Activation of eIF4E-binding-protein-1 rescues mTORC1-induced sarcopenia by expanding lysosomal degradation capacity

Background: Chronic mTORC1 activation in skeletal muscle is linked with age-associated loss of muscle mass and strength, known as sarcopenia. Genetic activation of mTORC1 by conditionally ablating mTORC1 upstream inhibitor TSC1 in skeletal muscle accelerates sarcopenia development in adult mice. Conversely, genetic suppression of mTORC1 downstream effectors of protein synthesis delays sarcopenia in natural aging mice. mTORC1 promotes protein synthesis by activating ribosomal protein S6 kinases (S6Ks) and inhibiting eIF4E-binding proteins (4EBPs). Whole-body knockout of S6K1 or muscle-specific over-expression of a 4EBP1 mutant transgene (4EBP1mt), which is resistant to mTORC1-mediated inhibition, ameliorates muscle loss with age and preserves muscle function by enhancing mitochondria activities, despite both transgenic mice showing retarded muscle growth at a young age. Why repression of mTORC1-mediated protein synthesis can mitigate progressive muscle atrophy and dysfunction with age remains unclear. Methods: Mice with myofiber-specific knockout of TSC1 (TSC1mKO), in which mTORC1 is hyperactivated in fully differentiated myofibers, were used as a mouse model of sarcopenia. To elucidate the role of mTORC1-mediated protein synthesis in regulating muscle mass and physiology, we bred the 4EBP1mt transgene or S6k1 floxed mice into the TSC1mKO mouse background to generate 4EBP1mt-TSC1mKO or S6K1-TSC1mKO mice, respectively. Functional and molecular analyses were performed to assess their role in sarcopenia development. Results: Here, we show that 4EBP1mt-TSC1mKO, but not S6K1-TSC1mKO, preserved muscle mass (36.7% increase compared with TSC1mKO, P < 0.001) and strength (36.8% increase compared with TSC1mKO, P < 0.01) at the level of control mice. Mechanistically, 4EBP1 activation suppressed aberrant protein synthesis (two-fold reduction compared with TSC1mKO, P < 0.05) and restored autophagy flux without relieving mTORC1-mediated inhibition of ULK1, an upstream activator of autophagosome initiation. We discovered a previously unidentified phenotype of lysosomal failure in TSC1mKO mouse muscle, in which the lysosomal defect was also conserved in the naturally aged mouse muscle, whereas 4EBP1 activation enhanced lysosomal protease activities to compensate for impaired autophagy induced by mTORC1 hyperactivity. Consequently, 4EBP1 activation relieved oxidative stress to prevent toxic aggregate accumulation (0.5-fold reduction compared with TSC1mKO, P < 0.05) in muscle and restored mitochondrial homeostasis and function. Conclusions: We identify 4EBP1 as a communication hub coordinating protein synthesis and degradation to protect proteostasis, revealing therapeutic potential for activating lysosomal degradation to mitigate sarcopenia

Prediction of the potential distribution of Chimonobambusa utilis (Poaceae, Bambusoideae) in China, based on the MaxEnt model

Chimonobambusa utilis is a unique edible bamboo species valued for its economic and nutritional benefits. However, its existence in natural habitats is at risk due to environmental shifts and human interventions. This research utilised the maximum entropy model (MaxEnt) to predict potential habitats for Ch. utilis in China, identifying key environmental factors influencing its distribution and analysing changes in suitable habitats under future climate conditions. The results show that the results of the MaxEnt model have high prediction accuracy, with an AUC (Area Under the receiver operating characteristic Curve) value of 0.997. Precipitation in the driest month (Bio14), altitude (Alt) and isothermality (Bio03) emerged as the primary environmental factors influencing the Ch. utilis distribution. Currently, the suitable habitats area for Ch. utilis is 10.55 × 104 km2. Projections for the 2050s and 2090s indicate potential changes in suitable habitats ranging from -3.79% to 10.52%. In general, the most suitable habitat area will decrease and shrink towards higher latitude areas in the future. This study provides a scientific basis for the introduction, cultivation and conservation of Ch. utilis

In situ characterizations for aqueous rechargeable zinc batteries

Abstract Recently, aqueous rechargeable zinc batteries (ARZBs) have become a hot topic in secondary batteries. Constant attention has witnessed the development of ARZBs, such as active materials, reaction mechanisms, and mass transport, and huge successes have been achieved. However, as the fundamental basis of battery monitoring in real‐time and the theories of ARZBs, the in situ characterization techniques are equally worth discussing but the relevant review remains missing. Herein, this review focuses on the in situ characterization techniques of visualization and spectroscopy characterizations for ARZBs. Typical research of the in situ techniques is comprehensively discussed, including the setup of the in situ cells, the working principle of characterizations, the application, and the analysis applied in ARZBs. With the help of in situ characterizations, the reaction dynamics, transport kinetics, and thermodynamics in ARZBs can be thoroughly researched. Finally, the current primary challenges and future opportunities faced by in situ techniques toward ARZBs are also summarized

Stoichiometric Characteristics of Leaf, Litter and Soil during Vegetation Succession in Maolan National Nature Reserve, Guizhou, China

Carbon (C), nitrogen (N), phosphorus (P) and potassium (K) are the main nutrient elements widely found in soil, litter and leaves, and their stoichiometric ratios are important indicators of ecosystem functions. However, there is little research on the effects that nutrient cycle and vegetation succession have on leaf, litter and soil nutrients and stoichiometric ratios, especially in the fragile karst areas. To reveal the nutrient cycling characteristics and ecosystem stability mechanism during vegetation succession, leaf, litter and soil samples were collected from the herbaceous community (HC), shrub community (SC), secondary forest community (SF) and primary forest community (PF) in a typical karst area at growth and senescence phases. The results showed that the nutrient contents and stoichiometric ratios of leaf, litter and soil in the main layers of each community were significantly different at the growth and senescence phase. The utilization efficiency of N in the leaves of the main layers of each succession community first decreased and then increased at different growth stages, and the utilization efficiency of P increased but the reabsorption rates of N and P showed a continuous decreasing trend. In addition, there was a significant allometric relationship between N and P contents in plant leaves during the growth phase. More importantly, the internal stability of N content in plant leaves was higher than the P content, suggesting that vegetation succession significantly affected leaf, litter and soil nutrient contents and their stoichiometric ratios in our study region. The strength of the relationship between them reflects the inheritance and co&ndash;variation of nutrient content to a certain extent, and the differences in the strategies that different species in the community use to adapt to the fragile karst environment. This study concludes that plants in the karst region mainly improve their P utilization efficiency to adapt to low phosphorus stress in soil and ensure the normal physiological and biochemical responses in the process of vegetation succession

Stoichiometric Characteristics of Leaf, Litter and Soil during Vegetation Succession in Maolan National Nature Reserve, Guizhou, China

Carbon (C), nitrogen (N), phosphorus (P) and potassium (K) are the main nutrient elements widely found in soil, litter and leaves, and their stoichiometric ratios are important indicators of ecosystem functions. However, there is little research on the effects that nutrient cycle and vegetation succession have on leaf, litter and soil nutrients and stoichiometric ratios, especially in the fragile karst areas. To reveal the nutrient cycling characteristics and ecosystem stability mechanism during vegetation succession, leaf, litter and soil samples were collected from the herbaceous community (HC), shrub community (SC), secondary forest community (SF) and primary forest community (PF) in a typical karst area at growth and senescence phases. The results showed that the nutrient contents and stoichiometric ratios of leaf, litter and soil in the main layers of each community were significantly different at the growth and senescence phase. The utilization efficiency of N in the leaves of the main layers of each succession community first decreased and then increased at different growth stages, and the utilization efficiency of P increased but the reabsorption rates of N and P showed a continuous decreasing trend. In addition, there was a significant allometric relationship between N and P contents in plant leaves during the growth phase. More importantly, the internal stability of N content in plant leaves was higher than the P content, suggesting that vegetation succession significantly affected leaf, litter and soil nutrient contents and their stoichiometric ratios in our study region. The strength of the relationship between them reflects the inheritance and co–variation of nutrient content to a certain extent, and the differences in the strategies that different species in the community use to adapt to the fragile karst environment. This study concludes that plants in the karst region mainly improve their P utilization efficiency to adapt to low phosphorus stress in soil and ensure the normal physiological and biochemical responses in the process of vegetation succession