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N6‐methyladenosine (m6A) is a well‐known modification of RNA. However, as a key m6A methyltransferase, METTL16 has not been thoroughly studied in gastric cancer (GC). Here, the biological role of METTL16 in GC and its underlying mechanism was studied. Immunohistochemistry was used to detect the expression of METTL16 and relationship between METTL16 level and prognosis of GC was analysed. CCK8, colony formation assay, EdU assay and xenograft mouse model were used to study the effect of METTL16. Regulatory mechanism of METTL16 in the progression of GC was studied through flow cytometry analysis, RNA degradation assay, methyltransferase inhibition assay, RT‐qPCR and Western blotting. METTL16 was highly expressed in GC cells and tissues and was associated with prognosis. In vitro and in vivo experiments confirmed that METTL16 promoted proliferation of GC cells and tumour growth. Furthermore, down‐regulation of METTL16 inhibited proliferation by G1/S blocking. Significantly, we identified cyclin D1 as a downstream effector of METTL16. Knock‐down METTL16 decreased the overall level of m6A and the stability of cyclin D1 mRNA in GC cells. Meanwhile, inhibition of methyltransferase activity reduced the level of cyclin D1. METTL16‐mediated m6A methylation promotes proliferation of GC cells through enhancing cyclin D1 expression.

Despite the wide applications, systematic mechanobiological investigation of 3D porous scaffolds has yet to be performed due to the lack of methodologies for decoupling the complex interplay between structural and mechanical properties. Here, we discover the regulatory effect of cryoprotectants on ice crystal growth and use this property to realize separate control of the scaffold pore size and stiffness. Fibroblasts and macrophages are sensitive to both structural and mechanical properties of the gelatin scaffolds, particularly to pore sizes. Interestingly, macrophages within smaller and softer pores exhibit pro-inflammatory phenotype, whereas anti-inflammatory phenotype is induced by larger and stiffer pores. The structure-regulated cellular mechano-responsiveness is attributed to the physical confinement caused by pores or osmotic pressure. Finally, in vivo stimulation of endogenous fibroblasts and macrophages by implanted scaffolds produce mechano-responses similar to the corresponding cells in vitro, indicating that the physical properties of scaffolds can be leveraged to modulate tissue regeneration. Cellular responses to mechanical stimulation have emerged as an important area of research. Here, the authors use cryoprotectant to control the pore size and mechanical properties of porous scaffolds without changing the scaffold composition to allow for the study of cellular mechano-responsiveness in 3D.

Allogeneic blood vessels are regarded as one of the best natural substitutes for diseased blood vessels due to their good vascular compliance and histocompatibility. Since the supply and demand of allograft blood vessels do not always match in time and space, a good preservation scheme for isolated blood vessels is essential. The abdominal aortas of 110 male Sprague–Dawley (SD) rats were randomly divided into three groups, including cold storage group (4°C) (CSG), frozen storage group (FSG) and ambient storage group (25 ± 2°C) (ASG). Seven time points of preservation for 1, 3, 5, 7, 14, 30 and 90 days were set for detection. The changes in vascular physiological function were evaluated by MTT test and vasoconstriction ability detection, and the changes in vascular wall structure were evaluated by the tension tolerance test and pathological staining. The vascular function of CSG was better than FSG within first the 7 days, but the result was opposite since the 14th day. The vascular wall structure, collagen and elastic fibres of vessels, in CSG, showed oedema within 30 days, and continuous disintegration and rupture at 90 days. The vessel wall structure of FSG remained intact within 90 days. The tensile strength of the vessels in CSG was better than that in FSG within 5 days, and there was no statistical difference between the two groups between the 7th and 30th day, and then, the FSG was higher than CSG on the 90th day. Both cold storage and frozen storage could be applied as safe and effective preservation schemes for isolated rat artery within first 30 days. Cold storage is recommended when the storage time is <14 days, and then, frozen storage is better.

In the present study, we summarized the TCM monomers related to inflammatory response, apoptosis, neuronal autophagy, oxidative stress, and nerve regeneration after SCI and explained the specific molecular mechanism of each TCM monomer. Combined with the results of our previous experiments,[2] we summarized that (1) TCM monomers inhibit the occurrence and development of inflammatory reactions through the Wnt/β-catenin/nuclear factor-kappa B (NF-κB) signaling pathway in SCI rats and (2) the neuronal inflammatory response regulated by the Wnt/β-catenin/NF-κB signaling pathway has a protective effect on neural function recovery in SCI rats [Figure 1]. Excessive neuronal apoptosis adversely affected the functional recovery after SCI and inhibited the recovery of tissue morphology and behavior. [...]neuronal apoptosis is also a potential target for SCI treatment. A notable detail that the current research on TCM monomers in SCI is in the stage of animal experiments, and it has not been clinically verified. [...]whether all TCM monomer extracts could be converted clinically is still unclear.

Background Transposable elements (TEs) are a significant component of eukaryotic genomes and play essential roles in genome evolution. Mounting evidence indicates that TEs are highly transcribed in early embryo development and contribute to distinct biological functions and tissue morphology. Results We examine the epigenetic dynamics of mouse TEs during the development of five tissues: intestine, liver, lung, stomach, and kidney. We found that TEs are associated with over 20% of open chromatin regions during development. Close to half of these accessible TEs are only activated in a single tissue and a specific developmental stage. Most accessible TEs are rodent-specific. Across these five tissues, 453 accessible TEs are found to create the transcription start sites of downstream genes in mouse, including 117 protein-coding genes and 144 lincRNA genes, 93.7% of which are mouse-specific. Species-specific TE-derived transcription start sites are found to drive the expression of tissue-specific genes and change their tissue-specific expression patterns during evolution. Conclusion Our results suggest that TE insertions increase the regulatory potential of the genome, and some TEs have been domesticated to become a crucial component of gene and regulate tissue-specific expression during mouse tissue development.

When an animal moves through the world, its brain receives a stream of information about the body’s translational velocity from motor commands and sensory feedback signals. These incoming signals are referenced to the body, but ultimately, they must be transformed into world-centric coordinates for navigation 1 , 2 . Here we show that this computation occurs in the fan-shaped body in the brain of Drosophila melanogaster . We identify two cell types, PFNd and PFNv 3 – 5 , that conjunctively encode translational velocity and heading as a fly walks. In these cells, velocity signals are acquired from locomotor brain regions 6 and are multiplied with heading signals from the compass system. PFNd neurons prefer forward–ipsilateral movement, whereas PFNv neurons prefer backward–contralateral movement, and perturbing PFNd neurons disrupts idiothetic path integration in walking flies 7 . Downstream, PFNd and PFNv neurons converge onto hΔB neurons, with a connectivity pattern that pools together heading and translation direction combinations corresponding to the same movement in world-centric space. This network motif effectively performs a rotation of the brain’s representation of body-centric translational velocity according to the current heading direction. Consistent with our predictions, we observe that hΔB neurons form a representation of translational velocity in world-centric coordinates. By integrating this representation over time, it should be possible for the brain to form a working memory of the path travelled through the environment 8 – 10 . Specific neurons in the fan-shaped body of the Drosophila brain convert translational information in relation to the fly’s body to externally referenced coordinates for navigation.

Skeletal muscle index (SMI), as an effective indicator of nutritional status, plays an important role in the prognosis of malignancy. However, the impact of skeletal muscle changes on tumor prognosis has not been systematically elaborated. We aimed to explore the value of skeletal muscle changes in the prognosis of distal cholangiocarcinoma (DCC) patients undergone pancreaticoduodenectomy (PD). Patients who underwent PD for DCC between 2015 and 2023 were included in this study. Demographic, laboratory and follow-up information was obtained. The cross-sectional images of skeletal muscle area at the level of the third lumbar spine was obtained based on computed tomography (CT), and the SMI was calculated by skeletal muscle mass through height squared normalization. Skeletal muscle index and skeletal muscle loss (SML) were obtained before PD and three to six months after surgery. Patients were classified into two groups (High-SML and Low-SML) based on the optimal SML cut-off value. The univariate and multivariate Cox proportional hazards analysis was conducted to evaluate the influence of SML in predicting over survival (OS) and recurrence free survival (RFS) of DCC. Of the 112 patients with distal cholangiocarcinoma, 55 (49%) were diagnosed with low SMI preoperatively. The best cut-off values of SML were − 4.01% and − 5.99% for OS and RFS. In multivariate analysis, tumor size  > 2.0 cm (hazard ratio (HR) = 1.90, P  = 0.017), poor differentiation (hazard ratio (HR) = 2.80, P > 0.001), higher SML (SML ≤ − 4.01%) (hazard ratio (HR) = 3.60, P  < 0.001), lymph metastasis (hazard ratio (HR) = 4.00, P  < 0.001) and vascular invasion (hazard ratio (HR) = 2.10, P  = 0.013) were independent risk factors forOS. Meanwhile, poor differentiation (hazard ratio (HR) = 1.90, P  = 0.043), higher SML (SML ≤ -5.99%) (hazard ratio (HR) = 3.80, P < 0.001) and lymph metastasis (hazard ratio (HR) = 2.60, P = 0.003) was an independent risk factor forRFS. The models combining SML and clinical characteristics had excellent predictive performance for OS and RFS. The nutritional status marker SML are effective and convenient indicators for predicting the long-term prognosis of DCC after PD, and the SMLafter PD is notable. The combination of CT quantified SML and clinical features can help clinicians predict the long-term survival of DCC patients after PD.

Microwave hyperthermia using the phased array applicator is a non-invasive treatment modality for breast cancer. Hyperthermia treatment planning (HTP) is critical to accurately treating breast cancer and avoiding damage to the patient’s healthy tissue. A global optimization algorithm, differential evolution (DE) algorithm, has been applied to optimize HTP for breast cancer and its ability to improve the treatment effect was proved by electromagnetic (EM) and thermal simulation results. DE algorithm is compared to time reversal (TR) technology, particle swarm optimization (PSO) algorithm, and genetic algorithm (GA) in HTP for breast cancer in terms of convergence rate and treatment results, such as treatment indicators and temperature parameters. The current approaches in breast cancer microwave hyperthermia still have the problem of hotspots in healthy tissue. DE enhances focused microwave energy absorption into the tumor and reduces the relative energy of healthy tissue during hyperthermia treatment. By comparing the treatment results of each objective function used in DE, the DE algorithm with hotspot to target quotient (HTQ) as the objective function has outstanding performance in HTP for breast cancer, which can increase the focused microwave energy of the tumor and decrease the damage to healthy tissue.

RNA viruses, being submicroscopic organisms, have intriguing biological makeups and substantially impact human health. Microscopic methods have been utilized for studying RNA viruses at a variety of scales. In order of observation scale from large to small, fluorescence microscopy, cryo-soft X-ray tomography (cryo-SXT), serial cryo-focused ion beam/scanning electron microscopy (cryo-FIB/SEM) volume imaging, cryo-electron tomography (cryo-ET), and cryo-electron microscopy (cryo-EM) single-particle analysis (SPA) have been employed, enabling researchers to explore the intricate world of RNA viruses, their ultrastructure, dynamics, and interactions with host cells. These methods evolve to be combined to achieve a wide resolution range from atomic to sub-nano resolutions, making correlative microscopy an emerging trend. The developments in microscopic methods provide multi-fold and spatial information, advancing our understanding of viral infections and providing critical tools for developing novel antiviral strategies and rapid responses to emerging viral threats.

Social isolation and loneliness have potent effects on public health 1 – 4 . Research in social psychology suggests that compromised sleep quality is a key factor that links persistent loneliness to adverse health conditions 5 , 6 . Although experimental manipulations have been widely applied to studying the control of sleep and wakefulness in animal models, how normal sleep is perturbed by social isolation is unknown. Here we report that chronic, but not acute, social isolation reduces sleep in Drosophila . We use quantitative behavioural analysis and transcriptome profiling to differentiate between brain states associated with acute and chronic social isolation. Although the flies had uninterrupted access to food, chronic social isolation altered the expression of metabolic genes and induced a brain state that signals starvation. Chronically isolated animals exhibit sleep loss accompanied by overconsumption of food, which resonates with anecdotal findings of loneliness-associated hyperphagia in humans. Chronic social isolation reduces sleep and promotes feeding through neural activities in the peptidergic fan-shaped body columnar neurons of the fly. Artificial activation of these neurons causes misperception of acute social isolation as chronic social isolation and thereby results in sleep loss and increased feeding. These results present a mechanistic link between chronic social isolation, metabolism, and sleep, addressing a long-standing call for animal models focused on loneliness 7 . Behavioural and transcriptomic analyses show that chronic social isolation of Drosophila  causes perturbed sleep and increased feeding, and induces a starvation-like brain state.