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1.
Plant Physiol Biochem ; 211: 108659, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38691875

RESUMEN

Chromium (Cr) contamination in agricultural soils poses a risk to crop productivity and quality. Emerging nano-enabled strategies show great promise in remediating soils contaminated with heavy metals and enhancing crop production. The present study was aimed to investigate the efficacy of nano silicon (nSi) in promoting wheat growth and mitigating adverse effects of Cr-induced toxicity. Wheat seedlings exposed to Cr (K2Cr2O7) at a concentration of 100 mg kg-1 showed significant reductions in plant height (29.56%), fresh weight (35.60%), and dry weight (38.92%) along with enhanced Cr accumulation in roots and shoots as compared to the control plants. However, the application of nSi at a concentration of 150 mg kg-1 showcased substantial mitigation of Cr toxicity, leading to a decrease in Cr accumulation by 27.30% in roots and 35.46% in shoots of wheat seedlings. Moreover, nSi exhibited the capability to scavenge oxidative stressors, such as hydrogen peroxide (H2O2), and malondialdehyde (MDA) and electrolyte leakage, while significantly enhancing gas exchange parameters, total chlorophyll content, and antioxidant activities (enzymatic and nonenzymatic) in plants grown in Cr-contaminated soil. This study further found that the reduced Cr uptake by nSi application was due to downregulating the expression of HMs transporter genes (TaHMA2 and TaHMA3), alongwith upregulating the expression of antioxidant-responsive genes (TaSOD and TaSOD). The findings of this investigation highlight the remarkable potential of nSi in ameliorating Cr toxicity. This enhanced efficacy could be ascribed to the distinctive size and structure of nSi, which augment its ability to counteract Cr stress. Thus, the application of nSi could serve as a viable solution for production of crops in metal contaminated soils, offering an effective alternative to time-consuming and costly remediation techniques.

2.
Transl Psychiatry ; 14(1): 202, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734669

RESUMEN

The pathogenesis of major depressive disorder (MDD) involves lipid metabolism. Our earlier research also revealed that MDD patients had much lower total cholesterol (TC) concentrations than healthy controls (HCs). However, it is still unclear why TC decreased in MDD. Here, based on the Ingenuity Knowledge Base's ingenuity pathway analysis, we found that sodium voltage-gated channel alpha subunit 11A (SCN11A) might serve as a link between low lipid levels and MDD. We analyzed the TC levels and used ELISA kits to measure the levels of SCN11A in the serum from 139 MDD patients, and 65 HCs to confirm this theory and explore the potential involvement of SCN11A in MDD. The findings revealed that TC levels were considerably lower and SCN11A levels were remarkably increased in MDD patients than those in HCs, while they were significantly reversed in drug-treatment MDD patients than in drug-naïve MDD patients. There was no significant difference in SCN11A levels among MDD patients who used single or multiple antidepressants, and selective serotonin reuptake inhibitors or other antidepressants. Pearson correlation analysis showed that the levels of TC and SCN11A were linked with the Hamilton Depression Rating Scales score. A substantial association was also found between TC and SCN11A. Moreover, a discriminative model made up of SCN11A was discovered, which produced an area under a curve of 0.9571 in the training set and 0.9357 in the testing set. Taken together, our findings indicated that SCN11A may serve as a link between low lipid levels and MDD, and showed promise as a candidate biomarker for MDD.


Asunto(s)
Colesterol , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/sangre , Femenino , Masculino , Adulto , Persona de Mediana Edad , Colesterol/sangre , Estudios de Casos y Controles , Antidepresivos/uso terapéutico
3.
J Med Chem ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739112

RESUMEN

Based on the close relationship between programmed death protein ligand 1 (PD-L1) and epidermal growth factor receptor (EGFR) in glioblastoma (GBM), we designed and synthesized a series of small molecules as potential dual inhibitors of EGFR and PD-L1. Among them, compound EP26 exhibited the highest inhibitory activity against EGFR (IC50 = 37.5 nM) and PD-1/PD-L1 interaction (IC50 = 1.77 µM). In addition, EP26 displayed superior in vitro antiproliferative activities and in vitro immunomodulatory effects by promoting U87MG cell death in a U87MG/Jurkat cell coculture model. Furthermore, EP26 possessed favorable pharmacokinetic properties (F = 22%) and inhibited tumor growth (TGI = 92.0%) in a GBM mouse model more effectively than Gefitinib (77.2%) and NP19 (82.8%). Moreover, EP26 increased CD4+ cells and CD8+ cells in tumor microenvironment. Collectively, these results suggest that EP26 represents the first small-molecule-based PD-L1/EGFR dual inhibitor deserving further investigation as an immunomodulating agent for cancer treatment.

4.
Leukemia ; 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643304

RESUMEN

Targeting the metabolic dependencies of acute myeloid leukemia (AML) cells is a promising therapeutical strategy. In particular, the cysteine and methionine metabolism pathway (C/M) is significantly altered in AML cells compared to healthy blood cells. Moreover, methionine has been identified as one of the dominant amino acid dependencies of AML cells. Through RNA-seq, we found that the two nucleoside analogs 8-chloro-adenosine (8CA) and 8-amino-adenosine (8AA) significantly suppress the C/M pathway in AML cells, and methionine-adenosyltransferase-2A (MAT2A) is one of most significantly downregulated genes. Additionally, mass spectrometry analysis revealed that Venetoclax (VEN), a BCL-2 inhibitor recently approved by the FDA for AML treatment, significantly decreases the intracellular level of methionine in AML cells. Based on these findings, we hypothesized that combining 8CA or 8AA with VEN can efficiently target the Methionine-MAT2A-S-adenosyl-methionine (SAM) axis in AML. Our results demonstrate that VEN and 8CA/8AA synergistically decrease the SAM biosynthesis and effectively target AML cells both in vivo and in vitro. These findings suggest the promising potential of combining 8CA/8AA and VEN for AML treatment by inhibiting Methionine-MAT2A-SAM axis and provide a strong rationale for our recently activated clinical trial.

5.
J Med Chem ; 67(8): 6253-6267, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38587857

RESUMEN

In this work, a novel series of heterotricyclic DNA-PK inhibitors were rationally designed, synthesized, and assessed for their biological activity. In the DNA-PK biochemical assay, most compounds displayed potent enzymatic activity, with IC50 values between 0.11 and 71.5 nM. Among them, SK10 exhibited the most potent DNA-PK-inhibitory activity (IC50 = 0.11 nM). Studies of the mechanism of action indicated that SK10 could lower γH2A.X expression levels and demonstrate optimal synergistic antiproliferative activity against Jurkat cells (IC50 = 25 nM) when combined with doxorubicin. Importantly, in CT26 and B16-F10 tumor-bearing mouse models, the combination therapies of SK10 with chemotherapeutic drug doxorubicin, a PD-L1 antibody, and SWS1 (a potent PD-L1 small-molecule inhibitor) demonstrated superior synergistic anticancer and potential immunomodulatory effects. Furthermore, SK10 possessed favorable in vivo pharmacokinetic properties [e.g., oral bioavailability (F) = 31.8%]. Taken together, SK10 represents a novel heterotricyclic DNA-PK inhibitor with antitumor immune effects and favorable pharmacokinetics.


Asunto(s)
Antineoplásicos , Disponibilidad Biológica , Proteína Quinasa Activada por ADN , Inhibidores de Proteínas Quinasas , Humanos , Animales , Proteína Quinasa Activada por ADN/antagonistas & inhibidores , Proteína Quinasa Activada por ADN/metabolismo , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/uso terapéutico , Administración Oral , Inmunoterapia/métodos , Doxorrubicina/farmacología , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Descubrimiento de Drogas , Ratones Endogámicos C57BL , Línea Celular Tumoral , Sinergismo Farmacológico , Femenino
6.
J Med Chem ; 67(8): 6027-6043, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38598179

RESUMEN

Targeting the programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway has evolved into one of the most promising strategies for tumor immunotherapy. Thus far, multiple monoclonal antibody drugs have been approved for treating a variety of tumors, while the development of small-molecule PD-1/PD-L1 inhibitors has lagged far behind, with only a few small-molecule inhibitors entering clinical trials. In addition to antibody drugs and small-molecule inhibitors, reducing the expression levels of PD-L1 has attracted extensive research interest as another promising strategy to target the PD-1/PD-L1 pathway. Herein, we analyze the structures and mechanisms of molecules that reduce PD-L1 expression and classify them as degraders and downregulators according to whether they directly bind to PD-L1. Moreover, we discuss the potential prospects for developing PD-L1-targeting drugs based on these molecules. It is hoped that this perspective will provide profound insights into the discovery of potent antitumor immunity drugs.


Asunto(s)
Antígeno B7-H1 , Receptor de Muerte Celular Programada 1 , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Regulación hacia Abajo/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/química , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/química , Transducción de Señal/efectos de los fármacos
7.
Sci Adv ; 10(16): eadi1782, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38630819

RESUMEN

Mutant isocitrate dehydrogenases (IDHs) produce R-2-hydroxyglutarate (R-2HG), which inhibits the growth of most acute myeloid leukemia (AML) cells. Here, we showed that necroptosis, a form of programmed cell death, contributed to the antileukemia activity of R-2HG. Mechanistically, R-2HG competitively inhibited the activity of lysine demethylase 2B (KDM2B), an α-ketoglutarate-dependent dioxygenase. KDM2B inhibition increased histone 3 lysine 4 trimethylation levels and promoted the expression of receptor-interacting protein kinase 1 (RIPK1), which consequently caused necroptosis in AML cells. The expression of RIPK3 was silenced because of DNA methylation in IDH-mutant (mIDH) AML cells, resulting in R-2HG resistance. Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG-induced necroptosis pathway in mIDH AML cells. Together, R-2HG induced RIPK1-dependent necroptosis via KDM2B inhibition in AML cells. The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG's intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.


Asunto(s)
Glutaratos , Leucemia Mieloide Aguda , Lisina , Humanos , Necroptosis , Leucemia Mieloide Aguda/tratamiento farmacológico , Apoptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo
8.
Bioorg Chem ; 147: 107376, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38640722

RESUMEN

The inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway with small molecules is a promising approach for cancer immunotherapy. Herein, novel small molecules compounds bearing various scaffolds including thiophene, thiazole, tetrahydroquinoline, benzimidazole and indazole were designed, synthesized and evaluated for their inhibitory activity against the PD-1/PD-L1 interaction. Among them, compound Z13 exhibited the most potent activity with IC50 of 189.6 nM in the homogeneous time-resolved fluorescence (HTRF) binding assay. Surface plasmon resonance (SPR) assay demonstrated that Z13 bound to PD-L1 with high affinity (KD values of 231 nM and 311 nM for hPD-L1 and mPD-L1, respectively). In the HepG2/Jurkat T co-culture cell model, Z13 decreased the viability rate of HepG2 cells in a concentration-dependent manner. In addition, Z13 showed significant in vivo antitumor efficacy (TGI = 52.6 % at 40 mg/kg) without obvious toxicity in the B16-F10 melanoma model. Furthermore, flow cytometry analysis demonstrated that Z13 inhibited tumor growth in vivo by activating the tumor immune microenvironment. These findings indicate that Z13 is a promising PD-1/PD-L1 inhibitor deserving further investigation.

9.
World J Gastrointest Surg ; 16(3): 816-822, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38577072

RESUMEN

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol is a comprehensive management modality that promotes patient recovery, especially in the patients undergoing digestive tumor surgeries. However, it is less commonly used in the appendectomy. AIM: To study the application value of ERAS in laparoscopic surgery for acute appendicitis. METHODS: A total of 120 patients who underwent laparoscopic appendectomy due to acute appendicitis were divided into experimental group and control group by random number table method, including 63 patients in the experimental group and 57 patients in the control group. Patients in the experimental group were managed with the ERAS protocol, and those in the control group were received the traditional treatment. The exhaust time, the hospitalization duration, the hospitalization expense and the pain score between the two groups were compared. RESULTS: There was no significant difference in age, gender, body mass index and Sunshine Appendicitis Grading System score between the experimental group and the control group (P > 0.05). Compared to the control group, the patients in the experimental group had earlier exhaust time, shorter hospitalization time, less hospitalization cost and lower degree of pain sensation. The differences were statistically significant (P < 0.01). CONCLUSION: ERAS could significantly accelerate the recovery of patients who underwent laparoscopic appendectomy for acute appendicitis, shorten the hospitalization time and reduce hospitalization costs. It is a safe and effective approach.

10.
Artículo en Chino | MEDLINE | ID: mdl-38563171

RESUMEN

Objective:To evaluate the expression of eosinophil cationic protein and myeloperoxidase in nasal secretions in different types of rhinitis, and to explore their values in the differential diagnosis of different types of rhinitis. Methods:Six hundred and eighty-four subjects were selected, including 62 subjects in the acute rhinitis group, 378 subjects in the allergic rhinitis group, 94 subjects in the vasomotor rhinitis group, 70 subjects in the eosinophilic non-allergic rhinitis group, and 80 subjects in the control group. Nasal secretion samples were collected from the five groups, and the percentages of inflammatory cells were counted by Rachel's staining, and the expression of ECP/MPO was detected by colloidal gold assay. The correlation between the clinical diagnosis, the inflammatory cells in the nasal secretions and the expression of ECP/MPO was analyzed. Results:Nasal cytological smears showed that compared with the control group, the percentage of eosinophils in the AR and NARES groups were significantly higher (P<0.05), while the percentage of neutrophils was not different (P>0.05); the percentage of neutrophils was significantly higher in the acute rhinitis group compared with the control group (P<0.05), while the percentage of eosinophils was not statistically different (P>0.05); in vasomotor rhinitis group, the eosinophils and neutrophils were not statistically different compared with the control group(P> 0.05). The colloidal gold results showed that there were differences in the expression of ECP/MPO in different types of rhinitis, among which 49 cases (79.0%) in the acute rhinitis group expressed ECP+/MPO+; 267 cases (70.6%) in the AR group and 56 cases (75.7%) in the NARES group expressed ECP+/MPO-; 80 cases (85.1%) in the vasomotor rhinitis group and 69 cases (86.3%) in the control group expressed ECP-/MPO-. Conclusion:The differences in ECP and MPO expression between different types of rhinitis have certain reference value for the differential diagnosis of different types of rhinitis and the selection of treatment programs.


Asunto(s)
Rinitis Vasomotora , Rinitis , Humanos , Eosinófilos/metabolismo , Oro Coloide/metabolismo , Mucosa Nasal/metabolismo , Peroxidasa/metabolismo , Rinitis/diagnóstico , Rinitis/metabolismo , Rinitis Vasomotora/metabolismo
11.
Appl Opt ; 63(10): 2621-2629, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38568545

RESUMEN

When a binocular vision sensor (BVS) is installed in a narrow space, traditional calibration methods are limited as all targets should be placed in more than three different positions. To solve this problem, an on-site calibration method based on the phase-shift algorithm is proposed in our paper. Intrinsic parameters of these two cameras should be first calibrated offline. Series of phase-shift patterns are projected onto any one target with known three-dimensional information to determine the relationship between two cameras. The target utilized in our proposed method can be selected arbitrarily, which is suitable to achieve the on-site calibration of BVS, especially in industrial vibration environments. Experiments are conducted to validate the effectiveness and robustness of our proposed method.

12.
Obes Facts ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38569473

RESUMEN

INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; P = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤ 23.9 kg/m2), those with Q4 (BMI ≥ 28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; P = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

13.
EMBO J ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605226

RESUMEN

Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.

14.
Adv Mater ; : e2401263, 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38678376

RESUMEN

Lithium-sulfur (Li-S) batteries stand out as one of the promising candidates for next-generation electrochemical energy storage technologies. A key requirement to realize high-specific-energy Li-S batteries is to implement low amount of electrolyte, often characterized by the electrolyte/sulfur (E/S) ratio. Low E/S ratio aggravates the known challenges for Li-S batteries and introduces new ones originated from the high concentration of polysulfides in limited electrolyte reservoir. In this review, the connections between the fundamental properties of electrolytes and the electrochemical/chemical reactions in Li-S batteries under lean electrolyte condition are elucidated. The emphasis is on how the solvating properties of the electrolyte affect the fate of polysulfides. Built upon the mechanistic analysis, different strategies to design lean electrolytes to improve the overall process of Li-S reactions and Li anode protection are discussed.

15.
J Med Chem ; 67(9): 6906-6921, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38663873

RESUMEN

DNA damage response (DDR) defects in cells play a crucial role in tumor development by promoting DNA mutations. These mutations create vulnerabilities specific to cancer cells, which can be effectively targeted through synthetic lethality-based therapies. To date, numerous small molecule DDR inhibitors have been identified, and some of them have already been approved for clinical use. However, due to the complexity of the tumor microenvironment, mutations may occur in the amino acid residues of DDR targets. These mutations can affect the efficacy of small molecule inhibitors targeting DDR pathways. Therefore, researchers have turned their attention to next-generation DNA damage repair modulators, particularly those based on PROTAC technology. From this perspective, we overviewed the recent progress on DDR-targeting PROTAC degraders for cancer therapy. In addition, we also summarized the biological functions of different DDR targets. Finally, the challenges and future directions for DDR-target PROTAC degraders are also discussed in detail.


Asunto(s)
Daño del ADN , Reparación del ADN , Humanos , Daño del ADN/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Animales , Proteolisis/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología
16.
Cephalalgia ; 44(3): 3331024241235193, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38501875

RESUMEN

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.


Asunto(s)
Cefalalgia Histamínica , Femenino , Humanos , Masculino , China/epidemiología , Cefalalgia Histamínica/diagnóstico , Cefalalgia Histamínica/epidemiología , Cefalalgia Histamínica/terapia , Estudios Longitudinales , Estudios Prospectivos , Adulto
17.
Toxicol Appl Pharmacol ; 484: 116884, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38442791

RESUMEN

BACKGROUND: The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. OBJECTIVE: This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia. METHODS: A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors. RESULTS: PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5. CONCLUSION: PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.


Asunto(s)
Lignanos , Osteoporosis , Pez Cebra , Humanos , Animales , Anciano , Simulación del Acoplamiento Molecular , Osteogénesis , Dexametasona/farmacología , Osteoporosis/inducido químicamente , Osteoporosis/prevención & control , Receptores Wnt , Diferenciación Celular
18.
Environ Res ; 252(Pt 1): 118811, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38555090

RESUMEN

Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 µg/L, 1 µg/L, and 2 µg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development. Expression of cardiac development-related genes (vmhc, myh6, nkx2.5, tbx5a, gata4, tbx2b, nppa) is dysregulated. Transgenic zebrafish Tg (fli1: EGFP) were used to explore the effects of TBT exposure on vascular development. It was found that TBT exposure could lead to impaired development of intersegmental vessels (ISVs), common cardinal vein (CCV), subintestinal vessels (SIVs) and cerebrovascular. The expression of vascular endothelial growth factor (VEGF) signaling pathway-related genes (flt1, flt4, kdr, vegfa) was downregulated. Biochemical indices showed that ROS and MDA levels were significantly elevated and that SOD and CAT activities were significantly reduced. The expression of key genes for prostacyclin synthesis (pla2, ptgs2a, ptgs2b, ptgis, ptgs1) is abnormal. Therefore, it is possible that oxidative stress induced by TBT exposure leads to the blockage of arachidonic acid (AA) production in zebrafish embryos, which affects prostacyclin synthesis and consequently the normal development of the heart and blood vessels in zebrafish embryos.

19.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): 392-395, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38437426

RESUMEN

An all-fiber temperature sensor employing intentional refractive index modulation is experimentally demonstrated. The sensor consists of four sections of polarization maintaining fiber (FPMF) sandwiched between multi-mode fiber (MMF). The stress region of two sections of polarization maintaining fibers (PMFs) is aligned and then anti-clockwise rotates one PMF in 10 deg angles while the other keeps still. Finally, the discharge proceeds. The remaining two PMFs are fusion spliced with the same method. Then the prepared FPMF-MMF structure is connected to the 3 dB coupler to construct a Sagnac loop. The temperature sensitivity reaches 1.49 nm/°C for a temperature range from 16°C to 55°C. The proposed temperature sensor with easy fabrication and good linearity in measuring temperature can be a promising candidate for various applications in environmental monitoring and industrial production.

20.
Math Biosci Eng ; 21(2): 2626-2645, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38454699

RESUMEN

Calculating single-source shortest paths (SSSPs) rapidly and precisely from weighted digraphs is a crucial problem in graph theory. As a mathematical model of processing uncertain tasks, rough sets theory (RST) has been proven to possess the ability of investigating graph theory problems. Recently, some efficient RST approaches for discovering different subgraphs (e.g. strongly connected components) have been presented. This work was devoted to discovering SSSPs of weighted digraphs by aid of RST. First, SSSPs problem was probed by RST, which aimed at supporting the fundamental theory for taking RST approach to calculate SSSPs from weighted digraphs. Second, a heuristic search strategy was designed. The weights of edges can be served as heuristic information to optimize the search way of $ k $-step $ R $-related set, which is an RST operator. By using heuristic search strategy, some invalid searches can be avoided, thereby the efficiency of discovering SSSPs was promoted. Finally, the W3SP@R algorithm based on RST was presented to calculate SSSPs of weighted digraphs. Related experiments were implemented to verify the W3SP@R algorithm. The result exhibited that W3SP@R can precisely calculate SSSPs with competitive efficiency.

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