ISRIB alleviates aging-associated brown fat UCP1 translational repression and thermogenic deficiency.

Upon cold exposure, aged people with lower metabolic rate cannot rapidly increase the higher levels of heat production, and are seriously threatened by the hypothermia, extensive cold stress responses and risk of mortality. Here, we show that brown fat thermogenic activity is obviously deficient in aged mice, associating with reduction of UCP1 expression and inhibition of its mRNA translation. As we considered, aging aggravates brown fat oxidative stress and activates the integrated stress response (ISR), inducing the phosphorylation of eIF2α to block the global mRNA translation. Therefore, small-molecule ISR inhibitor (ISRIB) treatment attenuates the higher level of eIF2α phosphorylation, restores the repression of Ucp1 mRNA translation and improves UCP1-mediated thermogenic function to defend cold stress in aged mice. Furthermore, ISRIB treatment increases the relative lower metabolic rates, and alleviates glucose intolerance and insulin resistance in aged mice. Thus, we have uncovered a promising drug that reverses the aged-related the deficiency of UCP1-mediated thermogenesis to combat cold stress and associated metabolic diseases.

Genetic analysis and transcriptome analysis of the mini mutant of the silkworm, Bombyx mori.

The expression levels of some intrinsic genes, protease activity, and regulation of signaling pathways were distinct during different growth and development stages in the silkworm, Bombyx mori. The silkworm mutant mini was discovered from the normal silkworm strain S8V, and the body-size of the mini mutant was smaller than the wild-type from the second-instar and the difference became more significant in the following stages. In this study, genetic analysis of mini mutant showed that mini mutant was controlled by a single recessive gene, manifested as homozygous lethal. Then, the transcriptome analysis of the mini mutant indicated that 2944 differentially expressed genes (DEGs) were identified from the silkworm in the 48 h of the second-instar, of which 1638 genes in the mini mutants were upregulated and 1306 genes were downregulated. These DEGs were mainly distributed in the biological process, cellular component, and molecular function. The functional annotation based on the KEGG database showed that these genes were mainly clustered in metabolic pathways, fatty acid metabolism pathways, ribosome biogenesis in eukaryotes, and so on. Further analysis indicated that some genes involved in the growth and metabolism including enzyme genes, juvenile hormone, and ecdysone exhibited different transcriptional levels. These results provided new experimental evidence regarding the mechanism of the underlying formation of mini mutants.

Design, Synthesis, and Biological Evaluation of Novel Cinnamide Derivatives as Neuroprotective Agents for the Treatment of Cerebral Ischemia.

BACKGROUND: Ischemic stroke, the most common type of cerebrovascular accident, is a major cause of severe disability among adults worldwide. Although there has been progress in interventions for ischemic stroke in the past decades, there is no effective treatment to prevent brain damage in acute ischemic stroke. Therefore, it is urgent to develop novel neuroprotective agents with a wide therapeutic time window to provide a better prognosis for ischemic stroke patients. OBJECTIVE: The current study aimed to synthesize novel derivatives with substituent cinnamide scaffolds, evaluate biological activity, and obtain neuroprotective agents. METHODS: The target compounds were synthesized using classical methods of medicinal chemistry. The neuroprotective effects in vitro against Glu-induced neurotoxicity injury were evaluated in PC12 cells by MTT assay. The cell apoptosis was analyzed by flow cytometer. The proteins were detected by western blotting. The neuroprotective activities in vivo were determined in two in vivo models of global and focal cerebral ischemia. RESULTS: Among the title compounds, 9t, 9u, 9y, and 9z exhibited good neuroprotection in vivo and in vitro, which were selected and further studied to determine their mechanism of action. 9t, 9u, 9y and 9z protected PC12 cells against glutamate-induced apoptosis in a dose-dependent manner via caspase-3 pathway. Moreover, the four compounds significantly reduced brain infarct area and exhibited excellent neuroprotective activities in the in vivo MCAO model. CONCLUSION: Compounds 9t, 9u, 9y, and 9z, as potent neuroprotective agents with anti- neurotoxicity activity in vitro and anticerebral infarction efficacy in vivo, might serve as a useful molecular tool for further physiology and pathophysiology function studies, leading to potential clinical therapeutic agents for ischemic injury.

Multi-Scale Microstructural Tailoring and Associated Properties of Press-Hardened Steels: A Review.

High-strength press-hardened steels (PHS) are highly desired in the automotive industry to meet the requirement of carbon neutrality. This review aims to provide a systematic study of the relationship between multi-scale microstructural tailoring and the mechanical behavior and other service performance of PHS. It begins with a brief introduction to the background of PHS, followed by an in-depth description of the strategies used to enhance their properties. These strategies are categorized into traditional Mn-B steels and novel PHS. For traditional Mn-B steels, extensive research has verified that the addition of microalloying elements can refine the microstructure of PHS, resulting in improved mechanical properties, hydrogen embrittlement resistance, and other service performance. In the case of novel PHS, recent progress has principally demonstrated that the novel composition of steels coupling with innovative thermomechanical processing can obtain multi-phase structure and superior mechanical properties compared with traditional Mn-B steels, and their effect on oxidation resistance is highlighted. Finally, the review offers an outlook on the future development of PHS from the perspective of academic research and industrial applications.

Effect of photodynamic therapy on resin-dentin bonding interface using different illumination times.

OBJECTIVES: The aim of the present study was to evaluate the effect of photodynamic therapy(PDT) on the resin-dentin bonding interface using different illumination time. METHODS: Seventy completed, isolated molar teeth were collected for this study, sixty of them were used in microtensile bond strength tests. These teeth were initially divided randomly in two main groups(n= 30) by the random number table method upon the type of using illumination or not, respectively. Then these groups followed by dividing each category in five subgroups(n = 6): group A, group B1,group B2, group B3, group B4, group a, group b1, group b2, group b3, group b4. After different treatment, the remaining teeth were made specimens which were observed the fracture modes and interfaces under a stereomicroscope and a scanning electron microscope(SEM). The dentin permeability of the specimens were evaluated by a confocal laser scanning microscopy(CLSM). To detect significance difference between means of different groups analysis of variance(ANOVA) was performed followed by LSD-t tests. RESULTS: There was a significant statistical difference in the microtensile bond strength of the different illumination time of PDT between four experimental groups and the control (P < 0.05). CONCLUSION: With the increase of the illumination time in PDT, the bonding strength between resin and dentin decreased gradually.

Which kind of nitrogen chemical states doped carbon dots loaded by g-C3N4 is the best for photocatalytic hydrogen production.

Recently, g-C3N4 (CN) loaded N-doped carbon dots (NCDs) have been widely studied as promising metal-free photocatalysts due to their impressive performance in hydrogen production. However, deep understanding of the effect of nitrogen chemical states on photocatalytic activity is still lacked. In this work, NCDs doped with pyrrole nitrogen, graphite/pyrrole nitrogen, and pyrrole/pyridine nitrogen were prepared and hybridized with g-C3N4. The characterizations revealed that, incorporation of pyrrole N-doped CDs into g-C3N4 (CN/NCDs-en) effectively enhanced the visible light absorption, facilitated electron-hole separation, and promoted the participation of photoexcited electrons in H2 evolution reaction. Moreover, theoretical calculation showed that, compared with graphite N and pyridine N, pyrrole N has the most appropriate H adsorption ability, which is conducive to the H2 formation. Under visible light irradiation, the CN/NCDs-en exhibited the best hydrogen evolution of 3028 µmol h-1 g-1. These results shed a light on the design and optimization of N-doped metal-free photocatalysts for H2 evolution reaction.

Comparative analysis of testis transcriptome between a genetic male sterile line (GMS) and its wild-type 898WB in silkworm, Bombyx mori.

The silkworm, Bombyx mori, is an important model organism of lepidopteran insects, and its testis is a main male reproductive organ and spermatogenesis place. Studying the testis helps to understand the mechanisms of genetic sterility of lepidopteran insects and to achieve sterile insect technique (SIT) for pest control. Herein, we performed a comparative transcriptome analysis of testes between three biological replicates of the GMS mutant and wild strain 898WB, respectively. In total, 1872 up-regulated genes and 1823 down-regulated genes were identified in the testis of the GMS mutant. Several genes contribute significantly to spermatogenesis and testis development, such as "serine/threonine protein kinase", "organic cation transporter protein", "tyrosine protein kinase", "lncRNAs" and "immune-associated genes". The KEGG pathway analysis shows that the DEGs were annotated to 123 pathways, and 10 pathways were significantly enriched, such as "metabolic pathway", "biosynthesis of amino acids", and "phagosome-lysosome pathway", which are associated with testis development and spermatogenesis. The results of the qPCR expression were consistent with the RNA-seq data, which shows that the RNA-seq results were accurate. The DEGs of the testes between GMS mutant and 898WB were screened by RNA-Seq technology, which provides a reliable reference to understand the molecule mechanism of male sterility of the GMS mutant.

phytanoyl-CoA dioxygenase domain-containing protein 1 plays an important role in egg shell formation of silkworm (Bombyx mori).

Yun7Ge is a giant egg mutant found in the silkworm variety Yun7. In comparison with the giant mutant Ge, the eggs of Yun7Ge are larger. The number of laid eggs and hatching rate of Yun7Ge are reduced, which is not conducive to reproduction. In this work, the target gene controlling giant egg trait is located on the Z chromosome and was determined through genetic analysis. Transcriptome results showed that phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1) on the Z chromosome was silenced, and the 25 chorion genes on chromosome 2 were remarkably downregulated. Sequence analysis showed that the 73.5 kb sequence including the PHYHD1 was replaced by a ~3.0 kb sequence. After knocking out the PHYHD1 by using CRISPR/Cas9, the chorion genes were significantly downregulated. Hence, the silencing of PHYHD1 leads to the downregulation of many chorion protein genes, thus directly causing giant eggs.

Transcriptome analysis of the eggs of the silkworm pale red egg (rep-1) mutant at 36 hours after oviposition.

The egg stage is one of the most critical periods in the life history of silkworms, during which physiological processes such as sex determination, tissue organ formation and differentiation, diapause and pigmentation occur. In addition, egg color gradually emerges around 36h after oviposition. The red egg mutant rep-1, which was recently discovered in the C1(H) wild-type, C1(H) exhibits a brown egg color. In this study, the transcriptome of the eggs was analyzed 36h after oviposition. Between the rep-1 mutant and the C1(H) wild-type, 800 differentially expressed genes (DEGs) were identified, including 325 up-regulated genes and 475 down-regulated genes. These DEGs were mainly involved in biological processes (metabolic process, cellular process, biological regulation and regulation of biological process and localization), cellular components (membrane, membrane part, cell, cell part and organelle) and molecular functions (binding, catalytic activity, transporter activity, structural molecule activity and molecular transducer activity). The pathway enrichment of these DEGs was performed based on the KEGG database, and the results indicated that these DEGs were mainly involved in pathways in the following categories: metabolic pathways, longevity-regulating pathway-multiple species, protein processing in endoplasmic reticulum, peroxisome, carbon metabolism and purine metabolism. Further analysis showed that a large number of silkworm growth- and development-related genes and ommochrome synthesis- and metabolism-related genes were differentially expressed, most of which were up-regulated in the mutant. Our research findings provide new experimental evidence for research on ommochrome pigmentation and lay the foundation for further research on the mechanism of the rep-1 mutant.

[Determination of 12 bisphenol substances in functional foods by QuEChERS and high performance liquid chromatography-tandem mass spectrometry].

A method based on high performance liquid chromatography-tandem mass spectrom- etry (HPLC-MS/MS) for the simultaneous determination of 12 bisphenol substances in functional foods (powder, tablet, capsule) was presented. The samples were extracted by acetonitrile containing 1% (v/v) acetic acid followed by further cleaned up using matrix solid-phase disper- sion to remove matrix interferences. The separation of the 12 bisphenol substances was performed on a Thermo Aquasil C18 column (150 mm x 4.6 mm, 3.0 µm), and determined in the positive and negative MRM modes by MS/MS using matrix-matched external standard method. The results demonstrated that the calibration curves were of good linearity with the correlation coefficients greater than 0.99. The limits of detection (LODs, S/N > 3) were in the range of 0.1-0.5 µg/kg and the limits of quantitation (LOQs, S/N > 10) were 0.4-1.7 µg/kg. The recoveries of the 12 bisphenol substances spiked at three levels (2.0, 5.0 and 10.0 µg/kg) in matrix ranged from 60.5% to 116.3% with the relative standard deviations (RSDs) of 6.8% to 11.2%. The established method is simple, time-saving and sensitive. It can meet the requirements for current regulations while achieving qualitative and quantitative determination of the 12 bisphenol substances in functional foods.