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1.
PeerJ ; 12: e17846, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224822

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic, which caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to a crisis with devastating disasters to global public economy and health. Several studies suggest that the SARS-CoV-2 nucleocapsid protein (N protein) is one of uppermost structural constituents of SARS-CoV-2 and is relatively conserved which could become a specific diagnostic marker. In this study, eight single domain antibodies recognized the N protein specifically which were named pN01-pN08 were screened using human phage display library. According to multiple sequence alignment and molecular docking analyses, the interaction mechanism between antibody and N protein was predicted. ELISA results indicated pN01-pN08 with high affinity to protein N. To improve their efficacy, two fusion proteins were prepared and their affinity was tested. These finding showed that fusion proteins had higher affinity than single domain antibodies and will be used as diagnosis for the pandemic of SARS-CoV-2.


Asunto(s)
Anticuerpos Antivirales , COVID-19 , Proteínas de la Nucleocápside de Coronavirus , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Anticuerpos de Dominio Único , Humanos , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/química , SARS-CoV-2/inmunología , Proteínas de la Nucleocápside de Coronavirus/inmunología , Proteínas de la Nucleocápside de Coronavirus/química , COVID-19/inmunología , COVID-19/diagnóstico , Anticuerpos Antivirales/inmunología , Afinidad de Anticuerpos , Fosfoproteínas/inmunología , Fosfoproteínas/química , Ensayo de Inmunoadsorción Enzimática/métodos , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Biblioteca de Péptidos
2.
Phytochemistry ; : 114270, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39222866

RESUMEN

The genus Valeriana is used in traditional Chinese medicine to treat nervous disorders, sleep disorders, epilepsy and skin diseases. A large number of sesquiterpenoids from this genus have been found to exhibit anti-inflammatory, antiproliferative, anti-influenza virus and neuroprotective activities. In order to discover more sesquiterpenoids with structural diversity and bioactivity from Valeriana plants, fifteen sesquiterpenoids, including ten undescribed ones, valernaenes A-J (1, 5-7, 9-11 and 13-15), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated by extensive spectroscopic techniques (1D, 2D NMR and HRESIMS) and electronic circular dichroism (ECD) calculation. Structurally, valernaenes C (6) and D (7) were two caryophyllane-type norsesquiterpenoids. In addition, valernaenes A (1) and F (10) exhibited anti-influenza virus activity with EC50 values of 38.76 ± 1.44 and 23.01 ± 4.89 µM, respectively. Furthermore, caryophyllenol A (2) showed promoting effect on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells with differentiation rate of 12.26% at a concentration of 10 µM. This study not only enriched the structural diversity of sesquiterpenoids in the genus Valeriana, but also provided theoretical basis for the discovery of anti-influenza virus and neuroprotective agents from this genus.

3.
ACS Nano ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39223995

RESUMEN

Combined photodynamic and photothermal therapy (PDT and PTT) can achieve more superior therapeutic effects than the sole mode by maximizing the photon utilization, but there remains a significant challenge in the development of related single-molecule photosensitizers (PSs), particularly those with type I photosensitization. In this study, self-assembly of squaraine dyes (SQs) is shown to be a promising strategy for designing PSs for combined type I PDT and PTT, and a supramolecular PS (TPE-SQ7) has been successfully developed through subtle molecular design of an indolenine SQ, which can self-assemble into highly ordered H-aggregates in aqueous solution as well as nanoparticles (NPs). In contrast to the typical quenching effect of H-aggregates on reactive oxygen species (ROS) generation, our results encouragingly manifest that H-aggregates can enhance type I ROS (•OH) generation by facilitating the intersystem crossing process while maintaining a high PTT performance. Consequently, TPE-SQ7 NPs with ordered H-aggregates not only exhibit superior combined therapeutic efficacy than the well-known PS (Ce6) under both normoxic and hypoxic conditions but also have excellent biosafety, making them have important application prospects in tumor phototherapy and antibacterial fields. This study not only proves that the supramolecular self-assembly of SQs is an effective strategy toward high-performance PSs for combined type I PDT and PTT but also provides a different understanding of the effect of H-aggregates on the PDT performance.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39219221

RESUMEN

Loss of osteogenic differentiation potential of osteoblasts has been associated with the pathogenesis of osteoporosis. Thus, stimulation of osteoblastic differentiation is a therapeutic strategy for osteoporosis. Relaxin-2 is a peptide hormone with potent biological functions. However, the effects of Relaxin-2 in osteoblastic differentiation and osteoporosis have not been reported before. Here, we report a novel physiological role of Relaxin-2 in promoting osteoblastic differentiation and mineralization of MC3T3-E1 cells. Our results indicate that exposure to Relaxin-2 upregulated the expression, and elevated the activity of alkaline phosphatase (ALP) when MC3T3-E1 cells were cultured in osteogenic differentiation medium (OM). Additionally, Relaxin-2 upregulated the mRNA levels of osteocalcin (ocn), osteopontin (opn), and collagen type I alpha 1 (Col1a1). The alizarin red S staining assay revealed that Relaxin-2 promoted the mineralization of MC3T3-E1 cells. We also found that Relaxin-2 increased the expression of Runx-2 as well as the epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR). Importantly, silencing of EGF abolished the effects of Relaxin-2 in osteoblastic differentiation and related gene expression. These findings suggest that Relaxin-2 stimulates osteogenic differentiation through activating EGF/EGFR signaling.

5.
Front Cell Infect Microbiol ; 14: 1413589, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170987

RESUMEN

Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.


Asunto(s)
Antivirales , ADN Viral , Guanina , Virus de la Hepatitis B , Hepatitis B Crónica , Viremia , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Masculino , Guanina/análogos & derivados , Guanina/uso terapéutico , Femenino , Adulto , Factores de Riesgo , Antivirales/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/efectos de los fármacos , ADN Viral/sangre , Antígenos e de la Hepatitis B/sangre , Cirrosis Hepática/virología , Carga Viral/efectos de los fármacos
6.
World J Gastrointest Surg ; 16(7): 2157-2166, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39087119

RESUMEN

BACKGROUND: Gastrointestinal symptoms are common in patients with uremia undergoing hemodialysis, and these symptoms seriously affect patients' prognosis. AIM: To assess the occurrence and factors influencing gastrointestinal symptoms in patients with uremia undergoing hemodialysis. METHODS: We retrospectively selected 98 patients with uremia who underwent regular hemodialysis treatment in the blood purification center of our hospital from December 2022 to December 2023. The gastrointestinal symptoms and scores of each dimension were evaluated using the Gastrointestinal Symptom Grading Scale (GSRS). Patients were divided into gastrointestinal symptoms and no gastrointestinal symptom groups according to whether they had gastrointestinal symptoms. The factors that may affect gastrointestinal symptoms were identified by single-factor analysis. Multiple logistic regression analysis was performed to identify independent risk factors for gastrointestinal symptoms. RESULTS: Gastrointestinal symptoms included indigestion, constipation, reflux, diarrhea, abdominal pain, and eating disorders, and the total average GSRS score was 1.35 ± 0.47. This study showed that age, number of tablets, dialysis time, glucocorticoid, parathyroid hormone (PTH), combined diabetes mellitus and C-reactive protein (CRP) were independent risk factors for gastrointestinal symptoms in patients with uremia undergoing hemodialysis, whereas body mass index (BMI), hemoglobin (Hb), and urea clearance index were independent protective factors (P < 0.05). CONCLUSION: Gastrointestinal symptoms are mostly mild in patients with uremia undergoing hemodialysis, most commonly including dyspepsia, eating disorders, and gastroesophageal reflux. The independent influencing factors mainly include the BMI, age, number of pills taken, dialysis time, urea clearance index, Hb, use of glucocorticoids, and thyroid hormone level. PTH, CRP, and diabetes are clinically related factors influencing the occurrence of gastrointestinal symptoms, and targeted prevention can be performed.

8.
Mitochondrial DNA B Resour ; 9(8): 991-994, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39108544

RESUMEN

The soft-shell clam Mya japonica (Jay, 1857) is a commercially important fishery resource. In this study, we identified the complete mitochondrial genome of M. japonica and performed a phylogenetic analysis to explore its genetic relationship with Mya arenaria. The genome is 21,396 bp in length and contains 13 protein-coding genes (PCGs), 23 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and 5 D-Loop control regions. The atp8 gene was annotated in Myidae for the first time. Notably, the genome contains an additional trnM, consistent with M. arenaria. The length of the cox2 gene is 1,947 bp, which is 513 bp longer than that in M. arenaria. Its base composition is 29.14% A, 37.26% T, 10.89% C, and 22.71% G. Phylogenetic analysis based on 12 PCGs and 2 rRNAs indicates that M. japonica and M. arenaria form a sister group. In this study, the identification and phylogenetic analysis of the complete mitochondrial genome of M. japonica provide significant information for future taxonomic and evolutionary research of the genus Mya.

9.
World J Clin Cases ; 12(22): 4897-4904, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39109021

RESUMEN

BACKGROUND: It has been confirmed that the increased posterior tibial slope over 12 degrees is a risk factor for anterior cruciate ligament injury, and varus deformity can aggravate the progression of medial osteoarthritis. AIM: To evaluate the efficacy of modified high tibial osteotomy (HTO) and anterior cruciate ligament reconstruction (ACLR) in the treatment of anterior cruciate ligament (ACL) injuries with varus deformities and increased posterior tibial slope (PTS) based on clinical and imaging data. METHODS: The patient data in this retrospective study were collected from 2019 to 2021. A total of 6 patients were diagnosed with ACL injury combined with varus deformities and increased PTS. All patients underwent modified open wedge HTO and ACLR. The degree of correction of varus deformity and the PTS was evaluated by radiography and magnetic resonance imaging. RESULTS: All 6 patients (6 knee joints) were followed up for an average of 20.8 ± 3.7 months. The average age at surgery was 29.5 ± 3.8 years. At the last follow-up, all patients resumed competitive sports. The International Knee Documentation Committee score increased from 50.3 ± 3.1 to 87.0 ± 2.8, the Lysholm score increased from 43.8 ± 4.9 to 86 ± 3.1, and the Tegner activity level increased from 2.2 ± 0.7 to 7.0 ± 0.6. The average movement distance of the tibia anterior translation was 4.8 ± 1.1 mm, medial proximal tibial angle (MPTA) was 88.9 ± 1.3° at the last follow-up, and the PTS was 8.4 ± 1.4°, both of which were significantly higher than those before surgery (P < 0.05). CONCLUSION: Modified open wedge HTO combined with ACLR can effectively treat patients with ACL ruptures with an associated increased PTS and varus deformity. The short-term effect is significant, but the long-term effect requires further follow-up.

10.
Plant J ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115017

RESUMEN

Demographic history and mutational load are of paramount importance for the adaptation of the endangered species. However, the effects of population evolutionary history and genetic load on the adaptive potential in endangered conifers remain unclear. Here, using population transcriptome sequencing, whole chloroplast genomes and mitochondrial DNA markers, combined with niche analysis, we determined the demographic history and mutational load for three threatened whitebark pines having different endangered statuses, Pinus bungeana, P. gerardiana and P. squamata. Demographic inference indicated that severe bottlenecks occurred in all three pines at different times, coinciding with periods of major climate and geological changes; in contrast, while P. bungeana experienced a recent population expansion, P. gerardiana and P. squamata maintained small population sizes after bottlenecking. Abundant homozygous-derived variants accumulated in the three pines, particularly in P. squamata, while the species with most heterozygous variants was P. gerardiana. Abundant moderately and few highly deleterious variants accumulated in the pine species that have experienced the most severe demographic bottlenecks (P. gerardiana and P. squamata), most likely because of purging effects. Finally, niche modeling showed that the distribution of P. bungeana might experience a significant expansion in the future, and the species' identified genetic clusters are also supported by differences in the ecological niche. The integration of genomic, demographic and niche data has allowed us to prove that the three threatened pines have contrasting patterns of demographic history and mutational load, which may have important implications in their adaptive potential and thus are also key for informing conservation planning.

11.
Artículo en Inglés | MEDLINE | ID: mdl-39190228

RESUMEN

PURPOSE: The aim of the current study was to investigate the mtDNA methylation levels and mtDNA copy numbers in the sperm of patients with asthenozoospermia and compare them to those observed in controls with normozoospermia. METHODS: Pyrosequencing analysis of the methylation levels of the mitochondrial D-loop and MT-CO1/chr1:631,907-632083/chrX:26,471,887-126,472,063 (hereinafter referred to as "MT-CO1-AVG") region and quantitative PCR analysis of the mtDNA copy number were performed on sperm from 30 patients with asthenozoospermia and 30 controls with normozoospermia. RESULTS: Compared with those of controls with normozoospermia, the methylation levels of D-loop and MT-CO1-AVG regions and mtDNA copy number were significantly higher in patients with asthenozoospermia. The methylation level of the D-loop region in patients with asthenozoospermia and controls with normozoospermia and that of MT-CO1-AVG region in patients with asthenozoospermia showed a decreasing tendency with increasing total sperm motility. A significant inverse correlation between the mtDNA copy number and total sperm motility was observed in patients with asthenozoospermia but not in controls with normozoospermia. In patients with asthenozoospermia, but not in controls with normozoospermia, we observed a significant inverse correlation between D-loop methylation levels and mtDNA copy number, while no significant correlation was observed between MT-CO1-AVG methylation levels and mtDNA copy number. CONCLUSION: These results reveal the occurrence of mtDNA methylation in human sperm and altered D-loop and MT-CO1-AVG methylation levels in patients with asthenozoospermia. Additional research is needed to determine the function of these features in the etiology and course of asthenozoospermia.

12.
Chem Biodivers ; : e202401767, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39185921

RESUMEN

Insect transient receptor potential vanilloid (TRPV) channels are critical targets for insecticides. In this study, various scaffold-hopping strategies were employed in the rational design of pyridylhydrazono derivatives as potential insect TRPV channels modulators. Insecticidal bioassay demonstrated that the initial target compounds exhibited lower insecticidal activity compared to pymetrozine, with the optimal compound B3 exhibiting a mortality rate of 53.3% against Aphis craccivora at 400 mg·L-1. Conformation analysis indicated that the high energy barrier required for the transition from the lowest-energy conformation to the active conformation may be a key factor contributing to the reduced insecticidal activities of the target compounds. Further structural optimizations aimed at reducing this energy barrier through binding mode-based conformation regulation led to the identification of optimal target 4-(3'-pyridylhydrazono)pyrazol-5-one derivatives C1 and C2. These compounds exhibited reduced transition energy barriers and improved insecticidal activity, with moderate mortality rate of 66.3% and 75.7% against A. craccivora at 400 mg·L-1, respectively. These findings provide valuable insights for future research on the discovery of insect TRPV modulators and have significant implications for the development of more effective agricultural insecticides.

13.
Toxicol Sci ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150890

RESUMEN

Phthalates are a class of known endocrine disrupting chemicals that are found in common everyday products. Several studies associate phthalate exposure with detrimental effects on ovarian function, including growth and development of the follicle and production of steroid hormones. We hypothesized that dysregulation of the ovary by phthalates may be mediated by phthalate toxicity towards granulosa cells, a major cell type in ovarian follicles responsible for key steps of hormone production and nourishing the developing oocyte. To test the hypothesis that phthalates target granulosa cells, we harvested granulosa cells from adult CD-1 mouse ovaries and cultured them for 96 hours in vehicle control, a phthalate mixture, or a phthalate metabolite mixture (0.1-100 µg/mL). After culture, we measured metabolism of the phthalate mixture into monoester metabolites by the granulosa cells, finding that granulosa cells do not significantly contribute to ovarian metabolism of phthalates. Immunohistochemistry of phthalate metabolizing enzymes in whole ovaries confirmed that these enzymes are not strongly expressed in granulosa cells of antral follicles and that ovarian metabolism of phthalates likely occurs primarily in the stroma. RNA sequencing of treated granulosa cells identified 407 differentially expressed genes, with overrepresentation of genes from lipid metabolic processes, cholesterol metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Expression of significantly differentially expressed genes related to these pathways was confirmed using qPCR. Our results agree with previous findings that phthalates and phthalate metabolites have different effects on the ovary, but both interfere with PPAR signaling in granulosa cells.

14.
J Hepatocell Carcinoma ; 11: 1569-1580, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156675

RESUMEN

Purpose: Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored. Methods: We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis. Results: The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival. Conclusion: The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.

15.
Se Pu ; 42(8): 812-818, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39086251

RESUMEN

Gel permeation chromatography coupled with light scattering (GPC-LS) is among the most common methods for determining the molar masses of polymers. GPC-LS is widely used in polymer science research and has been adopted for many industrial applications owing to its high sensitivity, accuracy, and precision. The determination of polymer molar masses using GPC-LS is an important experimental component of the "Polymer Physics Experiments" course. However, the present GPC-LS experimental teaching content tends to be overly simplistic and lacking in depth. Herein, the original experimental content is expanded and multiple sets of experiments are redesigned: (1) Using commercial polystyrene as an experimental sample, the molar mass, molar mass distribution, radius of gyration, and other molecular structure parameters are determined using GPC-LS; (2) Using two polyacrylonitriles with similar molecular structure parameters, subtle differences in the molar mass distributions of the samples are explored using differential mass distribution curves; (3) By comparing the chromatograms of a series of polyethylene glycols with different molar masses, the effect of molar mass on chromatographic peaks is investigated; and (4) For three different polymers (polyacrylonitrile, poly(methyl methacrylate), and poly(ß-cyclodextrin)), the polymer chain conformations are analyzed using conformation plots (i.e., radius of gyration vs. molar mass). In addition, the experimental teaching method is modified to convert passive learning into active learning, thereby improving the students' self-directed learning ability. This experimental teaching reform will help students obtain a more comprehensive understanding of GPC-LS principles and applications, stimulate their enthusiasm for learning, and improve the teaching quality of the experimental course.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39205497

RESUMEN

Melioration of the through-plane thermal conductivity (TC) of thermal interface materials (TIMs) is a sore need for efficient heat dissipation to handle an overheating concern of high-power-density electronics. Herein, we constructed a snail shell-like thermal conductive framework to facilitate vertical heat conduction in TIMs. With inspiration from spirally growing calcium carbonate platelets of snail shells, a facile double-microrod-assisted curliness method was developed to spirally coil boron nitride nanosheet (BNNS)/aramid nanofiber (ANF) laminates where interconnected BNNSs lie along the horizontal plane. Thus, vertical alignment of BNNSs in the resultant TIM was achieved, exhibiting a through-plane TC enhancement of ∼100% compared to the counterpart with randomly distributed BNNSs at the same BNNS addition (50 wt %). The Foygel's nonlinear model revealed that this unique snail shell-like BNNS framework reduced interfacial thermal resistance by 4 orders of magnitude. Our TIM showed superior interfacial thermal dissipation efficiency, leading to a temperature reduction of 42.6 °C for the LED chip compared to the aforementioned counterpart. Our work paves a valuable way for fabricating high-performance TIMs to ensure reliable operation of electrical devices.

17.
J Agric Food Chem ; 72(34): 18809-18815, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39145990

RESUMEN

Novel approaches for pest control are essential to ensure a sufficient food supply for the growing global population. The development of new insecticides must meet rigorous regulatory requirements for safety and address the resistance issues of existing insecticides. Proteolysis-targeting chimeras (PROTACs), originally developed for human diseases, show promise in agriculture. They offer innovative insecticides tailored to overcome resistance, opening avenues for agricultural applications. In this study, we developed small-molecule degraders by incorporating pomalidomide as an E3 ligand. These degraders were linked to a ligand (spirotetratmat enol) targeting the ACC protein through a flexible chain, aiming to achieve the efficient control of insects. Compounds 9a-9d were designed, synthesized, and evaluated for biological activities and mechanisms. Among them, 9b exhibited superior potency against Aphis craccivora (LC50 = 107.8 µg mL-1) compared to others and effectively degraded ACC proteins through the ubiquitin-proteasome system. These findings highlight the potential of utilizing PROTAC-based approaches in the development of insecticides for efficient pest control.


Asunto(s)
Acetil-CoA Carboxilasa , Insecticidas , Proteolisis , Insecticidas/química , Insecticidas/farmacología , Animales , Acetil-CoA Carboxilasa/metabolismo , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/antagonistas & inhibidores , Acetil-CoA Carboxilasa/química , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/química , Diseño de Fármacos , Talidomida/química , Talidomida/análogos & derivados , Talidomida/farmacología
18.
Anat Sci Int ; 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39217269

RESUMEN

Previous studies have reported that the lateral meniscus (LM) has two regions, the popliteal hiatus area (PH) with a scarce blood supply and the roots with an abundant one. However, the description of its vascular anatomy remains insufficient. We hypothesized that the difference in the width of the meniscus hilum (MH) affects the scarcity and abundance of blood supply to the LM. The MH is a concept proposed by us and is the only site of entrance or exit of blood vessels and nerves associated with the meniscus. The purpose of this study was to provide a structural explanation for the disparity of blood supply to the LM using the concept of MH. Sixteen knees were examined to investigate the blood supply to LM. In most areas, the femoral joint capsule (FJC) and tibial joint capsule (TJC) continued to the cranial and caudal edges of the LM, respectively. In the roots, the FJC and TJC covered the femoral and the outer-femoral surfaces. In contrast, the FJC in the PH did not attach to the cranial edge and only the TJC there did to the caudal edge of the LM. Histochemical examination showed that the blood vessels enter the LM via the MH. In the PH, the MH at the caudal edge was extremely narrow; and in the roots, the MH on the outer-femoral surfaces was wide. The results suggest that the difference in the width of the MH affected the scarcity and abundance of blood supply to the LM.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 999-1004, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39192389

RESUMEN

OBJECTIVE: To investigate the expression level of urothelial carcinoembryonic antigen 1 (lncRNA UCA1) in the bone marrow of acute myeloid leukemia (AML) patients, and to explore the clinical significance of lncRNA UCA1 expression level in AML patients. METHODS: Bone marrow samples of 50 AML patients were collected as experimental group, and bone marrow samples of 20 iron deficiency anemia (IDA) patients were collected as control group. The relevant clinicopathological characteristics of AML patients were collected. Real-time quantitative PCR (qRT-PCR) was used to detect the expression level of lncRNA UCA1 in the experimental and control groups, and the relationships between lncRNA UCA1 expression and clinical pathological characteristics and prognosis in AML patients were analyzed. Kaplan-Meier curves were used to analyze the effect of lncRNA UCA1 on the overall survival (OS) of AML patients; And Cox regression model was used to analyze the factors affecting the prognosis of AML patients. RESULTS: Compared with the control group, the expression level of lncRNA UCA1 was significantly elevated in patients with AML (P < 0.001); The proportion of patients with hemoglobin lower than 90 g/L in lncRNA UCA1 high expression group was significantly higher than that in lncRNA UCA1 low expression group (P =0.004); The expression level of lncRNA UCA1 was higher in M1, M2, and M4 subtypes, while it was lower in M0 and M5 subtypes, and the difference was statistically significant (P =0.009). There were no significant difference in sex, age, white blood cell (WBC) count, platelet (PLT) count, bone marrow blasts , chemotherapy regimen and efficacy, karyotype, gene mutation, and prognostic risk stratification between patients in UCA1 high expression group and those in UCA1 low expression group (all P > 0.05). The OS of patients with high expression of lncRNA UCA1 was significantly shorter than that of patients with low expression of lncRNA UCA1 (P =0.0229). CONCLUSION: The expression level of lncRNA UCA1 is significantly upregulated in AML patients. High expression of lncRNA UCA1 is associated with poor clinicopathological features and poor prognosis. Therefore, lncRNA UCA1 can be used as a prognostic indicator and a potential therapeutic target for AML patients.


Asunto(s)
Leucemia Mieloide Aguda , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Leucemia Mieloide Aguda/genética , Pronóstico , Médula Ósea/metabolismo , Masculino , Femenino , Relevancia Clínica
20.
Zhonghua Nan Ke Xue ; 30(7): 616-619, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39212396

RESUMEN

OBJECTIVE: To explore the effect of dietary modification-assisted multimodal therapy in the prevention and treatment of chronic prostatitis. METHODS: A total of 132 cases of chronic prostatitis treated in the Outpatient Department of our hospital were randomly divided into an observation group (n = 68) and a control group (n = 64), the former following the Mediterranean dietary pattern, the latter adhering to their own dietary habits, and meanwhile both receiving lifestyle guidance, psychological counseling, symptomatic medication and physiotherapy according to their specific symptoms. The patients were followed up for 4 weeks, therapeutic effects were observed and comparisons were made between the two groups in the NIH-CPSI scores before and after treatment. RESULTS: Compared with the baseline, the quality of life (QOL) scores, pain and urination discomfort scores and total NIH-CPSI scores were significantly decreased in both the observation and the control groups after treatment (P < 0.05), even more decreased in the former than in the latter, but with no statistically significant difference between the two (P > 0.05). The rate of therapeutic effectiveness was higher in the observation group than in the control (87.1% vs 79.7%, but showed no statistically significant difference between the two groups (P > 0.05). CONCLUSION: Multimodal therapy is suitable for the management of different clinical manifestations of individual patients, while dietary habits vary from person to person as well as from region to region. Therefore, scientific dietary modification for the prevention and treatment of CP/CPPS needs further exploration.


Asunto(s)
Prostatitis , Calidad de Vida , Humanos , Masculino , Prostatitis/terapia , Terapia Combinada , Enfermedad Crónica , Resultado del Tratamiento , Dieta Mediterránea , Estilo de Vida , Adulto
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