The Contrasting Effects of Two Distinct Exercise Training Modalities on Exhaustive Exercise-Induced Muscle Damage in Mice May Be Associated with Alterations in the Gut Microbiota.

Exhaustive exercise is known to induce muscle damage characterized by inflammation and oxidative stress. Although "regular" and "weekend warrior" exercise regimens have been shown to confer comparable health benefits in human studies, such as reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality, their differential impacts on muscle damage post-exhaustive exercise remain unclear. This study aimed to compare the effects of long-term, moderate-intensity (LTMI) and short-term, high-intensity (STHI) training modalities, matched for total exercise volume, on gut microbiota, short-chain fatty acids (SCFAs), and exhaustive exercise-induced muscle damage in mice, as well as to evaluate the correlation between these factors. LTMI is considered a regular exercise regimen, while STHI shares some similarities with the "weekend warrior" pattern, such as promoting exercise intensity and condensing training sessions into a short period. Our findings indicate that LTMI training significantly enhanced the abundance of SCFA-producing bacteria, including Akkermansia, Prevotellaceae_NK3B31_group, Odoribacter, Alistipes, and Lactobacillus, thereby increasing SCFA levels and attenuating muscle damage following exhaustive swimming. In contrast, STHI training increased the abundance of opportunistic pathogens such as Staphylococcus and Bilophila, without altering SCFA levels, and was associated with exacerbated muscle damage. Moreover, we observed a significant negative correlation between the abundance of SCFA-producing bacteria and SCFA levels with the expression of inflammatory cytokines in the muscle of mice post-exhaustive exercise. Conversely, the abundance of Staphylococcus and Bilophila showed a notable positive correlation with these cytokines. Additionally, the effects of LTMI and STHI on exhaustive exercise-induced muscle damage were transmissible to untrained mice via fecal microbiota transplantation, suggesting that gut microbiota changes induced by these training modalities may contribute to their contrasting impacts on muscle damage. These results underscore the significance of selecting an appropriate training modality prior to engaging in exhaustive exercise, with implications for athletic training and injury prevention.

Effects of fermentation on the structures of yellow compounds in citrus pomace.

To enhance the stability and light resistance of the yellow compounds in citrus pomace, our study successfully isolated and purified five compounds using ultrasonic-assisted extraction and column chromatography. The identified compounds include methyl linoleate, (2-ethyl)hexyl phthalate, 1,3-distearoyl-2-oleoylglycerol, 6,6-ditetradecyl-6,7-dihydroxazepin-2(3H)-one, and n-octadeca-17-enoic acid. The monomers extracted from fresh pomace, compounds 1 and 2, exhibit structural similarities to flavonoids and carotenoids. In contrast, the polymers isolated from fermented pomace, compounds 3, 4, and 5, share structural units with the fresh pomace compounds, indicating the transformation to stable polymeric forms. This suggests that the microbial fermentation process not only enhances the value of citrus pomace, but also provides a promising pathway for the synthesis of natural antioxidant yellow pigments with far-reaching theoretical and practical significance.

Interplay of Landau Quantization and Interminivalley Scatterings in a Weakly Coupled Moiré Superlattice.

Double-layer quantum systems are promising platforms for realizing novel quantum phases. Here, we report a study of quantum oscillations (QOs) in a weakly coupled double-layer system composed of a large-angle twisted-double-bilayer graphene (TDBG). We quantify the interlayer coupling strength by measuring the interlayer capacitance from the QOs pattern at low temperatures, revealing electron-hole asymmetry. At high temperatures when SdHOs are thermally smeared, we observe resistance peaks when Landau levels (LLs) from two moiré minivalleys are aligned, regardless of carrier density; eventually, it results in a 2-fold increase of oscillating frequency in D, serving as compelling evidence of the magneto-intersub-band oscillations (MISOs) in double-layer systems. The temperature dependence of MISOs suggests that electron-electron interactions play a crucial role and the scattering times obtained from MISO thermal damping are correlated with the interlayer coupling strength. Our study reveals intriguing interplays among Landau quantization, moiré band structure, and scatterings.

Entry pathways determined the effects of MPs on sludge anaerobic digestion system: The views of methane production and antibiotic resistance genes fates.

Sludge is one of the primary reservoirs of microplastics (MPs), and the effects of MPs on subsequent sludge treatment raised attention. Given the entry pathways, MPs would exhibit different properties, but the entry pathway-dependent effect of MPs on sludge treatment performance and the fates of antibiotic resistance genes (ARGs), another high-risk emerging contaminant, were seldom documented. Herein, MPs with two predominant entry pathways, including wastewater-derived (WW-derived) and anaerobic digestion-introduced (AD-introduced), were used to investigate the effects on AD performance and ARGs abundances. The results indicated that WW-derived MPs, namely the MPs accumulated in sludge during the wastewater treatment process, exhibited significant inhibition on methane production by 22.8%-71.6%, while the AD-introduced MPs, being introduced in the sludge AD process, slightly increased the methane yield by 4.7%-17.1%. Meanwhile, MPs were responsible for promoting transmission of target ARGs, and polyethylene terephthalate MPs (PET-MPs) showed a greater promotion effect (0.0154-0.0936) than polyamide MPs (PA-MPs) (0.0013-0.0724). Compared to size, entry pathways and types played more vital roles on MPs influences. Investigation on mechanisms based on microbial community structure revealed characteristics (aging degree and types) of MPs determined the differences of AD performance and ARGs fates. WW-derived MPs with longer aging period and higher aging degree would release toxics and decrease the activities of microorganisms, resulting in the negative impact on AD performance. However, AD-introduced MPs with short aging period exhibited marginal impacts on AD performance. Furthermore, the co-occurrent network analysis suggested that the variations of potential host bacteria induced by MPs with different types and aging degree attributed to the dissemination of ARGs. Distinctively from most previous studies, the MPs with different sizes did not show remarkable effects on AD performance and ARGs fates. Our findings benefited the understanding of realistic environmental behavior and effect of MPs with different sources.

Epitaxy of wafer-scale single-crystal MoS2 monolayer via buffer layer control.

Monolayer molybdenum disulfide (MoS2), an emergent two-dimensional (2D) semiconductor, holds great promise for transcending the fundamental limits of silicon electronics and continue the downscaling of field-effect transistors. To realize its full potential and high-end applications, controlled synthesis of wafer-scale monolayer MoS2 single crystals on general commercial substrates is highly desired yet challenging. Here, we demonstrate the successful epitaxial growth of 2-inch single-crystal MoS2 monolayers on industry-compatible substrates of c-plane sapphire by engineering the formation of a specific interfacial reconstructed layer through the S/MoO3 precursor ratio control. The unidirectional alignment and seamless stitching of MoS2 domains across the entire wafer are demonstrated through cross-dimensional characterizations ranging from atomic- to centimeter-scale. The epitaxial monolayer MoS2 single crystal shows good wafer-scale uniformity and state-of-the-art quality, as evidenced from the ~100% phonon circular dichroism, exciton valley polarization of ~70%, room-temperature mobility of ~140 cm2v-1s-1, and on/off ratio of ~109. Our work provides a simple strategy to produce wafer-scale single-crystal 2D semiconductors on commercial insulator substrates, paving the way towards the further extension of Moore's law and industrial applications of 2D electronic circuits.

Electron/infrared-phonon coupling in ABC trilayer graphene.

Stacking order plays a crucial role in determining the crystal symmetry and has significant impacts on electronic, optical, magnetic, and topological properties. Electron-phonon coupling, which is central to a wide range of intriguing quantum phenomena, is expected to be intricately connected with stacking order. Understanding the stacking order-dependent electron-phonon coupling is essential for understanding peculiar physical phenomena associated with electron-phonon coupling, such as superconductivity and charge density waves. In this study, we investigate the effect of stacking order on electron-infrared phonon coupling in graphene trilayers. By using gate-tunable Raman spectroscopy and excitation frequency-dependent near-field infrared nanoscopy, we show that rhombohedral ABC-stacked trilayer graphene has a significant electron-infrared phonon coupling strength. Our findings provide novel insights into the superconductivity and other fundamental physical properties of rhombohedral ABC-stacked trilayer graphene, and can enable nondestructive and high-throughput imaging of trilayer graphene stacking order using Raman scattering.

Pterostilbene Attenuates High-Intensity Swimming Exercise-Induced Glucose Absorption Dysfunction Associated with the Inhibition of NLRP3 Inflammasome-Induced IECs Pyroptosis.

The study investigated the effect of pterostilbene (PTE) on intestinal glucose absorption and its underlying mechanisms in high-intensity swimming exercise (HISE)-treated mice. Male C57BL/6 mice were treated with PTE for 4 weeks and performed high-intensity swimming training in the last week. Intestinal epithelial cells (IECs) were pretreated with 0.5 and 1.0 µM PTE for 24 h before being incubated in hypoxia/reoxygenation condition. Intestinal glucose absorption was detected by using an oral glucose tolerance test and d-xylose absorption assay, and the levels of factors related to mitochondrial function and pyroptosis were measured via western blot analyses, cell mito stress test, and quantitative real-time polymerase chain reaction. In vivo and in vitro, the results showed that PTE attenuated HISE-induced intestinal glucose absorption dysfunction and pyroptosis in mice intestine. Moreover, PTE inhibited NLRP3 inflammasome and the mitochondrial homeostasis as well as the ROS accumulation in IEC in vitro. Additionally, knockdown of SIRT3, a major regulator of mitochondria function, by siRNA or inhibiting its activity by 3-TYP abolished the effects of PTE on pyroptosis, mitochondrial homeostasis, and ROS generation of IEC in vitro. Our results revealed that PTE could alleviate HISE-induced intestinal glucose absorption dysfunction associated with the inhibition of NLRP3 inflammasome-induced IECs pyroptosis.

A liquid-free conducting ionoelastomer for 3D printable multifunctional self-healing electronic skin with tactile sensing capabilities.

Conductive elastomers with both softness and conductivity are widely used in the field of flexible electronics. Nonetheless, conductive elastomers typically exhibit prominent problems such as solvent volatilization and leakage, and poor mechanical and conductive properties, which limit their applications in electronic skin (e-skin). In this work, a liquid-free conductive ionogel (LFCIg) with excellent performance was fabricated by utilizing the innovative double network design approach based on a deep eutectic solvent (DES). The double-network LFCIg is cross-linked by dynamic non-covalent bonds, which exhibit excellent mechanical properties (2100% strain while sustaining a fracture strength of 1.23 MPa) and >90% self-healing efficiency, and a superb electrical conductivity of 23.3 mS m-1 and 3D printability. Moreover, the conductive elastomer based on LFCIg has been developed into a stretchable strain sensor that achieves accurate response recognition, classification, and identification of different robot gestures. More impressively, an e-skin with tactile sensing functions is produced by in situ 3D printing of sensor arrays on flexible electrodes to detect light weight objects and recognize the resulting spatial pressure variations. Collectively, the results demonstrate that the designed LFCIg has unparalleled advantages and presents wide application potential in flexible robotics, e-skin and physiological signal monitoring.

Tough and Robust Mechanically Interlocked Gel-Elastomer Hybrid Electrode for Soft Strain Gauge.

Soft strain gauges provide a flexible and versatile alternative to traditional rigid and inextensible gauges, overcoming issues such as impedance mismatch, the limited sensing range, and fatigue/fracture. Although several materials and structural designs are used to fabricate soft strain gauges, achieving multi-functionality for applications remains a significant challenge. Herein, a mechanically interlocked gel-elastomer hybrid material is exploited for soft strain gauge. Such a material design provides exceptional fracture energy of 59.6 kJ m-2 and a fatigue threshold of 3300 J m-2 , along with impressive strength and stretchability. The hybrid material electrode possesses excellent sensing performances under both static and dynamic loading conditions. It boasts a tiny detection limit of 0.05% strain, ultrafast time resolution of 0.495 ms, and high linearity. This hybrid material electrode can accurately detect full-range human-related frequency vibrations ranging from 0.5 to 1000 Hz, enabling the measurement of physiological parameters. Additionally, the patterned soft strain gauge, created through lithography, demonstrates superior signal-noise rate and electromechanical robustness against deformation. By integrating a multiple-channel device, an intelligent motion detection system is developed, which can classify six typical human body movements with the assistance of machine learning. This innovation is expected to drive advancements in wearable device technology.

Tough hydrogel with high water content and ordered fibrous structures as an artificial human ligament.

Natural biological tissues such as ligaments, due to their anisotropic across scale structure, have high water content, while still maintaining high strength and flexibility. Hydrogels are ideal artificial materials like human ligaments. However, conventional gel materials fail to exhibit high strength or fatigue resistance at high water content in human tissues. To address this challenge, we propose a simple integrated strategy to prepare an anisotropic hierarchical hydrogel architecture for artificial ligaments by combining freeze-casting assisted compression annealing and salting-out treatments. The hybrid polyvinyl alcohol hydrogels are of water content up to 79.5 wt%. Enhanced by the added carbon nanotubes, the hydrogels exhibit high strength of 4.5 MPa and a fatigue threshold of 1467 J m-2, as well as excellent stress sensitivity. The outstanding durability of the artificial ligament provides an all-around solution for biomedical applications.

Thermal Insulation and Flame Retardancy of the Hydroxyapatite Nanorods/Sodium Alginate Composite Aerogel with a Double-Crosslinked Structure.

As advanced thermal management materials, aerogels have great research value in the fields of engineering insulation, pipeline transportation, and packaging insulation. The composite interaction of the two-phase interface and the construction of a porous structure have an important impact on the thermal properties. Herein, a novel HANRs/SAB composite aerogel was prepared using sodium alginate (SA) with hydroxyapatite nanorods (HANRs), combined with boric acid crosslinking and freeze drying. In the prepared sample, the calcium ions in HANRs and SA formed the first layer of binding force and the chemical crosslinking of sodium alginate with boric acid formed the second layer of strong binding force, which effectively supported the skeleton of the aerogel and enhanced the overall mechanical properties. The modulus and maximum compressive strength of the obtained HANRs/SAB aerogel were 2.39 and 0.75 MPa, respectively, while the bulk density was 0.038-0.068 g·cm-3. Based on the prominent physical structure, the as-prepared HANRs/SAB aerogel exhibited good thermal insulation (∼35.15 mW·m-1·K-1) and outstanding flame retardant performance. Flame-retardant boric acid and high-thermal stability HANRs could effectively prevent heat transfer and organic combustion, thus resulting in an extremely low smoke gas release (11.3 m2 m-2). Therefore, the low-cost biopolymer composite aerogel based on a crosslinking strategy has broad application prospects in the field of thermal insulation and flame retardancy.

Size-dependent effects of microplastics on antibiotic resistance genes fate in wastewater treatment systems: The role of changed surface property and microbial assemblages in a continuous exposure mode.

Microplastics (MPs) were continuously transported to wastewater treatment systems and accumulated in sludge constantly, potentially affecting systems function and co-occurrent contaminants fate. However, previous studies were based on acute exposure of MPs, which could not reflect the dynamics of MPs accumulation. Herein, this study firstly raised a more realistic method to evaluate the practical impacts of MPs on systems purification efficiency and antibiotic resistance genes (ARGs) fate. Continuous exposure of MPs did not pose negative effects on nutrients removal, but significantly changed the occurrence patterns of ARGs. ARGs abundances increased by 42.8 % and 54.3 % when exposed to millimeter-size MPs (mm-MPs) polyamide and polyethylene terephthalate, but increased by 31.3 % and 39.4 % to micron-size MPs (µm-MPs), respectively. Thus, mm-MPs posed severer effects on ARGs than µm-MPs. Further, mm-MPs surface properties were obviously altered after long-term exposure (higher specific surface area and O-containing species), which benefited microbes attachment. More importantly, more taxa linkages and changed topological properties (higher average degree and average weight) of co-occurrent network were observed in sludge with mm-MPs than with µm-MPs, as well as totally different potential host bacteria of ARGs. Rough surface of MPs and closer relations between ARGs and bacteria taxa contributed to the propagation of ARGs, which accounted for the observed higher ARGs abundances of mm-MPs. This study demonstrated that long-term accumulation of MPs in wastewater treatment systems affected ARGs fate, and mm-MPs caused severer risk due to their enrichment of ARGs. The results would promote the understanding of MPs real environmental behavior and influences.

Pterostilbene attenuates intestinal epithelial barrier loss induced by high loading intensity of exercise.

Mounting evidence suggested that high loading intensity of exercise might be detrimental to human health, especially the gastrointestinal tract. Pterostilbene (PTE), derived from grapes and blueberries, might reach a high concentration of intestinal contents. Our study aimed to evaluate PTE's ability to prevent the loss of intestinal epithelial barrier in high loading intensity of exercise. The exercise model was established by the forced running of mice. An effective HPLC-UV method was developed to quantify PTE concentration in intestinal content. The mRNA changes were detected by quantitative polymerase chain reaction (qPCR). The structure of intestinal flora was analyzed by 16S rRNA sequencing. The PTE (100 mg/kg/d) could significantly attenuate exercise-induced intestinal epithelial barrier loss. Moreover, the HPLC-UV assay showed that the PTE concentration of intestinal content could last 12 h. Furthermore, the exercise increased the abundance of Alistipes, which was related to lipopolysaccharide (LPS) production but could not be reversed by PTE intervention. Besides, cell experiments showed that PTE could promote the expression of intestinal epithelial tight junction (TJ) molecules in vitro. In conclusion, PTE has a significant interest in preventing exercise-induced intestinal damage.

Dihydromyricetin-Encapsulated Liposomes Inhibit Exhaustive Exercise-Induced Liver Inflammation by Orchestrating M1/M2 Macrophage Polarization.

Exhaustive exercise (EE) induced hepatic inflammatory injury has been well reported. Dihydromyricetin (DHM) has shown anti-inflammatory bioactivity and hepatoprotective effects but is limited by poor bioavailability. Here, high-bioavailability DHM-encapsulated liposomes were synthesized and explored for their therapeutic potential and regulatory mechanisms in a hepatic inflammatory injury model. The animal model was established by swimming-to-exhaustive exercise in C57BL/6 mice, and the anti-inflammatory effects were detected after administration of DHM or DHM liposome. NIR fluorescence imaging was used to assess the potential of liver targeting. The DHM liposome-induced macrophage polarization was measured by flow cytometry ex vivo. The anti-inflammatory mechanism of DHM was studied in cell line RAW264.7 in vitro. Liposome encapsulation enhanced DHM bioavailability, and DHM liposome could alleviate liver inflammation more effectively. Moreover, DHM liposome targeted hepatic macrophages and polarized macrophages into an anti-inflammatory phenotype. The SIRT3/HIF-1α signaling pathway could be the major mechanism of DHM motivated macrophage polarization. Our study indicates that DHM liposomes can alleviate liver inflammation induced by EE through sustained releasing and hepatic targeting. It is a promising option to achieve the high bioavailability of DHM. Also, this study provides new insights into the regional immune effect of DHM against inflammation.

Corneal Endothelial Characteristics in Normal Chinese Han Children and Youngsters: A Study from the Specular Microscopy Descriptions.

Objective: To observe the morphological changes of corneal endothelial cells in healthy Chinese children and youngsters and analyze the sensitive and specificity of the endothelial assessments. Methods: 14,670 Chinese healthy volunteers enrolled were examined by specular microscopy, and the endothelial descriptive indexes: the central corneal thickness (CCT), endothelial cell density (ECD), coefficient of variation in average cell size (CV), the percentage of regular hexagonal cells (hexagonality, HEX), cell size of minimal cell (S min), cell size of maximal cell (S max), average cell size (S avg), and size of standard deviation of cell area (S sd) as well as sex and age were analyzed. Results: The average age of this study is 17.36 ± 7.58 (4-30) years. There is no sex predominance: 7,260 male (49.5%) and 7,410 female (50.5%). The mean CCT, ECD, CV, HEX, S min/max, S avg, and S sd are 529.94 ± 31.53 (437-644) µm, 3,051.28 ± 375.49 (2,031-4,074) cells/mm2, 28.34 ± 4.36 (18-40) %, 61.21 ± 10.29 (17-89) %, (147.79 ± 21.94 to 678.29 ± 120.96) µm2, 332.74 ± 44.62 µm2, and 95.02 ± 23.17 µm2, respectively. The CCTs keep consistency. The ECD decreased rate is 1.02%/year. The curve of ECD and hexagonality expresses the same linear tender. The CCT and endothelial evaluation indexes have no sex predominant (p > 0.05); the quantitative indicators: CCT, ECD, and HEX are significant negative associated with age (p = 0.001 or p < 0.001); the variability indexes: the CV, S min, S max, S avg, and S sd are positive correlation (p < 0.001). The coefficients of CCT, HE, and S min are -0.35, -0.59, and 1.17, respectively. Conclusions: The ECD decrease rate is 1.02%/year of the normal Chinese Han childhood to the earlier adulthood. The ages 4 to 12, 13 to 20, and 21 to 30 can be named as the childhood, puberty and adulthood from endothelial biologic identity. The HEX is the sensitivity marks for the polymorphisms while the S min is the specificity indicator CVs upon the Topcon Noncon Specular microscopy results.

Triggered azobenzene-based prodrugs and drug delivery systems.

Azobenzene-based molecules show unique trans-cis isomerization upon ultraviolet light irradiation, which induce the change of polarity, crystallinity, stability, and binding affinity with pharmacological target. Moreover, azobenzene is the substrate of azoreductase that is often overexpressed in many pathological sites, e.g. hypoxic solid tumor. Therefore, azobenzene can be a multifunctional molecule in material science, pharmaceutical science and biomedicine because of its sensitivity to light, hypoxia and certain enzymes, hence showing potential application in site-specific smart therapy. Herein we focus on the employment of azobenzene and its derivatives for engineering triggered prodrugs and drug delivery systems, and provide an overview of photoswitchable azo-based prodrugs, the associated problems regarding the reversible isomerization and tissue penetration of ultraviolet (UV) light, as well as the potential solutions. We also present the advance of azo-bearing delivery vehicles wherein azobenzene acts as the linker, capping agent, and building block, and discuss the corresponding mechanisms for controlled cargo release, endocytosis enhancement and sensitization of free radical cancer therapy.

Long-term high loading intensity of aerobic exercise improves skeletal muscle performance via the gut microbiota-testosterone axis.

Exercise is reported to play a crucial role in skeletal muscle performance. However, the underlying mechanism is still unknown. Thus, we investigated the effect of high-intensity aerobic exercise on skeletal muscle performance. In this study, the male C57BL/6J mice were accepted by high-intensity aerobic exercise for 8 weeks to establish an exercise model. It was observed that high-intensity aerobic exercise markedly affected the expression of genes in skeletal muscle. Moreover, high-intensity aerobic exercise significantly improved skeletal muscle grip strength and serum testosterone levels. HE staining showed that the cross-sectional area (CSA) of the skeletal muscle was successfully increased after 8 weeks of high-intensity aerobic exercise. Additionally, we found that high-intensity aerobic exercise changed gut microbiota structure by altering the abundance of Akkermansia, Allobaculum, and Lactobacillus, which might be related to testosterone production. However, the beneficial effects disappeared after the elimination of the gut microbiota and recovered after fecal microbiota transplantation (FMT) experiments for 1 week. These results indicated that the beneficial effects of high-intensity aerobic exercise on skeletal muscle were partly dependent on the gut microbiota. Our results suggested that long-term high loading intensity of aerobic exercise could improve skeletal muscle performance, which was probably due to the gut microbiota-testosterone axis.

Dihydromyricetin Attenuates High-Intensity Exercise-Induced Intestinal Barrier Dysfunction Associated with the Modulation of the Phenotype of Intestinal Intraepithelial Lymphocytes.

BACKGROUND: Exercise-induced gastrointestinal syndrome (GIS) has symptoms commonly induced by strenuous sports. The study aimed to determine the effect of dihydromyricetin (DHM) administration on high-intensity exercise (HIE)-induced intestinal barrier dysfunction and the underlying mechanism involved with intestinal intraepithelial lymphocytes (IELs). METHODS: The HIE model was established with male C57BL/6 mice using a motorized treadmill for 2 weeks, and DHM was given once a day by oral gavage. After being sacrificed, the small intestines of the mice were removed immediately. RESULTS: We found that DHM administration significantly suppressed HIE-induced intestinal inflammation, improved intestinal barrier integrity, and inhibited a HIE-induced increase in the number of IELs and the frequency of CD8αα+ IELs. Meanwhile, several markers associated with the activation, gut homing and immune functions of CD8αα+ IELs were regulated by DHM. Mechanistically, luciferase reporter assay and molecular docking assay showed DHM could activate the aryl hydrocarbon receptor (AhR). CONCLUSIONS: These data indicate that DHM exerts a preventive effect against HIE-induced intestinal barrier dysfunction, which is associated with the modulation of the quantity and phenotype of IELs in the small intestine. The findings provide a foundation to identify novel preventive strategies based on DHM supplementation for HIE-induced GIS.

TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner.

BACKGROUND: Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive. METHODS: RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism. RESULTS: We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-ß1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications. CONCLUSIONS: Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-ß1 signaling in regulating cancerous malignancies.

Hypoxia Improves Endurance Performance by Enhancing Short Chain Fatty Acids Production via Gut Microbiota Remodeling.

Hypoxia environment has been widely used to promote exercise capacity. However, the underlying mechanisms still need to be further elucidated. In this study, mice were exposed to the normoxia environment (21% O2) or hypoxia environment (16.4% O2) for 4 weeks. Hypoxia-induced gut microbiota remodeling characterized by the increased abundance of Akkermansia and Bacteroidetes genera, and their related short-chain fatty acids (SCFAs) production. It was observed that hypoxia markedly improved endurance by significantly prolonging the exhaustive running time, promoting mitochondrial biogenesis, and ameliorating exercise fatigue biochemical parameters, including urea nitrogen, creatine kinase, and lactic acid, which were correlated with the concentrations of SCFAs. Additionally, the antibiotics experiment partially inhibited hypoxia-induced mitochondrial synthesis. The microbiota transplantation experiment demonstrated that the enhancement of endurance capacity induced by hypoxia was transferable, indicating that the beneficial effects of hypoxia on exercise performance were partly dependent on the gut microbiota. We further identified that acetate and butyrate, but not propionate, stimulated mitochondrial biogenesis and promoted endurance performance. Our results suggested that hypoxia exposure promoted endurance capacity partially by the increased production of SCFAs derived from gut microbiota remodeling.