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Abstract Background At present, it has been found that many patients have acquired resistance to radiotherapy, which greatly reduces the effect of radiotherapy and further affects the prognosis. CircRNAs is involved in the regulation of radiosensitivity of many kinds of tumor cells. Therefore, the main purpose of this study is to explore the regulatory effect of CircRNA_101491 on radiosensitivity of ESCC and its related mechanism. Methods We established ESCC radiation-resistant cell line (KYSE150R cell) by gradient dose method, and tested the difference of KYSE150 between KYSE150R cell and parent cell in vitro. Then, after knocking down the expression of CircRNA_101491, a series of in vitro experiments were conducted to verify the effects of CircRNA_101491 on the phenotype and radiosensitivity of KYSE150R cells, and further analyzed the related regulatory mechanism. In addition, we also used the model of transplanted tumor in nude mice to investigate the effect of CircRNA_101491 on the radiosensitivity of ESCC in vivo. Results According to a series of in vitro experiments, we confirmed that KYSE150R cells lost the epithelial phenotype and obtained interstitial cell-like phenotype, and found that CircRNA_101491 was highly expressed in KYSE150R cells. In addition, we found that knocking down the expression of CircRNA_101491 will lift the inhibition of miR-125a-5p, and then reverse the process of EMT, accelerate the process of apoptosis, thus play a role in radiosensitization. The in vivo experiment of transplanted tumor in nude mice also showed that knocking down the expression of CircRNA_101491 could enhance the radiosensitivity of ESCC. Conclusion In conclusion, we confirmed that interfering with the expression of CircRNA_101491 can relieve the inhibition of miR-125a-5p, thus reverse the process of interstitial phenotype, accelerate the process of apoptosis, and enhance the radiosensitivity of ESCC.

Summary: Poor-quality (PQ) embryos are commonly formed in assisted reproduction and often discarded, but emerging evidence suggests that some can develop into healthy children. Here, we performed single-embryo transcriptome profiling of day 3 human embryos of both good quality (GQ) and PQ. Our analyses revealed that day 3 PQ embryos can be categorized into two distinct subgroups: genuine PQ (gPQ) and morphological PQ (mPQ) embryos. This was further supported by additional transcriptomic data of GQ and PQ embryos donated by the same individuals. gPQ embryos showed greater impairments in both RNA decay and zygotic genome activation (ZGA) compared to mPQ embryos. Blastocysts that emerged from PQ embryos, more likely from mPQ embryos, demonstrated transcriptomic similarity to normal blastocysts. We also identified genes highly upregulated in day 3 gPQ embryos. These molecular insights may improve embryo selection and offer valuable clues for enhancing embryo quality in the future.

Summary: Background: The E1A-associated protein p300 (p300) has emerged as a promising target for cancer therapy due to its crucial role in promoting oncogenic signaling pathways in various cancers, including prostate cancer. This need is particularly significant in prostate cancer. While androgen deprivation therapy (ADT) has demonstrated promising efficacy in prostate cancer, its long-term use can eventually lead to the development of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Notably, p300 has been identified as an important co-activator of the androgen receptor (AR), highlighting its significance in prostate cancer progression. Moreover, recent studies have revealed the involvement of p300 in AR-independent oncogenes associated with NEPC. Therefore, the blockade of p300 may emerge as an effective therapeutic strategy to address the challenges posed by both CRPC and NEPC. Methods: We employed AI-assisted design to develop a peptide-based PROTAC (proteolysis-targeting chimera) drug that targets p300, effectively degrading p300 in vitro and in vivo utilizing nano-selenium as a peptide drug delivery system. Findings: Our p300-targeting peptide PROTAC drug demonstrated effective p300 degradation and cancer cell-killing capabilities in both CRPC, AR-negative, and NEPC cells. This study demonstrated the efficacy of a p300-targeting drug in NEPC cells. In both AR-positive and AR-negative mouse models, the p300 PROTAC drug showed potent p300 degradation and tumor suppression. Interpretation: The design of peptide PROTAC drug targeting p300 is feasible and represents an efficient therapeutic strategy for CRPC, AR-negative prostate cancer, and NEPC. Funding: The funding details can be found in the Acknowledgements section.

Structural engineers are often required to draw two-dimensional engineering sketches for quick structural analysis, either by hand calculation or using analysis software. However, calculation by hand is slow and error-prone, and the manual conversion of a hand-drawn sketch into a virtual model is tedious and time-consuming. This paper presents a complete and autonomous framework for converting a hand-drawn engineering sketch into an analyzed structural model using a camera and computer vision. In this framework, a computer vision object detection stage initially extracts information about the raw features in the image of the beam diagram. Next, a computer vision number-reading model transcribes any handwritten numerals appearing in the image. Then, feature association models are applied to characterize the relationships among the detected features in order to build a comprehensive structural model. Finally, the structural model generated is analyzed using OpenSees. In the system presented, the object detection model achieves a mean average precision of 99.1%, the number-reading model achieves an accuracy of 99.0%, and the models in the feature association stage achieve accuracies ranging from 95.1% to 99.5%. Overall, the tool analyzes 45.0% of images entirely correctly and the remaining 55.0% of images partially correctly. The proposed framework holds promise for other types of structural sketches, such as trusses and frames. Moreover, it can be a valuable tool for structural engineers that is capable of improving the efficiency, safety, and sustainability of future construction projects.

Abstract When primary users of the spectrum use frequency channels intermittently, secondary users can selectively transmit without interfering with the primary users. The secondary users adjust the transmission power allocation on the frequency channels to maximize their information rate while reducing channel conflicts with the primary users. In this paper, the secondary users do not know the spectrum usage by the primary users or the channel gains of the secondary users. Based on the conflict warnings from the primary users and the signal-to-interference-plus-noise ratio measurement at the receiver, the secondary users adapt and improve spectrum utilization through deep reinforcement learning. The secondary users adopt the actor-critic deep deterministic policy gradient algorithm to overcome the challenges of large state space and large action space in reinforcement learning with continuous-valued actions. In addition, multiple secondary users implement multi-agent deep reinforcement learning under certain coordination. Numerical results show that the secondary users can successfully adapt to the spectrum environment and learn effective transmission policies.

Acute respiratory tract infections are a major public health problem and the leading cause of morbidity in children younger than 5 years old. This study investigated the potential reasons of unexplained acute respiratory infections in children in Xuzhou and its environs during 2018-2019.We collected pharyngeal swab samples from 411 children under the age of five who presented with symptoms of unexplained acute respiratory infection and were negative for bacteria, mycoplasma, and influenza viruses. Using viral metagenomic techniques, viral nucleic acids were extracted, enriched, and sequenced from the samples. Results indicated that Picornaviridae, Parvoviridae, Paramyxoviridae, Coronaviridae, and Anelloviridae were the five virus families with the highest relative content of sequence reads. And we detected 35 HBoV-positive and 12 HEV-positive samples out of 411 samples by the polymerase chain reaction (PCR). Partial or nearly complete genome sequences of viruses belonging to the families Picornaviridae, Parvoviridae, and Anelloviridae were characterized, and phylogenetic trees were constructed based on the nucleic acid or amino acid sequences of the predicted viral open reading frames (ORFs), as well as genotyping of the viruses. In addition, we observed recombination events in the Saffold virus and Coxsackievirus A9 by analyzing the genetic characteristics of the viruses revealed in this study. This study provides vital information for the prevention and treatment of acute respiratory infections in children younger than five years old.

Biosurfactants have significant applications in various industries, including microbial-enhanced oil recovery (MEOR). While the state-of-the-art genetic approaches can generate high-yield strains for biosurfactant production in fermenters, there remains a critical challenge in enhancing biosurfactant-producing strains for use in natural environments with minimal ecological risks. The objectives of this work are enhancing the strain’s capacity for rhamnolipids production and exploring the genetic mechanisms for its improvement. In this study, we employed atmospheric and room-temperature plasma (ARTP) mutagenesis to enhance the biosynthesis of rhamnolipids in Pseudomonas sp. L01, a biosurfactant-producing strain isolated from petroleum-contaminated soil. Following ARTP treatment, we identified 13 high-yield mutants, with the highest yield of 3.45 ± 0.09 g/L, representing a 2.7-fold increase compared to the parent strain. To determine the genetic mechanisms behind the enhanced rhamnolipids biosynthesis, we sequenced the genomes of the strain L01 and five high-yield mutants. A comparative genomic analysis suggested that mutations in genes related to the synthesis of lipopolysaccharides (LPS) and the transport of rhamnolipids may contribute to the improved biosynthesis. To the best of our knowledge, this is the first instance of utilizing the ARTP approach to improve rhamnolipid production in Pseudomonas strains. Our study provides valuable insights into the enhancement of biosurfactant-producing strains and the regulatory mechanisms of rhamnolipids biosynthesis.

The optical reference cavity in an ultrastable laser is sensitive to vibrations; the microvibrations in a space platform affect the accuracy and stability of such lasers. In this study, an active vibration isolation controller is proposed to reduce the effect of vibrations on variations in the cavity length and improve the frequency stability of ultrastable lasers. Based on the decentralized control strategy, we designed a state-differential feedback controller with a linear quadratic regulator (LQR) and added a disturbance observer (DOB) to estimate the source noise. Experiments were conducted using an active vibration isolation system; the results verified the feasibility and performance of the designed controller. The accelerations along the axis (Z-, X-, Y-) directions were suppressed in the low-frequency band within 200 Hz, and the root-cumulative power spectral densities (PSDs) declined to 1.17 × 10−5, 7.16 × 10−6, and 8.76 × 10−6 g. This comprehensive vibration met the requirements of an ultrastable laser.

Basic helix-loop-helix proteins (bHLHs) comprise one of the largest families of transcription factors in plants. They have been shown to be involved in responses to various abiotic stresses, such as drought, salinity, chilling, heavy metal toxicity, iron deficiency, and osmotic damages. By specifically binding to cis-elements in the promoter region of stress related genes, bHLHs can regulate their transcriptional expression, thereby regulating the plant’s adaptive responses. This review focuses on the structural characteristics of bHLHs, the regulatory mechanism of how bHLHs are involved transcriptional activation, and the mechanism of how bHLHs regulate the transcription of target genes under various stresses. Finally, as increasing research demonstrates that flavonoids are usually induced under fluctuating environments, the latest research progress and future research prospects are described on the mechanisms of how flavonoid biosynthesis is regulated by bHLHs in the regulation of the plant’s responses to abiotic stresses.

Long non-coding RNAs (lncRNAs) are major components of cellular transcripts that are arising as important players in various biological pathways. They have received extensive attention in recent years, regarded to be involved in both developmental processes and various diseases. Due to their specific expression and functional diversity in a variety of cancers, lncRNAs have promising applications in cancer diagnosis, prognosis and therapy. Studies have shown that lncRNAs with high specificity and accuracy have the potential to become biomarkers in cancers. LncRNAs can be noninvasively extracted from body fluids, tissues and cells, and can be used as independent or auxiliary biomarkers to improve the accuracy of diagnosis or prognosis. Currently, the most well-recognized lncRNA is PCA3, which has been approved for use in the diagnosis of prostate cancer. Moreover, the underlying mechanisms of lncRNAs were explored as therapeutic targets, which have been investigated in clinical trials of several cancers. In this review, we presented a compilation of recent publications, clinical trials and patents, addressing the potential of lncRNAs that could be considered as biomarkers or therapeutic targets, with the hopes of providing promised implications for future cancer therapy.

In this study, an active microvibration isolation system is developed for precision space payload. Vibrational environment affects the performance and reliability of measuring instruments. To improve the measurement accuracy of the precision space payload, an active vibration isolation system based on eight vibration isolation modules, which are applied for microvibration isolation on the satellite, is designed. A vibration suppression control strategy for multiple degrees of freedom is studied. A hybrid control method involving a feedback and a feedforward controller based on a nonlinear tracking differentiator and an nth-order weak integrator, respectively, was adopted to optimize the suppression effect of microvibration. As a result, the microvibration of the order of mg can be reduced to the order of μg through the active control of modules. Research experiment results show that the root cumulative power spectral density of the systemic sensitive frequency band in the range of 0.5–200 Hz, i.e., microvibration frequency band in the optical reference cavity, has been reduced to in the order of μg in three directions, which satisfied the requirements of aerospace engineering.

CO2 is the main source of greenhouse emission, and the environment problem caused by greenhouse effect has drawn worldwide attention. In most oilfields in China, a method of waterflooding is usually used to enhance oil recovery, which is favorable to carry out CO2 injection study. The CO2 injection in the water-flooded oilfields can not only store CO2, but also enhance the oil recovery. In this article, the core-flooding tests with refined oil were conducted to investigate CO2 displacement characteristic in water-saturated formation under different injection rate and water-flooded oil reservoir under different formation pressure and oil saturation, then the CO2 storage capacity was calculated. The testing result shows that the displacement efficiency increases with the rise of the CO2 injection rate, and the CO2 injection can enhance the oil recovery about 15% OOIP under the experimental condition. When injecting CO2 after the waterflooding, the CO2 storage capacity increases as the rise of the formation pressure. The core-flooding tests also indicate that when the initial oil saturation of reservoir prior CO2 injection is higher, the oil recovery will be higher when injecting the same pore volume (PV) of CO2, and the CO2 storage capacity will be larger.

Surfactant aggregates have long been considered as a tool to improve drug delivery and have been widely used in medical products. The pH-responsive aggregation behavior in anionic gemini surfactant 1,3-bis(N-dodecyl-N-propanesulfonate sodium)-propane (C12C3C12(SO3)2) and its mixture with a cationic monomeric surfactant cetyltrimethylammonium bromide (CTAB) have been investigated. The spherical-to-wormlike micelle transition was successfully realized in C12C3C12(SO3)2 through decreasing the pH, while the rheological properties were perfectly enhanced for the formation of wormlike micelles. Especially at 140 mM and pH 6.7, the mixture showed high viscoelasticity, and the maximum of the zero-shear viscosity reached 1530 Pa·s. Acting as a sulfobetaine zwitterionic gemini surfactant, the electrostatic attraction, the hydrogen bond and the short spacer of C12C3C12(SO3)2 molecules were all responsible for the significant micellar growth. Upon adding CTAB, the similar transition could also be realized at a low pH, and the further transformation to branched micelles occurred by adjusting the total concentration. Although the mixtures did not approach the viscosity maximum appearing in the C12C3C12(SO3)2 solution, CTAB addition is more favorable for viscosity enhancement in the wormlike-micelle region. The weakened charges of the headgroups in a catanionic mixed system minimizes the micellar spontaneous curvature and enhances the intermolecular hydrogen-bonding interaction between C12C3C12(SO3)2, facilitating the formation of a viscous solution, which would greatly induce entanglement and even the fusion of wormlike micelles, thus resulting in branched microstructures and a decline of viscosity.

Ship antiroll gyros are a type of equipment used to reduce ships’ roll angle, and their parameters are related to the parameters of a ship and wave, which affect gyro performance. As an alternative framework, we designed a calculation method for roll reduction rate and considered random waves to establish a gyro parameter optimization model, and we then solved it through the bacteria foraging optimization algorithm (BFOA) and pattern search optimization algorithm (PSOA) to obtain optimal parameter values. Results revealed that the two methods could effectively reduce the overall mass and floor space of the antiroll gyro and improved its antirolling effect. In addition, the convergence speed and antirolling effect of the BFOA were better than that of the PSOA.

Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance.

UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultured cells and in third instar larvae. We further showed that UTX mediates the expression of ku80 by the demethylation of H3K27me3 at the ku80 promoter upon exposure to ionizing radiation (IR) in a p53-dependent manner. UTX interacts physically with p53, and both UTX and p53 are recruited to the ku80 promoter following IR exposure in an interdependent manner. In contrast, the loss of utx has little impact on the expression of ku70, mre11, hid and reaper, suggesting the specific regulation of ku80 expression by UTX. Thus, our findings further elucidate the molecular function of UTX.