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1.
Neural Regen Res ; 20(2): 518-532, 2025 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38819064

RESUMO

JOURNAL/nrgr/04.03/01300535-202502000-00029/figure1/v/2024-05-28T214302Z/r/image-tiff Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell-derived neural stem cell exosomes (hiPSC-NSC-Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism. Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits, enhanced blood-brain barrier integrity, and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage. Additionally, hiPSC-NSC-Exos decreased immune cell infiltration, activated astrocytes, and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α post-intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion, thereby improving blood-brain barrier integrity. Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In summary, our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity, in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

2.
Org Lett ; 26(37): 7976-7980, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39240022

RESUMO

The use of an earth-abundant and inexpensive iron complex as a catalyst, coupled with near-infrared (NIR) light as the energy source, for radical reactions with alkyl halides has been far less developed. In this study, we report NIR light-mediated iron(I) dimer-catalyzed radical cascade reactions of fluoroalkyl bromides for the synthesis of ring-fused quinazolinones bearing a difluoromethyl group. In this process, the 3-bromo-1,10-phenanthroline ligand facilitates the reactivity of [CpFe(CO)2]2, thereby improving the efficiency of the reaction.

3.
J Am Chem Soc ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39295280

RESUMO

Metal-ligand cooperation (MLC) has emerged as a pivotal strategy for the catalytic activation of small molecules within both synthetic and biological arenas. Leveraging this approach, a suite of potent catalytic reactions─encompassing hydrogenation, hydroelementation, and dehydrogenative processes─have been realized, with notable advances in manganese catalysis in recent years. However, the activation of alkyl halides by Mn complexes, which typically requires strong reductants to form Mn(-I) complexes that are incompatible with standard cross-coupling conditions, remains a significant challenge. This limitation underscores the urgent need to investigate alternative methods for activating C(sp3)-X bonds using higher valence state Mn complexes. In response to this challenge, we present the synthesis, characterization, and reactivity of a new anionic Mn(I) complex featuring a redox-active dianionic ligand that induces multiple MLC functionalities. We have discovered an innovative mechanism of MLC, characterized by a single ligand transferring two electrons to the metal center. This novel process facilitates an orbital-symmetry-allowed nucleophilic attack on C(sp3)-X bonds, preserving manganese's oxidative state at +1. To the best of our knowledge, this is the first instance where the MLC strategy via a two-electron transfer process has been utilized to execute an SN2 nucleophilic attack at a C(sp3)-X bond by a relatively electron-deficient metal center like Mn(I). Additionally, the dianionic ligand of the anionic Mn(I) complex exhibits ambident nucleophilicity by reacting with different electrophiles, further highlighting its versatile reactivity.

4.
Cell Rep Med ; 5(9): 101709, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39226895

RESUMO

Cryptorchidism, commonly known as undescended testis, affects 1%-9% of male newborns, posing infertility and testis tumor risks. Despite its prevalence, the detailed pathophysiology underlying male infertility within cryptorchidism remains unclear. Here, we profile and analyze 46,644 single-cell transcriptomes from individual testicular cells obtained from adult males diagnosed with cryptorchidism and healthy controls. Spermatogenesis compromise in cryptorchidism links primarily to spermatogonium self-renewal and differentiation dysfunctions. We illuminate the involvement of testicular somatic cells, including immune cells, thereby unveiling the activation and degranulation of mast cells in cryptorchidism. Mast cells are identified as contributors to interstitial fibrosis via transforming growth factor ß1 (TGF-ß1) and cathepsin G secretion. Furthermore, significantly increased levels of secretory proteins indicate mast cell activation and testicular fibrosis in the seminal plasma of individuals with cryptorchidism compared to controls. These insights serve as valuable translational references, enriching our comprehension of testicular pathogenesis and informing more precise diagnosis and targeted therapeutic strategies for cryptorchidism.


Assuntos
Criptorquidismo , Perfilação da Expressão Gênica , Análise de Célula Única , Espermatogênese , Transcriptoma , Criptorquidismo/genética , Criptorquidismo/patologia , Criptorquidismo/metabolismo , Masculino , Humanos , Análise de Célula Única/métodos , Espermatogênese/genética , Transcriptoma/genética , Testículo/metabolismo , Testículo/patologia , Mastócitos/metabolismo , Mastócitos/patologia , Adulto , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Fibrose , Espermatogônias/metabolismo , Espermatogônias/patologia
5.
Orthop J Sports Med ; 12(9): 23259671241253551, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39291126

RESUMO

Background: The Chinese unique inlay Bristow (Cuistow) procedure is a modified Bristow surgery in which an inlay (mortise-and-tenon) structure is added to the contact surface between the coracoid tip and the glenoid. Patients who have undergone the Cuistow procedure have had satisfying clinical performance and excellent postoperative bone healing rates (96.1%). Purpose: To compare the clinical and radiographic outcomes after the arthroscopic Cuistow procedure and the arthroscopic Bristow procedure. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 91 patients who underwent either the Cuistow or Bristow procedure between January 2017 and March 2018 were selected, and 69 patients (70 shoulders; 35 in the Cuistow group and 35 in the Bristow group) were included. Clinical assessment at minimum 24 months postoperatively, including the visual analog scale for pain and instability, American Shoulder and Elbow Surgeons score, Rowe score, subjective shoulder value score, and active range of motion, was completed by independent observers and compared with values collected preoperatively. Assessment with 3-dimensional computed tomography scans was performed preoperatively; immediately after the operation; at 3, 6, and 12 months postoperatively; and at the final follow-up. Results: A total of 69 patients (70 shoulders) were included, with a mean follow-up duration of 34.41 ± 5.99 months (range, 24-50 months). Both groups saw significant improvement in visual analog scale for pain and instability, American Shoulder and Elbow Surgeons, Rowe, and subjective shoulder value scores at the final follow-up compared with the preoperative values (P < .001 for all), with no significant between-group differences on any clinical outcomes at the final follow-up. The 3-month postoperative graft union rate on computed tomography was significantly higher in the Cuistow group compared with the Bristow group (82.9% vs 51.4%, respectively, P = .003), although the graft union rate at the final follow-up was not significantly different (94.3% vs 85.7%, respectively; P = .449). Conclusion: Patients receiving the Cuistow procedure had equivalent clinical outcomes and a significantly higher bone union rate at 3 months postoperatively than those in the Bristow group. The inlay structure used in the Cuistow procedure was found to be associated with accelerated bone union.

6.
Pestic Biochem Physiol ; 204: 106101, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277423

RESUMO

Riptortus pedestris (Hemiptera: Alydidae), a common agricultural pest, is the major causative agent of "soybean staygreen." However, the interactions between chemosensory proteins (CSPs) in R. pedestris and host plant volatiles have yet to be comprehensively studied. In this study, we performed real-time fluorescence quantitative polymerase chain reaction (PCR) to analyze the antennal expression of RpedCSP22 and subsequently analyzed the interactions between 21 soybean volatiles, five aggregation pheromones, and RpedCSP22 protein in vitro using a protein expression system, molecular docking, site-directed mutagenesis, and fluorescence competitive binding experiments. The RpedCSP22 protein showed binding affinity to three soybean volatiles (benzaldehyde, 4-ethylbenzaldehyde, and 1-octene-3-ol), with optimal binding observed under neutral pH conditions, and lost binding ability after site-directed mutagenesis. In subsequent RNA interference (RNAi) studies, gene silencing was more than 90 %, and in silenced insects, electroantennographic responses were reduced by more than 75 % compared to non-silenced insects. Moreover, Y-tube olfactory behavioral assessments revealed that the attraction of R. pedestris to the three soybean volatiles was significantly attenuated. These findings suggest that RpedCSP22 plays an important role in the recognition of host plant volatiles by R. pedestris andprovides a theoretical basis for the development of novel inhibitors targeting pest behavior.


Assuntos
Glycine max , Proteínas de Insetos , Compostos Orgânicos Voláteis , Animais , Glycine max/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/química , Compostos Orgânicos Voláteis/metabolismo , Mutagênese Sítio-Dirigida , Simulação de Acoplamento Molecular , Hemípteros/metabolismo , Hemípteros/genética , Antenas de Artrópodes/metabolismo , Feromônios/metabolismo , Heterópteros/metabolismo , Heterópteros/genética
7.
Anim Nutr ; 18: 272-283, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39281046

RESUMO

Lauric acid (LA) has the possibility to improve milk production in dairy cows by improving mammary gland development, however, the mechanism by which it might regulate mammary gland development is unclear. The influence of LA on milk production, nutrient digestibility and the expression of proteins related to mammary gland development in dairy cows were evaluated. Forty primiparous Holstein dairy cows were divided into 4 groups in a randomized block design. Four treatments included the control (0 g/d LA per cow), low-LA (100 g/d LA per cow), medium-LA (200 g/d LA per cow), and high-LA (300 g/d LA per cow). Yields of milk, fat-corrected milk, and energy-corrected milk quadratically increased (P < 0.05), and yield and content of milk fat linearly increased (P < 0.05) with LA supplementation. Percentages of C12:0, C18:1 and C20:1 fatty acids in milk fat linearly increased (P < 0.05), but that of C16:0 fatty acid linearly decreased (P = 0.046). Supplementation of LA led to a linear and quadratical increase (P < 0.05) in digestibility of dry matter, organic matter, neutral detergent fibre and acid detergent fibre, and ruminal total volatile fatty acid concentration but a linear reduction (P = 0.018) in the ratio of acetate to propionate. The enzymatic activities of ruminal pectinase, xylanase, and α-amylase, and populations of total bacteria and anaerobic fungi increased linearly (P < 0.05), while populations of total protozoa and methanogens decreased linearly (P < 0.05) with increased LA addition. Following LA addition, blood glucose, triglyceride, estradiol, prolactin, and insulin-like growth factor 1 concentrations increased linearly (P < 0.05) and albumin and total protein concentrations increased quadratically (P < 0.05). Moreover, addition of 200 g/d LA promoted (P < 0.05) the expression of protein involved in mammary gland development and fatty acids synthesis. These results suggested that LA addition enhanced milk production and fatty acids synthesis by stimulating nutrient digestion, the expression of proteins associated with milk fat synthesis and mammary gland development.

8.
MedComm (2020) ; 5(10): e698, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39286777

RESUMO

Toremifene, a selective estrogen receptor modulator, is commonly used in China for premenopausal breast cancer patients. This real-world study aimed to compare patient-reported outcome (PRO) and survival between toremifene and aromatase inhibitor (AI) plus ovarian function suppression (OFS) in patients with moderate-/high-risk premenopausal hormone receptor (HR)-positive breast cancer. The primary endpoint was PROs, assessed using SF-36 and EQ-5D-5L questionnaires between January and March 2023. A total of 392 patients were included, with 171 receiving toremifene and 221 receiving AI. The toremifene group showed significantly higher scores in the role physical (p = 0.034) and mental health (p = 0.009) dimensions of SF-36 and lower anxiety/depression (AD) scores (p = 0.038) in EQ-5D-5L compared to AI group. The estimated 5- and 8-year disease-free survival (DFS) rates were similar in toremifene and AI groups: 96.5% versus 91.9%, and 87.4% versus 87.8% (p = 0.39), respectively. Adverse event rates were similar in two groups, except for a greater risk of endometrial thickening (p < 0.001) and a lower occurrence of morning stiffness (p < 0.001) in the toremifene compared to the AI group. Premenopausal HR-positive breast cancer patients receiving toremifene plus OFS had better role physical and mental health outcomes and lower AD dimensions than those receiving AI plus OFS. Both treatments had comparable DFS and favorable tolerability profiles.

9.
Sci Total Environ ; : 176303, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299339

RESUMO

The use of bio-based composites to enhance the methane production in anaerobic digestion has attracted considerable attention. Nevertheless, the study of electron transfer mechanisms and the applications of biochar/MnO2 (MBC) in complex systems remains largely unexplored. Biochar composited with MnO2 at 10:1 mass ratio (MBC10) increased the content of volatile fatty acids by 9.09 % during acidogenic phase. During the methanogenic experiments using acetate, cumulative methane production (CMP) rose by 5.83 %, and in the methanogenic experiments using food waste, CMP increased by 24.32 %. Microbial community analysis indicated an enrichment of Syntrophomonas, Bacilli, and Methanosaetaceae in the MBC10 group. This enrichment occurred mainly due to the redox capability of MnO2 enhancing MBC capacitance, thereby facilitating microbial electron transfer processes. Additionally, under 2 g/L ammonia nitrogen concentration and 30 g/L organic load, the CMP of MBC10 increased by 12.74 % and 9.44 %, respectively, compared to the BC600 group. This study illuminates MBC's electron transfer mechanisms and applications, facilitating its wider practical adoption and fostering future innovations.

10.
Chemosphere ; : 143358, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299463

RESUMO

Biochar modification is an effective approach to enhance its ability to promote anaerobic digestion (AD). Focusing on the physical properties of biochar, the impact of different particle sizes of biochar on AD of food waste (FW) at high organic loading rate (OLR) was investigated. Four biochar with different sizes (40 - 200 mesh) were prepared and used in AD systems at OLR 30 g VS/L. The research results found that biochar with a volume particle size of 102 µm (RBC-P140) had top-performance in promoting cumulative methane production, increasing by 13.20% compared to the control group. The analysis results of the variety in volatile acids and alkalinity in the system did not show a correlation with the size of biochar, but small size has the potential to improve the environmental tolerance of the system to high acidity. Microbial community analysis showed that the abundance of aceticlastic methanogen and the composition of zoogloea were optimized through relatively small-sized biochar. Through revealing the effect of biochar particle size on AD system at high OLR, this work provided theoretical guidance for regulating fermentation systems using biochar.

11.
Clin Epigenetics ; 16(1): 122, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39244604

RESUMO

BACKGROUND AND PURPOSE: Early detection, diagnosis, and treatment of colorectal cancer and its precancerous lesions can significantly improve patients' survival rates. The purpose of this research is to identify methylation markers specific to colorectal cancer tissues and validate their diagnostic capability in colorectal cancer and precancerous changes by measuring the level of DNA methylation in stool samples. METHOD: We analyzed samples from six cancer tissues and adjacent normal tissues and fecal samples from 758 participants, including 62 patients with interfering diseases. Bioinformatics databases were used to screen for candidate biomarkers for CRC, and quantitative methylation-specific PCR methods were applied for identification. The methylation levels of the candidate biomarkers in fecal and tissue samples were measured. Logistic regression and random forest models were built and validated using fecal sample data from one of the centers, and the independent or combined diagnostic value of the candidate biomarkers in fecal samples for CRC and precancerous lesions was analyzed. Finally, the diagnostic capability and stability of the model were validated at another medical center. RESULTS: This study identified two colorectal cancer CpG sites with tissue specificity. These two biomarkers have certain diagnostic power when used individually, but their diagnostic value for colorectal cancer and colorectal adenoma is more significant when they are used in combination. CONCLUSION: The results indicate that a DNA methylation biomarker combined diagnostic model based on two CpG sites, cg13096260 and cg12587766, has the potential for screening and diagnosing precancerous lesions and colorectal cancer. Additionally, compared to traditional diagnostic models, machine learning algorithms perform better but may yield more false-positive results, necessitating further investigation.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Metilação de DNA , Fezes , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/diagnóstico , Metilação de DNA/genética , Feminino , Masculino , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Fezes/química , Idoso , Ilhas de CpG/genética , Detecção Precoce de Câncer/métodos , Adulto
12.
Asian J Pharm Sci ; 19(4): 100946, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39246508

RESUMO

Acne vulgaris ranks as the second most prevalent dermatological condition worldwide, and there are still insufficient safe and reliable drugs to treat it. Cryptotanshinone (CTS), a bioactive compound derived from traditional Chinese medicine Salvia miltiorrhiza, has shown promise for treating acne vulgaris due to its broad-spectrum antimicrobial and significant anti-inflammatory properties. Nevertheless, its local application is hindered by its low solubility and poor skin permeability. To overcome these challenges, a carrier-free pure drug self-assembled nanosystem is employed, which can specifically modify drug molecules based on the disease type and microenvironment, offering a potential for more effective treatment. We designed and synthesized three distinct structures of cationic CTS-peptide conjugates, creating self-assembled nanoparticles. This study has explored their self-assembly behavior, skin permeation, cellular uptake, and both in vitro and in vivo anti-acne effects. Molecular dynamics simulations revealed these nanoparticles form through intermolecular hydrogen bonding and π-π stacking interactions. Notably, self-assembled nanoparticles demonstrated enhanced bioavailability with higher skin permeation and cellular uptake rates. Furthermore, the nanoparticles exhibited superior anti-acne effects compared to the parent drug, attributed to heightened antimicrobial activity and significant downregulation of the MAPK/NF-κB pathway, leading to reduced expression of pro-inflammatory factors including TNF-α, IL-1ß and IL-8. In summary, the carrier-free self-assembled nanoparticles based on CTS-peptide conjugate effectively address the issue of poor skin bioavailability, offering a promising new approach for acne treatment.

13.
J Cancer ; 15(16): 5462-5476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247603

RESUMO

Breast cancer (BC) is a prevalent malignancy globally. Autophagy plays a pivotal role in all stages of this disease, including development, metastasis, and onset. Therefore, it is envisaged that targeting cell autophagy through appropriate tactics would evolve into a novel breast cancer prevention and therapy strategy. A multitude of chemotherapeutic medications can stimulate autophagy in tumor cells. It has led to divergent opinions on the function of autophagy in cancer treatment, as both stimulating and blocking autophagy can improve the effectiveness of anticancer medications. Consequently, the decision of whether to stimulate or inhibit autophagy during breast cancer treatment has become crucial. Understanding the distinctive mechanisms of autophagy in BC and its significance in medication therapy might facilitate the creation of targeted treatment plans based on the roles particular to autophagy. This review summarizes recent studies on the autophagy mechanism in breast cancer and provides insights into autophagy-based BC therapeutic techniques, giving fresh avenues for future BC treatment.

14.
CNS Neurosci Ther ; 30(9): e70024, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39218798

RESUMO

AIMS: Type 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT-1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT-1 expression. METHODS: T2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT-1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long-term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT-1 in GFAP-Cre mice. Besides, AAV-Camkllα-hM4Di-mCherry was injected to inhibit neuronal hyperexcitability in CA1 region. RESULTS: Our study found T2DM but not A/S reduced GLT-1 expression in hippocampal astrocytes. Interestingly, GLT-1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT-1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT-1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction. CONCLUSIONS: These findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT-1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis.


Assuntos
Astrócitos , Diabetes Mellitus Tipo 2 , Regulação para Baixo , Transportador 2 de Aminoácido Excitatório , Hipocampo , Camundongos Endogâmicos C57BL , Complicações Cognitivas Pós-Operatórias , Animais , Transportador 2 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/biossíntese , Transportador 2 de Aminoácido Excitatório/genética , Astrócitos/metabolismo , Complicações Cognitivas Pós-Operatórias/etiologia , Complicações Cognitivas Pós-Operatórias/metabolismo , Hipocampo/metabolismo , Camundongos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Transgênicos
15.
Microsc Res Tech ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39257069

RESUMO

Dragonflies are some of the most stable and maneuverable flying organisms. To explore the mechanism of how dragonfly leading edges enhance flight lift, this article conducts a detailed study on the leading edge veins and the microstructures on them of dragonfly wings. Observations have discovered the special leading edge vein and the regularly distributed microstructures on the leading edge vein. A biomimetic model has been established, and computational fluid dynamics (CFD) simulation analysis has been conducted on the biomimetic model. The analysis explores the effects of microstructure characteristics, distribution patterns, and positions on the aerodynamic characteristics of dragonfly gliding. The analysis shows that the leading edge structure influences the incoming flow, simultaneously promotes the formation of the leading edge vortex (LEV), and increases the lift-to-drag ratio by up to 4%. A wing prototype featuring biomimetic microstructures is subsequently fabricated and tested in wind tunnel experiments. Compared with a control group without leading edge structures, the airflow passing through the biomimetic structures is influenced by the shape and arrangement of these structures. The smoother transition of the leading edge vein's shape facilitates the flow of air. The microstructures primarily filter and accelerate the airflow. The spacing of the microstructures affects the stability of the airflow, thereby influencing aerodynamic performance. Additionally, the middle-row arrangement of microstructures is more beneficial for gliding conditions, while the upper-row arrangement is more advantageous for flapping conditions. These findings enhance our understanding of insect wings and advance micro aerial vehicle applications. RESEARCH HIGHLIGHTS: This study observed the leading-edge veins and microstructures of dragonfly wings in detail. Using a biomimetic model and computational fluid dynamics (CFD) simulations, it was found that these leading-edge structures promote the formation of leading-edge vortices (LEV), increasing the lift-to-drag ratio by up to 4%. Wind tunnel experiments demonstrated that wings with biomimetic microstructures significantly improved airflow smoothness and lift compared with control wings. Additionally, the arrangement of microstructures greatly affects airflow stability and aerodynamic performance, with middle-row arrangements being more beneficial for gliding and upper-row arrangements for flapping conditions. These findings enhance our understanding of insect wings and provide innovative guidance for designing efficient micro aerial vehicles.

16.
J Biol Chem ; : 107770, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39270823

RESUMO

Dynamic ADP-ribosylation signalling is a crucial pathway that controls fundamental cellular processes, in particular, the response to cellular stresses such as DNA damage, reactive oxygen species and infection. In some pathogenic microbes the response to oxidative stress is controlled by a SirTM/zinc-containing macrodomain (Zn-Macro) pair responsible for establishment and removal of the modification, respectively. Targeting this defence mechanism against the host's innate immune response may lead to novel approaches to support the fight against emerging antimicrobial resistance. Earlier studies suggested that Zn-Macros play a key role in the activation of this defence. Therefore, we used phylogenetic, biochemical, and structural approaches to elucidate the functional properties of these enzymes. Using the substrate mimetic asparagine-ADP-ribose as well as the ADP-ribose product, we characterise the catalytic role of the zinc ion in the removal of the ADP-ribosyl modification. Furthermore, we determined structural properties that contribute to substrate selectivity within the different Zn-Macro branches. Together, our data not only give new insights into the Zn-Macro family but also highlight their distinct features that may be exploited for the development of future therapies.

17.
J Am Chem Soc ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264946

RESUMO

The ligated boryl radical (LBR) has emerged as a potent tool for activating alkyl halides in radical transformations through halogen-atom transfer (XAT). However, unactivated alkyl chlorides still present an open challenge for this strategy. We herein describe a new activation mode of the LBR for the activation of unactivated alkyl chlorides to construct a C(sp3)-C(sp3) bond. Mechanistic studies reveal that the success of the protocol relies on a radical replacement process between the LBR and unactivated alkyl chloride, forming an alkyl borane intermediate as the alkyl radical precursor. Aided with the additive K3PO4, the alkyl borane then undergoes one-electron oxidation, generating an alkyl radical. The incorporation of the radical replacement activation model to activate unactivated alkyl chlorides significantly enriches LBR chemistry, which has been applied to activate alkyl iodides, alkyl bromides, and activated alkyl chlorides via XAT.

19.
BMC Psychol ; 12(1): 469, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223690

RESUMO

In environments teeming with distractions, the ability to selectively focus on relevant information is crucial for advanced cognitive processing. Existing research using event-related potential (ERP) technology has shown active suppression of irrelevant stimuli during the consolidation phase of visual working memory (VWM). In previous studies, participants have always been given sufficient time to consolidate VWM, while suppressing distracting information. However, it remains unclear whether the suppression of irrelevant distractors requires continuous effort throughout their presence or whether this suppression is only necessary after the consolidation of task-relevant information. To address this question, our study examines whether distractor suppression is necessary in scenarios where consolidation time is limited. This research investigates the effect of varying presentation durations on the filtering of distractors in VWM. We tasked participants with memorizing two color stimuli and ignoring four distractors, presented for either 50 ms or 200 ms. Using ERP technology, we discovered that the distractor-induced distractor positivity (PD) amplitude is larger during longer presentation durations compared to shorter ones. These findings underscore the significant impact of presentation duration on the efficacy of distractor suppression in VWM, as prolonged exposure results in a stronger suppression effect on distractors. This study sheds light on the temporal dynamics of attention and memory, emphasizing the critical role of stimulus timing in cognitive tasks. These findings provide valuable insights into the mechanisms underlying VWM and have significant implications for models of attention and memory.


Assuntos
Atenção , Eletroencefalografia , Potenciais Evocados , Memória de Curto Prazo , Percepção Visual , Humanos , Memória de Curto Prazo/fisiologia , Atenção/fisiologia , Masculino , Feminino , Potenciais Evocados/fisiologia , Adulto Jovem , Adulto , Percepção Visual/fisiologia , Fatores de Tempo , Estimulação Luminosa
20.
PLoS One ; 19(9): e0308245, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39240851

RESUMO

In this paper, the buckling behaviour of rectangular and skew plates with elastically restrained edges subjected to non-uniform mechanical edge loading is investigated. An analysis method is developed for calculating the critical buckling load of plates using the Ritz method under non-uniform mechanical edge loading, in which the shape function is expressed as Legendre polynomials. The in-plane stress distribution under non-uniform mechanical edge loading is defined by the pre-buckling analysis. Contributions of elastic boundary conditions are taken into accounted by giving different edge spring stiffnesses. The proposed method for buckling analysis of plates is validated by the comparison of exiting results in literature. Finally, the effects of the edge restrained stiffness, non-uniform edge loading, skew angle, aspect ratio and combined compression-shear load are discussed by parametric analysis.


Assuntos
Estresse Mecânico , Elasticidade , Modelos Teóricos
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