Analysis on the Difference of Energy Evolution in the Process of Energy Storage Failure of Strong Coal Rush Rock Samples under Different Adaptive Modification Regulation Measures

Current energy to “release” after accumulating + first for the mechanism of rock bursts occurred in analysis of the strategy is accepted by many scholars, based on the existing means of prevention and control of percussive ground pressure, from the angle of the prevention and control of design of the mechanism of impact ground pressure energy regulation, namely, “weakened after the first release +” softened water injection measures and “lead after the first release +” drilling pressure relief measures, for the study of mining under the action of a strong shock tendentiousness rock energy regulatory mechanism; based on rock mechanics experiment, the analysis under different modification measures should be variant energy storage mechanisms of induced damage evolution of rock energy. The mechanism of energy evolution in the modification of strong bursting liability roof rock is revealed. The results show that different modification regulation measures can effectively change the physical and mechanical parameters of target rock samples and realize “hard rock softening or soft rock hardening.” Samples under different modification measures are classified as initial consolidation stage, elastic stage, stage of plastic deformation, yield failure stage, and late stage, the energy evolution is roughly the same as the sample complete natural condition, but the yield failure stage and the destruction of late stage have an obvious difference, which provides favorable conditions for impact ground pressure to prevent. With the help of three characteristic energy indexes of total strain, elastic strain energy, and dissipative strain energy of rock samples, the evolution law of energy indexes under different modification control measures is analyzed. The index of elastic energy consumption ratio is introduced as a precursor feature of rock instability and failure, which indicates the rock impact tendency to a certain extent. The energy regulation mechanisms of “first release+then weakening” water injection softening measures and “first release+then guidance” drilling pressure relief measures are explained theoretically, respectively. However, we should focus on the defects of the corresponding control measures and finally try to make a reasonable combination of different modification measures. Finally, the gradient pressure relief scheme should be considered in order to avoid large stress drop caused by large-scale pressure relief in the region and aggravate the instability of rock mass. The instability of rock mass is further aggravated.

XRCC4 and MRE11 Roles and Transcriptional Response to Repair of TALEN-Induced Double-Strand DNA Breaks

Double-strand breaks (DSB) are one of the most lethal forms of DNA damage that, if left unrepaired, can lead to genomic instability, cellular transformation, and cell death. In this work, we examined how repair of transcription activator-like effector nuclease (TALEN)-induced DNA damage was altered when knocking out, or inhibiting a function of, two DNA repair proteins, XRCC4 and MRE11, respectively. We developed a fluorescent reporter assay that uses TALENs to introduce DSB and detected repair by the presence of GFP fluorescence. We observed repair of TALEN-induced breaks in the XRCC4 knockout cells treated with mirin (a pharmacological inhibitor of MRE11 exonuclease activity), albeit with ~40% reduced efficiency compared to normal cells. Editing in the absence of XRCC4 or MRE11 exonuclease was robust, with little difference between the indel profiles amongst any of the groups. Reviewing the transcriptional profiles of the mirin-treated XRCC4 knockout cells showed 307 uniquely differentially expressed genes, a number far greater than for either of the other cell lines (the HeLa XRCC4 knockout sample had 83 genes, and the mirin-treated HeLa cells had 30 genes uniquely differentially expressed). Pathways unique to the XRCC4 knockout+mirin group included differential expression of p53 downstream pathways, and metabolic pathways indicating cell adaptation for energy regulation and stress response. In conclusion, our study showed that TALEN-induced DSBs are repaired, even when a key DSB repair protein or protein function is not operational, without a change in indel profiles. However, transcriptional profiles indicate the induction of unique cellular responses dependent upon the DNA repair protein(s) hampered.

Adenylate kinase 1 overexpression increases locomotor activity in medaka fish

Maintenance of the energy balance is indispensable for cell survival and function. Adenylate kinase (Ak) is a ubiquitous enzyme highly conserved among many organisms. Ak plays an essential role in energy regulation by maintaining adenine nucleotide homeostasis in cells. However, its role at the whole organism level, especially in animal behavior, remains unclear. Here, we established a model using medaka fish (Oryzias latipes) to examine the function of Ak in environmental adaptation. Medaka overexpressing the major Ak isoform Ak1 exhibited increased locomotor activity compared to that of the wild type. Interestingly, this increase was temperature dependent. Our findings suggest that cellular energy balance can modulate locomotor activity.

Transcriptomic Profiling in Mice With CB1 receptor Deletion in Primary Sensory Neurons Suggests New Analgesic Targets for Neuropathic Pain

Type 1 and type 2 cannabinoid receptors (CB1 and CB2, respectively) mediate cannabinoid-induced analgesia. Loss of endogenous CB1 is associated with hyperalgesia. However, the downstream targets affected by ablation of CB1 in primary sensory neurons remain unknown. In the present study, we hypothesized that conditional knockout of CB1 in primary sensory neurons (CB1cKO) alters downstream gene expression in the dorsal root ganglion (DRG) and that targeting these pathways alleviates neuropathic pain. We found that CB1cKO in primary sensory neurons induced by tamoxifen in adult Advillin-Cre:CB1-floxed mice showed persistent hyperalgesia. Transcriptome/RNA sequencing analysis of the DRG indicated that differentially expressed genes were enriched in energy regulation and complement and coagulation cascades at the early phase of CB1cKO, whereas pain regulation and nerve conduction pathways were affected at the late phase of CB1cKO. Chronic constriction injury in mice induced neuropathic pain and changed transcriptome expression in the DRG of CB1cKO mice, and differentially expressed genes were mainly associated with inflammatory and immune-related pathways. Nerve injury caused a much larger increase in CB2 expression in the DRG in CB1cKO than in wildtype mice. Interfering with downstream target genes of CB1, such as antagonizing CB2, inhibited activation of astrocytes, reduced neuroinflammation, and alleviated neuropathic pain. Our results demonstrate that CB1 in primary sensory neurons functions as an endogenous analgesic mediator. CB2 expression is regulated by CB1 and may be targeted for the treatment of neuropathic pain.

Functional Characterization of Melanocortin-3 Receptor in a Hibernating Cavefish Onychostoma macrolepis

Melanocortin-3 receptor (MC3R) plays an important role in the energy homeostasis of animals under different nutritional conditions. Onychostoma macrolepis is a hibernating cavefish found in the northern part of the Yangtze River, and its adaptation to a nutrient-poor environment has attracted growing interest. In this study, we characterized the protein structure of Onychostoma macrolepis Mc3r (omMc3r), examined its tissue distribution, and investigated its function in mediating cellular signaling. We showed that the CDS of omMc3r is 978 bp, encoding a putative protein of 325 amino acids. Homology and phylogenetic analyses indicated that omMc3r is evolutionary close to cyprinids. Real-time quantitative PCR (RT-qPCR) revealed that omMc3r was highly expressed in the liver and brain. The functions of omMc3r to mediate ligands activating downstream signaling have also been confirmed by using signal pathway-specific reporters. The four agonists α-MSH, β-MSH, NDP-MSH, and ACTH (1–24) can all activate the cAMP and MAPK/ERK signaling pathway, albeit with different potency orders. The “primitive” ligand ACTH (1–24) had the highest potency on the cAMP signaling pathway, while the synthetic ligand NDP-MSH had the highest activation effect on the MAPK/ERK signaling pathway. This research will lay the foundation for studying the energy regulation mechanism of cavefish in an oligotrophic environment.

Study Regarding Accounting Treatment of Green Certificates in Romania

Accounting regulations approved through Order 1802/2014 makes remarks regarding the reflection of green certificates in accounting. Green certificates are titles that attest the production of a quantity of electrical energy from renewable sources. These can be traded distinctly from the amount of electrical energy that they represent. A.N.R.E. (National Agency of Energy Regulation) rewards producers of renewable electricity to benefit the promotion of sustainable energy through green certificates. Electricity providers and some producers are required to purchase a number of green certificates on a quarterly basis. They are then required to transmit to the National Agency of Energy Regulation, in the specified format and by the deadline set by them, the quantities of electrical energy for which they need to purchase green certificates, in conformity with law 220/2008. The cost of green certificates is billed separately from the price of electric energy inaccounting tratament the invoice sent to the final customers. Providers or producers that do not meet the yearly quota must pay the value of green certificates not acquired in said timespan. According to the ministry’s of public finance Order 1802/2014, producers of renewable energy, that benefit from green certificates provided by the transport and system operator must register the green certificates received into their accountings using specific accounting accounts

miR1908-5p regulates energy homeostasis in hepatocyte models

We previously identified genomic variants that are quantitative trait loci for circulating miR-1908-5p and then showed this microRNA to causally associate with plasma levels of LDL-C, fasting blood glucose and HbA1c. The link to LDL-C was subsequently validated and clarified by the identification of a miR1908-5p-TGFB-LDLR regulatory axis. Here, we continue our investigations on miR1908-5p function by leveraging human primary hepatocytes and HuH-7 hepatoma models. Expression of miR1908-5p was shown to be sensitive to glucose and agents affecting glucose metabolism. Transcriptome-wide changes in primary hepatocytes and HuH-7 cells treated with a miR1908-5p mimic were investigated by enrichment approaches to identify targeted transcripts and cognate pathways. Significant pathways included autophagy and increased mitochondrial function. Reduced activation and/or levels of several key energy and metabolic regulators (AKT, mTOR, ME1, G6PD, AMPK and LKB) were subsequently confirmed in mimic treated HuH-7 cells. These effects were associated with reduced NADPH to NADP+ ratio in HuH-7 cells. LKB1 was validated as a direct target of miR1908-5p, the reintroduction of which was however insufficient to compensate for the impact of the miR1908-5p mimic on AMPK and ACC1. These findings implicate miR1908-5p in metabolic and energy regulation in hepatocyte models via multiple, independent, pathways.

Longitudinal Profiling in Phenotypic Metric of Aging: Insights From the Baltimore Longitudinal Study of Aging

It remains challenging to quantify the pace of aging across lifespan due to lack of comprehensive longitudinal measurements across wide range of age. In Baltimore Longitudinal Study of Aging, we have measured the longitudinal trajectories of more than 30 phenotypes across four pre-identified domain - body composition, energy regulation, homeostatic mechanisms and neurodegeneration/neuroplasticity, among participants with age between 20+ and 90+. We implemented a two-stage approach to summarize the longitudinal trajectories of these phenotypes across four domains into a summarized score. We demonstrated that higher summarized score (denoting for slower longitudinal phenotypic decline) is associated with slower decline in both cognitive and physical functions, across different stages of adulthood. Our results imply that deep longitudinal profiling contains rich information and may potentially replace diseases as an early endpoint in trials targeting at aging. Further, understanding the underpinning of longitudinal phenotypic trajectories may provide clues to the biological mechanisms of aging.

Endocrinopathies in Inborn Errors of Immunity

Inborn errors of immunity (IEI), caused by hereditary or genetic defects, are a group of more than 400 disorders, in which the immune system, including lymphocytes, neutrophils, macrophages, and complements, does not function properly. The endocrine system is frequently affected by IEI as an associated clinical feature and a complex network of glands which regulate many important body functions, including growth, reproduction, homeostasis, and energy regulation. Most endocrine disorders associated with IEI are hypofunction which would be treated with supplementation therapy, and early diagnosis and appropriate management are essential for favorable long-term outcomes in patients with IEI. In this review, we aimed to comprehensively summarize and discuss the current understanding on the clinical features and the pathophysiology of endocrine disorders in IEI. This review is composed with three parts. First, we discuss the two major pathophysiology of endocrinopathy in IEI, autoimmune response and direct effects of the responsible genes. Next, the details of each endocrinopathy, such as growth failure, hypothyroidism, hypoparathyroidism, adrenal insufficiency, diabetes mellitus (DM) are specified. We also illustrated potential endocrinopathy due to hematopoietic stem cell transplantation, including hypogonadism and adrenal insufficiency due to glucocorticoid therapy.