Unlocking the role of non-coding RNAs in prostate cancer progression: exploring the interplay with the Wnt signaling pathway.

Prostate cancer (PCa) is one of the most common cancers in males, exhibiting a wide spectrum of clinical manifestations that pose challenges in its diagnosis and treatment. The Wnt signaling pathway, a conserved and complex pathway, is crucial for embryonic development, tissue homeostasis, and various physiological processes. Apart from the classical Wnt/ß-catenin signaling pathway, there exist multiple non-classical Wnt signaling pathways, including the Wnt/PCP and Wnt/Ca2+ pathways. Non-coding RNAs (ncRNAs) are involved in the occurrence and development of PCa and the response to PCa treatment. ncRNAs are known to execute diverse regulatory roles in cellular processes, despite their inability to encode proteins. Among them, microRNAs, long non-coding RNAs, and circular RNAs play key roles in the regulation of the Wnt signaling pathway in PCa. Aberrant expression of these ncRNAs and dysregulation of the Wnt signaling pathway are one of the causes of cell proliferation, apoptosis, invasion, migration, and angiogenesis in PCa. Moreover, these ncRNAs affect the characteristics of PCa cells and hold promise as diagnostic and prognostic biomarkers. Herein, we summarize the role of ncRNAs in the regulation of the Wnt signaling pathway during the development of PCa. Additionally, we present an overview of the current progress in research on the correlation between these molecules and clinical features of the disease to provide novel insights and strategies for the treatment of PCa.

A Conceptual Strategy toward High-Reliability Metal-Thermoplastic Hybrid Structures Based on a Covalent-Bonding Mechanism.

Metal-thermoplastic hybrid structures have proven their effectiveness to achieve lightweight design concepts in both primary and secondary structural components of advanced aircraft. However, the drastic differences in physical and chemical properties between metal and thermoplastic make it challenging to fabricate high-reliability hybrid structures. Here, a simple and universal strategy to obtain strong hybrid structures thermoplastics is reported by regulating the bonding behavior at metal/thermoplastic interfaces. To achieve such, we first researched and uncovered the bonding mechanism at metal/thermoplastic interfaces by experimental methods and density functional theory (DFT) calculations. The results suggest that the interfacial covalency, which is formed due to the interfacial reaction between high-electronegativity elements of thermoplastics and metallic elements at metal surfaces, dominates the interfacial bonding interaction of metal-thermoplastic hybrid structures. The differences in electronegativity and atomic size between bonding atoms influence the covalent-bond strength and finally control the interfacial reliability of hybrid structures. Based on our covalent-bonding mechanism, the carboxyl functional group (COOH) is specifically grafted on polyetheretherketone (PEEK) by plasma polymerization to increase the density and strength of interfacial covalency and thus fabricate high-reliability hybrid structures between PEEK and A6061-T6 aluminum alloy. Current work provides an in-depth understanding of the bonding mechanism at metal-thermoplastics interfaces, which opens a fascinating direction toward high-reliability metal-thermoplastic hybrid structures.

Azetidinium Lead Halide Ruddlesden-Popper Phases.

A family of Ruddlesden-Popper (n = 1) layered perovskite-related phases, Az2PbClxBr4-x with composition 0 ≤ x ≤ 4 were obtained using mechanosynthesis. These compounds are isostructural with K2NiF4 and therefore adopt the idealised n = 1 Ruddlesden-Popper structure. A linear variation in unit cell volume as a function of anion average radius is observed. A tunable bandgap is achieved, ranging from 2.81 to 3.43 eV, and the bandgap varies in a second-order polynomial relationship with the halide composition.

A Few-Shot Learning-Based Siamese Capsule Network for Intrusion Detection with Imbalanced Training Data.

Network intrusion detection remains one of the major challenges in cybersecurity. In recent years, many machine-learning-based methods have been designed to capture the dynamic and complex intrusion patterns to improve the performance of intrusion detection systems. However, two issues, including imbalanced training data and new unknown attacks, still hinder the development of a reliable network intrusion detection system. In this paper, we propose a novel few-shot learning-based Siamese capsule network to tackle the scarcity of abnormal network traffic training data and enhance the detection of unknown attacks. In specific, the well-designed deep learning network excels at capturing dynamic relationships across traffic features. In addition, an unsupervised subtype sampling scheme is seamlessly integrated with the Siamese network to improve the detection of network intrusion attacks under the circumstance of imbalanced training data. Experimental results have demonstrated that the metric learning framework is more suitable to extract subtle and distinctive features to identify both known and unknown attacks after the sampling scheme compared to other supervised learning methods. Compared to the state-of-the-art methods, our proposed method achieves superior performance to effectively detect both types of attacks.

Progressive Polytypism and Bandgap Tuning in Azetidinium Lead Halide Perovskites.

Mixed halide azetidinium lead perovskites AzPbBr3-xXx (X = Cl or I) were obtained by mechanosynthesis. With varying halide composition from Cl- to Br- to I-, the chloride and bromide analogues both form in the hexagonal 6H polytype while the iodide adopts the 9R polytype. An intermediate 4H polytype is observed for mixed Br/I compositions. Overall, the structure progresses from 6H to 4H to 9R perovskite polytype with varying halide composition. Rietveld refinement of the powder X-ray diffraction patterns revealed a linear variation in unit cell volume as a function of the average radius of the anion, which not only is observed within the solid solution of each polytype (according to Vegard's law) but also extends uniformly across all three polytypes. This is correlated to a progressive (linear) tuning of the bandgap from 3.43 to 2.00 eV. Regardless of halide, the family of azetidinium halide perovskite polytypes are highly stable, with no discernible change in properties over more than 6 months under ambient conditions.

Electrochemical Insight into the Sodium-Ion Storage Mechanism on a Hard Carbon Anode.

Hard carbon (HC) has been actively investigated as a high-capacity and low-cost anode material for sodium-ion batteries (SIBs); however, its sodium-storage mechanism has remained controversial, which imposes great difficulties in the design and construction of better microstructured HC materials. To obtain a deeper understanding of the Na-storage mechanism, we comparatively investigated electrochemical behaviors of HC and graphite for Na- and Li-storage reactions. The experimental results reveal that the Na-storage reaction on HC at a low-potential plateau proceeds in a manner similar to the Li+-insertion reaction on graphite but very differently from the Li+-storage process on HC, suggesting that the Na-storage mechanism of HC at a low-voltage plateau operates through the Na+ intercalation into the graphitic layers for the formation of sodium-graphite intercalation compounds (Na-GICs) and is consistent with the "adsorption-intercalation" mechanism. Our work might provide new insight for designing better HC materials of high-energy density SIBs.

Indentation response in porcine brain under electric fields.

Electric fields in the environment can have profound effects on brain function and behavior. In clinical practice, some noninvasive/microinvasive therapies with electrical fields such as transcranial electrical stimulation (tES), deep brain stimulation (DBS), and electroconvulsive therapy (ECT) have emerged as powerful tools for the treatment of neuropsychiatric disorders and neuromodulation. Nonetheless, currently, most studies focus on the mechanisms and effects of therapies and do not to address the mechanical properties of brain tissue under electric fields. Thus, the mechanical behavior of brain tissue, which plays an important role in modulating both brain form and brain function, should be given attention. The present study addresses this paucity by presenting, for the first time, the mechanical properties of brain tissue under various intensities of direct current electric field (0, 2, 5, 10, 20, and 50 V) using a custom-designed indentation device. Prior to brain indentation, validation tests were performed in different hydrogels to ensure that there was no interference in the electric fields from the indentation device. Subsequently, the load trace data obtained from the indentation-relaxation tests was fitted to both linear elastic and viscoelastic models to characterize the sensitivity of the mechanical behavior of the brain tissue to the electric fields. The brain tissue was found to be softened at a higher electric field level and less viscous, and substantially responded more quickly with an increase in electric field. The explanations for the above behaviors were further discussed based on the analysis of the resistance and thermal responses during the testing process. Understanding the effect of electric fields on brain tissue at the mechanical level can provide a better understanding of the mechanisms of some therapies, which may be beneficial to guide therapy protocols.

Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside in the MPTP-induced mouse model of Parkinson's disease: Involvement of reactive oxygen species-mediated JNK, P38 and mitochondrial pathways.

Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress-induced neuron loss is thought to play a crucial role in the pathogenesis of PD. Previous work from our group suggests that 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG), an active component extracted from a traditional Chinese herb, Polygonum multiflorum thunb, can attenuate 1-methyl-4-phenyl pyridium-induced apoptosis in the neuronal cell line PC12, by inhibiting reactive oxygen species generation and modulating c-Jun N-terminal kinases (JNK) activation. Here, we investigated the protective effects of TSG against 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-induced loss of tyrosine hydroxylase positive cells in mice and the underlying mechanisms. The results showed that MPTP-induced loss of tyrosine hydroxylase positive cells and reactive oxygen species generation were prevented by TSG in a dose-dependent manner. The reactive oxygen species scavenger N-acetylcysteine could also mitigate reactive oxygen species generation. Moreover, JNK and P38 were activated by MPTP, but extracellular signal-regulated protein kinases phosphorylation did not change after MPTP treatment. TSG at different doses blocked the activation of JNK and P38. The protective effect of TSG was also associated with downregulation of the bax/bcl-2 ratio, reversed the release of cytochrome c and smac, and inhibited the activation of caspase-3, -6, and -9 induced by MPTP. In conclusion, our studies demonstrated that the protective effects of TSG in the MPTP-induced mouse model of PD are involved, at least in part, in controlling reactive oxygen species-mediated JNK, P38, and mitochondrial pathways.

A novel magnetic adsorbent based on waste litchi peels for removing Pb(II) from aqueous solution.

A new magnetic bioadsorbent, magnetic litchi peel (MLP), was synthesized by coating powdered litchi peel with Fe3O4, and was used for removing Pb(II) from aqueous solutions. The influencing factors, adsorption isotherms, kinetics, and thermodynamics of Pb(II) adsorption by MLP were investigated using batch assays. Optimum Pb(II) adsorption by MLP was achieved using a contact time of 120 min, an adsorbent dose of 5 g/L, and pH of 6.0. The adsorption equilibrium data conformed to the Langmuir isotherm model, yielding a maximum Pb(II) adsorption capacity of 78.74 mg/g. The adsorption kinetics for Pb(II) adsorption by MLP followed a pseudo-second-order model. The thermodynamic results suggested that Pb(II) adsorption by MLP was spontaneous and exothermic. Additionally, the magnetic adsorbent was easily and rapidly separated out of solution under an external magnetic field.

Comparative study on the adsorption capacity of raw and modified litchi pericarp for removing Cu(II) from solutions.

The adsorption of Cu(II) onto raw litchi pericarp (LP) and modified litchi pericarp (MLP) as a function of pH, adsorbent dose and contact time, were investigated. Adsorption equilibrium isotherms, kinetics, and thermodynamics were studied to characterize the adsorption process. Leaching assays were also conducted to evaluate the potential contamination risk of LP and MLP to aqueous systems. The maximum adsorption of Cu(II) onto MLP was occurred at the pH of 6.0, adsorbent dose of 10.0 g/L, and contact time of 60 min, respectively. The adsorption process of Cu(II) onto LP and MLP were described well by both Langmuir and Freundlich isotherms, and the adsorption kinetics of Cu(II) on MLP was pseudo-second-order. Cu(II) adsorption onto LP and MLP are both exothermic, while it is spontaneous for MLP, and non-spontaneous for LP. The maximum adsorption capacity of Cu(II) onto MLP was 23.70 mg/g, which was about 2.7 times higher than that of LP. Additionally, as compared to LP, the leaching amounts of TOC, TN, and TP from MLP were significantly reduced by a percentage of 27.0%, 90.3%, and 35.3%, respectively.

Protective effect of tetrahydroxystilbene glucoside on 6-OHDA-induced apoptosis in PC12 cells through the ROS-NO pathway.

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease. The molecule, 2,3,5,4'-tetrahydr- oxystilbene-2-O-ß-D-glucoside (TSG), is a potent antioxidant derived from the Chinese herb, Polygonum multiflorum Thunb. In this study, we investigated the protective effect of TSG against 6-hydroxydopamine-induced apoptosis in rat adrenal pheochromocytoma PC12 cells and the possible mechanisms. Our data demonstrated that TSG significantly reversed the 6-hydroxydopamine-induced decrease in cell viability, prevented 6-hydroxydopamine-induced changes in condensed nuclei and decreased the percentage of apoptotic cells in a dose-dependent manner. In addition, TSG slowed the accumulation of intracellular reactive oxygen species and nitric oxide, counteracted the overexpression of inducible nitric oxide syntheses as well as neuronal nitric oxide syntheses, and also reduced the level of protein-bound 3-nitrotyrosine. These results demonstrate that the protective effects of TSG on rat adrenal pheochromocytoma PC12 cells are mediated, at least in part, by the ROS-NO pathway. Our results indicate that TSG may be effective in providing protection against neurodegenerative diseases associated with oxidative stress.

Topiramate reduced sweat secretion and aquaporin-5 expression in sweat glands of mice.

Decreased sweat secretion is a primary side effect of topiramate in pediatric patients, but the mechanism underlying this effect remains unclear. This study aimed to better understand how topiramate decreases sweat secretion by examining its effect on the expression of carbonic anhydrase (CA) II and aquaporin-5 (AQP5), total CA activity, as well as on tissue morphology of sweat glands in mice. Both developing and mature mice were treated with a low (20 mg/kg/day) and high dose (80 mg/kg/day) of topiramate for 4 weeks. Sweat secretion was investigated by an established technique of examining mold impressions of hind paws. CA II and AQP5 expression levels were determined by immunofluorescence and immunoblotting and CA activity by a colorimetric assay. In mature mice, topiramate treatment decreased the number of pilocarpine reactive sweat glands from baseline in both the low and high dose groups by 83% and 75%, respectively. A similar decrease was seen in developing mice. Mature mice with reactive sweat glands that declined more than 25% compared to baseline were defined as anhidrotic mice. These mice did not differ from controls in average secretory coil diameter, CA II expression and CA activity. In contrast, anhidrotic mice did show a reduction in membrane AQP5 expression in sweat glands after topiramate delivery. Thus, sweat secretion and membrane AQP5 expression in mouse sweat glands decreased following topiramate administration. These results suggest dysregulation of AQP5 may be involved in topiramate-induced hypohidrosis and topiramate may serve as a novel therapy for hyperhidrosis.

Effects of topiramate on mouse eccrine sweat gland responsiveness to heat exposure.

Young mice (2 weeks old) were given topiramate daily for 1 month, and sudomotor function was evaluated utilizing impression mould techniques to determine the number of sweat glands reactive to heat exposure and sweat output per gland on the plantar surface of mice hind-paws. Immunohistochemical quantitation of protein gene product 9.5, choline acetyltransferase and tyrosine hydroxylase in footpads was determined after topiramate treatment. While a 25% decrease in the number of secreting sweat glands and a 42% decline in sweat output per gland were observed following topiramate treatment, no significant differences were noted in sudomotor innervation, expressed as length of choline acetyltransferase, tyrosine hydroxylase and protein gene product 9.5 immunoreactive nerve profiles in single secretory coils or in sweat gland sizes within the secretory coil area. Long-term topiramate stimulation resulted in a reduction in the number of reactive sweat glands, without changes in sweat gland innervation, suggesting that the diminished responsiveness of the glands to heat exposure induced by topiramate might have resulted from a decrease in the intrinsic regulatory activity of sweat glands, as opposed to the loss of periglandular neurotransmitters or the impairment of the structure of the glands.

Postnatal expression and denervation induced up-regulation of aquaporin-5 protein in rat sweat gland.

The evolution of aquaporin-5 (AQP5) expression during postnatal development has not been defined in the sweat gland. Previous studies have suggested that AQP isoforms in several peripheral targets are regulated by a neural mechanism. We have examined, in rat sweat glands, the expression of AQP5 during postnatal development and the effects of denervation on AQP5 expression. Both AQP5 mRNA and protein begin to be expressed at postnatal day 10, before sweat-secretory responsiveness first appears; this expression coincides with the occurrence of vasoactive intestinal peptide (VIP) immunoreactivity. Early noradrenergic and later cholinergic interaction between sweat glands and their innervation are disrupted by neonatal chemical sympathectomy or postnatal severance of the sciatic nerve. Examination of such denervated developing rats has shown that secretory responsiveness fails to arise later in the adults, and AQP5 immunostaining increases in the denervated glands, whereas gland morphogenesis and the occurrence of AQP5 expression proceed normally. Immunobloting has revealed an increase of AQP5 abundance after the denervated mature glands lose their secretory ability. These findings suggest that AQP5 protein is necessary for sweat secretion, and that the expression of AQP5 in rat sweat glands is independent of sympathetic innervation. Our data also indicate that factor(s) regulating the normal morphological development of sweat gland might be responsible for controlling AQP5 expression.