Pharmacological inhibition of EZH2 using a covalent inhibitor suppresses human ovarian cancer cell migration and invasion.

Metastasis is the cause of poor prognosis in ovarian cancer (OC). Enhancer of Zeste homolog 2 (EZH2), a histone-lysine N-methyltransferase enzyme, promotes OC cell migration and invasion by regulating the expression of tissue inhibitor of metalloproteinase-2 (TIMP2) and matrix metalloproteinases-9 (MMP9). Hence, we speculated that EZH2-targeting therapy might suppress OC migration and invasion. In this study, the expression of EZH2, TIMP2, and MMP9 in OC tissues and cell lines was analyzed using The Cancer Genome Atlas (TCGA) database and western blotting, respectively. The effects of SKLB-03220, an EZH2 covalent inhibitor, on OC cell migration and invasion were investigated using wound-healing assays, Transwell assays, and immunohistochemistry. TCGA database analysis confirmed that the EZH2 and MMP9 mRNA expression was significantly higher in OC tissues, whereas TIMP2 expression was significantly lower than that in normal ovarian tissues. Moreover, EZH2 negatively correlated with TIMP2 and positively correlated with MMP9 expression. In addition to the anti-tumor activity of SKLB-03220 in a PA-1 xenograft model, immunohistochemistry results showed that SKLB-03220 markedly increased the expression of TIMP2 and decreased the expression of MMP9. Additionally, wound-healing and Transwell assays showed that SKLB-03220 significantly inhibited the migration and invasion of both A2780 and PA-1 cells in a concentration-dependent manner. SKLB-03220 inhibited H3K27me3 and MMP9 expression and increased TIMP2 expression in PA-1 cells. Taken together, these results indicate that the EZH2 covalent inhibitor SKLB-03220 inhibits metastasis of OC cells by upregulating TIMP2 and downregulating MMP9, and could thus serve as a therapeutic agent for OC.

The impact of social relationships on the risk of stroke and post-stroke mortality: a systematic review and meta-analysis.

BACKGROUND: The association between poor social relationships and post-stroke mortality remains uncertain, and the evidence regarding the relationship between poor social relationships and the risk of stroke is inconsistent. In this meta-analysis, we aim to elucidate the evidence concerning the risk of stroke and post-stroke mortality among individuals experiencing a poor social relationships, including social isolation, limited social networks, lack of social support, and loneliness. METHODS: A thorough search of PubMed, Embase, and the Cochrane Library databases to systematically identify pertinent studies. Data extraction was independently performed by two researchers. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using either a random-effects or fixed-effects model. Sensitivity analyses were conducted to evaluate the reliability of the results. Random-effects meta-regression was performed to explore the sources of heterogeneity in stroke risk estimates between studies. Assessment for potential publication bias was carried out using Egger's and Begg's tests. RESULTS: Nineteen studies were included, originating from 4 continents and 12 countries worldwide. A total of 1,675,707 participants contributed to this meta-analysis. Pooled analyses under the random effect model revealed a significant association between poor social relationships and the risk of stroke (OR = 1.30; 95%CI: 1.17-1.44), as well as increased risks for post-stroke mortality (OR = 1.36; 95%CI: 1.07-1.73). Subgroup analyses demonstrated associations between limited social network (OR = 1.52; 95%CI = 1.04-2.21), loneliness (OR = 1.31; 95%CI = 1.13-1.51), and lack of social support (OR = 1.66; 95%CI = 1.04-2.63) with stroke risk. The meta-regression explained 75.21% of the differences in reported stroke risk between studies. Random-effect meta-regression results indicate that the heterogeneity in the estimated risk of stroke may originate from the continent and publication year of the included studies. CONCLUSION: Social isolation, limited social networks, lack of social support, and feelings of loneliness have emerged as distinct risk factors contributing to both the onset and subsequent mortality following a stroke. It is imperative for public health policies to prioritize the multifaceted influence of social relationships and loneliness in stroke prevention and post-stroke care. TRIAL REGISTRATION: The protocol was registered on May 1, 2024, on the Prospero International Prospective System with registration number CRD42024531036.

Hierarchies in Visual Pathway: Functions and Inspired Artificial Vision.

The development of artificial intelligence has posed a challenge to machine vision based on conventional complementary metal-oxide semiconductor (CMOS) circuits owing to its high latency and inefficient power consumption originating from the data shuffling between memory and computation units. Gaining more insights into the function of every part of the visual pathway for visual perception can bring the capabilities of machine vision in terms of robustness and generality. Hardware acceleration of more energy-efficient and biorealistic artificial vision highly necessitates neuromorphic devices and circuits that are able to mimic the function of each part of the visual pathway. In this paper, we review the structure and function of the entire class of visual neurons from the retina to the primate visual cortex within reach (Chapter 2) are reviewed. Based on the extraction of biological principles, the recent hardware-implemented visual neurons located in different parts of the visual pathway are discussed in detail in Chapters 3 and 4. Furthermore, valuable applications of inspired artificial vision in different scenarios (Chapter 5) are provided. The functional description of the visual pathway and its inspired neuromorphic devices/circuits are expected to provide valuable insights for the design of next-generation artificial visual perception systems.

An in-sensor humidity computing system for contactless human-computer interaction.

Being capable of processing large amounts of redundant data and decreasing power consumption, in-sensor computing approaches play significant roles in neuromorphic computing and are attracting increasing interest in perceptual information processing. Herein, we proposed a high performance humidity-sensitive memristor based on a Ti/graphene oxide (GO)/HfOx/Pt structure and verified its potential for application in remote health management and contactless human-machine interfaces. Since GO possesses abundant hydrophilic groups (carbonyl, epoxide, and hydroxyl), the memristor shows a high humidity sensitivity, fast response, and wide response range. By utilizing the proton-modulated redox reaction, humidity exposure to the memristor induces a dynamic change in the switching between high and low resistance states, ensuring essential synaptic learning functions, such as paired-pulse facilitation, spike number-dependent plasticity, and spike amplitude-dependent plasticity. More importantly, based on the humidity-induced salient features originating from the abundant hydrophilic functional groups in GO, we have implemented a noncontact human-machine interface utilizing the respiratory mode in humans, demonstrating the potential of promoting health monitoring applications and effectively blocking virus transmission. In addition, the high recognition accuracy of contactless handwriting in a 5 × 5 array artificial neural network was successfully achieved, which is attributed to the excellent emulated synaptic behaviors. This study provides a feasible method to develop an excellent humidity-sensitive memristor for constructing efficient in-sensor computing for application in health management and contactless human-computer interaction.

A Near-Infrared Retinomorphic Device with High Dimensionality Reservoir Expression.

Physical reservoir-based reservoir computing (RC) systems for intelligent perception have recently gained attention because they require fewer computing resources. However, the system remains limited in infrared (IR) machine vision, including materials and physical reservoir expression power. Inspired by biological visual perception systems, the study proposes a near-infrared (NIR) retinomorphic device that simultaneously perceives and encodes narrow IR spectral information (at ≈980 nm). The proposed device, featuring core-shell upconversion nanoparticle/poly (3-hexylthiophene) (P3HT) nanocomposite channels, enables the absorption and conversion of NIR into high-energy photons to excite more photo carriers in P3HT. The photon-electron-coupled dynamics under the synergy of photovoltaic and photogating effects influence the nonlinearity and high dimensionality of the RC system under narrow-band NIR irradiation. The device also exhibits multilevel data storage capability (≥8 levels), excellent stability (≥2000 s), and durability (≥100 cycles). The system accurately identifies NIR static and dynamic handwritten digit images, achieving recognition accuracies of 91.13% and 90.07%, respectively. Thus, the device tackles intricate computations like solving second-order nonlinear dynamic equations with minimal errors (normalized mean squared error of 1.06 × 10⁻3 during prediction).

Development of Bio-Voltage Operated Humidity-Sensory Neurons Comprising Self-Assembled Peptide Memristors.

Biomimetic humidity sensors offer a low-power approach for respiratory monitoring in early lung-disease diagnosis. However, balancing miniaturization and energy efficiency remains challenging. This study addresses this issue by introducing a bioinspired humidity-sensing neuron comprising a self-assembled peptide nanowire (NW) memristor with unique proton-coupled ion transport. The proposed neuron shows a low Ag+ activation energy owing to the NW and redox activity of the tyrosine (Tyr)-rich peptide in the system, facilitating ultralow electric-field-driven threshold switching and a high energy efficiency. Additionally, Ag+ migration in the system can be controlled by a proton source owing to the hydrophilic nature of the phenolic hydroxyl group in Tyr, enabling the humidity-based control of the conductance state of the memristor. Furthermore, a memristor-based neuromorphic perception neuron that can encode humidity signals into spikes is proposed. The spiking characteristics of this neuron can be modulated to emulate the strength-modulated spike-frequency characteristics of biological neurons. A three-layer spiking neural network with input neurons comprising these highly tunable humidity perception neurons shows an accuracy of 92.68% in lung-disease diagnosis. This study paves the way for developing bioinspired self-assembly strategies to construct neuromorphic perception systems, bridging the gap between artificial and biological sensing and processing paradigms.

Cryptotanshinone induces melanoma cancer cells apoptosis via ROS-mitochondrial apoptotic pathway and impairs cell migration and invasion.

Melanoma is the most serious type of skin cancer because it is highly frequency of drug resistance and can spread earlier and more quickly than other skin cancers. The objective of this research was to investigate the anticancer effects of cryptotanshinone on human melanoma cells in vitro, and explored its mechanisms of action. Our results have shown that cryptotanshinone could inhibit cell proliferation in human melanoma cell lines A2058, A375, and A875 in a dose- and time-dependent manner. In addition, flow cytometry assay showed that cryptotanshinone inhibited the proliferation of human melanoma cell line A375 by blocking cell cycle progression in G2/M phase and inducing apoptosis in a concentration-dependent manner. Moreover, western blot analysis indicated that the occurrence of its apoptosis was associated with upregulation of cleaved caspases-3 and pro-apoptotic protein Bax while downregulation of anti-apoptotic protein Bcl-2. Meanwhile, cryptotanshinone could decrease the levels of reactive oxygen species (ROS). Furthermore, cryptotanshinone also blocked A375 cell migration and invasion in vitro which was associated with the downregulation with MMP-9. Taken together, these results suggested that cryptotanshinone might be a potential drug in human melanoma treatment by inhibiting proliferation, inducing apoptosis via ROS-mitochondrial apoptotic pathway and blocking cell migration and invasion.