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MAB phases represent a class of ternary layered transition metal borides that are structurally analogous to the well-established MAX phase, and they exhibit promising potential in various applications, including mechanics, catalysis, wave-absorption, batteries, and high-temperature environments. However, only a few MAB phases have been experimentally synthesized, making the exploration of new phases a pressing challenge. In this study, three potential Ti-based MABs (Ti2AlB2, Ti3AlB4 and Ti4AlB6) are predicted via first-principles calculations and density functional theory (DFT). The computational analyses confirm the thermodynamic and mechanical stability of these phases, with their lattice parameters determined, providing valuable references for future experimental endeavors. Crystal structure analysis reveals a distinctive feature of MABs, the B–B zigzag chains, which are absent in MAX phases, endowing them with superior in-plane strength. Mechanical analyses show that these compounds exhibit elastic anisotropy, which is closely related to the microstructure of Ti–B slices. Electronic studies confirm the metallic nature of these compounds, while the highly reactive Al atomic layer suggests a significant potential for selectively etching to yield two-dimensional (2D) MBene. Optical studies indicate that these compounds possess excellent polarization and dielectric loss capabilities, making them promising candidates for next-generation materials in photo-thermal conversion, sensing and wave-absorbing devices.

Abstract Purpose To compare clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) created with the single covered-uncovered stent (Viatorr TIPS Endoprosthesis) versus covered stent (Fluency) versus a combination of covered and uncovered stent. Materials and methods From May 2016 and July 2019, a total of 180 liver cirrhosis patients with recurrent variceal bleeding underwent TIPS creation with single covered-uncovered stent (n = 63) or covered stent (n = 41) or a covered and uncovered stent combination (n = 76). Shunt dysfunction, rebleeding, overt hepatic encephalopathy and mortality was estimated using the Kaplan–Meier method and compared with the log-rank test. Results The difference of baseline characteristics among these three groups were not significant. The included patients had a median age of 51 years (IQR 43–61), and 101 (56.1%) were men. The 1-year and 2-year shunt dysfunction rates were 1.6% and 3.2% in the single covered-uncovered stent group, 7.3% and 7.3% in the covered stent group and 5.3% and 6.6% in the combination group, respectively. There was no significant difference among groups [Hazard Ratio (HR) (95%CI): 1 vs 2.29 (0.38 − 13.72) vs 2.10 (0.41 − 10.83); P = 0.913]. No significant differences in the incidence of all-cause rebleeding were observed between the groups at 1 year (Viatorr vs Fluency vs combination: 11.1% vs 17.1% vs 10.5%) as well as 2 years (15.9% vs 17.1% vs 11.8%), with the HR (95%CI) being 1 vs 1.27 (0.5—3.21) vs 0.74 (0.30–1.82); P = 0.475). The 1-year and 2-year incidence of overt hepatic encephalopathy were 30.2% and 30.2% in the single covered-uncovered stent group, 22.0% and 22.0% in the covered stent group and 25.0% and 25.0% in the combination group, respectively. However, there was no significant difference among these three groups (P = 0.402). In addition, there was no significant difference in the 1-year and 2-year mortality (6.3% and 7.9% vs. 4.9% and 9.8% vs. 6.6% and 9.2%, P = 0.606). Conclusion No significant difference was observed among different stent groups. Fluency covered stent and the generic bare stent/Fluency covered stent was not an unreasonable alternative to the Viatorr stent for TIPS creation.

AbstractObjective The aim of this retrospective study was to investigate the short-term and long-term efficacy of high-intensity focused ultrasound (HIFU) therapy for abdominal wall endometriosis (AWE) and explore its potential influencing factors.Materials and methods A total of 80 patients with AWE who underwent HIFU therapy were retrospectively analyzed. Follow-ups were also conducted to evaluate the changes in lesion size and pain relief. Multivariate logistic regression analysis was applied to investigate factors influencing HIFU therapy for AWE.Results Among the 80 patients with AWE who received HIFU therapy, the effective rates were 76.3%, 80.5%, and 90.5% after 3, 12 and 24 months of follow-up, respectively. Multivariate logistic regression analysis revealed that the AWE lesion diameter and sonication intensity had statistically significant effects on the 3-month and 12-month efficacy of HIFU therapy for AWE, while age, BMI, disease duration, average sonication power and grey-scale changes did not have statistically significant effects. Four patients with AWE experienced recurrence after HIFU therapy, for a three-year cumulative recurrence rate of 6.3%. Furthermore, ten patients required reintervention after treatment, for a five-year cumulative reintervention rate of 13.9%.Conclusions This study further confirmed the safety and effectiveness of HIFU therapy for AWE. Factors such as AWE lesion diameter and sonication intensity have been identified as key influencers affecting the short-term and long-term efficacy of HIFU therapy for AWE. The first two years following HIFU therapy constitute crucial periods for observation, and judiciously extending follow-up intervals during this timeframe is advised.

Objectives: This pharmacovigilance analysis was conducted to assess the safety signals of FMS-related tyrosine kinase 3 (FLT3) inhibitors in a real-world setting using the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Design: We analyzed adverse event (AE) reports related to FLT3 inhibitors submitted to the FAERS database from the first quarter of 2015 to the fourth quarter of 2022. Disproportionality analysis was used to identify AEs of FLT3 inhibitors in the FAERS database. Results: A total of 55,393 AE reports were identified, of which 5938, 44,013, and 5442 were attributed to midostaurin, sorafenib, and gilteritinib, respectively, as primary suspects. Compared to the full database, significant safety signals at the system organ class level were observed for midostaurin (blood and lymphatic system disorders and hepatobiliary disorders), sorafenib (skin and subcutaneous tissue disorders and hepatobiliary disorders), and gilteritinib (investigations, blood and lymphatic system disorders, infections and infestations, and hepatobiliary disorders). All the drugs studied were associated with hepatobiliary disorders. The most prominent AEs associated with midostaurin, sorafenib, and gilteritinib were cytopenia, palmar-plantar erythrodysesthesia syndrome, and increased blast cell count, respectively. Compared with chemotherapy, midostaurin and gilteritinib showed a higher risk of electrocardiogram QT prolongation, gastrointestinal hemorrhage, cerebral hemorrhage, and increased white blood cell count. Gilteritinib had the highest overall death percentage (30.28%), whereas sorafenib had the lowest (23.06%). Conclusion: Mining AE signals using the FAERS database provides a method for analyzing the safety of FLT3 inhibitors in post-marketing. We found several significant AE signals that corresponded to previous studies; however, some AE signals were not mentioned in the drug instructions. Our study could provide a direction for follow-up real-world studies to verify the results further.

In 2019 as a national key research program, the Development and Effectiveness Evaluation of an Innovative Health Management Model – Internet plus Medical Alliance-based Co-prevention and Co-management on Cardio-cerebrovascular Diseases was initiated in several regions including Shanghai and Guangzhou municipality and Xinjiang Uygur Autonomous Region. The ROCCIPI framework refers to a way of identifying and analyzing fundamental causes of problems in health policy through interrelated thinking patterns of seven elements: rule, opportunity, capacity, communication, interest, process and ideology. The framework could provide an evidence-based strategic approach to solve health policy problems. In this article, we try to identify and analyze the progress and problems in the implementation of the innovative health management at 21 comprehensive demonstration regions in China based on the ROCCIPI framework. Specific suggestions are also presented for promoting the comprehensive disease prevention and management project.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive scarring interstitial lung disease with an unknown cause. Some patients may experience acute exacerbations (AE), which result in severe lung damage visible on imaging or through examination of tissue samples, often leading to high mortality rates. However, the etiology and pathogenesis of AE-IPF remain unclear. AE-IPF patients exhibit diffuse lung damage, apoptosis of type II alveolar epithelial cells, and an excessive inflammatory response. Establishing a reliable animal model of AE is critical for investigating the pathogenesis. Recent studies have reported a variety of animal models for AE-IPF, each with its own advantages and disadvantages. These models are usually established in mice with bleomycin-induced pulmonary fibrosis, using viruses, bacteria, small peptides, or specific drugs. In this review, we present an overview of different AE models, hoping to provide a useful resource for exploring the mechanisms and targeted therapies for AE-IPF.

Abstract The escalating demand for sophisticated carbon products, including carbon black, carbon nanotubes (CNTs), and graphene, has yet to be adequately addressed by conventional techniques with respect to large‐scale, efficient, and controllable carbon material synthesis. Molten pyrolysis emerges as a propitious strategy for generating such high‐value carbon materials. Abundant carbon sources encompassing methane (CH4), carbon dioxide (CO2), biomass, and plastics can undergo thermal decomposition into carbon constituents within molten metal or salt media. This methodology not only obviates dependence on traditional fossil fuels but additionally enables modulation of carbon material morphologies by varying the molten media, thereby presenting substantial potential for effective and controlled carbon material fabrication. In this review, we examine the capacity of molten pyrolysis in producing high‐value carbon materials derived from CH4, CO2, biomass, and plastics. Concurrently, we present a detailed overview of the potential applications of this novel methodology, particularly emphasizing its relevance in the fields of supercapacitors, flexible materials, and electrochemical cells. Furthermore, we contemplate future trajectories for molten pyrolysis, accentuating that amalgamation with auxiliary processes or technologies—like renewable energy systems and carbon capture and storage—represents a remarkably promising route for continued investigation.

Abstract Female infertility is a worldwide concern that impacts the quality of life and well-being of affected couples. Failure of embryo implantation is a major cause of early pregnancy loss and is precisely regulated by a programmed molecular mechanism. Recent studies have shown that proper trophoblast adhesion and invasion are essential for embryo implantation. However, the potential regulatory mechanism involved in trophoblast adhesion and invasion has yet to be fully elucidated. KRT18 has been reported to play a critical role in early embryonic development, but its physiological function in embryo implantation remains unclear. In the present study, we revealed that KRT18 was highly expressed in trophoblast cells and that knockdown of KRT18 in mouse embryos inhibited embryo adhesion and implantation. In vitro experiments further showed that silencing KRT18 disturbed trophoblast migration and invasion. More importantly, we provide evidence that KRT18 directly binds to and stabilizes cell surface E-cadherin in trophoblast cells through microscale thermophoresis (MST) analysis and molecular biology experiments. In brief, our data reveal that KRT18, which is highly expressed in trophoblast cells, plays an important role in the regulation of trophoblast invasion and adhesion during embryo implantation by directly binding to E-cadherin.

IntroductionIdiopathic pulmonary fibrosis (IPF) is characterized by progressive lung dysfunction due to excessive collagen production and tissue scarring. Despite recent advancements, the molecular mechanisms remain unclear.MethodsRNA sequencing identified 475 differentially expressed genes (DEGs) in the TGF-β1-induced primary lung fibrosis model. Gene expression chips GSE101286 and GSE110147 from NCBI gene expression omnibus (GEO) database were analyzed using GEO2R, revealing 94 DEGs in IPF lung tissue samples. The gene ontology (GO) and pathway enrichment, Protein-protein interaction (PPI) network construction, and Maximal Clique Centrality (MCC) scoring were performed. Experimental validation included RT-qPCR, Immunohistochemistry (IHC), and Western Blot, with siRNA used for gene knockdown. A co-expression network was constructed by GeneMANIA.ResultsGO enrichment highlighted significant enrichment of DEGs in TGF-β cellular response, connective tissue development, extracellular matrix components, and signaling pathways such as the AGE-RAGE signaling pathway and ECM-receptor interaction. PPI network analysis identified hub genes, including FN1, COL1A1, POSTN, KIF11, and ECT2. CALD1 (Caldesmon 1), CDH2 (Cadherin 2), and POSTN (Periostin) were identified as dysregulated hub genes in both the RNA sequencing and GEO datasets. Validation experiments confirmed the upregulation of CALD1, CDH2, and POSTN in TGF-β1-treated fibroblasts and IPF lung tissue samples. IHC experiments probed tissue-level expression patterns of these three molecules. Knockdown of CALD1, CDH2, and POSTN attenuated the expression of fibrotic markers (collagen I and α-SMA) in response to TGF-β1 stimulation in primary fibroblasts. Co-expression analysis revealed interactions between hub genes and predicted genes involved in actin cytoskeleton regulation and cell-cell junction organization.ConclusionsCALD1, CDH2, and POSTN, identified as potential contributors to pulmonary fibrosis, present promising therapeutic targets for IPF patients.

The HIV-1 provirus mainly consists of internal coding region flanked by 1 long terminal repeats (LTRs) at each terminus. The LTRs play important roles in HIV-1 reverse transcription, integration, and transcription. However, despite of the significant study advances of the internal coding regions of HIV-1 by using definite reference classification, there are no systematic and phylogenetic classifications for HIV-1 5' LTRs, which hinders our elaboration on 5' LTR and a better understanding of the viral origin, spread and therapy. Here, by analyzing all available resources of 5' LTR sequences in public databases following 4 recognized principles for the reference classification, 83 representatives and 14 consensus sequences were identified as representatives of 2 groups, 6 subtypes, 6 sub-subtypes, and 9 CRFs. To test the reliability of the supplemented classification system, the constructed references were applied to identify the 5' LTR assignment of the 22 clinical isolates in China. The results revealed that 16 out of 22 tested strains showed a consistent subtype classification with the previous LTR-independent classification system. However, 6 strains, for which recombination events within 5' LTR were demonstrated, unexpectedly showed a different subtype classification, leading a significant change of binding sites for important transcription factors including SP1, p53, and NF-κB. The binding change of these transcriptional factors would probably affect the transcriptional activity of 5' LTR. This study supplemented a unified classification system for HIV-1 5' LTRs, which will facilitate HIV-1 characterization and be helpful for both basic and clinical research fields.

Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance.

The aim of this study is to produce a biodegradable food packaging material that reduces environmental pollution and protects food safety. The effects of total solids content, substrate ratio, polyphenol content, and magnetic stirring time on bovine bone gelatin/sodium carboxymethylcellulose nanoemulsion (BBG/SCMC–NE) were investigated using particle size, PDI, turbidity, rheological properties, and zeta potential as evaluation indexes. The micro, structural, antioxidant, encapsulation, and release properties were characterized after deriving its optimal preparation process. The results showed that the nanoemulsion was optimally prepared with a total solids content of 2%, a substrate ratio of 9:1, a polyphenol content of 0.2%, and a magnetic stirring time of 60 min. SEM showed that the nanoemulsion showed a dense and uniform reticulated structure. FTIR and XRD results showed that covalent cross-linking of proteins and polysaccharides altered the structure of gelatin molecular chains to a more compact form but did not change its semi-crystalline structure. DSC showed that the 9:1 BBG/SCMC–NE had a higher thermal denaturation temperature and greater thermal stability, and its DPPH scavenging rate could reach 79.25% and encapsulation rate up to 90.88%, with excellent slow-release performance. The results of the study provide basic guidance for the preparation of stable active food packaging with excellent properties.

It is believed that human Influenza HA glycoprotein attaches to alpha2-6 linked sialic acids (SA) on cells, while avian viruses bind to alpha2-3 linked sialic acids, therewith contributing to host tropism. Here, Liu et al. show that mixing low-affinity alpha2-3 SA with low amounts of high-affinity alpha2-6 SA increases binding and entry of human viruses and the converse for avian virus. This shows that receptor recognition is not as strict as currently assumed and provides evidence that heteromultivalent interactions between human/avian HA and SA contributes to host adaptation.

Primary liver cancer (PLC) that originates in the liver is a malignant tumor with the worst prognosis. Hepatocellular carcinoma (HCC) is the most common type of PLC. Most PLC cases are diagnosed at advanced stages mainly due to their insidious onset and rapid progression. Patients with PLC undergo surgical intervention or localized treatment, but their survival is often affected by its high relapse rate. Medical treatment is the primary option for patients with liver cancer, especially with advanced extrahepatic metastases. Molecular targeted therapy exerts an anti-tumor effect by acting on various signaling pathways involved in molecular pathogenesis; however, high drug resistance and low therapeutic responsiveness of PLC to molecular targets challenge the treatment option. In recent years, after surgical intervention, radiotherapy, chemotherapy, and/or molecular targeted therapy, autologous cell immunotherapy has been adopted for PLC. As a typical autologous cell immunotherapy, CAR T-cell therapy uses genetically modified T cells to express tumor-specific chimeric antigen receptors (CARs). Its targeting ability, persistent nature, and tumor-killing function result in a significant impact on the treatment of hematological tumors. However, no breakthrough has happened in the research specific to the curation of lung cancer, liver cancer, breast cancer, and other common solid tumors. In this context, a combination of molecular targeted therapy and CAR T-cell therapy was used to treat a patient with advanced HCC to achieve a partial remission(PR) and facilitate further liver transplantation.

ABSTRACT Enterovirus D68 (EV-D68) is an emerging pathogen associated with mild to severe respiratory disease. Since 2014, EV-D68 is also linked to acute flaccid myelitis (AFM), causing paralysis and muscle weakness in children. However, it remains unclear whether this is due to an increased pathogenicity of contemporary EV-D68 clades or increased awareness and detection of this virus. Here, we describe an infection model of primary rat cortical neurons to study the entry, replication, and functional consequences of different EV-D68 strains, including historical and contemporary strains. We demonstrate that sialic acids are important (co)receptors for infection of both neurons and respiratory epithelial cells. Using a collection of glycoengineered isogenic HEK293 cell lines, we show that sialic acids on either N-glycans or glycosphingolipids can be used for infection. Additionally, we show that both excitatory glutamatergic and inhibitory GABA-ergic neurons are susceptible and permissive to historical and contemporary EV-D68 strains. EV-D68 infection of neurons leads to the reorganization of the Golgi-endomembranes forming replication organelles, first in the soma and later in the processes. Finally, we demonstrate that the spontaneous neuronal activity of EV-D68-infected neuronal network cultured on microelectrode arrays (MEA) is decreased, independent of the virus strain. Collectively, our findings provide novel insights into neurotropism and -pathology of different EV-D68 strains, and argue that it is unlikely that increased neurotropism is a recently acquired phenotype of a specific genetic lineage. IMPORTANCE Acute flaccid myelitis (AFM) is a serious neurological illness characterized by muscle weakness and paralysis in children. Since 2014, outbreaks of AFM have emerged worldwide, and they appear to be caused by nonpolio enteroviruses, particularly enterovirus-D68 (EV-D68), an unusual enterovirus that is known to mainly cause respiratory disease. It is unknown whether these outbreaks reflect a change of EV-D68 pathogenicity or are due to increased detection and awareness of this virus in recent years. To gain more insight herein, it is crucial to define how historical and circulating EV-D68 strains infect and replicate in neurons and how they affect their physiology. This study compares the entry and replication in neurons and the functional consequences on the neural network upon infection with an old “historical” strain and contemporary “circulating” strains of EV-D68.

Introduction“Sonic seasoning” is when music influences the real taste experiences of consumers. “Self-construal” is how individuals perceive, understand, and interpret themselves. Numerous studies have shown that independent and interdependent self-construal priming can affect a person's cognition and behavior; however, their moderating effect on the sonic seasoning effect remains unclear.MethodsThis experiment was a 2 (self-construal priming: independent self-construal or interdependent self-construal) × 2 (chocolate: milk chocolate or dark chocolate) × 2 (emotional music: positive emotional music or negative emotional music) mixed design, and explored the moderating role of self-construal priming and the effect of emotional music on taste by comparing participants' evaluations of chocolates while listening to positive or negative music after different levels of self-construal priming.ResultsAfter initiating independent self-construal, participants increased their ratings of milk chocolate sweetness when listening to music that elicited positive emotions, t(32) = 3.11, p = 0.004, Cohen's d = 0.54, 95% CI = [0.33, 1.61]. In contrast, interdependent self-construal priming led participants to perceive dark chocolate as sweeter when they heard positive music, t(29) = 3.63, p = 0.001, Cohen's d = 0.66, 95%CI = [0.44, 1.56].DiscussionThis study provides evidence for improving people's individual eating experience and enjoyment of food.

To improve the performance of aluminized propellants, it is important to study the mechanism of agglomeration and approve the methods of inhibiting agglomeration. In this study, organic fluoride was added to the propellants and the dynamic combustion process of the propellants was obtained through visual combustion test system. At the same time, an algorithm which can detect the size of particles out of focus more accurately is also proposed. Then, the agglomeration behaviors, as well as the size distribution of initial condensed products and final condensed products, during the combustion of propellants are discussed. The influence of organic fluoride additive on the evolution of condensed products and the distribution of their sizes were also analyzed. The results show that the condensed products had a coral structure, and underwent the stages of exposure, accumulation, splicing, separation, and combustion to evolve into oxidation cap structures. When organic fluoride is added, special flocculent products were formed instead of coral-like products and the AlF3 was found in the condensed products. Besides, detailed behaviors of condensed products have been found in the gas. The products with an oxidation cap still subsequently interacted with one another in the gas, including through re-fusion and re-separation. The distribution of the initial products was relatively concentrated and stable while that of the final products exhibited a prominent trend of increasing first, then decreasing, and gradually stabilizing. Besides, with the addition of organic fluoride, the main combustion products were converted α - Al2O3 and θ - Al2O3 to γ - Al2O3 and δ - Al2O3, indicating that the addition of organic fluoride significantly improved the performance of the aluminized propellants in terms of suppressing the size of the condensed products.

Abstract Background Human endogenous retroviruses (HERVs) result from ancestral infections caused by exogenous retroviruses that became incorporated into the germline DNA and evolutionarily fixed in the human genome. HERVs can be transmitted vertically in a Mendelian fashion and be stably maintained in the human genome, of which they are estimated to comprise approximately 8%. HERV-K (HML1-10) transcription has been confirmed to be associated with a variety of diseases, such as breast cancer, lung cancer, prostate cancer, melanoma, rheumatoid arthritis, and amyotrophic lateral sclerosis. However, the poor characterization of HML-9 prevents a detailed understanding of the regulation of the expression of this family in humans and its impact on the host genome. In light of this, a precise and updated HERV-K HML-9 genomic map is urgently needed to better evaluate the role of these elements in human health. Results We report a comprehensive analysis of the presence and distribution of HERV-K HML-9 elements within the human genome, with a detailed characterization of the structural and phylogenetic properties of the group. A total of 23 proviruses and 47 solo LTR elements were characterized, with a detailed description of the provirus structure, integration time, potential regulated genes, transcription factor binding sites (TFBS), and primer binding site (PBS) features. The integration time results showed that the HML-9 elements found in the human genome integrated into the primate lineage between 17.5 and 48.5 million years ago (mya). Conclusion The results provide a clear characterization of HML-9 and a comprehensive background for subsequent functional studies.

In this paper, a novel flow perturbation model meant to investigate the effects of incoming wind shear on a hypersonic inlet/isolator is presented. This research focuses on the transient shock/boundary layer interaction and shock train flow evolution in a hypersonic inlet/isolator with an on-design Mach number of 6.0 under incoming wind shear at high altitudes, precisely at an altitude of 30 km with a magnitude speed of 80 m/s. Despite the low intensity of wind shear at high altitudes, the results reveal that wind shear significantly disrupts the inlet/isolator flowfield, affecting the shock wave/boundary layer interaction in the unthrottled state, which drives the separation bubble at the throat to move downstream and then upstream. Moreover, the flowfield behaves as a hysteresis phenomenon under the effect of wind shear, and the total pressure recovery coefficients at the throat and exit of the inlet/isolator increase by approximately 10% to 12%. Furthermore, this research focuses on investigating the impact of wind shear on the behavior of the shock train. Once the inlet/isolator is in a throttled state, wind shear severely impacts the motion of the shock train. When the downstream backpressure is 135 times the incoming pressure (p0), the shock train first moves upstream and gradually couples with a cowl shock wave/boundary layer interaction, resulting in a more significant separation at the throat, and then moves downstream and decouples from the separation bubble at the throat. However, if the downstream backpressure increases to 140 p0, the shock train enlarges the separation bubble, forcing the inlet/isolator to fall into the unstart state, and it cannot be restarted. These findings emphasize the need to consider wind shear effects in the design and operation of hypersonic inlet/isolator.

The decidualization of endometrial stroma is critical for pregnancy maintenance. Here the authors reveal that Menin ensures the expression of PTX3 through H3K4me3 modification, to balance the BMP and FGF signal in the decidua for normal pregnancy.

Network intrusion detection plays a crucial role in ensuring network security by distinguishing malicious attacks from normal network traffic. However, imbalanced data affects the performance of intrusion detection system. This paper utilizes few-shot learning to solve the data imbalance problem caused by insufficient samples in network intrusion detection, and proposes a few-shot intrusion detection method based on prototypical capsule network with the attention mechanism. Our method is mainly divided into two parts, a temporal-spatial feature fusion method using capsules for feature extraction and a prototypical network classification method with attention and vote mechanisms. The experimental results demonstrate that our proposed model outperforms state-of-the-art methods on imbalanced datasets.

In view of the urgent demand for wide speed range and high-performance power for next generation aircraft, near space multi-functional platform and the first stage of TSTO (two-stage-to-orbit) transportation system, this paper timely puts forward an innovative turbo-rocket combined cycle propulsion scheme named NUAA-PTRE (Pre-cooled Turbo-Rocket Engine designed by Nanjing University of Aeronautics and Astronautics) under Ma 0–5. In the scheme, hydrocarbon fuel at normal temperature is employed to pre-cool incoming air, and the chemical heat sink of fuel cracking is utilized sufficiently, which expends flight Mach number range of aircraft effectively. In this paper, the performance characteristics of the engine such as thrust, specific impulse under Ma 0–5 and 0–30km in the flight envelope are studied. The influence of air pre-cooling on the performance at Ma 4–5 is evaluated. This paper points out that the pre-cooling of incoming air by pyrolysis of endothermic hydrocarbon fuel above Ma 4/880 K can broaden the working Mach number range of the engine and improve the performance of the engine at high Mach number. The pre-cooled turbo-rocket combined cycle propulsion scheme of NUAA-PTRE, proposed in this paper meets the working requirements of full speed range from Ma 0–5 and full airspace from 0–30 km, and can be used to support the application of next generation aircraft.

Beef skin gelatin can be used as a good substitute for animal fat in meat patties. In this paper, the effect of different parameters on low-fat beef patties with cowhide gelatin substituted for beef fat (0, 25%, 50%, 75%, 100%) prepared by ultra-high pressure assisted technology was investigated by texture, cooking loss, and sensory scores. The beef patties were also stored at 0–4 °C for 0, 7, 14, 21, and 28 d. The differences and changing rules of fatty acid and amino acid compositions and contents of beef patties with different fat contents were investigated by simulating gastrointestinal digestion in vitro. The optimal process formulation of low-fat beef patties with cowhide gelatin was determined by experimental optimization as follows: ultra-high pressure 360 MPa, ultra-high of pressure time of 21 min, NaCl addition of 1.5%, compound phosphate addition of 0.3%. The addition of cowhide gelatin significantly increased monounsaturated fatty acids, polyunsaturated fatty acids, amino acid content, and protein digestibility of beef patties (p < 0.05). Moreover, with the extension of storage time, the content of saturated fatty acids was significantly higher (p < 0.05), the content of monounsaturated and polyunsaturated fatty acids was significantly lower (p < 0.05), the content of amino acids was significantly lower (p < 0.05), and protein digestibility was significantly lower (p < 0.05) under all substitution ratios. Overall, beef patties with 75% and 100% substitution ratios had better digestibility characteristics. The results of this study provide a theoretical basis for gelatin’s potential as a fat substitute for beef patties and for improving the quality of low-fat meat products.

Immune genes play an important role in the development and progression of acute myeloid leukemia (AML). However, the role of immune genes in the prognosis and microenvironment of AML remains unclear. In this study, we analyzed 151 AML patients in the TCGA database for relevant immune cell infiltration. AML patients were divided into high and low immune cell infiltration clusters based on ssGSEA results. Immune-related pathways, AML pathways and glucose metabolism pathways were enriched in the high immune cell infiltration cluster. Then we screened the differential immune genes between the two immune cell infiltration clusters. Nine prognostic immune genes were finally identified in the train set by LASSO-Cox regression. We constructed a model in the train set based on the nine prognostic immune genes and validated the predictive capability in the test set. The areas under the ROC curve of the train set and the test set for ROC at 1, 3, 5 years were 0.807, 0.813, 0.815, and 0.731, 0.745, 0.830, respectively. The areas under ROC curve of external validation set in 1, 3, and 5 years were 0.564, 0.619, and 0.614, respectively. People with high risk scores accompanied by high TMB had been detected with the worst prognosis. Single-cell sequencing analysis revealed the expression of prognostic genes in AML cell subsets and pseudo-time analysis described the differentiation trajectory of cell subsets. In conclusion, our results reveal the characteristics of immune microenvironment and cell subsets of AML, while it still needs to be confirmed in larger samples studies. The prognosis model constructed with nine key immune genes can provide a new method to assess the prognosis of AML patients.

Enterococci and Escherichia coli are opportunistic pathogens of poultry and are associated with embryo and neonatal chick mortality. We have recently demonstrated that 56% of dead broiler chicken embryos in commercial hatcheries in western Canada were due to the coinfection of Enterococcus species and E. coli. The objective of this study was to investigate the host-pathogen interactions of Enterococcus faecalis and E. coli in developing chicken embryos. Embryonating eggs at 12 d of incubation were dipped in a solution of E. faecalis and/or E. coli for 30 s to expose the eggshell to study the migration and colonization of E. faecalis and E. coli in the internal organs of chicken embryos and subsequent neonatal chicken mortality following hatch. A multidrug-resistant E. faecalis isolate from a dead chicken embryo and an E. faecalis isolate from a case of yolk sac infection were able to colonize the internal organs of chicken embryos rapidly compared to an E. faecalis isolate from a healthy chicken without affecting viability or hatchability of embryos. Although E. faecalis colonized internal organs of chicken embryos, no evidence of inflammation of these organs nor the expression of virulence genes of E. faecalis was observed. Although E. faecalis and E. coli alone did not affect the viability of embryos, a significantly high neonatal chicken mortality (27%) was observed following exposure of embryos to both E. faecalis and E. coli. Upregulation of IL-1 and CXCR4 was evident 48 h before peak mortality of neonatal chickens; this could suggest a possible link of cytokine dysregulation to increased mortality in coinfected neonatal chickens. However, further studies are warranted to investigate this issue vis-à-vis coinfection with E. faecalis and E. coli in chicken embryos and neonatal chickens.

ABSTRACT The long terminal repeats (LTRs) of human endogenous retroviruses (HERVs) are distributed throughout the human genome and provide favorable conditions to regulate the expression of their adjacent genes. HML-2 is the most biologically active subgroup of the HERV-K family, and expression of its members has been associated with many cancer types. The LTRs of HML-2 have been classified into three subgroups (LTR5A, LTR5B, and LTR5Hs) based on phylogenetic analyses. The current study aimed to explore the LTR transcriptional activity differences among the three subtypes and further explore the underlying factors. A total of 43 LTR5A elements, 62 LTR5B elements, and 194 LTR5Hs elements were selected. A phylogenetic tree showed that the LTR5Hs group was clearly separated from the LTR5A and LTR5B groups. A luciferase reporter assay indicated that LTR5Hs had the strongest promoter activity, followed by LTR5A and LTR5B. To investigate the underlying factors, LTR5Hs was divided into 4 sections, and the homologous fragments in LTR5B were replaced successively. Replacement of the third section (−263 to 0) significantly increased LTR5B activity. Subsequent mutation experiments revealed that the increased transcriptional activity was induced by the TATA box and the two p53 binding sites within the section. Further interference with TP53 significantly decreased LTR5Hs transcriptional activity. Chromatin immunoprecipitation (ChIP) and CUT&Tag experiments finally confirmed the direct binding of the p53 protein with the two LTR5Hs p53 binding sites. Overall, the two p53 binding sites in the third section (−263 to 0) of LTR5Hs were revealed to play critical roles in the difference in transcriptional activity among the three subtypes. IMPORTANCE Human endogenous retroviruses (HERVs) were integrated into the human genome in ancient times and have been coevolving with the host. Since the Human Genome Project, HERVs have attracted increasing attention. Many studies have focused on their characterization, evolution, and biological function. In particular, the expression of HERV-K has been associated with many diseases, such as germ cell tumors, neurotoxicity, ovarian cancer, prostate cancer, and melanoma. Indeed, two HML-2-produced proteins, Np9 and Rec, are associated with certain cancers. However, their roles in these disease associations remain unclear. The current work focused on subgroup HML-2 of HERV-K, which is recognized as the most biologically active subgroup, and aimed to explore the mechanistic basis of transcriptional activity. The results revealed that p53 deeply determined the activity of HML-2 LTR5Hs. p53 is a rather important tumor suppressor protein. It can regulate the expression of genes related to cell cycle arrest, organic processes, and apoptosis in response to cellular stress and is critical for the control of homeostasis. Previous ChIP and expression studies of individual genes suggested that p53 sites in HERV LTRs may be part of the p53 transcription program and directly regulate p53 target genes in a species-specific manner. However, the exact function of p53 in the regulation of HERV LTR expression is largely elusive. Our results clearly demonstrated the interaction between LTR5Hs of HML-2 and p53. They are of great significance for the future comprehensive study of the physiological and pathological functions of LTRs of HERVs.

Abstract Synthetic CpG-ODNs can promote antimicrobial immunity in neonatal chicks by enriching immune compartments and activating immune cells. Activated immune cells undergo profound metabolic changes to meet cellular biosynthesis and energy demands and facilitate the signaling processes. We hypothesize that CpG-ODNs induced immune activation can change the host’s metabolic demands in neonatal chicks. Here, we used NMR-based metabolomics to explore the potential of immuno-metabolic interactions in the orchestration of CpG-ODN-induced antimicrobial immunity. We administered CpG-ODNs to day-old broiler chicks via intrapulmonary (IPL) and intramuscular (IM) routes. A negative control group was administered IPL distilled water (DW). In each group (n = 60), chicks (n = 40) were challenged with a lethal dose of Escherichia coli, two days post-CpG-ODN administration. CpG-ODN administered chicks had significantly higher survival (P

Seven new phenylhexanoids, (S)-(+)-3,4-dihydroxy-11-methoxyphenylhex-9-one (1), (E) 3,4-dihydroxy-phenylhex-10-en-9-one (2), (E)-4-hydroxyphenylhex-10-en-9-one (3), (R)-(−)-3,4,11-trihydroxyphenylhex-9-one 11-O-β-d-glucopyranoside (4), (R)-(−)-4,11-dihydroxyphenylhex-9-one 11-O-β-d-glucopyranoside (5), phenylhex-4,9,11-triol 11-O-β-d-glucopyranoside (6), and 9-O-acetyl-phenylhex-4,9,11-triol 11-O-β-d-glucopyranoside (7), were isolated and identified from Tibetan medicine Saxifraga umbellulata var. pectinate. The antioxidant activities of these compounds were evaluated using the DPPH and ABTS radical scavenging experiments. In the ABTS experiment, compounds 1 (IC50 13.99 ± 2.53 μM) and 2 (IC50 13.11 ± 0.94 μM) exhibited significantly better antioxidant activity than L-ascorbic acid (IC50 23.51 ± 0.44 μM).

BackgroundsGrowth differentiation factor 15 (GDF-15) is a highly divergent member of the TGF-β superfamily and has been implicated in various biological functions. However, the expression of GDF-15 in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is unclear.MethodThe study included 47 AE-IPF patients, 61 stable IPF (S-IPF) subjects, and 31 healthy controls (HCs). Serum GDF-15 levels and their expression in the lung were measured. The correlation between serum GDF-15 and other clinical parameters and the risk factors for AE occurrence and the survival of IPF patients were analyzed.ResultsSerum GDF-15 levels were significantly elevated in AE-IPF patients (1279.22 ± 540.02 pg/ml) as compared with HCs (891.30 ± 479.90 pg/ml) or S-IPF subjects (107.82 ± 14.21 pg/ml) (both p < 0.001). The protein and mRNA expressions of GDF-15 in the lung of AE-IPF patients were significantly increased as compared with S-IPF cases (p = 0.007 and p = 0.026, respectively). The serum GDF-15 level was correlated with the clinical variables of inflammation, metabolism, and disease severity in IPF subjects (all p < 0.05). The GDF-15 serum concentration was significantly higher in decedents than in survivors (p = 0.005). A serum GDF-15 level above 989.3 pg/ml was a risk factor for AE occurrence (p = 0.04), and the level above 1,075.76 pg/ml was an independent predictor for survival in IPF cases (p = 0.007).ConclusionsThe GDF-15 level was significantly elevated in subjects with AE-IPF. GDF-15 could be a promising biomarker for AE occurrence and survival in IPF patients.

BackgroundHepatocellular carcinoma (HCC) remains a worldwide burden. However, the mechanisms behind the malignant biological behavior of HCC remain unclear. The homeobox (HOX) family could act as either promoters or suppressors in different kinds of malignancies. Our study discovered the role of HOXB5 in regulating HCC progression.MethodsThe HOXB5 expression was assessed by RT-PCR analysis in human HCC samples and cell lines. HOXB5 transcriptional regulation of the EGFR was verified by the luciferase reporter assay and chromatin immunoprecipitation experiment. The oncogenic role of HOXB5 in HCC progression was analyzed by CCK8, colony-forming, and transwell assays.ResultsUpregulation of HOXB5 was found in human HCC, and was strongly correlated with HCC tumor size, tumor-nodule metastasis, TNM stage, and relatively unfavorable OS and DFS. Ectopic expression of HOXB5 promoted the capacity of cell growth and clonogenicity, while the inhibition of HOXB5 decreased the proliferation and clonogenicity potential in vitro by CCK8 and colony-forming assays. In addition, HOXB5 also promoted cell migration by transwell experiment. Mechanism studies elucidated that HOXB5 triggers HCC progression via direct transcriptional activation of EGFR. The upregulation of HOXB5 is regulated by miR-200a-3p and miR-181-5p. Transfection of miR-200a-3p and miR-181-5p mimics blocked the cell proliferation and migration regulated by HOXB5, while overexpression of the 3′-UTR mutant HOXB5 abolished the suppressive effect of miR-200a-3p and miR-181-5p, but not the wild-type HOXB5.ConclusionHOXB5 is a promising prognostic factor in human HCC. Targeting miR-200a-3p and the miR-181-5p/HOXB5/EGFR signaling pathway may provide new options for the treatment strategies of HCC.

N6-Methyladenosine-related long noncoding RNAs play an essential role in many cancers’ development. However, the relationship between m6A-related lncRNAs and acute myelogenous leukemia (AML) prognosis remains unclear. We systematically analyzed the association of m6A-related lncRNAs with the prognosis and tumor immune microenvironment (TME) features using the therapeutically applicable research to generate effective treatment (TARGET) database. We screened 315 lncRNAs associated with AML prognosis and identified nine key lncRNAs associated with m6A by the LASSO Cox analysis. A model was established based on these nine lncRNAs and the predictive power was explored in The Cancer Genome Atlas (TCGA) database. The areas under the ROC curve of TARGET and TCGA databases for ROC at 1, 3, and 5 years are 0.701, 0.704, and 0.696, and 0.587, 0.639, and 0.685, respectively. The nomogram and decision curve analysis (DCA) showed that the risk score was more accurate than other clinical indicators in evaluating patients’ prognoses. The clusters with a better prognosis enrich the AML pathways and immune-related pathways. We also found a close correlation between prognostic m6A-related lncRNAs and tumor immune cell infiltration. LAG3 expression at the immune checkpoint was lower in the worse prognostic cluster. In conclusion, m6A-related lncRNAs partly affected AML prognosis by remodeling the TME and affecting the anticarcinogenic ability of immune checkpoints, especially LAG3 inhibitors. The prognostic model constructed with nine key m6A-related lncRNAs can provide a method to assess the prognosis of AML patients in both adults and children.

Duodenal varices are an uncommon presentation of portal hypertension and can result in significant gastrointestinal bleeding with a high mortality. Diagnosis can be difficult and therapeutic options limited. We present a case of upper gastrointestinal bleeding in a woman aged 54 years with primary biliary cholangitis who was ultimately diagnosed with ectopic duodenal variceal bleed, which was successfully treated with transjugular intrahepatic portosystemic shunt. Transjugular intrahepatic portosystemic shunt provide an effective treatment for ectopic duodenal variceal bleed caused by liver cirrhosis, though interventional radiologists need to remain aware of and vigilant for the complications and risks of this treatment option.

Objective To establish an analysis method for detecting 9 sweeteners including acesulfame, sodium saccharin, cyclamate, aspartame, sucralose, neotame, alitame, stevioside and steviobioside in spirits by using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Methods After the sample was heated by boiling water bath to remove ethanol, it was detected by UPLC-MS/MS. The sweeteners were separated by UPLC with water (containing 10 mmol/L ammonium acetate) -methanol gradient elution in a HSS T3 chromatography column (2.1 mm×100 mm, 1.7 μm), and qualified/quantified by mass spectrometry with electron spray ionization multiple reaction monitoring mode. Results The linearity of the 9 sweeteners in the range was good, and the correlation coefficient was above 0.999. The recovery of the method was 85.2%-102.8%, the relative standard deviation (RSD) was 3.8%-7.3%. The detection limit was 0.3-1.5 μg/kg. Conclusion The method is simple, rapid and reproducible, and can be used for the detection of 9 sweeteners in spirits.

The establishment of pregnancy in human necessitates appropriate decidualization of stromal cells, which involves steroids regulated periodic transformation of endometrial stromal cells during the menstrual cycle. However, the potential molecular regulatory mechanism underlying the initiation and maintenance of decidualization in humans is yet to be fully elucidated. In this investigation, we document that SOX4 is a key regulator of human endometrial stromal cells decidualization by directly regulating FOXO1 expression as revealed by whole genomic binding of SOX4 assay and RNA sequencing. Besides, our immunoprecipitation and mass spectrometry results unravel that SOX4 modulates progesterone receptor (PGR) stability through repressing E3 ubiquitin ligase HERC4-mediated degradation. More importantly, we provide evidence that dysregulated SOX4–HERC4–PGR axis is a potential cause of defective decidualization and recurrent implantation failure in in-vitro fertilization (IVF) patients. In summary, this study evidences that SOX4 is a new and critical regulator for human endometrial decidualization, and provides insightful information for the pathology of decidualization-related infertility and will pave the way for pregnancy improvement.

Approximately 75% of failed pregnancies are considered to be due to embryo implantation failure or defects. Nevertheless, the explicit signaling mechanisms governing this process have not yet been elucidated. Here, we found that conditional deletion of the Shp2 gene in mouse uterine stromal cells deferred embryo implantation and inhibited the decidualization of stromal cells, which led to embryonic developmental delay and to the death of numerous embryos mid-gestation, ultimately reducing female fertility. The absence of Shp2 in stromal cells increased the proliferation of endometrial epithelial cells, thereby disturbing endometrial epithelial remodeling. However, Shp2 deletion impaired the proliferation and polyploidization of stromal cells, which are distinct characteristics of decidualization. In human endometrial stromal cells (hESCs), Shp2 expression gradually increased during the decidualization process. Knockout of Shp2 blocked the decidual differentiation of hESCs, while Shp2 overexpression had the opposite effect. Shp2 knockout inhibited the proliferation of hESCs during decidualization. Whole gene expression profiling analysis of hESCs during the decidualization process showed that Shp2 deficiency disrupted many signaling transduction pathways and gene expression. Analyses of hESCs and mouse uterine tissues confirmed that the signaling pathways extracellular regulated protein kinases (ERK), protein kinase B (AKT), signal transducer and activator of transcription 3 (STAT3) and their downstream transcription factors CCAAT/enhancer binding protein β (C/EBPβ) and Forkhead box transcription factor O1 (FOXO-1) were involved in the Shp2 regulation of decidualization. In summary, these results demonstrate that Shp2 plays a crucial role in stromal decidualization by mediating and coordinating multiple signaling pathways in uterine stromal cells. Our discovery possibly provides a novel key regulator of embryo implantation and novel therapeutic target for pregnancy failure.

A model of a NUAA-PTRE pre-cooled air turbine engine was established. The design point parameters of the engine were optimized, including the pressure ratio, air flow rate of the compressor, efficiency, throat area, and efficiency of the turbine. The air flow rate at the engine operating point was 142.73 kg/s. High performance of the key components under a wide range of working conditions was realized after optimization. To achieve the indicators of the overall scheme, adaptability studies of key components were conducted. A three-stage variable geometry design was applied to the inlet. The pre-cooler was optimized with a power-to-weight ratio of over 100 kW/kg and a compactness of 278 m2/m3. The built-in rocket gas generator and dual-component injector were developed, and the combustion and heat transfer processes were simulated. The overall optimization design of the NUAA-PTRE and the adaptive design of the components were completed, and high performance of the engine in a wide range of flight conditions at Ma 0~5 and altitude 0~25 km was achieved.

Background: The worldwide outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become an urgent public health problem. High mortality and lack of effective treatments further pose new challenges to control this infection. However, studies about the evaluation of available antibiotics for CRKP infection are limited. The present study aimed to compare the efficacy of polymyxin B versus ceftazidime-avibactam (CAZ/AVI) in Chinese patients with CRKP infections and to identify risk factors affecting 7-day bacterial eradication and 28-day all-cause mortality.Methods: From January 8, 2018, to July 6, 2020, a total of 115 adult CRKP infected patients from two tertiary teaching hospitals in Shanghai, China were enrolled based on the inclusion and exclusion criteria. By reviewing electronic medical records of these patients, demographic and clinical data were extracted. The selected patients were divided into polymyxin B and CAZ/AVI groups according to primary antibiotic exposure to compare therapeutic effects. Binary logistic and cox’s regression analysis were performed to identify risk factors for 7-day bacterial eradication and all-cause mortality.Results: One hundred and five patients were treated with polymyxin B (67.8%) or CAZ/AVI (32.2%). Patients in the CAZ/AVI group had significantly lower rates of 28-day mortality (8.1 vs 29.5%, p = 0.013), higher microbiological eradication and 28-day clinical success. Multivariate analysis showed that Charlson comorbidity index (≥3) and prior antibiotic use within 90 days were independent risk factors for poor microbiological eradication. Cox’s regression analysis indicated that the length of hospitalization after CRKP infection and baseline creatinine clearance negatively affected 28-day mortality.Conclusion: CAZ/AVI was more effective than polymyxin B and appeared to be a promising drug for CRKP infection, especially for critically ill patients.

To survive, cells must constantly resist mechanical stress. In plants, this involves the reinforcement of cell walls, notably through microtubule-dependent cellulose deposition. How wall sensing might contribute to this response is unknown. Here, we tested whether the microtubule response to stress acts downstream of known wall sensors. Using a multistep screen with 11 mutant lines, we identify FERONIA (FER) as the primary candidate for the cell's response to stress in the shoot. However, this does not imply that FER acts upstream of the microtubule response to stress. In fact, when performing mechanical perturbations, we instead show that the expected microtubule response to stress does not require FER. We reveal that the feronia phenotype can be partially rescued by reducing tensile stress levels. Conversely, in the absence of both microtubules and FER, cells appear to swell and burst. Altogether, this shows that the microtubule response to stress acts as an independent pathway to resist stress, in parallel to FER. We propose that both pathways are required to maintain the mechanical integrity of plant cells.

Background: Endogenous retrovirus (ERV) elements can act as proximal regulatory elements in promoting interferon (IFN) responses. Previous relevant studies have mainly focused on IFN-stimulated genes (ISGs). However, the role of ERV elements as cis-regulatory motifs in regulating genes of the JAK–STAT pathway remains poorly understood. In our study, we analyzed the changes in ERV elements and genes under both IFN stimulation and blockade of the signaling pathway. Methods: The effects of interferon on cells under normal conditions and knockout of the receptor were compared based on the THP1_IFNAR1_KO and THP1_IFNAR2_mutant cell lines. The correlation between differentially expressed ERVs (DHERVs) and differentially expressed genes (DEGs) as DEHERV-G pairs was explored with construction of gene regulatory networks related to ERV and induced by proinflammatory cytokines. Results: A total of 430 DEHERV loci and 190 DEGs were identified in 842 DEHERV-G pairs that are common to the three groups. More than 87% of DEHERV-G pairs demonstrated a consistent expression pattern. ISGs such as AIM2, IFIT1, IFIT2, IFIT3, STAT1, and IRF were activated via the JAK–STAT pathway in response to interferon stimulation. Thus, STAT1, STAT2, and IRF1 appear to play core roles in regulatory networks and are closely associated with ERVs. Conclusions: The RNA expression of ISGs and ERV elements is correlated, indicating that ERV elements are closely linked to host innate immune responses.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive scarring disease with unknown etiology. The evidence of a pathogenic role for transforming growth factor‐beta (TGF‐β) in the development and progression of IPF is overwhelming. In the present study, we investigated the role of interleukin‐22 (IL‐22) in the pathogenesis of IPF by regulating the TGF‐β pathway. We measured parameters and tissue samples from a clinical cohort of IPF. IL‐22R knock out (IL‐22RA1−/−) and IL‐22 supplementation mouse models were used to determine if IL‐22 is protective in vivo. For the mechanistic study, we tested A549, primary mouse type II alveolar epithelial cell, human embryonic lung fibroblast, and primary fibroblast for their responses to IL‐22 and/or TGF‐β1. In a clinical cohort, the expression level of IL‐22 in the peripheral blood and lung tissues of IPF patients was lower than healthy controls, and the lower IL‐22 expression was associated with poorer pulmonary function. IL‐22R−/− mice demonstrated exacerbated inflammation and fibrosis. Reciprocally, IL‐22 augmentation by intranasal instillation of recombinant IL‐22 repressed inflammation and fibrotic phenotype. In vitro, IL‐22 treatment repressed TGF‐β1 induced gene markers representing epithelial‐mesenchymal‐transition and fibroblast‐myofibroblast‐transition, likely via the inhibition of TGF‐β receptor expression and subsequent Smad2/3 activation. IL‐22 appears to be protective against pulmonary fibrosis by inhibiting TGF‐β1 signaling, and IL‐22 augmentation may be a promising approach to treat IPF.

The forms of U-shaped UHPFRC beams have not been investigated for the highway footbridge. Compared with the traditional section forms, the U-shaped UHPFRC beams can reduce the material consumption under the condition of providing the same bearing capacity. Furthermore, prestressed U-shaped UHPFRC beams are rarely reported in the existing research. This paper explores the flexural behavior of prestressed ultrahigh-performance fiber-reinforced concrete (UHPFRC) beam bridge having unique design and the material properties of prestressed reinforcement combined with UHPFRC. Based on the unique shape of the U beam, the flexural performance test of the full-scale model of the prestressed UHPFRC U beam is conducted. Then, the finite element model considering material nonlinearity and structural ductility is established using Midas FEA software. Finally, the failure mode, failure process, cracking moment, ultimate moment, and strain of the full-scale model are studied. The calculation formulas of the flexural capacity of UHPFRC U beam considering ductile failure are derived. The comparative analysis results show that the prestressed UHPFRC U beam has an excellent flexural performance. The bending failure of a U-shaped beam belongs to the group of ductile failures, which is characterized by the main crack along the central rib and the loading center, which is accompanied by multiple microcracks. The failure process can be divided into four stages: linear deformation, microcracks development, main cracks development, and bearing capacity decline. The incorporation of steel fiber and the interaction between UHPFRC and reinforcement can effectively reduce the development of cracks. The U-beam bending moment is 50–55% of the ultimate bending moment. In the UHPFRC bridge design, the deformation can be used as a control index, and material advantages of the UHPFRC can be used to a certain extent. The strain-hardening characteristics of the UHPFRC are obvious in the loading process. The finite element analysis results show that the maximum strain value appears at the central rib, followed by the transverse strain value of the bottom plate, while the minimum strain is the longitudinal strain value of the bottom plate. The deformation of the rib plate is the largest, and the strain of the other measuring points changes slowly. The farther away from the center the measurement point is, the slower its strain changes. Therefore, the load is mainly caused by the central rib and the loading center plate. With the increase in the deformation, the load on both sides continuously moves to the central rib along the plate surface. This study can provide a useful reference for theoretical analysis and design of prestressed U-UHPFRC bridges.

The size distribution of condensed products during the combustion of aluminized propellants and flow characteristics of the gas-solid two-phase flow in solid rocket motor were studied in this paper. Firstly, based on the laser scattering technology, an online detection system for condensed products in plume was established, and the size detection of condensed products in the plume of solid rocket motor is carried out. Secondly, a numerical model of two-phase flow in solid rocket motor is established by combining the real size distribution of products in the plume with discrete phase model through the Rosin-Rammler distribution function. Besides, numerical simulation research is carried out under the same experimental conditions, focusing on the influence of condensed products with real size on the characteristics of solid rocket motor. The results show that the innovation measurement system can be used to obtain the size distribution characteristic of condensed products in the plume. At the particle size of stable stage, the mean size, Dv50, is 104 μm, which is the smallest among all stages. It is also suggested that condensed products at the end stage have the most impact on the flow behavior in solid rocket motor, in that the shock structure, Mach number, and temperature distribution in the near field of plume are significantly changed.

Dalbergia sissoo is a woody plant with economic and medicinal value. As the pharmacological qualities and properties of the wood from this plant primarily depend on its extractives, in this study, the metabolomic analysis of extractives from its stems was carried out using UPLC-MS/MS. A total of 735 metabolites were detected from two groups of samples, heartwood and sapwood, with the largest number of terpenoids in type and the largest number of flavonoids in quantity. The PCA and cluster analysis showed significant differences in the metabolite composition between the two groups. The differential metabolites were mainly organic oxygen compounds, flavonoids, and isoflavones. Among the 105 differential metabolites, 26 metabolites were significantly higher in relative content in sapwood than in heartwood, while the other 79 metabolites were significantly higher in relative content in heartwood than in sapwood. KEGG metabolic pathway enrichment analysis showed that these differential metabolites were mainly enriched in three metabolic pathways: Flavonoid biosynthesis, isoflavonoid biosynthesis, and flavonoid and flavonol biosynthesis. This study provides a reference for metabolomics studies in Dalbergia and other woody plants.

Abstract Background In plants, the shoot apical meristem (SAM) has two main functions, involving the production of all aerial organs on the one hand and self-maintenance on the other, allowing the production of organs during the entire post-embryonic life of the plant. Transcription factors, microRNA, hormones, peptides and forces have been involved in meristem function. Whereas phosphatidylinositol phosphates (PIPs) have been involved in almost all biological functions, including stem cell maintenance and organogenesis in animals, the processes in meristem biology to which PIPs contribute still need to be delineated. Results Using biosensors for PI4P and PI(4,5)P2, the two most abundant PIPs at the plasma membrane, we reveal that meristem functions are associated with a stereotypical PIP tissue-scale pattern, with PI(4,5)P2 always displaying a more clear-cut pattern than PI4P. Using clavata3 and pin-formed1 mutants, we show that stem cell maintenance is associated with reduced levels of PIPs. In contrast, high PIP levels are signatures for organ-meristem boundaries. Interestingly, this pattern echoes that of cortical microtubules and stress anisotropy at the meristem. Using ablations and pharmacological approaches, we further show that PIP levels can be increased when the tensile stress pattern is altered. Conversely, we find that katanin mutant meristems, with increased isotropy of microtubule arrays and slower response to mechanical perturbations, exhibit reduced PIP gradients within the SAM. Comparable PIP pattern defects were observed in phospholipase A3β overexpressor lines, which largely phenocopy katanin mutants at the whole plant level. Conclusions Using phospholipid biosensors, we identified a stereotypical PIP accumulation pattern in the SAM that negatively correlates with stem cell maintenance and positively correlates with organ-boundary establishment. While other cues are very likely to contribute to the final PIP pattern, we provide evidence that the patterns of PIP, cortical microtubules and mechanical stress are positively correlated, suggesting that the PIP pattern, and its reproducibility, relies at least in part on the mechanical status of the SAM.

Aims: We investigated the association between vascular medication adherence, assessed by different methods, and the risk of cardio-cerebrovascular events and all-cause mortality. Methods: A meta-analysis with a systematic search of PubMed, Web of Science, EMBASE, and Cochrane databases from inception date to 21 June 2021 was used to identify relevant studies that had evaluated the association between cardiovascular medication adherence levels and cardiovascular events (CVEs), stroke, and all-cause mortality risks. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects meta-analysis. Restricted cubic splines were used to model the dose-response association. Results: We identified 46 articles in the dose-response meta-analysis. The dose-response analysis indicated that a 20% increment in cardiovascular medication, antihypertensive medication, and lipid-lowering medication adherence level were associated with 9% (RR: 0.91, 95% CI 0.88–0.94), 7% (RR 0.93, 95% CI: 0.84–1.03), and 10% (RR 0.90, 95% CI: 0.88–0.92) lowers risk of CVEs, respectively. The reduced risk of stroke respectively was 16% (RR: 0.84, 95% CI: 0.81–0.87), 17% (RR 0.83, 95% CI: 0.78–0.89), and 13% (RR 0.87, 95% CI: 0.84–0.91). The reduced risk of all-cause mortality respectively was 10% (RR: 0.90, 95% CI: 0.87–0.92), 12% (RR 0.88, 95% CI: 0.82–0.94), and 9% (RR 0.91, 95% CI: 0.89–0.94). Conclusions: A better medication adherence level was associated with a reduced risk of cardio-cerebrovascular events and all-cause mortality.

Abstract Background Chinese rural communities living among species-rich forests have little documentation on species used to make handicrafts and construction materials originating from the surrounding vegetation. Our research aimed at recording minor wood uses in the Heihe valley in the Qinling mountains. Methods We carried out 37 semi-structured interviews in seven villages. Results We documented the use of 84 species of plants. All local large canopy trees are used for some purpose. Smaller trees and shrubs which are particularly hard are selectively cut. The bark of a few species was used to make shoes, hats, steamers and ropes, but this tradition is nearly gone. A few species, mainly bamboo, are used for basket making, and year-old willow branches are used for brushing off the chaff during wheat winnowing. Conclusions The traditional use of wood materials documented suggests that some rare and endangered tree species may have been selectively cut due to their valuable wood, e.g. Fraxinus mandshurica and Taxus wallichiana var. chinensis. Some other rare species, e.g. Dipteronia sinensis, are little used and little valued.

Many plants grow organs and tissues with twisted shapes. Arabidopsis mutants with impaired microtubule dynamics exhibit such a phenotype constitutively. Although the activity of the corresponding microtubule regulators is better understood at the molecular level, how large-scale twisting can emerge in the mutants remains largely unknown. Classically, oblique cortical microtubules would constrain the deposition of cellulose microfibrils in cells, and such conflicts at the cell level would be relaxed at the tissue scale by supracellular torsion. This model implicitly assumes that cell-cell adhesion is a key step to transpose local mechanical conflicts into a macroscopic twisting phenotype. Here we tested this prediction using the quasimodo1 mutant, which displays cell-cell adhesion defects. Using the spriral2/tortifolia1 mutant with hypocotyl helical growth, we found that qua1-induced cell-cell adhesion defects restore straight growth in qua1-1 spr2-2. Detached cells in qua1-1 spr2-2 displayed helical growth, confirming that straight growth results from the lack of mechanical coupling between cells rather than a restoration of SPR2 activity in the qua1 mutant. Because adhesion defects in qua1 depend on tension in the outer wall, we also showed that hypocotyl twisting in qua1-1 spr2-2 could be restored when decreasing the matrix potential of the growth medium, i.e., by reducing the magnitude of the pulling force between adjacent cells, in the double mutant. Interestingly, the induction of straight growth in qua1-1 spr2-2 could be achieved beyond hypocotyls, as leaves also displayed a flat phenotype in the double mutant. Altogether, these results provide formal experimental support for a scenario in which twisted growth in spr2 mutant would result from the relaxation of local mechanical conflicts between adjacent cells via global organ torsion.

Histone methylation levels, which are determined by the action of both histone demethylases and methyltransferases, impact multiple biological processes by affecting gene expression activity. Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. The functions of methionine metabolic enzymes in regulating biological processes as well as the interaction between the methionine pathway and histone methylation, however, are still not fully understood. Here, we report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone methylation levels. Reduction of little imaginal discs (LID) histone demethylase, but not lysine-specific demethylase 2 (KDM2) demethylase, is able to counter the effects on histone methylation due to reduction of SAM synthetase (SAM-S). Taken together, these results reveal an essential role of key enzymes that control methionine metabolism and histone methylation. Additionally, these findings are an indication of a strong connection between metabolism and epigenetics.