Search Results (192)

The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global issue since 2019. The prominent characteristic of SARS-CoV-2 is the presence of the spike (S) protein protruding from the virus particle envelope. The S protein is a major drug and vaccine target because it initiates the key step in infection. Medicinal herbs are a potential treatment option to enhance immunity to fight viral infections. Caesalpinia sappan L. has been reported to display promising anti-viral activities. Specifically, brazilin (BRA), a major bioactive compound in C. sappan, was reported to play a role in inhibiting viral infection. Thus, the ability of BRA as a COVID-19 treatment was tested. The S protein was used as the BRA target of this work. Understanding the binding mechanism of BRA to the S protein is crucial for future utilisation of C. sappan as a COVID-19 treatment or other coronavirus-caused pandemics. Here, we performed molecular docking of BRA onto the S protein receptor binding domain (RBD) and multimerisation (MM) pockets. Molecular dynamics (MD) simulations were conducted to study the stability of binding to glycosylated and non-glycosylated S protein constructs. BRA can bind to the Receptor-binding motif (RBM) on an RBD surface stably; however, it is too large to fit into the MM pocket, resulting in dissociation. Nonetheless, BRA is bound by residues near the S1/S2 interface. We found that glycosylation has no effect on BRA binding, as the proposed binding site is far from any glycans. Our results thus indicate that C. sappan may act as a promising preventive and therapeutic alternative for COVID-19 treatment. Full article

Pulmonary fibrosis (PF) is a progressive lung disease with a poor prognosis. Pirfenidone (PFD) can slow down the decline of lung function, but defects in efficacy and accompanying side effects limit its application; hence, implementing methods including combination therapy might be a viable option. Given this, we hypothesized that combining timosaponin BII (TS BII) with PFD might offer a more effective treatment approach. Bleomycin-induced rodent PF model and TGF-β1-induced cellular epithelial–mesenchymal transition (EMT) model were applied in the study. The results showed that the combination of TS BII and PFD was more effective in reducing the production of IL-1β, TNF-α, collagen fibers, hydroxyproline, and MDA. Moreover, the combination treatment could better restore levels SOD and GSH-Px. In addition, TS BII combined with PFD could downregulate the expression of NF-κB and the ratio of p-IκBα/IκBα, and modulate the aberrant expression of epithelial–mesenchymal transition markers. In addition, the combination treatment could regulate the intestinal flora of PF mice. It is worth noting that among the above results, there were significant differences (p < 0.05) between the combination group and either the TS BII or PFD monotherapy group. These findings indicate that the combination of TS BII and PFD has a synergistic effect in the treatment of PF and represents a promising treatment strategy. Full article

Background/Objectives: According to previous research, the process of autophagy in myeloid neoplasms has proven to be ambivalent depending on the type and stage of the disease. The aim of our work was to investigate the mechanism of autophagy in patients with primary and secondary myelofibrosis. Methods: Based on the RT-PCR method, we retrospectively analyzed the expression of Beclin-1 and LC3B-II in bone marrow cells of patients with primary and secondary myelofibrosis (74 participants) compared to the control group which had patients with lymphoma in a localized stage without bone marrow infiltration (11 participants). Results: There was no statistically significant difference in the expression of Beclin-1 and LC3B-II between patients with primary and secondary myelofibrosis and control participants. Among patients with primary myelofibrosis, higher expression of LC3B-II was statistically significantly associated with lower DIPSS. Higher Beclin-1 expression was statistically significantly associated with better patient survival. Conclusions: Our results suggest that the upregulation of autophagy genes may be associated with favorable prognosis and survival of patients with myelofibrosis. Full article

Autophagy is a critical mechanism by which methamphetamine (METH) induces neuronal damage and neurotoxicity. Prolonged METH exposure can result in the accumulation of autophagosomes within cells. The autophagy process encompasses several essential vesicle-related biological steps, collectively referred to as the autophagic flux. However, the precise mechanisms by which METH modulates the autophagic flux and the underlying pathways remain to be elucidated. In this study, we utilized a chronic METH exposure mouse model and cell model to demonstrate that METH treatment leads to an increase in p62 and LC3B-II and the accumulation of autophagosomes in striatal neurons and SH-SY5Y cells. To assess autophagic flux, this study utilized autophagy inhibitors and inducers. The results demonstrated that the lysosomal inhibitor chloroquine exacerbated autophagosome accumulation; however, blocking autophagosome formation with 3-methyladenine did not prevent METH-induced autophagosome accumulation. Compared to the autophagy activator rapamycin, METH significantly reduced autophagosome–lysosome fusion, leading to autophagosome accumulation. Rab7a is a critical regulator of autophagosome–lysosome fusion. Although Rab7a expression was upregulated in SH-SY5Y cells and brain tissues after METH treatment, immunoprecipitation experiments revealed weakened interactions between Rab7a and the lysosomal protein RILP. Overexpression of active Rab7a (Rab7a Q67L) significantly alleviated the METH-induced upregulation of LC3-II and p62. PTEN, a key regulator of Rab7a dephosphorylation, was downregulated following METH treatment, resulting in decreased Rab7a dephosphorylation and reduced Rab7a activity, thereby contributing to autophagosome accumulation. We further investigated the role of neuronal exosomes in the autophagy process. Our results demonstrated that the miRNA expression profiles in exosomes released by METH-induced SH-SY5Y cells were significantly altered, with 122 miRNAs upregulated and 151 miRNAs downregulated. KEGG and GO enrichment analyses of these differentially expressed miRNAs and their target genes revealed significant associations with the autophagy pathway and potential regulation of PTEN expression. Our experiments confirmed that METH-induced exosomes reduced PTEN expression levels and decreased Rab7a dephosphorylation, thereby exacerbating autophagic flux impairment and autophagosome accumulation. In conclusion, our study indicated that METH and its induced neuronal exosomes downregulate PTEN expression, leading to reduced Rab7a dephosphorylation. This, in turn, hinders the fusion of autophagosomes and lysosomes, ultimately resulting in autophagic flux impairment and neuronal damage. Full article

Bismuth-based perovskite derivatives, (CH₃NH₃)₃Bi₂I₉ (MBI), are promising non-toxic light-absorbing materials widely used in various photoelectric devices because of their excellent stability. However, MBI-based perovskite solar cells (PSCs) are limited by poor film quality, and the performance of such a device is far behind that of lead-based PSCs. In this work, the crystal structure and morphological properties of MBI films were compared across different preparation methods. The two-step vapor-assisted method can prepare continuous dense MBI films because MBI crystal nucleation is induced by the BiI₃ seed layer. The MBI film grown by this method is better for the production of excellent PSCs compared to the film prepared by the solution method. The best photovoltaic device based on the MBI film could obtain a power conversion efficiency of 1.13%. An MBI device is stored in the glove box for 60 days, and the device’s performance is maintained at 99%. These results indicate that the vapor-assisted deposition of MBI films can be an effective method to improve the performance of bismuth-based planar PSCs. Full article

Niacinamide, a derivative of vitamin B3, has been shown to reduce skin pigmentation (i.e., acting as a brightening agent) and inflammatory responses such as dermatitis and acne vulgaris. However, niacinamide is a hydrophilic compound and poor partitioning to the lipid matrix in the uppermost layer of the skin (the stratum corneum or SC) limits its delivery to the skin. This necessitates the use of penetration enhancers to increase its bio-availability. In this study, we used computer simulations to investigate the skin penetration of niacinamide alone and in combination with other brightening agents that are also shown to be skin penetration enhancers, namely undecylenoyl phenylalanine (Sepiwhite^®), bisabolol, or sucrose dilaurate. Molecular dynamics simulations were performed to reveal molecular interactions of these brightening agents with a lipid bilayer model that mimics the SC lipid matrix. We observed minimal penetration of niacinamide into the SC lipid bilayer when applied alone or in combination with any one of the three compounds. However, when all three compounds were combined, a notable increase in penetration was observed. We showed a 32% increase in the niacinamide diffusivity in the presence of three other brightening agents, which also work as penetration enhancers for niacinamide. These findings suggest that formulations containing multiple brightening agents, which work as penetration enhancers, may improve skin penetration of niacinamide and enhance the effectiveness of the treatment. Full article

Copper (Cu) is a global environmental pollutant that poses a serious threat to humans and ecosystems. Copper induces developmental neurotoxicity, but the underlying molecular mechanisms are unknown. Neurons are nonrenewable, and they are unable to mitigate the excessive accumulation of pathological proteins and organelles in cells, which can be ameliorated by autophagic degradation. In this study, we established an in vitro model of Cu²⁺-exposed (0, 15, 30, 60 and 120 μM) SH-SY5Y cells to explore the role of autophagy in copper-induced developmental neurotoxicity. The results showed that copper resulted in the reduction and shortening of neural synapses in differentiated cultured SH-SY5Y cells, a downregulated Wnt signaling pathway, and nuclear translocation of β-catenin. Exposure to Cu²⁺ increased autophagosome accumulation and autophagic flux blockage in terms of increased sequestosome 1 (p62/SQSTM1) and microtubule-associated protein 1 light chain 3B (LC3B) II/LC3BI expressions and inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway. Furthermore, copper induced apoptosis, characterized by increased expressions of Bcl2 X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and decreased expression of B-cell lymphoma 2 (Bcl2). Compared with the 120 μM Cu²⁺ exposure group alone, autophagy activator rapamycin pretreatment increased expression of Wnt and β-catenin nuclear translocation, decreased expression of LC3BII/LC3BI and p62, as well as upregulated expression of Bcl2 and downregulated expressions of caspase 3 and PARP. In contrast, after autophagy inhibitor chloroquine pretreatment, expressions of Wnt and β-catenin nuclear translocation were decreased, expression levels of LC3BII/LC3BI and p62 were upregulated, expression of Bcl2 was decreased, while expression levels of caspase 3, Bax, and PARP were increased. In conclusion, the study demonstrated that autophagosome accumulation and autophagic flux blockage were associated with copper-induced developmental neurotoxicity via the Wnt signaling pathway, which might deepen the understanding of the developmental neurotoxicity mechanism of environmental copper exposure. Full article

Adjuvants are a diverse group of substances that can be added to vaccines to enhance antigen-specific immune responses and improve vaccine efficacy. The first adjuvants, discovered almost a century ago, were soluble crystals of aluminium salts. Over the following decades, oil emulsions, vesicles, oligodeoxynucleotides, viral capsids, and other complex organic structures have been shown to have adjuvant potential. However, the detailed mechanisms of how adjuvants enhance immune responses remain poorly understood and may be a barrier that reduces the rational selection of vaccine components. Previous studies on mechanisms of action of adjuvants have focused on how they activate innate immune responses, including the regulation of cell recruitment and activation, cytokine/chemokine production, and the regulation of some “immune” genes. This approach provides a narrow perspective on the complex events involved in how adjuvants modulate antigen-specific immune responses. A comprehensive and efficient way to investigate the molecular mechanism of action for adjuvants is to utilize systems biology approaches such as transcriptomics in so-called “systems vaccinology” analysis. While other molecular biology methods can verify if one or few genes are differentially regulated in response to vaccination, systems vaccinology provides a more comprehensive picture by simultaneously identifying the hundreds or thousands of genes that interact with complex networks in response to a vaccine. Transcriptomics tools such as RNA sequencing (RNA-Seq) allow us to simultaneously quantify the expression of practically all expressed genes, making it possible to make inferences that are only possible when considering the system as a whole. Here, we review some of the challenges in adjuvant studies, such as predicting adjuvant activity and toxicity when administered alone or in combination with antigens, or classifying adjuvants in groups with similar properties, while underscoring the significance of transcriptomics in systems vaccinology approaches to propel vaccine development forward. Full article

This work describes a novel method for converting bismuth triiodide (BiI₃) microplates into bismuth oxyiodide (BiOI) nanoflakes under ultrasonic irradiation. To produce BiOI nanoflakes with a high yield and high purity, the conversion process was carefully adjusted. Rapid reaction kinetics and increased mass transfer are benefits of the ultrasonic-assisted approach that result in well-defined converted BiOI nanostructures with superior characteristics. The produced BiOI nanoflakes were examined utilizing a range of analytical methods, such as Transmission Electron Microscopy (TEM), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The progress in the ultrasonic conversion process with time was monitored through diffuse reflectance spectroscopy (DRS). The outcomes demonstrated the effective conversion of BiI₃ microplates into crystalline, homogeneous, high-surface-area BiOI nanoflakes. Additionally, the degradation of organic dyes (methylene blue) under ultraviolet (UV) light irradiation was used to assess the photocatalytic efficacy of the produced BiOI nanoflakes. Because of their distinct morphology and electrical structure, the BiOI nanoflakes remarkably demonstrated remarkable photocatalytic activity, outperforming traditional photocatalysts. The ability of BiOI nanoflakes to effectively separate and utilize visible light photons makes them a viable option for environmental remediation applications. This work not only shows the promise of BiOI nanoflakes for sustainable photocatalytic applications but also demonstrates a simple and scalable approach to their manufacturing. The knowledge gathered from this work opens up new avenues for investigating ultrasonic-assisted techniques for creating sophisticated nanomaterials with customized characteristics for a range of technological uses. Full article

The incidence of breast implant illness (BII) and BII-related explant procedures has not decreased with current surgical and treatment techniques. It is speculated the main underlying cause of BII complications is the result of chronic, sub-clinical infections residing on and around the implant. The infection, and subsequent biofilm, produce antagonistic compounds that drive chronic inflammation and immune responses. In this study, the microbial communities in over 600 consecutive samples of infected explant capsules and tissues were identified via next-generation sequencing to identify any commonality between samples. The majority of the bacteria identified were Gram-positive, with Cutibacterium acnes and Staphylococcus epidermidis being the dominant organisms. No correlation between sample richness and implant filling was found. However, there was a significant correlation between sample richness and patient age. Due to the complex nature, breast augmentation failures may be better addressed from a holistic approach than one of limited scope. Full article

Aging is an inevitable biological process that contributes to the onset of age-related diseases, often as a result of mitochondrial dysfunction. Understanding the mechanisms behind aging is crucial for developing therapeutic interventions. This study investigates the effects of curcumin on postmitotic cellular lifespan (PoMiCL) during chronological aging in yeast, a widely used model for human postmitotic cellular aging. Our findings reveal that curcumin significantly prolongs the PoMiCL of wildtype yeast cells, with the most pronounced effects observed at lower concentrations, indicating a hormetic response. Importantly, curcumin also extends the lifespan of postmitotic cells with mitochondrial deficiencies, although the hormetic effect is absent in these defective cells. Mechanistically, curcumin inhibits TORC1 activity, enhances ATP levels, and induces oxidative stress. These results suggest that curcumin has the potential to modulate aging and offer therapeutic insights into age-related diseases, highlighting the importance of context in its effects. Full article

Robots are now widely used in assembly tasks. However, when robots perform the automatic assembly of Multi-Pin Circular Connectors (MPCCs), the small diameter of the pins and the narrow gaps between them present significant challenges. During the assembly process, the robot’s end effector can obstruct the view, and the contact between the pins and the corresponding holes is completely blocked, making this task more precise and challenging than the common peg-in-hole assembly. Therefore, this paper proposes a robotic assembly strategy for MPCCs that includes two main aspects: (1) we employ a vision-based Deep Siamese Neural Network (DSNN) model to address the most challenging peg-in-hole alignment problem in MPCC assembly. This method avoids the difficulties of modeling in traditional control strategies, the high training costs, and the low sample efficiency in reinforcement learning. (2) This paper constructs a complete practical assembly system for MPCCs, covering everything from gripping to final screwing. The experimental results consistently demonstrate that the assembly system integrated with the DSNN can effectively accomplish the MPCC assembly task. Full article

Couroupita guianensis, a medicinal plant autochthonal to South America and South India, is widely used in the ethnomedicine of the indigenous peoples of these regions thanks to its alleged antimicrobial, anti-inflammatory, antioxidant and wound-healing properties. The majority of studies have mainly analyzed organic extracts of the Indian plant’s flowers and leaves, with limited research on its bark decoction, traditionally used in Amazonian shamanic medicine. In this study, we investigated the anticancer effects of the bark decoction and its main fractions obtained through chromatographic separation, as well as the underlying molecular mechanisms in AGS gastric cancer cells. Viability, cell proliferation, cell cycle, apoptosis and protein expression related to these processes were evaluated. Both the bark decoction and fraction III significantly inhibited cell viability, and the cytotoxic effect was linked to cell cycle blockade and the induction of apoptosis also through an engulfment of the autophagic flux. Increased expression or activation of the key proteins (p53, p21, cdk2, Bak, caspases, pAMPK, pAkt, beclin, p62 and LC3BII) involved in these processes was observed. The results obtained confirmed an important anticancer effect of C. guianensis bark decoction, providing scientific validation for its use in traditional medicine and highlighting its potential as a therapeutic agent against gastric cancer. Full article

Autonomous pollination robots have been widely discussed in recent years. However, the accurate estimation of flower poses in complex agricultural environments remains a challenge. To this end, this work proposes the implementation of a transformer-based architecture to learn the translational and rotational errors between the pollination robot’s end effector and the target object with the aim of enhancing robotic pollination efficiency in cross-breeding tasks. The contributions are as follows: (1) We have developed a transformer architecture model, equipped with two feedforward neural networks that directly regress the translational and rotational errors between the robot’s end effector and the pollination target. (2) Additionally, we have designed a regression loss function that is guided by the translational and rotational errors between the robot’s end effector and the pollination targets. This enables the robot arm to rapidly and accurately identify the pollination target from the current position. (3) Furthermore, we have designed a strategy to readily acquire a substantial number of training samples from eye-in-hand observation, which can be utilized as inputs for the model. Meanwhile, the translational and rotational errors identified in the end-manipulator Cartesian coordinate system are designated as loss targets simultaneously. This helps to optimize the training of the model. We conducted experiments on a realistic robotic pollination system. The results demonstrate that the proposed method outperforms the state-of-the-art method, in terms of both accuracy and efficiency. Full article

Rotenone (ROT), the most significant rotenoid, which has shown anticancer activity, has also been reported to be toxic to normal cells, inducing Parkinson’s disease (PD)-like neuronal loss with aggregation of α-synuclein (α-syn). To reduce the adverse effects of ROT, its derivative, rotenoisin A (ROA), is obtained by directly irradiating a ROT solution in methanol using γ-rays, which has been reported for potential anticancer properties. However, its PD-inducing effects have not yet been researched or reported. This study sought to compare the activities of ROA and ROT on the aggregation of α-syn, apoptosis, and autophagy in SH-SY5Y cells. ROA decreased cell survival less when compared with ROT on SH-SY5Y cells at 48 h in a dose-dependent manner. ROT (0.5 and 1 μM) and ROA (4 and 5 μM) decreased the expression of tyrosine hydroxylase. Western blot analysis of the Triton X-100 insoluble fraction revealed that both ROT and ROA significantly increased the levels of oligomeric, dimeric, and monomeric phosphorylated Serine129 α-syn and total monomeric α-syn. Moreover, both compounds decreased the proportion of neuronal nuclei, the neurofilament-heavy chain, and β3-tubulin. The phosphorylation of ERK and SAPK were reduced, whereas ROA did not act on Akt. Additionally, the increased Bax/Bcl-2 ratio further activated the downstream caspases cascade. ROT promoted the LC3BII/I ratio and p62 levels; however, different ROA doses resulted in different effects on autophagy while inducing PD-like impairments in SH-SY5Y cells. Full article