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1.
Aging (Albany NY) ; 16(11): 9876-9898, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38843385

RESUMO

Estrogen is thought to have a role in slowing down aging and protecting cardiovascular and cognitive function. However, high doses of estrogen are still positively associated with autoimmune diseases and tumors with systemic inflammation. First, we administered exogenous estrogen to female mice for three consecutive months and found that the aorta of mice on estrogen develops inflammatory manifestations similar to Takayasu arteritis (TAK). Then, in vitro estrogen intervention was performed on mouse aortic vascular smooth muscle cells (MOVAS cells). Stimulated by high concentrations of estradiol, MOVAS cells showed decreased expression of contractile phenotypic markers and increased expression of macrophage-like phenotypic markers. This shift was blocked by tamoxifen and Krüppel-like factor 4 (KLF4) inhibitors and enhanced by Von Hippel-Lindau (VHL)/hypoxia-inducible factor-1α (HIF-1α) interaction inhibitors. It suggests that estrogen-targeted regulation of the VHL/HIF-1α/KLF4 axis induces phenotypic transformation of vascular smooth muscle cells (VSMC). In addition, estrogen-regulated phenotypic conversion of VSMC to macrophages is a key mechanism of estrogen-induced vascular inflammation, which justifies the risk of clinical use of estrogen replacement therapy.


Assuntos
Estrogênios , Subunidade alfa do Fator 1 Induzível por Hipóxia , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like , Macrófagos , Músculo Liso Vascular , Proteína Supressora de Tumor Von Hippel-Lindau , Animais , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/efeitos dos fármacos , Feminino , Estrogênios/farmacologia , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Transdiferenciação Celular/efeitos dos fármacos , Fenótipo , Aorta/patologia , Aorta/efeitos dos fármacos , Inflamação/metabolismo
2.
Chembiochem ; : e202400269, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923255

RESUMO

The human malaria parasite Plasmodium falciparum (P. falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti-P. falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P. falciparum. Our results reveal that ubiquitin carboxyl-terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6' region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P. falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti-malarial agents in the future.

3.
Adv Sci (Weinh) ; : e2402673, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38923273

RESUMO

Facile evaluation of formation kinetics of key intermediate is crucial for a comprehensive understanding of electrochemical ammonia oxidation reaction (AOR) mechanisms and the design of efficient electrocatalysts. Currently, elucidating the formation kinetics of key intermediate associated with rate-determining step is still challenging. Herein, 4-phtalamide-N-(4'-methylcoumarin) naphthalimide (CF) is developed as a molecular probe to detect N2H4 intermediate during AOR via electrochemiluminescence (ECL) and further investigated the formation kinetics of N2H4 on Pt catalysts with different crystal planes. CF probe can selectively react with N2H4 to release ECL substance luminol. Thus, N2H4 intermediate as a key intermediate can be sensitively and selectively detected by ECL during AOR. For the first time, Pt(100) facet is discovered to exhibit faster N2H4 formation kinetics than Pt(111) facet, which is further confirmed by Density functional theory calculation and the finite element simulation. The AOR mechanism under the framework of Gerischer and Mauerer is further validated by examining N2H4 formation kinetics during the dimerization process (NH2 coupling). The developed ECL active probe and the discovered facet-dependent formation kinetics of key intermediates provide a promising new tool and strategy for the understanding of electrochemical AOR mechanisms and the design of efficient electrocatalysts.

4.
Reprod Domest Anim ; 59(6): e14647, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38924282

RESUMO

Endometritis is a common postpartum disease in cows. It delays uterine involution and impairs normal physiological function. This can result in long-term or even lifelong infertility and cause significant losses to the dairy farming industry. Traditional treatments like antibiotics possess certain shortcomings, such as antibiotic residues, the abuse of antibiotics, and increased antimicrobial resistance of pathogens. Alternative treatment strategies are needed to minimize the utilization of antibiotics in dairy production. As an essential trace element in animals, selenium (Se) plays a vital role in regulating immune function, the inflammatory response, and oxidative stress, affecting the speed and completeness of tissue repair. This paper reviewed previous studies to analyse the potential of Se in the prevention and treatment of bovine endometritis, aiming to provide a new direction to increase production capacity in the future.


Assuntos
Doenças dos Bovinos , Endometrite , Selênio , Animais , Bovinos , Endometrite/veterinária , Endometrite/prevenção & controle , Endometrite/tratamento farmacológico , Feminino , Selênio/uso terapêutico , Selênio/administração & dosagem , Selênio/farmacologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos
5.
PLoS One ; 19(6): e0304052, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913628

RESUMO

A diaphragm pump is a type of volumetric pump that has excellent sealing performance. An electromagnetic diaphragm pump is a kind of widely adopted diaphragm pump that has a simple structure, low power loss, and high cost performance. However, the calculation method of deformation for the electromagnetic diaphragm pump rubber diaphragm is presently lacking. Herein, a calculating method of deformation for the electromagnetic diaphragm pump rubber diaphragm is proposed. By establishing and analyzing a deformation model of the electromagnetic diaphragm pump rubber diaphragm, a theoretical relationship between the deformation of the electromagnetic diaphragm pump rubber diaphragm, the size of the electromagnetic diaphragm pump rubber diaphragm and the pressure of fluid is determined. The experimental results indicate that the biggest difference between the tested axial deformation and the calculated axial deformation of the electromagnetic diaphragm pump rubber diaphragm is 0.04 mm and the calculation results show agreement with the experimental results.


Assuntos
Fenômenos Eletromagnéticos , Borracha , Borracha/química , Desenho de Equipamento , Modelos Teóricos
6.
Front Immunol ; 15: 1380982, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915416

RESUMO

Introduction: Viral infections have been implicated as a risk factor for laryngeal cancer. Given the possible effects of Corona virus disease 2019 (COVID-19) on the laryngeal tissue, we investigated the causal link between COVID-19 and laryngeal cancer using a two-sample Mendelian randomization (MR) approach. Methods: We utilized genetic data from the 5th Genome-wide association studies (GWAS) edition of the COVID-19 Host Genetics Initiative (published on January 18, 2021) and a large-scale laryngeal cancer GWAS comprising 180 cases and 218,612 controls of European ancestry. We applied inverse variance weighting, MR Egger, and weighted median methods to infer causality. We performed sensitivity analysis using the "leave-one-out" method to verify robustness. Results: We found no evidence of a causal association between gene-predicted COVID-19 and laryngeal cancer [Odds ratio (OR)=0.24 (95% Confidence intervals (CI), 0.05-1.26), P=0.09]. However, we observed significant inverse associations between gene-predicted COVID-19 hospitalization [OR=0.51 (95% CI, 0.28-0.95), P=0.03] and severe patients [OR=0.62 (95% CI, 0.43-0.90), P=0.01] and laryngeal cancer. Notably, the study detected important genetic variants, such as rs13050728, that modulate the expression of interferon alpha receptor 2 (IFNAR2), indicating possible roles for immune response pathways in both COVID-19 and cancer. Discussion: This study reveals a potential interaction between COVID-19 severity, genetic factors, and laryngeal cancer, underscoring the importance of investigating the immune response mechanisms in both conditions. These findings contribute to the understanding of the complex interactions between COVID-19 and laryngeal cancer and may guide future research on the role of immune response, particularly involving IFNAR2.


Assuntos
COVID-19 , Estudo de Associação Genômica Ampla , Neoplasias Laríngeas , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/imunologia , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/virologia , Neoplasias Laríngeas/imunologia , SARS-CoV-2/fisiologia , Predisposição Genética para Doença , Fatores de Risco
7.
BMC Med Imaging ; 24(1): 160, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926814

RESUMO

PURPOSE: This study aimed to investigate the feasibility of using computed tomography (CT) attenuation values to differentiate hypodense brain lesions, specifically acute ischemic stroke (AIS) from asymmetric leukoaraiosis (LA) and old cerebral infarction (OCI). MATERIALS AND METHODS: This retrospective study included patients with indeterminate hypodense lesions identified via brain CT scans conducted between June 2019 and June 2021. All lesions were confirmed through head MRI/diffusion-weighted imaging within 48 h after CT. CT attenuation values of hypodense lesions and symmetrical control regions were measured. Additionally, CT attenuation value difference (ΔHU) and ratio (RatioHU) were calculated. One-way analysis of variance (ANOVA) was used to compare age and CT parameters (CT attenuation values, ΔHU and RatioHU) across the groups. Finally, receiver operating characteristic (ROC) analysis was performed to determine the cutoff values for distinguishing hypodense lesions. RESULTS: A total of 167 lesions from 146 patients were examined. The CT attenuation values for AIS(n = 39), LA(n = 53), and OCI(n = 75) were 18.90 ± 6.40 HU, 17.53 ± 4.67 HU, and 11.90 ± 5.92 HU, respectively. The time interval between symptom onset and CT scans for AIS group was 32.21 ± 26.85 h. ANOVA revealed significant differences among the CT parameters of the hypodense lesion groups (all P < 0.001). The AUC of CT values, ΔHU, and RatioHU for distinguishing AIS from OCI were 0.802, 0.896 and 0.878, respectively (all P < 0.001). Meanwhile, the AUC for distinguishing OCI from LA was 0.789, 0.883, and 0.857, respectively (all P < 0.001). Nevertheless, none of the parameters could distinguish AIS from LA. CONCLUSION: CT attenuation parameters can be utilized to differentiate between AIS and OCI or OCI and LA in indeterminate hypodense lesions on CT images. However, distinguishing AIS from LA remains challenging.


Assuntos
Infarto Cerebral , Estudos de Viabilidade , AVC Isquêmico , Leucoaraiose , Tomografia Computadorizada por Raios X , Humanos , Leucoaraiose/diagnóstico por imagem , Masculino , Feminino , Idoso , Estudos Retrospectivos , AVC Isquêmico/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Diagnóstico Diferencial , Infarto Cerebral/diagnóstico por imagem , Curva ROC , Idoso de 80 Anos ou mais
8.
Bioengineering (Basel) ; 11(6)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38927814

RESUMO

Visualizing the decision-making process is a key aspect of research regarding explainable arrhythmia recognition. This study proposed a visualized lead selection method to classify arrhythmia for multi-lead ECG signals. The proposed method has several advantages, as it uses a visualized approach to select effective leads, avoiding redundant leads and invalid information. It also captures the temporal dependencies of ECG signals and the complementary information between leads. The method deployed a lead activation heatmap (LA heatmap) based on a lead-wise network to select the proper 5 leads from 12-lead ECG heartbeats extracted from the public 2018 Chinese Physiological Signal Challenge database (CPSC 2018 DB), which were then fed into a ResBiTime network combining bidirectional long short-term memory (Bi-LSTM) networks and residual connections for a classification task of nine heartbeat categories (i.e., N, AF, I-AVB, RBBB, PAC, PVC, STD, LBBB, and STE). The results indicate an average precision of 93.25%, an average recall of 93.03%, an average F1-score of 0.9313, and that the proposed method can effectively extract additional information from ECG heartbeat data.

9.
J Craniofac Surg ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856234

RESUMO

BACKGROUND: The posterior auricular flap has long been favored for repairing skin defects on the ear's surface. However, achieving optimal esthetic outcomes in ear reconstruction requires a flexible approach to flap transfer methods. While bipedicle advancement flaps are commonly used for body wound coverage, they are rarely used in auricular defect repair. OBJECTIVE: To propose a modified flap transfer approach based on the orientation of the auricular defect's long axis and assess the postoperative esthetic outcomes. METHODS: The authors reported 12 patients treated using 2 distinct flap transfer techniques. Mild to moderate helix soft tissue defects remained after excision of the masses. A direct island flap was created for patients with longitudinal defects to cover the defect. For patients with transverse defects, a combination of bipedicle and island flaps was used for repair. Scar quality and esthetic outcomes were assessed at least 6 months postsurgery using the Scar Cosmesis Assessment and Rating scale. RESULTS: All patients experienced no serious complications and achieved excellent cosmetic results. Patients undergoing combined flap transfer exhibited relatively more favorable esthetic outcomes. CONCLUSION: The authors propose a novel concept for repairing helix soft tissue defects by designing local flaps based on the direction of the defect's long axis. For repairing helix soft tissue defects with a long axis parallel to the auricular edge, the combined utilization of bipedicle advancement flap and island rotation flap transfer should be consideration more.

10.
J Biol Chem ; : 107472, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38879005

RESUMO

African swine fever virus (ASFV) causes severe disease in domestic pigs and wild boars, seriously threatening the development of the global pig industry. Type I interferon (IFN-I) is an important component of innate immunity, inducing the transcription and expression of antiviral cytokines by activating Janus-activated kinase-signal transducer and activation of transcription (JAK-STAT) signal transduction. However, the underlying molecular mechanisms by which ASFV antagonizes IFN-I signaling have not been fully elucidated. Therefore, using co-immunoprecipitation, confocal microscopy and dual luciferase reporter assay methods, we investigated these mechanisms and identified a novel ASFV immunosuppressive protein, pB475L, which interacts with the C-terminal domain of STAT2. Consequently, pB475L inhibited IFN-I signaling by inhibiting STAT1 and STAT2 heterodimerization and nuclear translocation. Furthermore, we constructed an ASFV-B475L7PM mutant strain by homologous recombination, finding that ASFV-B475L7PM attenuated the inhibitory effects on IFN-I signaling compared to wild-type ASFV. In summary, this study reveals a new mechanism by which ASFV impairs host innate immunity.

11.
Front Microbiol ; 15: 1405115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873144

RESUMO

Fusarium crown rot (FCR) is one of the most important soilborne diseases affecting wheat production. To investigate the diversity of the pathogens causing this disease, 199 diseased wheat samples were collected from 13 cities in Shandong province. In total, 468 isolates were obtained, and from these isolates, 11 Fusarium species were identified based on phylogenetic analyses with the translation elongation factor-1α (TEF-1α), RNA polymerase II largest subunit (RPB1), and RNA polymerase II second largest subunit (RPB2) gene sequences. Of these Fusarium isolates, 283 were identified as Fusarium pseudograminearum and the remaining isolates were identified as Fusarium graminearum (n = 113), Fusarium sinensis (n = 28), Fusarium acuminatum (n = 18), Fusarium incarnatum (n = 13), Fusarium ipomoeae (n = 5), Fusarium flocciferum (n = 3), Fusarium proliferatum (n = 2), Fusarium asiaticum (n = 1), Fusarium culmorum (n = 1), and Fusarium oxysporum (n = 1), suggesting that F. pseudograminearum is the dominant pathogen of FCR of wheat in Shandong province. Pathogenicity tests demonstrated that all 11 Fusarium species could cause typical symptoms of FCR on wheat seedlings. The results of the study indicate that a greater diversity of Fusarium species can cause FCR of wheat in Shandong province than that has been previously reported. This is the first report in the world of Fusarium incarnatum, Fusarium ipomoeae, and Fusarium flocciferum as pathogens causing FCR in wheat.

12.
J Blood Med ; 15: 265-273, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895162

RESUMO

Purpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China. Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and ß - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis. Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and ß globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes. Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin.

13.
ACS Appl Mater Interfaces ; 16(24): 31341-31347, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38853459

RESUMO

Sulfide-based solid electrolytes with high ionic conductivity have attracted a lot of attention. However, the incompatibility and interfacial instability of sulfides with the lithium metal anode have emerged as pivotal constraints on their development. To address this challenge, we proposed and successfully synthesized the BH4- doped argyrodite-type electrolyte Li6PS5Cl0.9(BH4)0.1 by mechanical ball milling and annealing. This electrolyte not only exhibits an exceptionally high ionic conductivity of 2.83 × 10-3 S cm-1 at 25 °C but also demonstrates outstanding electrochemical stability. The Li/Li6PS5Cl0.9(BH4)0.1/Li symmetric cell can stably run for more than 400 h at a current density of 0.2 mA cm-2. In sharp contrast, although the F- doped sample, Li6PS5Cl0.3F0.7, can highly improve Li6PS5Cl's electrochemical stability, the ionic conductivity will reduce dramatically to 6.63 × 10-4 S cm-1. The stepwise current method reveals a critical current density of 3.5 mA cm-2 for Li6PS5Cl0.9(BH4)0.1, which makes it a competitive sulfide-based solid electrolyte. This research offers valuable insights for designing new borohydride-containing solid electrolytes.

14.
BMJ Open ; 14(6): e080243, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834324

RESUMO

OBJECTIVES: To reveal the association between a sedentary lifestyle and the prevalence of primary osteoporosis (POP). DESIGN: A community-based cross-sectional study was conducted. SETTING: This study was conducted in communities in Hefei city, Anhui province, China. PARTICIPANTS: A total of 1346 residents aged 40 and above underwent POP screening via calcaneus ultrasound bone mineral density (BMD) testing and completed a questionnaire survey. OUTCOME MEASURES: The average daily sitting time was included in the study variable and used to assess sedentary behaviour. The 15 control variables included general information, dietary information and life behaviour information. Logistic regression was used to analyse the association between the POP prevalence and study or control variables in different models. RESULTS: 1346 participants were finally included in the study. According to the 15 control variables, the crude model and 4 models were established. The analysis revealed that the average daily sitting time showed a significant correlation with the prevalence of POP in the crude model (OR=2.02, 95% CI=1.74 to 2.36, p<0.001), Model 1 (OR=2.65, 95% CI=2.21 to 3.17, p<0.001), Model 2 (OR=2.63, 95% CI=2.19 to 3.15, p<0.001), Model 3 (OR=2.62, 95% CI=2.18 to 3.15, p<0.001) and Model 4 (OR=2.58, 95% CI=2.14 to 3.11, p<0.001). Besides, gender, age and body mass index showed a significant correlation with the POP prevalence in all models. CONCLUSIONS: This study suggests a potential association between a sedentary lifestyle and the prevalence of POP within the Chinese population. Modifying sedentary behaviours could contribute to a reduction in POP risk. However, longitudinal cohort studies are necessary to confirm this hypothesis in the future.


Assuntos
Osteoporose , Comportamento Sedentário , Humanos , Estudos Transversais , China/epidemiologia , Feminino , Pessoa de Meia-Idade , Masculino , Osteoporose/epidemiologia , Prevalência , Idoso , Adulto , Densidade Óssea , Fatores de Risco , Modelos Logísticos , Inquéritos e Questionários , Calcâneo/diagnóstico por imagem , População do Leste Asiático
15.
J Perianesth Nurs ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38842952

RESUMO

PURPOSE: This study aimed to determine the effect of a forced-air warming blanket placed on different body parts on the core temperature of patients undergoing elective open abdominal surgery. DESIGN: Prospective, single-center, randomized, controlled, single-blind trial. METHODS: A total of 537 patients who underwent open abdominal surgery were randomized into groups A, B, and C and provided with different forced-air warming blankets. Group A was given an upper body blanket, group B a lower body blanket, and group C an underbody blanket. The incidence of intraoperative hypothermia, the time maintaining the core temperature over 36 â„ƒ before hypothermia, the duration of hypothermia, the rewarming rate, and relevant complications were compared among three groups. FINDINGS: Intraoperative hypothermia occurred in 51.4% of patients in group B, 37.6% of patients in group A, and 34.1% of patients in group C (P = .002). Maintaining the core temperature above 36 â„ƒ was longer before hypothermia in groups A and C (log-rank P = .006). In groups A and C, the duration of hypothermia was shorter, the rewarming rate was higher, and the incidence of shivering and postoperative nausea and vomiting were lower, compared to group B. CONCLUSIONS: In patients undergoing elective open abdominal surgery, a forced-air warming blanket on the upper body part or underbody area decreased intraoperative hypothermia, prolonged the time to maintain the core temperature above 36 â„ƒ before hypothermia, and could better prevent further hypothermia when the core temperature had decreased below 36 â„ƒ. In addition, it was significantly superior in reducing shivering and postoperative nausea and vomiting in the postanesthesia care unit.

16.
J Med Chem ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912577

RESUMO

Aberrant activation of the Wnt/ß-catenin signaling is associated with tumor development, and blocking ß-catenin/BCL9 is a novel strategy for oncogenic Wnt/ß-catenin signaling. Herein, we presented two novel ß-catenin variations and exposed conformational dynamics in several ß-catenin crystal structures at the BCL9 binding site. Furthermore, we identified a class of novel urea-containing compounds targeting ß-catenin/BCL9 interaction. Notably, the binding modalities of inhibitors were greatly affected by the conformational dynamics of ß-catenin. Among them, 28 had a strong affinity for ß-catenin (Kd = 82 nM), the most potent inhibitor reported. In addition, 13 and 35 not only activate T cells but also promote the antigen presentation of cDC1, showing robust antitumor efficacy in the CT26 model. Collectively, our study demonstrated a series of potent small-molecule inhibitors targeting ß-catenin/BCL9, which can enhance antigen presentation and activate cDC1 cells, delivering a potential strategy for boosting innate and adaptive immunity to overcome immunotherapy resistance.

17.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1169-1176, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38886414

RESUMO

In recent years, a surge in drought occurrences has dramatically impacted tree growth worldwide. We examined the ecological resilience of Larix principis-rupprechtii plantations with varying densities (1950, 2355, and 2595 trees·hm-2) at the Saihanba Mechanical Forest Farm, by extracting the increment cores using the standard dendrochronological method to measure individual-tree basal area increments (BAI) as part of our assessment of ecological resilience, including resistance (Rt), recovery (Rc), and resilience (Rs). The results showed that drought events occurred in 2006-2010, 2015, and 2018. The Rt for L. principis-rupprechtii plantations varied from 0.76 to 2.01 across three drought events, indicating generally high resistance, except for the plantation with 2355 trees·hm-2 during the second dry year (Rt=0.69). The Rt for the plantation with 2595 trees·hm-2 significantly decreased across all drought events, while no significant change was observed in the plantations with 1950 and 2355 trees·hm-2. The Rc showed no differences in response to a single drought event across plantation densities, with a significant upward trend for all the densities with each occurrence of drought event. There was no significant difference in the resilience of different densities of L. principis-rupprechtii to the first drought event, whereas the plantation with 2595 trees·hm-2 exhibited significantly lower Rs during the second and third drought events compared with 1950 and 2355 trees·hm-2, respectively. During the 2015 drought event, plantation with 2595 trees·hm-2 experienced a significant growth decline (radial growth change rate was -26.5%), while no such decline was observed in the plantations with 1950 and 2355 trees·hm-2. Overall, the plantation with 2595 trees·hm-2 demonstrated the lowest resilience to drought events.


Assuntos
Secas , Larix , Larix/crescimento & desenvolvimento , China , Ecossistema , Densidade Demográfica
18.
Curr Med Sci ; 44(3): 475-484, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38748372

RESUMO

Proton-activated G protein-coupled receptors (GPCRs), initially discovered by Ludwig in 2003, are widely distributed in various tissues. These receptors have been found to modulate the immune system in several inflammatory diseases, including inflammatory bowel disease, atopic dermatitis, and asthma. Proton-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular pH. This detection triggers downstream signaling pathways within the cells, ultimately influencing the function of immune cells. In this review, we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.


Assuntos
Imunomodulação , Inflamação , Receptores Acoplados a Proteínas G , Transdução de Sinais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/imunologia , Humanos , Inflamação/metabolismo , Inflamação/imunologia , Animais , Prótons , Asma/imunologia , Asma/metabolismo , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Concentração de Íons de Hidrogênio
19.
Anal Chem ; 96(23): 9438-9446, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38804325

RESUMO

A high-sensitivity fiber-optic photoacoustic (PA) gas microsensor is demonstrated with dual enhancement based on acoustics and detection. Due to the characteristic of small size, a Helmholtz resonator is integrated into a miniature PA sensor. The acoustically amplified PA signal is detected by a high-sensitivity fiber Fabry-Perot (F-P) interferometric cantilever. The first-order resonant frequencies of the interferometric cantilever and Helmholtz resonator are matched by subtle adjustments. The weak PA signal is significantly enhanced in a volume of only 0.35 mL, which breaks the volume limitation of the resonance modes in traditional PA sensing systems. To improve the resolution of the microsensor, a white light interferometry (WLI)-based spectral demodulation algorithm is utilized. The experimental results indicate that the minimum detection limit of acetylene (C2H2) drops to about 15 ppb with an averaging time of 100 s, corresponding to the normalized noise equivalent absorption (NNEA) coefficient of 2.7 × 10-9 W·cm-1·Hz-1/2. The dual resonance enhanced fiber-optic PA gas microsensor has the merits of high sensitivity, intrinsic safety, and compact structure.

20.
Am J Chin Med ; 52(3): 841-864, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716618

RESUMO

A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet in vivo. Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group in vitro and in vivo. Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Apoptose , Autofagia , Diabetes Mellitus Experimental , Quercetina , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Proteínas Quinases Ativadas por AMP/metabolismo , Ratos Sprague-Dawley , Ratos , Modelos Animais de Doenças , Miocárdio/metabolismo , Miocárdio/patologia , Estreptozocina , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/prevenção & controle , Fitoterapia , Proteína Beclina-1/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações
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