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Some circular RNAs (circRNAs) were found to be translated through IRES-driven mechanism, however the scope and functions of circRNA translation are unclear because endogenous IRESs are rare. To determine the prevalence and mechanism of circRNA translation, we develop a cell-based system to screen random sequences and identify 97 overrepresented hexamers that drive cap-independent circRNA translation. These IRES-like short elements are significantly enriched in endogenous circRNAs and sufficient to drive circRNA translation. We further identify multiple trans -acting factors that bind these IRES-like elements to initiate translation. Using mass-spectrometry data, hundreds of circRNA-coded peptides are identified, most of which have low abundance due to rapid degradation. As judged by mass-spectrometry, 50% of translatable endogenous circRNAs undergo rolling circle translation, several of which are experimentally validated. Consistently, mutations of the IRES-like element in one circRNA reduce its translation. Collectively, our findings suggest a pervasive translation of circRNAs, providing profound implications in translation control. Unbiased screen of random sequences identified many short IRES-like elements to drive circular RNA translation and hundreds of rolling circle translation events, suggesting a pervasive cap-independent translation in human transcriptome.

The thermodynamics of the Bardeen black hole in asymptotically flat space is investigated with the corrected first law of thermodynamics via Rényi statistics. The nonextensive parameter λ gives the possibility to the thermal stability of Bardeen black hole, and there is a Hawking–Page phase transition in the grand canonical ensemble (fixed the potential), which is similar to the cases of Bardeen black hole and corrected Bardeen black hole in asymptotically anti-de Sitter (AdS) space via standard Gibbs–Boltzmann (GB) statistics. By introducing the general Smarr formula via Rényi statistics, the thermodynamic pressure P is defined with the parameter λ and its conjugate quantity V is the thermodynamic volume (not a geometric spherical volume with horizon radius r h ). The thermodynamics of the asymptotically flat Bardeen black hole via Rényi statistics in the canonical ensemble (fixed the charge q ) behaves like the van der Waals system, which is also same as the asymptotically Bardeen-AdS black hole via GB statistics. The analogy between the thermodynamics of the asymptotically flat Bardeen black hole from Rényi statistics and the Bardeen-AdS black hole from GB statistics makes us to consider what is the relation between the nonextensive parameter λ and the cosmological constant Λ .

Fiber Bragg grating (FBG) sensor has a lot of advantages over the resistance strain gauge and has been used in many applications. However, there are few applications of rotor blade dynamic measurement in helicopter flight. In this paper, a method for blade dynamic strain measurement using an FBG sensor in a helicopter’s real flight is presented. The corresponding measurement system is established and can eliminate the effects of the helicopter’s electromagnetic environment on the electrical sensing components in the measurement system with the orthogonal frequency-division multiplexing modulation. The measured dynamic strains on the rotor blades of the helicopter in real flight contain six harmonic frequencies with the vibration characteristics of rotor blades, indicating that the established FBG measurement method and system have practical engineering applications.

Fibre lasers operating at the mid-IR have attracted enormous interest due to the plethora of applications in defence, security, medicine, and so on. However, no continuous-wave (CW) fibre lasers beyond 4 μm based on rare-earth-doped fibres have been demonstrated thus far. Here, we report efficient mid-IR laser emission from HBr-filled silica hollow-core fibres (HCFs) for the first time. By pumping with a self-developed thulium-doped fibre amplifier seeded by several diode lasers over the range of 1940–1983 nm, narrow linewidth mid-IR emission from 3810 to 4496 nm has been achieved with a maximum laser power of about 500 mW and a slope efficiency of approximately 18%. To the best of our knowledge, the wavelength of 4496 nm with strong absorption in silica-based fibres is the longest emission wavelength from a CW fibre laser, and the span of 686 nm is also the largest tuning range achieved to date for any CW fibre laser. By further reducing the HCF transmission loss, increasing the pump power, improving the coupling efficiency, and optimizing the fibre length together with the pressure, the laser efficiency and output power are expected to increase significantly. This work opens new opportunities for broadly tunable high-power mid-IR fibre lasers, especially beyond 4 μm.

Progression through the mitotic cell cycle requires periodic regulation of gene function at the levels of transcription, translation, protein-protein interactions, post-translational modification and degradation. However, the role of alternative splicing (AS) in the temporal control of cell cycle is not well understood. By sequencing the human transcriptome through two continuous cell cycles, we identify ~1300 genes with cell cycle-dependent AS changes. These genes are significantly enriched in functions linked to cell cycle control, yet they do not significantly overlap genes subject to periodic changes in steady-state transcript levels. Many of the periodically spliced genes are controlled by the SR protein kinase CLK1, whose level undergoes cell cycle-dependent fluctuations via an auto-inhibitory circuit. Disruption of CLK1 causes pleiotropic cell cycle defects and loss of proliferation, whereas CLK1 over-expression is associated with various cancers. These results thus reveal a large program of CLK1-regulated periodic AS intimately associated with cell cycle control. Mitosis is a key step in the normal life cycle of a cell, during which one cell divides into two new cells. As a cell progresses through the cell cycle, it must carefully regulate its gene activity to switch particular genes on or off at specific moments. When a gene is activated its sequence is first copied into a temporary molecule called a transcript. These transcripts are then edited to form templates to build proteins. One way that a transcript can be edited is via a process called alternative splicing, in which different pieces of the transcript are cut and pasted together to form different versions of the final template. This allows different instructions to be obtained from a single gene, introducing an added layer of biological complexity. However, the role of alternative splicing in the timing of key events of the cell life cycle is not well understood. Dominguez et al. have now looked for the genes that undergo alternative splicing during the cell cycle. The sequences of gene transcripts produced within human cells were collected while the cells went through two rounds of division. This approach revealed that around 1,300 genes are spliced in different ways at different stages of each cell cycle. Many of these genes were known to play roles in controlling the cell’s life cycle, but few of the genes showed large changes in the amount of total transcript that is generated over time. Dominguez et al. also showed that an enzyme called CLK1 influences about half of the 1,300 periodically spliced genes during the cell cycle. The production of CLK1 is itself carefully controlled throughout the cell cycle, and the enzyme’s activity prevents its own overproduction. Further experiments showed that blocking CLK1’s activity while a cell is replicating its DNA halts the cell cycle, but blocking this enzyme’s activity after the cell had replicated its DNA did not. Given this pivotal role in the cell cycle, Dominguez et al. also examined the role of CLK1 in cancer cells and found that high levels of CLK1 in tumours were linked to lower survival rates. These findings indicate that CLK1 warrants further investigation, particularly in relation to its role in cancer.

A systematic, unbiased screen for general intronic splicing enhancers (ISEs) identified >100 ISEs that promote intron splicing but inhibit splicing in exons. Putative trans -factors for clusters of ISEs were identified, validated and were found to control ISE activity in a context-dependent manner. Altogether, the data provide a comprehensive picture of how ISEs function depending on their location and cognate trans -factors. Most human genes produce multiple splicing isoforms with distinct functions. To systematically understand splicing regulation, we conducted an unbiased screen and identified >100 intronic splicing enhancers (ISEs), clustered by sequence similarity. All ISEs functioned in multiple cell types and in heterologous introns, and patterns of distribution and conservation across pre-mRNA regions were similar to those of exonic splicing silencers. Consistently, all ISEs inhibited use of splice sites from exons. Putative trans -factors of each ISE group were identified and validated. Five distinct groups were recognized by hnRNP H and hnRNP F, whose C-terminal domains were sufficient to render context-dependent activities of ISEs. The sixth group was controlled by factors that either activate or suppress splicing. We provide a comprehensive picture of general ISE activities and suggest new models of how single elements can function oppositely, depending on locations and binding factors.

Thalidomide and its analogs are molecular glues (MGs) that lead to targeted ubiquitination and degradation of key cancer proteins via the cereblon (CRBN) E3 ligase. Here, we develop a direct-to-biology (D2B) approach for accelerated discovery of MGs. In this platform, automated, high throughput, and nano scale synthesis of hundreds of pomalidomide-based MGs was combined with rapid phenotypic screening, enabling an unprecedented fast identification of potent CRBN-acting MGs. The small molecules were further validated by degradation profiling and anti-cancer activity. This revealed E14 as a potent MG degrader targeting IKZF1/3, GSPT1 and 2 with profound effects on a panel of cancer cells. In a more generalized view, integration of automated, nanoscale synthesis with phenotypic assays has the potential to accelerate MGs discovery. Targeted protein degradation (TPD) is an emerging therapeutic that can lead to proteasomal degradation of target proteins. Here, the authors combine nano-scale, automated synthesis and cell-based, direct-to-biology screening, allowing them to discover and profile Molecular Glues (MGs) degrading substrates via the Cereblon E3 ubiquitin ligase.

Complex diseases often exhibit sex dimorphism in morbidity and prognosis, many of which are age-related. However, the underlying mechanisms of sex-dimorphic aging remain foggy, with limited studies across multiple tissues. We systematically analyzed ~17,000 transcriptomes from 35 human tissues to quantitatively evaluate the individual and combined contributions of sex and age to transcriptomic variations. We discovered extensive sex dimorphisms during aging with distinct patterns of change in gene expression and alternative splicing (AS). Intriguingly, the male-biased age-associated AS events have a stronger association with Alzheimer’s disease, and the female-biased events are often regulated by several sex-biased splicing factors that may be controlled by estrogen receptors. Breakpoint analysis showed that sex-dimorphic aging rates are significantly associated with decline of sex hormones, with males having a larger and earlier transcriptome change. Collectively, this study uncovered an essential role of sex during aging at the molecular and multi-tissue levels, providing insight into sex-dimorphic regulatory patterns.

The advanced water treatment taken by organic micro-pollution or microbiological pollution water resource has been a hot issue of public concern. In this article, novel quaternary ammonium salt functionalized β-cyclodextrin polyurethane (QAS-β-CDPU) microparticles were successfully constructed for above-mentioned pollutants removal. By adjusting the proportion of the chlorine-containing monomers, we studied the effect of different quaternization degree (0%, 20%, 40%, 60%) on solvent resistance and thermal stability. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are recognized as significant human bacterial pathogens, which were used as model bacteria to investigate the antibacterial activity by contact-killing tests. Methylene blue (MB) served as a toxic organic model to quantify the dye wastewater remediation efficiency. Research shows that the reaction of β-cyclodextrin and diisocyanate can form a cyclodextrin-based carbamate network structure. Since both the cyclodextrin cavity and the carbamate network may remove the dye, the obtained polymer has a double advantage. Besides, the presence of quaternary ammonium groups enables QAS-β-CDPU microparticles to possess good bactericidal properties. When the quaternization degree is 60%, sterilization rates of QAS-β-CDPU microparticles are over 96% for S. aureus and E. coli. On basis of this simple, green and economical synthetic route, QAS-β-CDPU microparticles have the potential to become an ideal multifunctional material in water purification.Graphic AbstractNovel quaternary ammonium salt functionalized β-cyclodextrin polyurethane (QAS-β-CDPU) microparticles were successfully constructed for removing bacteria and dyes from wastewater.

Early brain injury (EBI) is involved in the process of cerebral tissue damage caused by subarachnoid hemorrhage (SAH), and multiple mechanisms, such as apoptosis and inflammation, participate in its development. Mangiferin (MF), a natural C-glucoside xanthone, has been reported to exert beneficial effects against several types of organ injury by influencing various biological progresses. The current study aimed to investigate the potential of MF to protect against EBI following SAH via histological and biological assessments. A rat perforation model of SAH was established, and MF was subsequently administered via intraperitoneal injection at a low and a high dose. High-dose MF significantly lowered the mortality of SAH animals and ameliorated their neurological deficits and brain edema. MF also dose-relatedly attenuated SAH-induced oxidative stress and decreased cortical cell apoptosis by influencing mitochondria-apoptotic proteins. In addition, MF downregulated the activation of the NLRP3 inflammasome and NF- κ B as well as the production of inflammatory cytokines, and the expression of Nrf2 and HO-1 was upregulated by MF. The abovementioned findings indicate that MF is neuroprotective against EBI after SAH and Nrf2/HO-1 cascade may play a key role in mediating its effect through regulation of the mitochondrial apoptosis pathway and activation of the NLRP3 inflammasome and NF- κ B.