KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mice learn from the predator-attack experience to accelerate flight behavior via optimizing the strategy of environment exploration.

Efficiently avoiding predators is critical for animal survival. However, little is known about how the experience of predator attack affects behaviors in predator defense. Here, we caught mice by tail to simulate a predator attack. We found that the experienced mice accelerated the flight in response to the visual threaten cue. Single predator attack didn't induce anxiety but increased the activity of innate fear or learning related nucleus. The predator attack induced acceleration of flight was partly rescued when we used drug to block protein synthesis which is critical in the learning process. The experienced mice significantly reduced the focused exploration on the floor during the environment exploration, which might facilitate the discovery of predator. These results suggest that mice could learn from the experience of predator attack to optimize their behavioral pattern to detect the predator cue immediately and response intensely, and therefore increase the probability of survival.

A simple threat-detection strategy in mice.

BACKGROUND: Avoiding danger and accessing environmental resources are two fundamental, yet conflicting, survival instincts across species. To maintain a balance between these instincts, animals must efficiently distinguish approaching threats from low-threat cues. However, little is known about the key visual features that animals use to promptly detect such imminent danger and thus facilitate an immediate and appropriate behavioral response. RESULTS: We used an automatic behavior detection system in mice to quantify innate defensive behaviors, including freezing, flight, and rearing, to a series of looming visual stimuli with varying expanding speeds and varying initial and final sizes. Looming visual stimuli within a specific "alert range" induced flight behavior in mice. Looming stimuli with an angular size of 10-40° and an expanding speed of 57-320°/s were in this range. Stimuli with relatively low expanding speeds tended to trigger freezing behavior, while those with relatively high expanding speeds tended to trigger rearing behavior. If approaching objects are in this "alert range," their visual features will trigger a flight response; however, non-threatening objects, based on object size and speed, will not. CONCLUSIONS: These results indicate a simple strategy in mice that is used to detect predators and suggest countermeasures that predators may have taken to overcome these defensive strategies.

Ni(HCO3)2 nanosheet/nickel tetraphosphate (Ni(P4O11)) nanowire composite as a high-performance electrode material for asymmetric supercapacitors.

Nickel compounds, especially Ni(HCO3)2 (here denoted as NiC), have been widely combined with other materials to obtain composites with a more favorable structure that exhibit excellent electrochemical performance as supercapacitors. Unfortunately, the complicated processes for preparing such composites directly restrict their further application. Herein, we prepared a NiC/nickel tetraphosphate (Ni(P4O11)) nanocomposite (NiC/NiP) by introducing [Formula: see text] ions into the NiC reaction system; this composite can be applied in high-performance supercapacitors. The micromorphology of NiC/NiP material displayed an appropriate combination of NiP nanowires and thin NiC nanosheets, which provide sufficient active sites, short ion diffusion paths and fast ion diffusion speeds. NiC/NiP material exhibited an excellent rate performance of 70.2% retained capacity, although the current was increased by 15 times (1196 F g-1 at 2.0 A g-1 and 840 F g-1 at 30 A g-1). The energy density of a NiC/NiP//active carbon (AC) asymmetric supercapacitor fabricated in 6 M KOH was as much as 39.02 W h kg-1 and 26.67 W h kg-1 under corresponding power densities of 160 W kg-1 and 8000 W kg-1, respectively. The asymmetric supercapacitor delivered a stable cyclic performance of 78% capacitive retention after 5000 continuous charge/discharge cycles. More importantly, a 2.5 V light-emitting diode was lit successfully by two NiC/NiP//AC asymmetric supercapacitors in series. These results confirm that NiC/NiP nanocomposite has great potential in practical applications of electrochemical energy storage devices.

Facile preparation of a self-assembled Artemia cyst shell-TiO2-MoS2 porous composite structure with highly efficient catalytic reduction of nitro compounds for wastewater treatment.

The catalytic reduction of nitro compounds is currently a hot research area, how to efficiently and stably degrade such toxic and harmful substances has become the research goal of many researchers. In this work, an Artemia cyst shell (ACS)-TiO2-MoS2 ternary porous structure was proposed and prepared as a catalyst for the reduction of 2-nitroaniline (2-NA) and 4-nitrophenol (4-NP). The ACS has a large number of porous structures, exhibits a good binding ability with TiO2 and MoS2, and provides a large number of active sites for the catalytic reduction process. The obtained composite material has a good reduction effect on 4-NP and 2-NA, with a good stability and recyclability, which is obviously higher than the reduction effect of ACS-TiO2 and MoS2 under the same conditions. This work provides ideas for the design of porous catalytic materials.

GLP-1RA Liraglutide and Semaglutide Improves Obesity-Induced Muscle Atrophy via SIRT1 Pathway.

Background: Obesity is related to the loss of skeletal muscle mass and function (sarcopenia). The co-existence of obesity and sarcopenia is called sarcopenic obesity (SO). Glucagon like peptide-1 receptor agonists (GLP-1RA) are widely used in the treatment of diabetes and obesity. However, the protective effects of GLP-1RA on skeletal muscle in obesity and SO are not clear. This study investigated the effects of GLP-1RA liraglutide and semaglutide on obesity-induced muscle atrophy and explored the underlying mechanisms. Methods: Thirty-six male C57BL/6J mice were randomly divided into two groups and fed a regular diet and a high-fat diet for 18 weeks, respectively. After establishing an obesity model, mice were further divided into six groups: control group, liraglutide (LIRA) group, semaglutide (SEMA) group, high-fat diet (HFD) group, HFD + LIRA group, HFD + SEMA group, and subcutaneous injection for 4 weeks. The body weight, muscle mass, muscle strength, glycolipid metabolism, muscle atrophy markers, myogenic differentiation markers, GLUT4 and SIRT1 were analyzed. C2C12 myotube cells treated with palmitic acid (PA) were divided into four groups: control group, PA group, PA + LIRA group, PA + SEMA group. The changes in glucose uptake, myotube diameter, lipid droplet infiltration, markers of muscle atrophy, myogenic differentiation markers, GLUT4 and SIRT1 were analyzed, and the changes in related indicators were observed after the addition of SIRT1 inhibitor EX527. Results: Liraglutide and semaglutide reduced HFD-induced body weight gain, excessive lipid accumulation and improved muscle atrophy. Liraglutide and semaglutide eliminated the increase of muscle atrophy markers in skeletal muscle and C2C12 myotubes. Liraglutide and semaglutide restored impaired glucose tolerance and insulin resistance. However, these beneficial effects were attenuated by inhibiting SIRT1 expression. Conclusion: Liraglutide and semaglutide protects skeletal muscle against obesity-induced muscle atrophy via the SIRT1 pathway.

Iron overload induces islet ß cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway.

Background: Recent studies have shown that the accumulation of free iron and lipid peroxides will trigger a new form of cell death-ferroptosis. This form of cell death is associated with a variety of diseases, including type 2 diabetes. We hypothesize that iron overload may play a role in driving glucose metabolism abnormalities by inducing endoplasmic reticulum stress that mediates ferroptosis in islet ß cells. In this study, we tested this conjecture from in vivo and in vitro experiments. Methods: We established a mouse iron overload model by intraperitoneal injection of iron dextrose (50 mg/kg) and an iron overload cell model by treating MIN6 cells with ferric ammonium citrate (640 µmol/L, 48 h) in vitro. The iron deposition in pancreatic tissue was observed by Prussian blue staining, and the pathological changes in pancreatic tissues by HE staining and the protein expression level by pancreatic immunohistochemistry. In the cellular experiments, we detected the cell viability by CCK8 and observed the cellular ultrastructure by transmission electron microscopy. We also used MDA and ROS kits to detect the level of oxidative stress and lipid peroxidation in cells. Western blotting was performed to detect the expression levels of target proteins. Results: Iron overload induces MIN6 cell dysfunction, leading to increased fasting blood glucose, impaired glucose tolerance, and significantly decreased insulin sensitivity in mice. This process may be related to the ferroptosis of islet ß cells and the activation of ASK1/P-P38/CHOP signaling pathway.

An iterative neural processing sequence orchestrates feeding.

Feeding requires sophisticated orchestration of neural processes to satiate appetite in natural, capricious settings. However, the complementary roles of discrete neural populations in orchestrating distinct behaviors and motivations throughout the feeding process are largely unknown. Here, we delineate the behavioral repertoire of mice by developing a machine-learning-assisted behavior tracking system and show that feeding is fragmented and divergent motivations for food consumption or environment exploration compete throughout the feeding process. An iterative activation sequence of agouti-related peptide (AgRP)-expressing neurons in arcuate (ARC) nucleus, GABAergic neurons in the lateral hypothalamus (LH), and in dorsal raphe (DR) orchestrate the preparation, initiation, and maintenance of feeding segments, respectively, via the resolution of motivational conflicts. The iterative neural processing sequence underlying the competition of divergent motivations further suggests a general rule for optimizing goal-directed behaviors.

An Infrared Touch System for Automatic Behavior Monitoring.

Key requirements of successful animal behavior research in the laboratory are robustness, objectivity, and high throughput, which apply to both the recording and analysis of behavior. Many automatic methods of monitoring animal behavior meet these requirements. However, they usually depend on high-performing hardware and sophisticated software, which may be expensive. Here, we describe an automatic infrared behavior-monitor (AIBM) system based on an infrared touchscreen frame. Using this, animal positions can be recorded and used for further behavioral analysis by any PC supporting touch events. This system detects animal behavior in real time and gives closed-loop feedback using relatively low computing resources and simple algorithms. The AIBM system automatically records and analyzes multiple types of animal behavior in a highly efficient, unbiased, and low-cost manner.

Epitaxial growth of dual-color-emitting organic heterostructures via binary solvent synergism driven sequential crystallization.

The controlled construction of organic heterostructured architectures derived from molecules with similar nucleation thresholds and concentrations has been rare and remains a great challenge. Herein, we report a sequential epitaxial growth to synthesize dual-color-emitting organic heterostructures with 9,10-bis(phenylethynyl)anthracene (BPEA) microwire trunks and tris-(8-hydroxyquinoline)aluminium (Alq3) microstructure branches by an anti-solvent induced sequential crystallization strategy. During the epitaxial growth process, the hydrogen-bonding interactions of the anti-solvent and solvent cause a large change in the solubility and crystallization rate of BPEA and Alq3 molecules in the mixed system, which facilitates sequential crystallization of organic molecule pairs with similar nucleation thresholds and concentrations into desired heterostructures by manipulating the synergism of anti-solvents and solvents. The Förster resonant energy transfer process in heterostructures could be modulated by varying the structure of heterostructures, such as the shape, amount and angles of the branches. The present synthesis strategy provides a unique insight into the detailed formation mechanism of complex organic heterostructures, further guiding the construction of more functional heterostructure materials.