possible probiotic agent for alleviating DSS-induced acute colitis.

6.
BMC Med Imaging ; 24(1): 116, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773384

RESUMEN

OBJECTIVE: Evaluation of the predictive value of one-stop energy spectrum and perfusion CT parameters for microvessel density (MVD) in colorectal cancer cancer foci. METHODS: Clinical and CT data of 82 patients with colorectal cancer confirmed by preoperative colonoscopy or surgical pathology in our hospital from September 2019 to November 2022 were collected and analyzed retrospectively. Energy spectrum CT images were measured using the Protocols general module of the GSI Viewer software of the GE AW 4.7 post-processing workstation to measure the CT values of the arterial and venous phase lesions and the neighboring normal intestinal wall in a single energy range of 40 kev∼140 kev, and the slopes of the energy spectrum curves (λ) were calculated between 40 kev-90 kev; Iodine concentration (IC), Water concentration (WC), Effective-Z (Eff-Z) and Normalized iodine concentration (NIC) were measured by placing a region of interest (ROI) on the iodine concentration map and water concentration map at the lesion and adjacent to the normal intestinal wall.Perfusion CT images were scanned continuously and dynamically using GSI Perfusion software and analyzed by applying CT Perfusion 4.0 software.Blood volume (BV), blood flow (BF), surface permeability (PS), time to peak (TTP), and mean transit time (MTT) were measured respectively in the lesion and adjacent normal colorectal wall. Based on the pathological findings, the tumors were divided into a low MVD group (MVD < 35/field of view, n = 52 cases) and a high MVD group (MVD ≥ 35/field of view, n = 30 cases) using a median of 35/field of view as the MVD grouping criterion. The collected data were statistically analyzed, the subjects' operating characteristic curve (ROC) was plotted, and the area under curve (AUC), sensitivity, specificity, and Yoden index were calculated for the predicted efficacy of each parameter of the energy spectrum and perfusion CT and the combined parameters. RESULTS: The CT values, IC, NIC, λ, Eff-Z of 40kev∼140kev single energy in the arterial and venous phase of colorectal cancer in the high MVD group were higher than those in the low MVD group, and the differences were all statistically significant (p < 0.05). The AUC of each single-energy CT value in the arterial phase from 40 kev to 120 kev for determining the high or low MVD of colorectal cancer was greater than 0.8, indicating that arterial stage has a good predictive value for high or low MVD in colorectal cancer; AUC for arterial IC, NIC and IC + NIC were all greater than 0.9, indicating that in arterial colorectal cancer, both single and combined parameters of spectral CT are highly effective in predicting the level of MVD. The AUC of 40 kev to 90 kev single-energy CT values in the intravenous phase was greater than 0.9, and its diagnostic efficacy was more representative; The AUC of IC and NIC in venous stage were greater than 0.8, which indicating that the IC and NIC energy spectrum parameters in venous stage colorectal cancer have a very good predictive value for the difference between high and low MVDs, with the greatest diagnostic efficacy in IC.The values of BV and BF in the high MVD group were higher than those in the low MVD group, and the differences were statistically significant (P < 0.05), and the AUC of BF, BV, and BV + BF were 0.991, 0.733, and 0.997, respectively, with the highest diagnostic efficacy for determining the level of MVD in colorectal cancer by BV + BF. CONCLUSION: One-stop CT energy spectrum and perfusion imaging technology can accurately reflect the MVD in living tumor tissues, which in turn reflects the tumor angiogenesis, and to a certain extent helps to determine the malignancy, invasion and metastasis of living colorectal cancer tumor tissues based on CT energy spectrum and perfusion parameters.


Asunto(s)
Neovascularización Patológica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neovascularización Patológica/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Adulto , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/irrigación sanguínea , Neoplasias del Recto/patología , Anciano de 80 o más Años , Densidad Microvascular , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/patología , Valor Predictivo de las Pruebas , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/irrigación sanguínea , Angiogénesis
7.
BMC Gastroenterol ; 24(1): 176, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773485

RESUMEN

BACKGROUND: Angiogenesis is a critical step in colorectal cancer growth, progression and metastasization. CT are routine imaging examinations for preoperative clinical evaluation in colorectal cancer patients. This study aimed to investigate the predictive value of preoperative CT enhancement rate (CER) and CT perfusion parameters on angiogenesis in colorectal cancer, as well as the association of preoperative CER and CT perfusion parameters with serum markers. METHODS: This retrospective analysis included 42 patients with colorectal adenocarcinoma. Median of microvessel density (MVD) as the cut-off value, it divided 42 patients into high-density group (MVD ≥ 35/field, n = 24) and low-density group (MVD < 35/field, n = 18), and 25 patients with benign colorectal lesions were collected as the control group. Statistical analysis of CER, CT perfusion parameters, serum markers were performed in all groups. Receiver operating curves (ROC) were plotted to evaluate the diagnostic efficacy of relevant CT perfusion parameters for tumor angiogenesis; Pearson correlation analysis explored potential association between CER, CT perfusion parameters and serum markers. RESULTS: CER, blood volume (BV), blood flow (BF), permeability surface (PS) and carbohydrate antigen 19 - 9 (CA19-9), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), trefoil factor 3 (TFF3), vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma were significantly higher than those in the control group, the parameters in high-density group were significantly higher than those in the low-density group (P < 0.05); however, the time to peak (TTP) of patients in colorectal adenocarcinoma were significantly lower than those in the control group, and the high-density group showed a significantly lower level compared to the low-density group (P < 0.05). The combined parameters BF + TTP + PS and BV + BF + TTP + PS demonstrated the highest area under the curve (AUC), both at 0.991. Pearson correlation analysis showed that the serum levels of CA19-9, CA125, CEA, TFF3, and VEGF in patients showed positive correlations with CER, BV, BF, and PS (P < 0.05), while these indicators exhibited negative correlations with TTP (P < 0.05). CONCLUSIONS: Some single and joint preoperative CT perfusion parameters can accurately predict tumor angiogenesis in colorectal adenocarcinoma. Preoperative CER and CT perfusion parameters have certain association with serum markers.


Asunto(s)
Adenocarcinoma , Antígeno Carcinoembrionario , Neoplasias Colorrectales , Neovascularización Patológica , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/irrigación sanguínea , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adenocarcinoma/irrigación sanguínea , Anciano , Neovascularización Patológica/diagnóstico por imagen , Neovascularización Patológica/sangre , Tomografía Computarizada por Rayos X/métodos , Antígeno Carcinoembrionario/sangre , Biomarcadores de Tumor/sangre , Adulto , Densidad Microvascular , Antígeno CA-19-9/sangre , Curva ROC , Factor A de Crecimiento Endotelial Vascular/sangre , Volumen Sanguíneo , Cuidados Preoperatorios/métodos
8.
Rev Assoc Med Bras (1992) ; 70(5): e20231694, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38775515

RESUMEN

OBJECTIVE: The objective of this study was to explore the relationship between serum soluble fms-like tyrosine kinase 1 and the severity of acute pancreatitis and its diagnostic utility. METHODS: This study was carried out by searching Chinese and English literature from the establishment of the database to July 9, 2023, systematically, and assessing the quality and heterogeneity of the articles included. RESULTS: Thirteen studies with a total of 986 patients were included. Patients with severe acute pancreatitis showed higher levels of soluble fms-like tyrosine kinase 1 compared with mild acute pancreatitis [weighted mean difference=76.64 pg/mL, 95% confidence interval (95%CI 50.39-102.89, p<0.001)]. Soluble fms-like tyrosine kinase 1 predicted pooled sensitivity, specificity, and area under the curve were 79%, 74%, and 0.85 for severe acute pancreatitis, with some heterogeneity (I2>50% or p<0.05). In the subgroup analysis, cutoff >150 pg/mL was found to be a heterogeneous factor. CONCLUSION: Soluble fms-like tyrosine kinase 1 is a reliable tool for identifying acute pancreatitis severity, but only as a screening tool.


Asunto(s)
Biomarcadores , Pancreatitis , Índice de Severidad de la Enfermedad , Humanos , Pancreatitis/sangre , Pancreatitis/diagnóstico , Enfermedad Aguda , Biomarcadores/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Sensibilidad y Especificidad , Valor Predictivo de las Pruebas
9.
Heliyon ; 10(10): e30910, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38778933

RESUMEN

According to the Standard of Chinese Medicinal Materials of Shaanxi Province (2015 edition), Salvia miltiorrhiza caulis et folium is the dried stems and leaves of Salvia miltiorrhiza, which could activate blood and dispell blood stasis, clear the mind and remove annoyance. In this study, the dynamic absorption changes of phenolic acids (FS) and phenolic acids-flavonoids (FT) in rats after oral administration were studied by UPLC-TQ/MS/MS, to elucidate the pharmacokinetics of seven major bioactive components of the stem-leaf of Salvia miltiorrhiza in vivo. The results showed that the pharmacokinetic parameters of FS and FT were significantly different in normal rats and model rats. Compared with the control group, after injecting 10 % polymer dextran 500 into the tail vein to establish a model of microcirculation disturbance, the Cmax of caffeic acid decreased. The Cmax of rosmarinic acid and lithospermic acid increased. Danshensu showed a decrease in CLz/F, accompanied by an increase in both AUC0-t and AUC0-∞. The AUC0-t of lithospermic acid was also increased. These results indicated that microcirculation disturbance could decrease the absorption of caffeic acid while increasing the absorption of danshensu, rosmarinic acid and lithospermic acid. After oral administration of FT, the Cmax of danshensu and the AUC0-t of caffeic acid were increased significantly, suggesting that the presence of flavonoids may promote the absorption and exposure of phenolic acids in vivo. This study provides a reference for the elucidation of the in vivo substances and the mechanisms of action of FS and FT from the stem-leaf of Salvia miltiorrhiza.

10.
Heliyon ; 10(9): e30363, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38694116

RESUMEN

Due to the importance of accurate diagnosis and prompt treatment of this condition, the medical world is searching for a solution for its early detection and efficient treatment. Heart disease is one of the leading causes of death in modern society. With the development of computer science today, this issue can be resolved using computers. Data mining is one of the solutions for diagnosing this illness. One of the cutting-edge disciplines, data mining, can aid in better decision-making in many areas of medicine, including disease diagnosis and treatment. In order to improve diagnosis accuracy, a combination method using the evolutionary algorithms locust and support vector machine has been tested in this study. Use should be made of heart disease. Because of the hybrid nature of this approach, normalization is actually carried out in three steps: first, by using pre-processing operations to remove unknown and outlier data from the data set; second, by using the locust evolutionary algorithm to choose the best features from the available features; and third, by classifying the data set using a support vector machine. The accuracy criterion for the proposed method compared to Niobizin methods, neural networks, and J48 trees improved by 18 %, 30 %, and 24 %, respectively, after implementing it on the data set and comparing it with other algorithms used in the field of heart disease diagnosis.

11.
Clin Immunol ; 264: 110234, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38740111

RESUMEN

BACKGROUND: Natural anti-cytokine autoantibodies can regulate homeostasis of infectious and inflammatory diseases. The anti-cytokine autoantibody profile and relevance to the pathogenesis of asthma are unknown. We aim to identify key anti-cytokine autoantibodies in asthma patients, and reveal their immunological function and clinical significance. METHODS: A Luciferase Immunoprecipitation System was used to screen serum autoantibodies against 11 key cytokines in patients with allergic asthma and healthy donors. The antigen-specificity, immunomodulatory functions and clinical significance of anti-cytokine autoantibodies were determined by ELISA, qPCR, neutralization assays and statistical analysis, respectively. Potential conditions for autoantibody induction were revealed by in vitro immunization. RESULTS: Of 11 cytokines tested, only anti-IL-33 autoantibody was significantly increased in asthma, compare to healthy controls, and the proportion positive was higher in patients with mild-to-moderate than severe allergic asthma. In allergic asthma patients, the anti-IL-33 autoantibody level correlated negatively with serum concentration of pathogenic cytokines (e.g., IL-4, IL-13, IL-25 and IL-33), IgE, and blood eosinophil count, but positively with mid-expiratory flow FEF25-75%. The autoantibodies were predominantly IgG isotype, polyclonal and could neutralize IL-33-induced pathogenic responses in vitro and in vivo. The induction of the anti-IL-33 autoantibody in blood B-cells in vitro required peptide IL-33 antigen along with a stimulation cocktail of TLR9 agonist and cytokines IL-2, IL-4 or IL-21. CONCLUSIONS: Serum natural anti-IL-33 autoantibodies are selectively induced in some asthma patients. They ameliorate key asthma inflammatory responses, and may improve lung function of allergic asthma.

12.
Mol Genet Metab Rep ; 39: 101088, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38736698

RESUMEN

Isovaleric acidemia (IVA) is a rare autosomal recessive disorder that manifests as a deficiency of isovaleryl-CoA dehydrogenase (IVD), a key enzyme in leucine metabolism. The clinical presentations associated with IVD deficiency are variable and include feeding intolerance, vomiting, metabolic acidosis, ketonemia, "sweaty feet" odor, lethargy, coma and even death. Tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS) methods were used to perform organic acid analysis of blood and urine samples from IVA patients, and the genetic analysis included next generation sequencing (NGS) and Sanger sequencing of the IVD gene. Here, we report the case of an almost seven-year-old male patient from a Chinese family who was asymptomatic during the newborn period, including the clinical manifestations and examination results. Genetic analysis revealed a previously unreported compound heterozygous variant in the IVD gene: c.593G > C (p.W198S) and c.859C > T (p.R287W).

13.
J Ovarian Res ; 17(1): 98, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38725001

RESUMEN

Ovarian Hyperstimulation Syndrome (OHSS) is a systemic condition marked by the enlargement of the ovaries and heightened vascular permeability. And hypothyroidism (HT) emerges as a potential risk factor for OHSS occurrence. This review presented a comprehensive summary of pertinent case reports involving patients diagnosed with both HT and OHSS. Detailed exploration was conducted into their clinical presentations, diagnostic methodologies, and treatment modalities. Additionally, the review delved into potential interaction mechanisms between HT and OHSS, encompassing various aspects including hormone levels. Moreover, management strategies for mitigating the risk of OHSS in HT patients were thoroughly reviewed and the importance of monitoring thyroid function in those experiencing OHSS was emphasized. This review indicated that the association between HT and OHSS, underscoring its multifaceted complexity. It could accentuate the ongoing necessity for rigorous research and clinical refinement to deepen our comprehension of this association and to bolster diagnostic and therapeutic methodologies for optimal patient care. In conclusion, this review offered valuable insights for future research directions and clinical practices for patients afflicted with OHSS and HT.


Asunto(s)
Hipotiroidismo , Síndrome de Hiperestimulación Ovárica , Humanos , Síndrome de Hiperestimulación Ovárica/complicaciones , Síndrome de Hiperestimulación Ovárica/terapia , Síndrome de Hiperestimulación Ovárica/etiología , Hipotiroidismo/complicaciones , Femenino , Factores de Riesgo
14.
Nanomaterials (Basel) ; 14(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38727341

RESUMEN

The rough morphology at the growth surface results in the non-uniform distribution of indium composition, intentionally or unintentionally doped impurity, and thus impacts the performance of GaN-based optoelectronic and vertical power electronic devices. We observed the morphologies of unintentionally doped GaN homo-epitaxially grown via MOCVD and identified the relations between rough surfaces and the miscut angle and direction of the substrate. The growth kinetics under the effect of the Ehrlich-Schwoebel barrier were studied, and it was found that asymmetric step motions in samples with a large miscut angle or those grown at high temperature were the causes of step-bunching. Meandering steps were believed to be caused by surface free energy minimization for steps with wide terraces or deviating from the [11¯00] m-direction.

15.
Cell Rep ; 43(5): 114231, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38733588

RESUMEN

Mutations in the SRCAP gene are among the genetic alterations identified in autism spectrum disorders (ASD). However, the pathogenic mechanisms remain unclear. In this study, we demonstrate that Srcap+/- mice manifest deficits in social novelty response, as well as increased repetitive behaviors, anxiety, and impairments in learning and memory. Notably, a reduction in parvalbumin-positive neurons is observed in the retrosplenial cortex (RSC) and dentate gyrus (DG) of these mice. Through RNA sequencing, we identify dysregulation in 27 ASD-related genes in Srcap+/- mice. Specifically, we find that Srcap regulates expression of Satb2 via H2A.z in the promoter. Therapeutic intervention via retro-orbital injection of adeno-associated virus (AAV)-Satb2 in neonatal Srcap+/- mice leads to amelioration of the neurodevelopmental and ASD-like abnormalities. Furthermore, the expression of Satb2 only in the RSC of adolescent mice rectifies social novelty impairments. These results underscore the pivotal role of Srcap in neurodevelopment, by regulating Satb2, providing valuable insights for the pathophysiology of ASD.

16.
Eur J Med Chem ; 271: 116461, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38691891

RESUMEN

Owing to the global health crisis of resistant pathogenic infections, researchers are emphasizing the importance of novel prevention and control strategies. Existing antimicrobial drugs predominantly target a few pathways, and their widespread use has pervasively increased drug resistance. Therefore, it is imperative to develop new antimicrobial drugs with novel targets and chemical structures. The de novo cysteine biosynthesis pathway, one of the microbial metabolic pathways, plays a crucial role in pathogenicity and drug resistance. This pathway notably differs from that in humans, thereby representing an unexplored target for developing antimicrobial drugs. Herein, we have presented an overview of cysteine biosynthesis pathways and their roles in the pathogenicity of various microorganisms. Additionally, we have investigated the structure and function of enzymes involved in these pathways as well as have discussed drug design strategies and structure-activity relationships of the enzyme inhibitors. This review provides valuable insights for developing novel antimicrobials and offers new avenues to combat drug resistance.


Asunto(s)
Cisteína , Descubrimiento de Drogas , Cisteína/metabolismo , Cisteína/química , Cisteína/biosíntesis , Humanos , Relación Estructura-Actividad , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Estructura Molecular , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/biosíntesis , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Pruebas de Sensibilidad Microbiana , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/metabolismo
17.
Angew Chem Int Ed Engl ; : e202400823, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735839

RESUMEN

Separating acetylene from carbon dioxide is important but highly challenging due to their similar molecular shapes and physical properties. Adsorptive separation of carbon dioxide from acetylene can directly produce pure acetylene but is hardly realized because of relatively polarizable acetylene binds more strongly. Here, we reverse the CO2 and C2H2 separation by adjusting the pore structures in two isoreticular ultramicroporous metal-organic frameworks (MOFs). Under ambient conditions, copper isonicotinate (Cu(ina)2), with relatively large pore channels shows C2H2-selective adsorption with a C2H2/CO2 selectivity of 3.4, whereas its smaller-pore analogue, copper quinoline-5-carboxylate (Cu(Qc)2) shows an inverse CO2/C2H2 selectivity of 5.6. Cu(Qc)2 shows compact pore space that well matches the optimal orientation of CO2 but is not compatible for C2H2. Neutron powder diffraction experiments confirmed that CO2 molecules adopt preferential orientation along the pore channels during adsorption binding, whereas C2H2 molecules bind in an opposite fashion with distorted configurations due to their opposite quadrupole moments. Dynamic breakthrough experiments have validated the separation performance of Cu(Qc)2 for CO2/C2H2 separation.

18.
Environ Pollut ; 351: 124090, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38697249

RESUMEN

Indoor formaldehyde poses a significant carcinogenic risk to human health, making its removal imperative. Electro-Fenton degradation has emerged as a promising technology for addressing this concern. In the electro-Fenton system, ·OH is identified as the primary active species responsible for formaldehyde removal. Hence, its generation and utilization are pivotal for the system's effectiveness and economy. Experimental and quantum chemical methods were employed to investigate the effects and mechanisms of nitrogen doping on various aspects influencing ·OH generation and utilization. Results indicate that nitrogen doping synergistically enhances the generation and utilization of ·OH, leading to an improved formaldehyde removal efficiency in nitrogen-doped cathodic systems. The dominant nitrogen type influencing ·OH generation and utilization varies across different stages. Pyridinic nitrogen facilitates H2O2 adsorption through hydrogen bonding, while pyrrolic and graphitic nitrogen contribute to formaldehyde adsorption and catalyze the conversion of H2O2 to ·OH. Both pyridinic nitrogen and pyrrolic nitrogen boost the degradation of formaldehyde by ·OH. In comparison to the unmodified system, the modified system with NAC-GF/700C as cathode exhibits remarkable improvements. The formaldehyde removal efficiency has increased twofold, and energy consumption reduced by 73.45%. Furthermore, the system demonstrates excellent cyclic stability. These advancements can be attributed to the activation temperature, which leads to the appropriate types and high content of nitrogen elements in NAC-GF/700C. The research represents an important step towards more economical and efficient electro-Fenton technology for indoor formaldehyde removal.

19.
Biosens Bioelectron ; 258: 116343, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38718636

RESUMEN

Recently, the non-covalently activated supramolecular scaffold method has become a prominent research area in the field of intelligent materials. Here, the inorganic clay (LP) promoted the AIE properties of 4,4',4″,4‴-(ethene-1,1,2,2-tetrayltetrakis(benzene-4,1-diyl))tetrakis(1-ethylpyridin-1-ium) (P-TPE), showing an astonishing 42-fold enhancement of the emission intensity of the yellow-green luminescence and a 34-fold increase of the quantum yield via organic-inorganic supramolecular strategy as well as the efficient light-harvesting properties (energy transfer efficiency up to 33 %) after doping with the dye receptor Rhodamine B. Furthermore, the full-color spectral regulation, including white light, was achieved by adjusting the ratio of the donor to the acceptor component and co-assembling with the carbon dots (CD). Interestingly, this TPE-based non-covalently activated full-color supramolecular light-harvesting system (LHS) could be achieved not only in aqueous media but also in the hydrogel and the solid state. More importantly, this panchromatic tunable supramolecular LHS exhibited the multi-mode and quadruple digital logic encryption property as well as the specific detection ability towards the perfluorobutyric acid and the perfluorobutanesulfonic acid, which are harmful to human health in drinking water. This result develops a simple, convenient and effective approach for the intelligent anti-counterfeiting and the pollutant sensing.


Asunto(s)
Técnicas Biosensibles , Contaminantes Químicos del Agua , Técnicas Biosensibles/métodos , Contaminantes Químicos del Agua/análisis , Colorantes Fluorescentes/química , Fluorocarburos/química , Luminiscencia , Silicatos/química , Rodaminas/química , Límite de Detección , Puntos Cuánticos/química
20.
Adv Mater ; : e2403447, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728424

RESUMEN

Artificial sensory systems with synergistic touch and pain perception hold substantial promise for environment interaction and human-robot communication. However, the realization of biological skin-like functional integration of sensors with sensitive touch and pain perception still remains a challenge. Here, a concept is proposed of suspended electronic skins enabling 3D deformation-mechanical contact interactions for achieving synergetic ultrasensitive touch and adjustable pain perception. The suspended sensory system can sensitively capture tiny touch stimuli as low as 0.02 Pa and actively perceive pain response with reliable 5200 cycles via 3D deformation and mechanical contact mechanism, respectively. Based on the touch-pain effect, a visualized feedback demo with miniaturized sensor arrays on artificial fingers is rationally designed to give a pain perception mapping on sharp surfaces. Furthermore, the capability is shown of the suspended electronic skin serving as a safe human-robot communication interface from active and passive view through a feedback control system, demonstrating potential in bionic electronics and intelligent robotics.

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