Two conserved epigenetic regulators prevent healthy ageing.

It has long been assumed that lifespan and healthspan correlate strongly, yet the two can be clearly dissociated1-6. Although there has been a global increase in human life expectancy, increasing longevity is rarely accompanied by an extended healthspan4,7. Thus, understanding the origin of healthy behaviours in old people remains an important and challenging task. Here we report a conserved epigenetic mechanism underlying healthy ageing. Through genome-wide RNA-interference-based screening of genes that regulate behavioural deterioration in ageing Caenorhabditis elegans, we identify 59 genes as potential modulators of the rate of age-related behavioural deterioration. Among these modulators, we found that a neuronal epigenetic reader, BAZ-2, and a neuronal histone 3 lysine 9 methyltransferase, SET-6, accelerate behavioural deterioration in C. elegans by reducing mitochondrial function, repressing the expression of nuclear-encoded mitochondrial proteins. This mechanism is conserved in cultured mouse neurons and human cells. Examination of human databases8,9 shows that expression of the human orthologues of these C. elegans regulators, BAZ2B and EHMT1, in the frontal cortex increases with age and correlates positively with the progression of Alzheimer's disease. Furthermore, ablation of Baz2b, the mouse orthologue of BAZ-2, attenuates age-dependent body-weight gain and prevents cognitive decline in ageing mice. Thus our genome-wide RNA-interference screen in C. elegans has unravelled conserved epigenetic negative regulators of ageing, suggesting possible ways to achieve healthy ageing.

KLF10/CBS increases the sensitivity of gastric carcinoma cells to methionine restriction by promoting sulfur transfer pathway.

Gastric cancer metastasis is a major cause of poor prognosis. Our previous research showed that methionine restriction (MR) lowers the invasiveness and motility of gastric carcinoma. In this study, we investigated the particular mechanisms of MR on gastric carcinoma metastasis. In vitro, gastric carcinoma cells (AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45) were grown in an MR medium for 24 h. In vivo, BALB/c mice were given a methionine-free (Met-) diet. Transwell assays were used to investigate cell invasion and migration. The amounts of Krüppel like factor 10 (KLF10) and cystathionine ß-synthase (CBS) were determined using quantitative real-time PCR and Western blot. To determine the relationship between KLF10 and CBS, chromatin immunoprecipitation and a dual-luciferase reporter experiment were used. Hematoxylin-eosin staining was used to detect lung metastasis. Liquid chromatography-mass spectrometry was used to determine cystathionine content. MR therapy had varying effects on the invasion and migration of gastric carcinoma cells AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45. KLF10 was highly expressed in AGS cells but poorly expressed in KATO III cells. KLF10 improved MR's ability to prevent gastric carcinoma cell invasion and migration. In addition, KLF10 may interact with CBS, facilitating transcription. Further detection revealed that inhibiting the KLF10/CBS-mediated trans-sulfur pathway lowered Met-'s inhibitory effect on lung metastasis development. KLF10 transcription activated CBS, accelerated the trans-sulfur pathway, and increased gastric carcinoma cells' susceptibility to MR.

HDAC6-Activatable Multifunctional Near-Infrared Probe for Glioma Cell Detection and Elimination.

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor associated with limited treatment options and high drug resistance, presenting significant challenges in the pursuit of effective treatment strategies. Epigenetic modifications have emerged as promising diagnostic biomarkers and therapeutic targets for GBM. For instance, histone deacetylase 6 (HDAC6) has been identified as a potential pharmacological target for GBM. Furthermore, the overexpression of monoamine oxidase A (MAO A) in glioma has been linked to tumor progression, making it an attractive target for therapy. In this study, we successfully engineered HDAC-MB, an activatable multifunctional small-molecule probe with the goal of efficiently detecting and killing glioma cells. HDAC-MB can be selectively activated by HDAC6, leading to the "turn on" of near-infrared fluorescence and effective inhibition of MAO A, along with potent photodynamic therapy (PDT) effects. Consequently, HDAC-MB not only enables the imaging of HDAC6 in live glioma cells but also exhibits the synergistic effect of MAO A inhibition and PDT, effectively inhibiting glioma invasion and inducing cellular apoptosis. The distinctive combination of features displayed by HDAC-MB positions it as a versatile and highly effective tool for the accurate diagnosis and treatment of glioma cells. This opens up opportunities to enhance therapy outcomes and explore future applications in glioma theranostics.

Methionine restriction attenuates the migration and invasion of gastric cancer cells by inhibiting nuclear p65 translocation through TRIM47.

The prevention and treatment of gastric cancer has been the focus and difficulty of medical research. We aimed to explore the mechanism of inhibiting migration and invasion of gastric cancer cells by methionine restriction (MR). The human gastric cancer cell lines AGS and MKN45 cultured with complete medium (CM) or medium without methionine were used for in vitro experiments. MKN45 cells were injected tail vein into BALB/c nude mice and then fed with normal diet or methionine diet for in vivo experiments. MR treatment decreased cell migration and invasion, increased E-cadherin expression, decreased N-cadherin and p-p65 expressions, and inhibited nuclear p65 translocation of AGS and MKN45 cells when compared with CM group. MR treatment increased IκBα protein expression and protein stability, and decreased IκBα protein ubiquitination level and TRIM47 expression. TRIM47 interacted with IκBα protein, and overexpression of TRIM47 reversed the regulatory effects of MR. TRIM47 promoted lung metastasis formation and partially attenuated the effect of MR on metastasis formation in vivo compared to normal diet group mice. MR reduces TRIM47 expression, leads to the degradation of IκBα, and then inhibits the translocation of nuclear p65 and the migration and invasion of gastric cancer cells.

Mechanical Bond Induced Enhancement and Purification of Pyrene Emission in the Solid State.

To address key concerns on solid-state pyrene-based luminescent materials, we propose a novel and efficient mechanical bond strategy. This strategy results in a transformation from ACQ to AIE effect and a remarkable enhancement of pyrene emission in the solid state. Moreover, an unusual purification of emission is also achieved. Through computational calculation and experimental characterisation, finally determined by X-ray diffraction analysis, we prove that the excellent emissions result from mechanical bond induced refinement of molecular arrangements, including reduced π-π stacking, well-ordered packing and enhanced structural stability. This work demonstrates the potential of mechanical bond in the field of organic luminescent molecules, providing a new avenue for developing high-performance organic luminescent materials.

Upregulation of E-cadherin by the combination of methionine restriction and HDAC2 intervention for inhibiting gastric carcinoma metastasis.

Invasion and metastasis are the leading causes of death in individuals with malignant tumors, including gastric cancer. In this study, we aim to explore the effect and related mechanisms of methionine restriction (MR) on gastric carcinoma metastasis. In the MR cell model, gastric carcinoma cells are cultured in the MR medium, and in the animal model, BALB/c nude rodents are administered with a methionine-free diet after receiving injections of MKN45 cells into the caudal vein. Transwell assay is used to detect cell invasion and migration. Chromatin immunoprecipitation is performed to investigate the levels of H3K9me2, H3K27Ac, and H3K27me3 in the E-cadherin promoter. The results show that MR inhibits gastric carcinoma cell migration, invasion, and lung metastasis. MR increases E-cadherin while reducing the H3K27me3 level in the E-cadherin promoter. E-cadherin expression in gastric carcinoma cells is adversely regulated by HDAC2. Overexpressing HDAC2 reduces the H3K27Ac level in the E-cadherin promoter, while interfering with HDAC2 increases the H3K27Ac level. HDAC2 interference under MR conditions further upregulates E-cadherin expression and inhibits gastric carcinoma cell migration, invasion, and lung metastasis. MR combined with HDAC2 interference promotes E-cadherin expression by mediating the methylation and acetylation of E-cadherin, thus inhibiting the invasion, migration, and lung metastasis of gastric carcinoma cells. Our study provides a new theoretical basis for the inhibitory effect of MR on gastric cancer.

An activatable azophenyl fluorescent probe for hypoxic fluorescence imaging in living cells.

Cellular hypoxia is a common pathological process in various diseases. Detecting cellular hypoxia is of great scientific significance for early diagnosis of tumors. The hypoxia fluorescence probe analysis method can efficiently and conveniently evaluate the hypoxia status in tumor cells. These probes are covalently linked by hypoxic recognition groups and organic fluorescent molecules. Currently, the fluorescent molecules used in these probes often exhibit the aggregation-caused quenching effect, which is not conducive to fluorescence imaging in water. Herein, an activatable hypoxia fluorescence probe was constructed by covalently linking aggregation-induced emission luminogens to the hypoxic recognition group azobenzene. It does not emit fluorescence in solution and in solid state under light excitation due to the presence of photosensitive azo bonds. It can be cleaved by intracellular azoreductase into fluorescent amino derivatives with aggregation-induced emission characteristic. As the concentration of oxygen in cells decreases, its fluorescence intensity increases, making it suitable for fluorescence imaging to detect hypoxic environment in live cancer cells. This work broadens the molecular design approach for activatable hypoxia fluorescent probes.

Robust Intelligent Monitoring and Measurement System toward Downhole Dynamic Liquid Level.

Dynamic liquid level monitoring and measurement in oil wells is essential in ensuring the safe and efficient operation of oil extraction machinery and formulating rational extraction policies that enhance the productivity of oilfields. This paper presents an intelligent infrasound-based measurement method for oil wells' dynamic liquid levels; it is designed to address the challenges of conventional measurement methods, including high costs, low precision, low robustness and inadequate real-time performance. Firstly, a novel noise reduction algorithm is introduced to effectively mitigate both periodic and stochastic noise, thereby significantly improving the accuracy of dynamic liquid level detection. Additionally, leveraging the PyQT framework, a software platform for real-time dynamic liquid level monitoring is engineered, capable of generating liquid level profiles, computing the sound velocity and liquid depth and visualizing the monitoring data. To bolster the data storage and analytical capabilities, the system incorporates an around-the-clock unattended monitoring approach, utilizing Internet of Things (IoT) technology to facilitate the transmission of the collected dynamic liquid level data and computed results to the oilfield's central data repository via LoRa and 4G communication modules. Field trials on dynamic liquid level monitoring and measurement in oil wells demonstrate a measurement range of 600 m to 3000 m, with consistent and reliable results, fulfilling the requirements for oil well dynamic liquid level monitoring and measurement. This innovative system offers a new perspective and methodology for the computation and surveillance of dynamic liquid level depths.

Establishment of a Homologous Silencing System with Intact-Plant Infiltration and Minimized Operation for Studying Gene Function in Herbaceous Peonies.

Gene function verification is a crucial step in studying the molecular mechanisms regulating various plant life activities. However, a stable and efficient homologous genetic transgenic system for herbaceous peonies has not been established. In this study, using virus-induced gene silencing technology (VIGS), a highly efficient homologous transient verification system with distinctive advantages was proposed, which not only achieves true "intact-plant" infiltration but also minimizes the operation. One-year-old roots of the representative species, Paeonia lactiflora Pall., were used as the materials; prechilling (4 °C) treatment for 3-5 weeks was applied as a critical precondition for P. lactiflora to acquire a certain chilling accumulation. A dormancy-related gene named HOMEOBOX PROTEIN 31 (PlHB31), believed to negatively regulate bud endodormancy release (BER), was chosen as the target gene in this study. GFP fluorescence was detected in directly infiltrated and newly developed roots and buds; the transgenic plantlets exhibited remarkably earlier budbreak, and PlHB31 was significantly downregulated in silenced plantlets. This study established a homologous transient silencing system featuring intact-plant infiltration and minimized manipulation for gene function research, and also offers technical support and serves as a theoretical basis for gene function discovery in numerous other geophytes.

Patterned Photonic Actuators with Dynamic Shape-Morphing and Color-Changing Capabilities Fabricated by Athermal Embossing Technology.

Stimuli-responsive patterned photonic actuators, characterized by their patterned nano/microscale structures and capacity to demonstrate synergistic color changes and shape morphing in response to external stimuli, have attracted intense scientific attention. However, traditional patterned photonic actuator systems still face limitations such as cumbersome and time-consuming preparation processes and small-scale deformations. Herein, we introduce a facile approach involving an athermal embossing technique to rapidly fabricate patterned photonic actuators based on near-infrared (NIR) light-responsive liquid crystal elastomers. The resulting patterned photonic actuators demonstrate remarkable features, including brilliant angle-dependent structural color, complex three-dimensional actuation, and good color durability under NIR light stimulation. As illustrative demonstrations of the proof-of-concept, we fabricate two light-fuelled patterned photonic soft actuators: a butterfly-inspired actuator that can produce wing-flapping dynamic changes in structural color, and an origami crane-shaped actuator with shape memory, structural color information storage, and dynamic display properties. This strategy provides distinct insights into the design and fabrication of various patterned photonic soft robotic devices and intelligent actuators.

Responsive Organic Fluorescent Aggregates Based on Ion-π Interactions Away from Fluorescent Conjugated Groups.

Responsive organic luminescent aggregates have a wide range of application fields, but currently there is still a lack of reasonable molecular design strategies. Introducing ion-π interactions into molecules can effectively alter their luminescent properties. However, current research typically focuses on ion localization at luminescent conjugated groups with the strong interaction forces. In this work, we introduce the flexible alkoxy chain spacers between fluorescent conjugated groups and ion-π interaction sites, and then adjust the fluorescence performance of the molecule by changing the strength of ion-π interactions. Bromine ion-based molecules with strong ion-π interactions exhibit high and stable fluorescence quantum yields in crystals and amorphous powders under the external stimuli. Hexafluorophosphate ion-based molecules with weak ion-π interactions have the high fluorescence quantum yield in crystals and very low fluorescence quantum yield in amorphous powders, showing variable fluorescence intensities under external stimuli. This demonstrates a new class of responsive organic luminescent solid-state materials.

The suppression of hyperlipid diet-induced ferroptosis of vascular smooth muscle cells protests against atherosclerosis independent of p53/SCL7A11/GPX4 axis.

Ferroptosis as a novel programmed cell death that involves metabolic dysfunction due to iron-dependent excessive lipid peroxidation has been implicated in atherosclerosis (AS) development characterized by disrupted lipid metabolism, but the atherogenic role of ferroptosis in vascular smooth muscle cells (VSMCs), which are principal components of atherosclerotic plaque fibrous cap, remains unclear. The aim of this study was to determine the effects of ferroptosis on AS induced by lipid overload, and the effects of that on VSMCs ferroptosis. We found intraperitoneal injection of Fer-1, a ferroptosis inhibitor, ameliorated obviously high-fat diet-induced high plasma levels of triglycerides, total cholesterol, low-density lipoprotein, glucose and atherosclerotic lesions in ApoE-/- mice. Moreover, in vivo and in vitro, Fer-1 reduced the iron accumulation of atherosclerotic lesions through affecting the expression of TFR1, FTH, and FTL in VSMCs. Interestingly, Fer-1 did augment nuclear factor E2-related factor 2/ferroptosis suppressor protein 1 to enhance endogenous resistance to lipid peroxidation, but not classic p53/SCL7A11/GPX4. Those observations indicated inhibition of VSMCs ferroptosis can improve AS lesions independent of p53/SLC7A11/GPX4, which preliminarily revealed the potential mechanism of ferroptosis in aortic VSMCs on AS and provided new therapeutic strategies and targets for AS.

Hypoxia-Responsive Photosensitizer Targeting Dual Organelles for Photodynamic Therapy of Tumors.

Developing safe and precise image-guided photodynamic therapy is a challenge. In this study, the hypoxic properties of solid tumors are exploited to construct a hypoxia-responsive photosensitizer, TPA-Azo. Introducing the azo group into the photosensitizer TPA-BN with aggregation-induced emission quenches its fluorescence. When the nonfluorescent TPA-Azo enters hypoxic tumors, it is reduced by the overexpressed azoreductase to generate a fluorescent photosensitizer TPA-BN with an amino group that exhibits fluorescence-activatable image-guided photodynamic therapy with dual-organelle (lipid droplets and lysosomes) targeting. This design strategy provides a basis for the development of fluorescence-activatable photosensitizers.

Performance of polar coded probabilistic shaped PAM8 with systematic interleaver and identically distributed pilot in weak turbulence.

In this paper, for the first time to the best of our knowledge, we investigate the experiment of polar coded probabilistic shaped 8-ary pulse amplitude modulation (PS-PAM8) in weak turbulence. A systematic interleaver (SIL) is proposed to improve the polar code performance for PS-PAM8, compatible with the 5 G channel coding standard. Considering the effects of turbulence and shaped constellations, the pilot with identical distributions as the transmitted data is used for dynamic channel estimation to avoid demodulation failure. Moreover, the application of hybrid equalization with nonlinear and linear equalizers effectively reduces the receiver sensitivity. In 25 GBd transmission over a 4 m free-space link, the transmission performance of polar coded PAM8 schemes with SIL is better than that of the low-density parity check code by 1.0 dB, and the power budget is further saved by 0.72∼0.83 dB after linear equalization. Meanwhile, the shaping gains of polar coded PS-PAM8 with SIL and hybrid equalization are up to 2.0 dB at 1.5 bits/channel use. In addition, different weak turbulence conditions can be generated inside a chamber, and the observed channel fading is consistent with the log-normal model. The results show that the proposed polar coded PS scheme can improve the Q-factor by 0.49∼1.74 dB in different turbulence conditions.

Screening and identification of key chromatin regulator biomarkers for ankylosing spondylitis and drug prediction: evidence from bioinformatics analysis.

BACKGROUND: Ankylosing spondylitis (AS) is one of the most common immune-mediated arthritic diseases worldwide. Despite considerable efforts to elucidate its pathogenesis, the molecular mechanisms underlying AS are still not fully understood. METHODS: To identify candidate genes involved in AS progression, the researchers downloaded the microarray dataset GSE25101 from the Gene Expression Omnibus (GEO) database. They identified differentially expressed genes (DEGs) and functionally enriched them for analysis. They also constructed a protein-protein interaction network (PPI) using STRING and performed cytoHubba modular analysis, immune cell and immune function analysis, functional analysis and drug prediction.The results showed that DEGs were mainly associated with histone modifications, chromatin organisation, transcriptional coregulator activity, transcriptional co-activator activity, histone acetyltransferase complexes and protein acetyltransferase complexes. RESULTS: The researchers analysed the differences in expression between the CONTROL and TREAT groups in terms of immunity to determine their effect on TNF-α secretion. By obtaining hub genes, they predicted two therapeutic agents, AY 11-7082 and myricetin. CONCLUSION: The DEGs, hub genes and predicted drugs identified in this study contribute to our understanding of the molecular mechanisms underlying the onset and progression of AS. They also provide candidate targets for the diagnosis and treatment of AS.

Levels and diverse composition profiles of chlorinated paraffins in indoor dust: possible sources and potential human health related concerns.

Chlorinated paraffins (CPs), a group of mixtures with different carbon chain lengths and chlorine contents, are widely used as plasticizers and flame retardants in various indoor materials. CPs could be released from CP-containing materials into the ambient environment and then enter the human body via inhalation, dust ingestion and dermal absorption, resulting in potential effects on human health. In this study, we collected residential indoor dust in Wuhan, the largest city in central China, and focused on the co-occurrence and composition profiles of CPs as well as the resultant human risk via dust ingestion and dermal absorption. The results indicated that CPs with C9-40 were ubiquity in indoor dust with medium-chain CPs (MCCPs, C14-17) as the main components (6.70-495 µg g-1), followed by short-chain CPs (SCCPs, C10-13) (4.23-304 µg g-1) and long-chain (LCCPs, C≥18) CPs (3.68-331 µg g-1). Low levels (not detected-0.469 µg g-1) of very short-chain CPs (vSCCPs, C9) were also found in partial indoor dust. The dominant homolog groups were C9 and Cl6-7 groups for vSCCPs, C13 and Cl6-8 groups for SCCPs, C14 and Cl6-8 groups for MCCPs, and C18 and Cl8-9 groups for LCCPs. Based on the measured concentrations, vSCCPs, SCCPs, MCCPs, and LCCPs posed limited human health risks to local residents via dust ingestion and dermal absorption.

Delay Minimization in RIS-Assisted URLLC Systems under Reliability Constraints.

The ultra-reliable and low-latency communication (URLLC) systems are expected to support the stringent quality of service (QoS) demands in the Internet of Things (IoT) networks. In order to support the strict latency and reliability constraints, it is preferable to deploy a reconfigurable intelligent surface (RIS) in the URLLC systems to improve the link quality. In this paper, we focus on the uplink of an RIS-assisted URLLC system, and we propose to minimize the transmission latency under the reliability constraints. To solve the non-convex problem, a low-complexity algorithm is proposed by using the Alternating Direction Method of Multipliers (ADMM) technique. The RIS phase shifts optimization, which is typically non-convex, is efficiently solved by formulating as a Quadratically Constrained Quadratic Programming (QCQP) problem. Simulation results verify that our proposed ADMM-based method is able to achieve better performance than the conventional semi-definite relaxation (SDR)-based method with lower computational complexity. Our proposed RIS-assisted URLLC system is able to significantly reduce the transmission latency, which highlights the great potential in deploying RIS in the IoT networks with strict reliability requirements.

Springtail-inspired Light-driven Soft Jumping Robots Based on Liquid Crystal Elastomers with Monolithic Three-leaf Panel Fold Structure.

Jump is an important form of motion that enables animals to escape from predators, increase their range of activities, and better adapt to the environment. Inspired by springtails, we describe a light-driven soft jumping robot based on a double-folded liquid crystal elastomer (LCE) ribbon actuator with a monolithic three-leaf panel fold structure. This robot can achieve remarkable jumping height, jumping distance, and maximum take-off velocity, of up to 87 body length (BL), 65 BL, and 930 BL s-1 , respectively, under near-infrared light irradiation. Further, it is possible to control the height, distance, and direction of jump by changing the size and crease angle of the double-folded LCE ribbon actuators. These robots can efficiently jump over obstacles and can jump continuously, even in complex environments. Our simple design strategy improves the performance of jumping actuators and we expect it to have a wide-ranging impact on the strength, continuity, and adaptability of future soft robots.

Multimodal Self-sustainable Autonomous Locomotions of Light-driven Seifert Ribbon Actuators based on Liquid Crystal Elastomers.

Multimodal self-sustainable autonomous locomotions integrated into one individual system, are high-level intelligent behavioral characteristics of living organisms and are the scientific hotspot of bionic soft actuators. Here, we report a light-fueled soft actuator with multimodal self-sustainable movements based on a Seifert ribbon bounded by a Hopf link. The Seifert ribbon actuator can self-sense the illumination area adjustment, and the actuation component becomes either a discontinuous strip-like structure or a continuous toroidal structure, which can realize adaptive switches between self-sustained oscillatory and rotary motions. The two motion modes are applied to the self-oscillatory piezoelectric generation and self-rotational work multiplication of cargo transport, respectively. The unique smartness of Seifert surface topology advances the level of actuation intelligence with broad implications for the adaptability, multifunctionality, and autonomy of soft robots.

An Activatable NIR Probe for the Detection and Elimination of Senescent Cells.

Cellular senescence is involved in diverse physiological processes. Accumulation of senescent cells can lead to numerous age-related diseases. Therefore, it is of great significance to develop chemical tools to effectively detect and eliminate senescent cells. Till date, a dual functional probe that could detect and eliminate senescent cells has yet been accomplished. Herein, a ß-gal-activated probe, MB-ßgal, based on the methylene blue (MB) fluorophore, was designed to detect and eliminate senescent cells. In the absence of ß-gal, the probe showed no fluorescence and its 1O2 production efficiency was suppressed simultaneously. On the other hand, MB-ßgal could be specifically activated by the high level of ß-gal in senescent cells, thus, releasing free MB with near-infrared (NIR) fluorescence and high 1O2 production efficiency under light irradiation. MB-ßgal demonstrated a fast response, high sensitivity, and high selectivity in detecting ß-gal in an aqueous solution and was further applied to visualization and ablation of senescent cells. As a proof of concept, the dual functions of MB-ßgal were successfully demonstrated in senescent HeLa cells and mouse embryonic fibroblast cells.