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1.
Medicine (Baltimore) ; 103(19): e38073, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728513

RESUMO

The objective of this study is to evaluate the pattern of bone mineral density (BMD) in native Jiaxing women, and to investigate their awareness of osteoporosis. A total of 538 native Jiaxing women aged 40 to 60 years were recruited from January 2022 to December 2023 when they had routine examinations in the physical examination center of Jiaxing Maternal and Child Health Hospital. The Chinese version of Osteoporosis Prevention and Cognition Tool was used to evaluate participants' cognitive level of osteoporosis. BMD of participants' lumbar spine (L1-L4) and left hip (Neck/Troch/Ward) was measured by dual-energy X-ray absorptiometry. The mean total score of the awareness about osteoporosis (general knowledge, complications, and prevention) was 22.08 ±â€…2.74, which was suboptimal. The higher the education level, the higher the score of awareness (P < .01). Medical staff had the highest awareness rate of osteoporosis and the farmer had the lowest. Lumber spine and hip BMD of all sites was significantly decreased with increasing age (P < .001). Premenopausal women had higher BMD than postmenopausal women at all lumbar spine and hip sites (P < .01). The overall frequency of osteoporosis was 10.8% in the lumbar spine, 8.6% in the total hip, and 17.7% in either site. Osteoporosis and osteopenia are highly prevalent among native Jiaxing women but their awareness of osteoporosis is inadequate. To reduce the prevalence of osteoporosis, especially among the unemployed, we should carry out effective health education through multimedia to raise their awareness of osteoporosis. In addition, menopausal hormone therapy should also be considered in menopausal women.


Assuntos
Absorciometria de Fóton , Densidade Óssea , Conhecimentos, Atitudes e Prática em Saúde , Vértebras Lombares , Osteoporose , Humanos , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Osteoporose/epidemiologia , Vértebras Lombares/diagnóstico por imagem
2.
J Colloid Interface Sci ; 669: 679-687, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38733879

RESUMO

Nanoscale graphene-semiconductor composite photocatalysts with fascinating properties in the photocatalytic hydrogen evolution have inspired numerous interests in broad research fields. The architectures with efficient light response and promoting charge separation at the interface between reduced graphene oxide (RGO) and semiconductor are critical, yet synthesizing them remains a formidable challenge. Herein, the photodiode array-like LaNiO3/N,P-RGO (LNO/N,P-RGO) nanoreactor was constructed using an innovative strategy of acid etching-induced nanocutting self-assembly. Ammonium dihydrogen phosphate working as both a nitrogen phosphorus co-dopant and an acid etching reagent, cuts perovskite LaNiO3 (LNO) nanoparticles into nanorods, which are bonded evenly on the nitrogen phosphorus co-doped reduced graphene oxide (N,P-RGO) to form an n-n semiconductor heterojunction LNO/N,P-RGO as a photodiode array-like nanoreactor via hydrothermal treatment. The photodiode array-like nanostructure exposes more active sites that are conducive to light absorption. The robust Ni-C and P-O bonds promote the narrowing of space-charge region at the interface by UV irradiation, thereby improving the transport of photogenerated carriers by visible light irradiation. The LNO/N,P-RGO nanoreactor exhibits excellent photocatalytic hydrogen evolution performance with a yield of up to 354 µmol g-1 h-1 under UV-visible light, which is 50 times higher than that of pure perovskite LNO, and it also displays favorable recycling stability.

3.
Natl Sci Rev ; 11(6): nwae147, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38746688

RESUMO

A small fraction of NOx (<1%) always exists in CO2 feedstock (e.g. exhausted gas), which can significantly reduce the efficiency of CO2 electroreduction by ∼30%. Hence, electrochemical denitrification is the precondition of CO2 electroreduction. The pH effect is a key factor, and can be used to tune the selectivity between N2 and N2O production in electrochemical denitrification. However, there has been much controversy for many years about the origin of pH dependence in electrocatalysis. To this end, we present a new scheme to accurately model the pH dependence of the electrochemical mechanism. An extremely small pH variation from pH 12.7 to pH 14 can be accurately reproduced for N2O production. More importantly, the obviously different pH dependence of N2 production, compared to N2O, can be attributed to a cascade path. In other words, the N2 was produced from the secondary conversion of the as-produced N2O molecule (the major product), instead of the original reactant NO. This is further supported by more than 35 experiments over varying catalysts (Fe, Ni, Pd, Cu, Co, Pt and Ag), partial pressures (20%, 50% and 100%) and potentials (from -0.2 to 0.2 V vs. reversible hydrogen electrode). All in all, the insights herein overturn long-lasting views in the field of NO electroreduction and suggest that rational design should steer away from catalyst engineering toward reactor optimization.

4.
BMC Anesthesiol ; 24(1): 174, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745175

RESUMO

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Relação Dose-Resposta a Droga , Duodenoscópios , Hipnóticos e Sedativos , Humanos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Masculino , Feminino , Hipnóticos e Sedativos/administração & dosagem , Idoso , Alfentanil/administração & dosagem , Pessoa de Meia-Idade , Benzodiazepinas/administração & dosagem
5.
J Am Chem Soc ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38723620

RESUMO

It has been reported that it was selective to produce ammonia on metallic cobalt in the electrocatalytic nitric oxide reduction reaction (eNORR), where hexagonal close-packed (hcp) cobalt outperforms face-centered cubic (fcc) cobalt. However, hydroxylamine is more selectively produced on a cobalt single-atom catalyst (Co-SAC). Herein, we uncover the structural sensitivity over hcp-Co, fcc-Co, and Co-SAC in eNORR by employing a recently developed constant potential simulation method and microkinetic modeling. It was found that the superior activity for ammonia production on hcp-Co can be attributed to its facile electron and proton transfer and a stronger lateral suppression effect from NO* over fcc-Co. The exceptional hydroxylamine selectivity on Co-SAC is due to the modified electronic structure, namely, a positively charged active center. It was found that it is more favorable to produce NOH* over hcp-Co and fcc-Co, while HNO* is more preferable on Co-SAC, which are firmly correlated with the vertical and strong NO adsorption on the former and the moderate adsorption on the latter. In other words, a key factor for selectivity control is the first step of NO* protonation. Therefore, the local structure and electronic structure of the catalysts can be critical in regulating the activity and selectivity in eNORR.

6.
Waste Manag ; 182: 271-283, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38688046

RESUMO

High water and pharmaceutical and care products (PPCPs) bounded in sludge flocs limit its utilization and disposal. The advanced oxidation process of perxymonosulfate (PMS) catalyzed by iron salts has been widely used in sludge conditioning. In this study, two iron-rich minerals pyrite and siderite were proposed to enhance sludge dewatering performance and remove the target contaminant of triclosan (TCS). The permanent release of Fe2+ in the activation of PMS made siderite more effective in enhancing sludge dewater with capillary suction time (CST) diminishing by 60.5 %, specific resistance to filtration (SRF) decreasing by 79.2 %, and bound water content (BWC) dropping from 37.1 % to 2.6 % at siderite/PMS dosages of 0.36/0.20 mmol/g-TSS after 20 min of pretreatment. Pyrite/PMS performed slightly inferior under the same conditions and the corresponding CST and SRF decreased by 51.5 % and 71.8 % while the BWC only declined to 17.8 %. Rheological characterization was employed to elucidate the changes in sludge dewatering performance, with siderite/PMS treated sludge showing a 48.3 % reduction in thixotropy, higher than 28.4 % of pyrite/PMS. Oscillation and creep tests further demonstrated the significantly weakened viscoelastic behavior of the sludge by siderite/PMS pretreatment. For TCS mineralization removal, siderite/PMS achieved a high removal efficiency of 43.9 %, in comparison with 39.9 % for pyrite/PMS. The reduction in the sludge solids phase contributed the most to the TCS removal. Free radical quenching assays and EPR spectroscopy showed that both siderite/PMS and pyrite/PMS produced SO4-·  and ·OH, with the latter acting as the major radicals. Besides, the dosage of free radicals generated from siderite/PMS exhibited a lower time-dependence, which also allowed it to outperform in destroying EPS matrix, neutralizing the negative Zeta potential of sludge flocs, and mineralizing macromolecular organic matter.


Assuntos
Ferro , Peróxidos , Esgotos , Triclosan , Eliminação de Resíduos Líquidos , Esgotos/química , Triclosan/química , Ferro/química , Eliminação de Resíduos Líquidos/métodos , Peróxidos/química , Poluentes Químicos da Água/química , Minerais/química , Oxirredução
7.
Sci Total Environ ; 929: 172351, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38615783

RESUMO

Whole-lake microalgal biomass surveys were carried out in Lake Balaton to investigate the seasonal, spatial, and temporal changes of benthic algae, as well as to identify the drivers of the phytobenthos. Phytobenthos was controlled mainly by light: the highest benthic algal biomass was in the shallow littoral region characterized by large grain size (sand) with good light availability but lower nutrient content in the sediment. During the investigated period, phytoplankton biomass showed a significant decrease in almost the entire lake. At the same time, the biomass of benthic algae increased significantly in the eastern areas, increasing the contribution of total lake microalgae biomass (from 20 % to 27 %). Benthic algal biomass increase can be explained by the better light supply, owing to the artificially maintained high water level which greatly mitigates water mixing. The decrease in planktonic algal biomass could be attributed to increased zooplankton grazing, which is otherwise negatively affected by mixing. As a result of the high water level, the trophic structure of the lake has been rearranged in recent decades with a shift from the planktonic life form to the benthic one while the nutrient supply has largely remained unchanged.


Assuntos
Biomassa , Monitoramento Ambiental , Lagos , Microalgas , Microalgas/fisiologia , Lagos/química , Fitoplâncton , Plâncton , Zooplâncton , Eutrofização
8.
Biochem Genet ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656671

RESUMO

Elderly patients infected with severe acute respiratory syndrome coronavirus 2 are at higher risk of severe clinical manifestation, extended hospitalization, and increased mortality. Those patients are more likely to experience persistent symptoms and exacerbate the condition of basic diseases with long COVID-19 syndrome. However, the molecular mechanisms underlying severe COVID-19 in the elderly patients remain unclear. Our study aims to investigate the function of the interaction between disease-characteristic genes and immune cell infiltration in patients with severe COVID-19 infection. COVID-19 datasets (GSE164805 and GSE180594) and aging dataset (GSE69832) were obtained from the Gene Expression Omnibus database. The combined different expression genes (DEGs) were subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Diseases Ontology functional enrichment analysis, Gene Set Enrichment Analysis, machine learning, and immune cell infiltration analysis. GO and KEGG enrichment analyses revealed that the eight DEGs (IL23A, PTGER4, PLCB1, IL1B, CXCR1, C1QB, MX2, ALOX12) were mainly involved in inflammatory mediator regulation of TRP channels, coronavirus disease-COVID-19, and cytokine activity signaling pathways. Three-degree algorithm (LASSO, SVM-RFE, KNN) and correlation analysis showed that the five DEGs up-regulated the immune cells of macrophages M0/M1, memory B cells, gamma delta T cell, dendritic cell resting, and master cell resisting. Our study identified five hallmark genes that can serve as disease-characteristic genes and target immune cells infiltrated in severe COVID-19 patients among the elderly population, which may contribute to the study of pathogenesis and the evaluation of diagnosis and prognosis in aging patients infected with severe COVID-19.

9.
iScience ; 27(5): 109698, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38655198

RESUMO

Mounting evidence supports the role of neuroinflammation in radiation-induced brain injury (RIBI), a chronic disease characterized by delayed and progressive neurological impairment. Asparagine endopeptidase (AEP), also known as legumain (LGMN), participates in multiple malignancies and neurodegenerative diseases and may potentially be involved in RIBI. Here, we found AEP expression was substantially elevated in the cortex and hippocampus of wild-type (Lgmn+/+) mice following whole-brain irradiation. Lgmn knockout (Lgmn-/-) alleviated neurological impairment caused by whole-brain irradiation by suppressing neuronal senescence. Bulk RNA and metabolomic sequencing revealed AEP's involvement in the antigen processing and presentation pathway and neuroinflammation. This was further confirmed by co-culturing Lgmn+/+ primary neurons with the conditioned media derived from irradiated Lgmn+/+ or Lgmn-/- primary microglia. Furthermore, esomeprazole inhibited the enzymatic activity of AEP and RIBI. These findings identified AEP as a critical factor of neuroinflammation in RIBI, highlighting the prospect of targeting AEP as a therapeutic approach.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38663025

RESUMO

OBJECTIVE: Personalized precision medicine can be facilitated by clinically available preoperative microvascular invasion (MVI) prediction models that are reliable and postoperative MVI pathological grade-related recurrence prediction models that are accurate. In this study, we aimed to compare different mathematical models to derive the best preoperative prediction and postoperative recurrence prediction models for MVI. METHODS: A total of 143 patients with hepatocellular carcinoma (HCC) whose clinical, laboratory, imaging, and pathological data were available were included in the analysis. Logistic regression, Cox proportional hazards regression, LASSO regression with 10-fold cross-validation, stepwise regression, and random forest methods were used for variable screening and predictive modeling. The accuracy and validity of seven preoperative MVI prediction models and five postoperative recurrence prediction models were compared in terms of C-index, net reclassification improvement, and integrated discrimination improvement. RESULTS: Multivariate logistic regression analysis revealed that a preoperative nomogram model with the variables cirrhosis diagnosis, alpha-fetoprotein > 400, and diameter, shape, and number of lesions can predict MVI in patients with HCC reliably. Postoperatively, a nomogram model with MVI grade, number of lesions, capsule involvement status, macrovascular invasion, and shape as the variables was selected after LASSO regression and 10-fold cross-validation analysis to accurately predict the prognosis for different MVI grades. The number and shape of the lesions were the most common predictors of MVI preoperatively and recurrence postoperatively. CONCLUSIONS: Our study identified the best statistical approach for the prediction of preoperative MVI as well as postoperative recurrence in patients with HCC based on clinical, imaging, and laboratory tests results. This could expedite preoperative treatment decisions and facilitate postoperative management.

11.
Tree Physiol ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676919

RESUMO

Studying the response of physiological and xylem anatomical traits under cadmium (Cd) stress is helpful to understand plants' response to heavy metal stress. Here, seedlings of Pinus thunbergii were treated with 50, 100 and 150 mg/kg Cd2+ for 28 days. Cd and nonstructural carbohydrate (NSC) content of leaves, stems and roots, root Cd2+ flux, Cd distribution pattern in stem xylem and phloem, stem xylem hydraulic traits, cell wall component fractions of stems and roots, phytohormonal content such as abscisic acid (ABA), gibberellic acid 3 (GA3), molecule -indole-3-acetic acid (IAA) and jasmonic acid (JA) from both leaves and roots, as well as xylem anatomical traits from both stems and roots were measured. Root Cd2+ flux increased from 50 to 100 mmol/L Cd2+ stress, however, decreased at 150 mmol/LCd2+. Cellulose and hemicellulose in leaves, stems and roots did not change significantly under Cd stress, while pectin decreased significantly. The NSC content of both leaves and stems showed significant changes under Cd stress while the root NSC content was not affected. In both leaves and roots, the ABA content significantly increased under Cd stress, while the GA3, IAA and JA-ME content significantly decreased. Both xylem hydraulic conductivity and xylem water potential decreased with Cd stress, however, tracheid diameter and double wall thickness of the stems and roots were not affected. High Cd intensity was found in both the stem xylem and phloem in all Cd stressed treatments. Our study highlighted the in-situ observation of Cd distribution in both the xylem and phloem, and demonstrated the instant response of physiological traits such as xylem water potential, xylem hydraulic conductivity, root Cd2+ flux, NSC content, as well as phytohormonal content under Cd stress, and the less affected traits such as xylem anatomical traits, cellulose and hemicellulose.

12.
World J Psychiatry ; 14(3): 398-408, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38617980

RESUMO

BACKGROUND: For children and adolescents, deliberate self-harm (DSH) is becoming a mental health problem of concern. Despite several studies on the prevalence and factors of DSH in the world, there is little information on DSH among children and adolescents in China. This study explores the prevalence, types, associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China. AIM: To understand the situation of DSH among hospitalized children and adolescents and its related factors. METHODS: In this study, we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019, extracted the demographic and clinical data of all patients, and analyzed clinical risk factors of DSH. RESULTS: A total of 239 (16.90%) patients engaged in at least one type of DSH in our study. Cutting (n = 115, 48.12%) was the most common type of DSH. Females (n = 171, 71.55%) were more likely to engage in DSH than males (n = 68, 28.45%). DSH was positively associated with depressive disorders [OR = 3.845 (2.196-6.732); P < 0.01], female [OR = 2.536 (1.815-3.542); P < 0.01], parental marital status [OR = 5.387 (2.254-12.875); P < 0.01] and negative family history of psychiatric illness [OR = 7.767 (2.952-20.433); P < 0.01], but not with occupation, substance use and history of physical abuse. CONCLUSION: Our findings suggest that for patients with depression, females, an abnormal marriage of parents, and no history of mental illness, attention should be paid to the occurrence of DSH.

13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 389-394, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660841

RESUMO

OBJECTIVE: To investigate the effects of elesclomol-Cu (ES-Cu) on the proliferation and cuproptosis of human acute myeloid leukemia (AML) cells. METHODS: The effects of ES-Cu on the proliferation of AML cells and the AML cells pre-treated with ammonium tetrathiomolybdate (TTM) were examined by CCK-8 assay. The Calcein/PI kit was used to detected the changes in activity and cytotoxicity of AML cells induced by ES-Cu. Flow cytometry and Cytation3 fully automated cell imaging multifunctional detection system were used to analyze DCFH-DA fluorescence intensity, so as to determine the level of reactive oxygen species (ROS). The GSH and GSSG detection kits were used to measure the intracellular GSH content. Western blot was used to detected the expression of cuproptosis-related proteins ATP7B, FDX1, DLAT and DPYD. RESULTS: ES-Cu inhibited the proliferation of Kasumi-1 and HL-60 cells in a concentration-dependent manner (r Kasumi-1=-0.99, r HL-60=-0.98). As the concentration of ES-Cu increased, the level of intracellular ROS also increased (P <0.01-0.001). TTM could significantly reverse the inhibitory effect of ES-Cu on cell proliferation and its promoting effect on ROS. With the increase of ES-Cu concentration, the content of GSH was decreased (r =-0.98), and Western blot showed that the protein expressions of ATP7B, FDX1, DLAT and DPYD were significantly reduced (P <0.05). CONCLUSION: ES-Cu can induce cuproptosis in AML cells, which provides a new idea for the treatment of AML.


Assuntos
Proliferação de Células , Hidrazinas , Leucemia Mieloide Aguda , Molibdênio , Espécies Reativas de Oxigênio , Humanos , Proliferação de Células/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células HL-60 , Linhagem Celular Tumoral , Cobre/farmacologia
14.
Front Immunol ; 15: 1363278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601160

RESUMO

Purpose: A mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process. Methods: Cardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process. Results: Cardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes. Conclusion: We are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.


Assuntos
Macrófagos , Fagocitose , Camundongos , Animais , Inflamação/metabolismo , Interferons/metabolismo , Análise de Sequência de RNA
15.
J Med Chem ; 67(8): 6456-6494, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38574366

RESUMO

Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer.


Assuntos
DNA , Descoberta de Drogas , Interleucina-17 , Bibliotecas de Moléculas Pequenas , Interleucina-17/metabolismo , Interleucina-17/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , DNA/metabolismo , DNA/química , Humanos , Animais , Relação Estrutura-Atividade , Ligação Proteica , Camundongos
16.
Analyst ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639445

RESUMO

Anisotropic growth of nanomaterials enables advances in building diverse and complex architectures, which exhibit unique properties and enrich the choice of nano-building modules for electrochemical sensor devices. Herein, an anisotropic growth method was proposed to anchor gold nanoparticles (AuNPs) onto both ends of quasi-two-dimensional CdSe semiconductor quantum nanoplatelets (NPLs), appearing with a monodisperse and uniform nano-dumbbell shape. Then, these AuNPs were exploited as natural anchor points and further initiated self-assembly to create complex architectures via dithiol bridges. Detailed studies illustrated that the covalent Se-Au bonds facilitate effective charge transfer in the internal metal-semiconductor (M-S) electric field. The narrowed energy gap and up-shifted highest occupied molecular orbital were favored for electron removal during the electro-oxidation process. The ultrathin CdSe NPLs supplied a large specific surface area, carrying remaining holes and abundant active sites for target electro-catalysis. As a result, using the assembled complex as the electrode matrix with well-connected electronic circuits, a reliable electrochemical sensor was achieved for enrofloxacin detection. Under the optimal conditions, the current response exhibits two linear dynamic ranges, 0.01-10.0 µM and 10.0-250 µM, and the detection limit was calculated as 0.0026 µM. This work not only opens up broad application prospects for heterogeneous M-S combinations as effective electrochemical matrixes but also develops reliable antibiotic assays for food and environmental safety.

17.
Int J Ophthalmol ; 17(4): 638-645, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638263

RESUMO

AIM: To investigate the protective effects, antioxidant potential, and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) injury in a mouse model of glaucoma. METHODS: The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining. Intracellular reactive oxygen species (ROS) production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry. The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina. The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatography-mass spectroscopy (LC-MS) and untargeted metabolomics analyses. RESULTS: Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro. Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model. Untargeted metabolomics analyses showed that eicosane increased multiple metabolites, including L-arginine and L-carnitine, in the retina. CONCLUSION: Eicosane has protective effects, antioxidant potential, and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.

18.
Adv Mater ; : e2312685, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618925

RESUMO

Mn-based mullite oxides AMn2O5 (A = lanthanide, Y, Bi) is a novel type of ternary catalyst in terms of their electronic and geometric structures. The coexistence of pyramid Mn3+-O and octahedral Mn4+-O makes the d-orbital selectively active toward various catalytic reactions. The alternative edge- and corner-sharing stacking configuration constructs the confined active sites and abundant active oxygen species. As a result, they tend to show superior catalytic behaviors and thus gain great attention in environmental treatment and energy conversion and storage. In environmental applications, Mn-based mullites have been demonstrated to be highly active toward low-temperature oxidization of CO, NO, volatile organic compounds (VOCs), etc. Recent research further shows that mullites decompose O3 and ozonize VOCs from -20 °C to room temperature. Moreover, mullites enhance oxygen reduction reactions (ORR) and sulfur reduction reactions (SRR), critical kinetic steps in air-battery and Li-S batteries, respectively. Their distinctive structures also facilitate applications in gas-sensitive sensing, ionic conduction, high mobility dielectrics, oxygen storage, piezoelectricity, dehydration, H2O2 decomposition, and beyond. A comprehensive review from basic physicochemical properties to application certainly not only gains a full picture of mullite oxides but also provides new insights into designing heterogeneous catalysts.

19.
BMC Ophthalmol ; 24(1): 148, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566041

RESUMO

BACKGROUND: Bilateral retinal detachment and choroidal detachment in a patient are rare occurrences. The presence of bilateral diabetic retinopathy (DR) in such a case is even rarer and complicates the condition. CASE PRESENTATION: In this study, we document a case of unconventional VKH. Manifestations in this patient included intense peripheral retinal detachment and choroidal detachment, along with vitreous opacities akin to cotton wool spots, concurrent with DR. The diagnosis was considered as probable VKH with DR. Treatment according to VKH protocols, including high-dose corticosteroids, yielded positive results. CONCLUSIONS: VKH can co-occurrence with DR. VKH manifestations vary, and early, aggressive, and long-term treatment is essential. The complexity of treatment increases with concurrent DR, necessitating the use of immunosuppressants.


Assuntos
Efusões Coroides , Diabetes Mellitus , Retinopatia Diabética , Papiledema , Descolamento Retiniano , Síndrome Uveomeningoencefálica , Humanos , Síndrome Uveomeningoencefálica/complicações , Síndrome Uveomeningoencefálica/diagnóstico , Síndrome Uveomeningoencefálica/tratamento farmacológico , Descolamento Retiniano/etiologia , Descolamento Retiniano/complicações , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Papiledema/etiologia
20.
Int Wound J ; 21(4): e14862, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572823

RESUMO

Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co-expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re-epithelialization and accelerated wound healing in a full-thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.


Assuntos
Pele , Cicatrização , Humanos , Pele/metabolismo , Reepitelização , Mucosa Bucal , Fibroblastos/metabolismo , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo
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