Search

Abstract Surgery is the mainstay of treatment modality for malignant melanoma. However, the deteriorative hypoxic microenvironment after surgery is recognized as a stemming cause for tumor recurrence/metastasis and delayed wound healing. Here we design and construct a sprayable therapeutic hydrogel (HIL@Z/P/H) encapsulating tumor-targeted nanodrug and photosynthetic cyanobacteria (PCC 7942) to prevent tumor recurrence/metastasis while promote wound healing. In a postsurgical B16F10 melanoma model in female mice, the nanodrug can disrupt cellular redox homeostasis via the photodynamic therapy-induced cascade reactions within tumor cells. Besides, the photosynthetically generated O2 by PCC 7942 can not only potentiate the oxidative stress-triggered cell death to prevent local recurrence of residual tumor cells, but also block the signaling pathway of hypoxia-inducible factor 1α to inhibit their distant metastasis. Furthermore, the long-lasting O2 supply and PCC 7942-secreted extracellular vesicles can jointly promote angiogenesis and accelerate the wound healing process. Taken together, the developed HIL@Z/P/H capable of preventing tumor recurrence/metastasis while promoting wound healing shows great application potential for postsurgical cancer therapy.

Abstract Background Severe acute respiratory syndrome coronavirus 2 will coexist with humans for a long time, and it is therefore important to develop effective treatments for coronavirus disease 2019 (COVID-19). Recent studies have demonstrated that antiviral therapy is a key factor in preventing patients from progressing to severe disease, even death. Effective and affordable antiviral medications are essential for disease treatment and are urgently needed. Azvudine, a nucleoside analogue, is a potential low-cost candidate with few drug interactions. However, validation of high-quality clinical studies is still limited. Methods This is a multicentre, randomized, double-blind, placebo-controlled phase III clinical trial involving 1096 adult patients with mild-to-moderate symptoms of COVID-19 who are at high risk for progression to severe COVID-19. Patients will be randomized to (1) receive azvudine tablets 5 mg daily for a maximum of 7 days or (2) receive placebo five tablets daily. All participants will be permitted to use a standard treatment strategy except antiviral therapy beyond the investigational medications. The primary outcome will be the ratio of COVID-19-related critical illness and all-cause mortality among the two groups within 28 days. Discussion The purpose of this clinical trial is to determine whether azvudine can prevent patients at risk of severe disease from progressing to critical illness and death, and the results will identify whether azvudine is an effective and affordable antiviral treatment option for COVID-19. Trial registration ClinicalTrials.gov NCT05689034. Registered on 18 January 2023.

Abstract Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C–C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague–Dawley rats underwent surgical AAA formation using porcine pancreatic elastase and received daily β-aminopropionitrile to promote AAA rupture. Rats with AAAs received either a standard diet, ketogenic diet (KD), or exogenous KBs (EKB). Rats receiving KD and EKB reached a state of ketosis and had significant reduction in AAA expansion and incidence of rupture. Ketosis also led to significantly reduced aortic CCR2 content, improved MMP balance, and reduced ECM degradation. Consistent with these findings, we also observed that Ccr2−/− mice have significantly reduced AAA expansion and rupture. In summary, this study demonstrates that CCR2 is essential for AAA expansion, and that its modulation with ketosis can reduce AAA pathology. This provides an impetus for future clinical studies that will evaluate the impact of ketosis on human AAA disease.

Ureide permeases (UPSs) mediate the transport of ureides, including allantoin and allantoate, which act as nitrogen-transporting compounds in plants and have recently been found to play a role in cellular signaling. To date, UPSs have not been reported in potato, and their identification is important for further function studies and for understanding molecular mechanisms of plant adverse responses. Based on potato genomic data, we identified 10 StUPS genes in potato (Solanum tuberosum L.). Then, we conducted a comprehensive study of the identified StUPS genes using bioinformatics methods. Genome phylogenetic and genomic localization analyses revealed that StUPSs can be classified into four categories, are highly homologous to Arabidopsis thaliana UPS members, and are distributed on three chromosomes. The six StUPS genes were investigated by RT–qPCR, and the findings indicated that all of these genes are involved in the response to several stresses, including low nitrogen, cold, ABA, salt, H2O2, and drought. This study establishes a strong theoretical framework for investigating the function of potato UPS genes, as well as the molecular mechanisms underlying the responses of these genes to various environmental stresses.

The backless cable-stayed bridge has the advantages of beautiful shape and reasonable force, but due to the low overall stiffness of the bridge pylon during cantilever construction, it is susceptible to the effect of solar temperature. To reveal the temperature deformation laws and achieve accurate alignment prediction during the installation process of steel–concrete composite pylons in complex environments, a refined numerical simulation model for the 3D bridge temperature field was established based on the proposed automatic sunshine-shadow recognition method. Subsequently, the optimal time periods for construction control are provided. The results of the study show that, during the cantilever construction of the bridge pylon, one pylon column will shade the other pylon column, resulting in asynchronous deformation that can reach 7.6 mm. The effect of solar temperature on the displacement of the bridge pylon is significant, where the maximum daily change in transverse displacement in the cantilevered state of the pylon can reach 33.6 mm, and the maximum change in cable force value can reach 52 kN. In order to mitigate the effect of solar radiation, the best construction time for the bridge pylon is 19:30~9:30, while the tensioning and measurement of the cable should be avoided from 6:00~18:00. This strategy ensures that the control of the pylon top displacement is maintained within 1/4000 of the pylon height, and the error in cable force is kept within 5%.

Endogenous retroviruses (ERVs) originate from ancestral germline infections caused by exogenous retroviruses. Throughout evolution, they have become fixed within the genome of the animals into which they were integrated. As ERV elements coevolve with the host, they are normally epigenetically silenced and can become upregulated in a series of physiological and pathological processes. Generally, a detailed ERV profile in the host genome is critical for understanding the evolutionary history and functional performance of the host genome. We previously characterized and cataloged all the ERV-K subtype HML-8 loci in the human genome; however, this has not been done for the chimpanzee, the nearest living relative of humans. In this study, we aimed to catalog and characterize the integration of HML-8 in the chimpanzee genome and compare it with the integration of HML-8 in the human genome. We analyzed the integration of HML-8 and found that HML-8 pervasively invaded the chimpanzee genome. A total of 76 proviral elements were characterized on 23/24 chromosomes, including detailed elements distribution, structure, phylogeny, integration time, and their potential to regulate adjacent genes. The incomplete structure of HML-8 proviral LTRs will undoubtedly affect their activity. Moreover, the results indicated that HML-8 integration occurred before the divergence between humans and chimpanzees. Furthermore, chimpanzees include more HML-8 proviral elements (76 vs. 40) and fewer solo long terminal repeats (LTR) (0 vs. 5) than humans. These results suggested that chimpanzee genome activity is less than the human genome and that humans may have a better ability to shape and screen integrated proviral elements. Our work is informative in both an evolutionary and a functional context for ERVs.

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.

The temperature change caused by hydration leads to early-age cracking in concrete box girder. The early-age cracking risk is further improved with low air temperature and large daily temperature difference, especially in Northwest China. To fill this gap, a temperature experiment and numerical simulation were performed on an actual concrete box girder segment in Northwest China. The temperature field, thermal stress and cracking risk were analyzed using evolution curves, distribution curves and contours. The key parameters that influence the hydration heat temperature, including the cement hydration heat release, cement content, height-width ratio of web, initial temperature, convective coefficient of top plate surface, were analyzed. An anti-cracking case based on parameters analysis was put forward. The results indicated that the temperature evolution can be divided into three stages: warming, cooling and environment significantly impacting. Along the thickness of each plate, temperature distributed is single peak in the center. Along the width or height, temperature distributed is double peaks at axillary position for the top and bottom plates, and single peak in center for the web. The axillary position and web have high thermal stress and significant cracking risks. The temperature difference of each plate, and the early-age cracking risk can be reduced by effectively adjusting the key parameters. Among these, the former two parameters are the most significant factors. The maximum cracking risk can be decreased by 15.7% for every 50 kJ/kg hydration heat reduction. The maximum cracking risk can be decreased by 13.1% for every 50 kg/m3 cement content reduction.

Abstract Glycyrrhiza polysaccharide (GCP) is a natural plant active polysaccharide extracted from traditional Chinese medicine licorice. In this research, we studied the antiviral activity of glycyrrhiza polysaccharide against porcine reproductive and respiratory syndrome virus (PRRSV), a virus of the Arteriviridae family, with a high rate of variation and has caused huge economic losses to the pig industry in various countries since its discovery. Our results show that GCP can inhibit PRRSV replication in a dose-dependent manner. Furthermore, GCP could inhibit the mRNA expression of receptor genes CD163 and NF-κB p65 and promote the mRNA expression of the SLA-7 gene. Because of these results, GCP can be used as a candidate drug to prevent and treat PRRS.

The BTB/POZ (broad-complex, tramtrack, and bric-a-brac) family of proteins is widespread in plants and animals and plays important roles in growth, development, metabolism, and environmental responses. There are few reports on BTB family genes in potato. In this study, 34 sequences containing conserved BTB domains were obtained from the potato gene database, and the phylogenetic, physical, and chemical properties, gene structure, conserved motif, domain, and chromosomal localization of the potato BTB protein family were analyzed via bioinformatics methods. In addition, we used qRT-PCR to detect 12 selected StBTB genes. The results confirmed that these genes are involved in cold, ABA, salt, hydrogen peroxide (H2O2), drought, and low-nitrogen stress, which is highly important for elucidating BTB family members and studying stress response and tolerance mechanisms. This study provides a theoretical basis for the study of the function and expression of potato BTB and lays a solid foundation for further understanding the molecular mechanism of the potato BTB gene under various environmental stresses.

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.

Based on a real engineering case, this study employs the MIDAS finite element software to model the reinforced high embankment slope using anti-sliding piles. The accuracy of the finite element method is verified by comparing calculated outcomes with field monitoring data. Expanding on this foundation, an analysis of factors influencing the reinforced high embankment slope is undertaken to scrutinize the impact of diverse elements on the slope and ascertain the optimal reinforcement strategy. The results reveal the following: The principal displacement observed in the high embankment slope is a vertical settlement, which escalates with the backfill height. Notably, the highest settlement does not manifest at the summit of the initial slope; instead, it emerges close to the summits of the subsequent two slopes. However, the maximum horizontal displacement at the slope’s zenith diminishes as the fill height increases—a trend that aligns with both field observations and finite element computations. The examination of the influence of anti-sliding pile reinforcement on the high embankment slope unveils that factors like the length, diameter, spacing, and positioning of the anti-sliding piles exert minor impacts on vertical settlement, while variations in the parameters of the anti-sliding piles significantly affect the slope’s horizontal displacement. When using anti-sliding piles to reinforce multi-level high embankment slopes, factoring in the extent of horizontal displacement variation and potential cost savings, the optimal parameters for the anti-sliding piles are a length of 15 m, a diameter of 1.5 m, and a spacing of 2.5 m, presenting the most effective combination to ensure superior slope stability and support.

Abstract Background Whole lung lavage (WLL) has been recognized as the most effective therapy of severe pulmonary alveolar proteinosis (PAP). Most centers perform the lavage of each lung in two sessions under general anesthesia at an interval of several days to weeks. Compared with two-session WLL, one-session bilateral sequential WLL only requires general anesthesia once. However, the safety of one-session WLL in PAP patients has not been assessed by large cohort studies. In this study, we aimed to investigate the association between the mode of WLL procedure (one-session or two-session) and the risk of periprocedural complications in PAP patients. Methods In this single-center retrospective cohort study, we included adult patients who were diagnosed as PAP and had undergone WLL procedures under general anesthesia from 2000 to 2022. Patients requiring extra-corporeal oxygenation during WLL were excluded. Since some patients received multiple WLL procedures, we considered each procedure in one-session or two-session group as a unique unit in our analysis. The primary outcome was the occurrence of any complications during hospitalization, including termination of WLL procedure due to fluid leakage or refractory hypoxemia, bronchospasm, delayed endotracheal extubation, cardiovascular event, pneumothorax, and fever. Results We included a total of 175 WLL procedures (118 patients), with 48 in the two-session group and 127 in the one-session group. Periprocedural complications occurred in 17 (35.4%) and 39 (30.7%) procedures in the two-session and the one-session groups, respectively. The risk of periprocedural complications did not differ significantly between groups, after adjusting the unbalanced confounders in a multivariable model (odds ratio 0.95, 95% confidence interval 0.34 to 2.69, P 0.929) or by inverse probability of treatment weighting (odds ratio 0.70, 95% confidence interval 0.30 to 1.54, P 0.379). Compared with the two-session WLL group, the one-session WLL group had a shorter postprocedural length of hospitalization and comparable decrease in alveolar-arterial oxygen tension gradient from baseline. Conclusions One-session bilateral WLL was not associated with an increased risk of periprocedural complications compared with two-session WLL in PAP patients. Experienced physicians may consider performing one-session WLL in view of the comparable safety and efficacy and potential advantages of saving time.

To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140 mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca. 10 nm in water was confirmed by dynamic and static light scattering techniques. In a breast cancer mouse model, in vivo biodistribution studies revealed that the 64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents. PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals, while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection, enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.

IntroductionSuper-enhancers (SEs) are clusters of enhancers that act synergistically to drive the high-level expression of genes involved in cell identity and function. Although SEs have been extensively investigated in humans and mice, they have not been well characterized in pigs.MethodsHere, we identified 42,380 SEs in 14 pig tissues using chromatin immunoprecipitation sequencing, and statistics of its overall situation, studied the composition and characteristics of SE, and explored the influence of SEs characteristics on gene expression.ResultsWe observed that approximately 40% of normal enhancers (NEs) form SEs. Compared to NEs, we found that SEs were more likely to be enriched with an activated enhancer and show activated functions. Interestingly, SEs showed X chromosome depletion and short interspersed nuclear element enrichment, implying that SEs play an important role in sex traits and repeat evolution. Additionally, SE-associated genes exhibited higher expression levels and stronger conservation than NE-associated genes. However, genes with the largest SEs had higher expression levels than those with the smallest SEs, indicating that SE size may influence gene expression. Moreover, we observed a negative correlation between SE gene distance and gene expression, indicating that the proximity of SEs can affect gene activity. Gene ontology enrichment and motif analysis revealed that SEs have strong tissue-specific activity. For example, the CORO2B gene with a brain-specific SE shows strong brain-specific expression, and the phenylalanine hydroxylase gene with liver-specific SEs shows strong liver-specific expression.DiscussionIn this study, we illustrated a body map of SEs and explored their functions in pigs, providing information on the composition and tissue-specific patterns of SEs. This study can serve as a valuable resource of gene regulatory and comparative analyses to the scientific community and provides a theoretical reference for genetic control mechanisms of important traits in pigs.

Colorectal cancer is one of the malignant tumors with the highest mortality rate in the world. Survival rates vary significantly among patients at various stages of the disease. A biomarker capable of early diagnosis is required to facilitate the early detection and treatment of colorectal cancer. Human endogenous retroviruses (HERVs) are abnormally expressed in various diseases, including cancer, and have been involved in cancer development. Real-time quantitative PCR was used to detect the transcript levels of HERV-K(HML-2) gag, pol, and env in colorectal cancer to systematically investigate the connection between HERV-K(HML-2) and colorectal cancer. The results showed that HERV-K(HML-2) transcript expression was significantly higher than healthy controls and was consistent at the population and cell levels. We also used next-generation sequencing to identify and characterize HERV-K(HML-2) loci that were differentially expressed between colorectal cancer patients and healthy individuals. The analysis revealed that these loci were concentrated in immune response signaling pathways, implying that HERV-K impacts the tumor-associated immune response. Our results indicated that HERV-K might serve as a screening tumor marker and a target for tumor immunotherapy in colorectal cancer.

Bridge failure, which is generally associated with serious economic and life losses, is defined as the incapacity of a constructed bridge or its components to perform as specified in the design and construction requirements. This paper presents an overview of current researches on the typical characteristics and causes of bridge failures based on 10 former investigations. Principal causes can be divided into internal causes and external causes or natural factors and human factors. Design error, construction mistakes, hydraulic, collision, and overload are the top 5 leading causes of bridge failures, resulting in more than 70% of the bridge failures. Causes of bridge failures are closely related to regional economy, structural type, type of use, material type, and service age. The failure rate is very high for steel bridges, which is inseparable from excessive emphasis on structure strength but lack of consideration on structure stability and fatigue in early years. Researchers need to strengthen their research on the stability and fatigue of steel bridges, as well as inspection and maintenance. Extreme loads such as flood, collision, and overload contribute to a large number of bridge failures because of the lack of extreme loads data and design theory defects. It is critical for such bridges to have sufficient redundancy and capacity protection measures to reduce the probability of bridge failure due to extreme loads. Previous statistical methods and classification methods for the characteristics and causes of bridge failures lack unified standards, and a more scientific method needs to be established. A comprehensive electronic database on bridge damage and failures needs to be developed to establish damage models and conduct forensic studies to improve the design theory and specifications.

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.

All over the world, truss structures are commonly used in long-span bridge. Since joint is the weakest part of this structure, this paper proposes a novel type in which different brace members are used in the concrete filled box section K-joints. This novel type is designed as rectangular compression brace with the brace width to chord ratio β

Steam flooding is an effective development method for heavy oil reservoirs, and the steam flooding assisted by the profile control system can plug the dominant channels and further improve the recovery factor. High-temperature-resistant foam as a profile control system is a hot research topic, and the key lies in the optimal design of the foam system. In this paper, lignin was modified by sulfonation to obtain a high-temperature-resistant modified lignin named CRF; the foaming agent CX-5 was confirmed to have good high-temperature foaming ability by reducing the surface tension; the formula of the profile control system (A compound system of CRF and CX-5, abbreviated as PCS) and the best application parameters were optimized by the foam resistance factor. Finally, the effect of PCS-assisted steam flooding in enhanced oil recovery was evaluated by single sand packing tube flooding, three parallel tube flooding, and large-scale sand packing model flooding experiments. The results show that CX-5 has a good high-temperature foaming performance; the foam volume can reach more than 180 mL at 300 °C, and the half-life is more than 300 s. The optimal PCS formulation is 0.3 wt% CRF as an oil displacement agent + 0.5 wt% CX-5 as a foaming agent. The optimal gas–liquid ratio range is 1:2 to 2:1, and the high pressure and permeability are more conducive to the generation and stability of the foam. Compared with steam flooding, PCS-assisted steam flooding can improve oil recovery by 9% and 7.9% at 200 °C and 270 °C, respectively. PCS can effectively improve the heterogeneity of the reservoir, and increase the oil recovery of the three-parallel tube flooding experiment by 28.7%. Finally, the displacement results of the sand-packing model with large dimensions show that PCS can also expand the swept volume of the homogeneous model, but the effect is 9.46% worse than that of the heterogeneous model.

To facilitate the first application of the novel concrete-filled built-up K-joints with different brace sections in truss bridges, the present paper aims to determine their practicability through a comparison with integral joints. First, a structural analysis was carried out using the MIDAS CIVIL software to evaluate the loading applied to the structure. Additionally, boundary condition analysis was carried out. After that, the symmetric multi-planar joints were developed, using Abaqus 6.14 for the strength verification and the failure mode identification. These were followed by the multi-planar joints estimate cost. The results indicated that for positive bending, the novel joint deformed by 2.01 mm, compared to 4.83 mm for the integral joint in the serviceability limit state. These deformations were equal to 5.58 mm and 7.68 mm, respectively, in the negative bending. Verification under the ultimate limit state indicated a deformation of 10.43 mm for the novel joint type and 16.59 mm for the integral joint in the positive bending, whereas deformations of 15.89 mm and 16.82 mm were indicated in the negative bending. Moreover, a failure mode analysis showed a buckling of the arc yielding for the novel joint type and a buckling of the gusset plate for the integral joint. Finally, the results showed that the novel type of joint was more expensive by about CNY 111,286.06.

This study is aimed at evaluating the effects of dietary protein-to-energy ratios on the growth, immunological response, antioxidative capacity, liver and intestinal histology, and growth-related gene expression of hybrid yellow catfish (Pelteobagrus fulvidraco ♀ × Pelteobagrus vachelli ♂). Eight diets were formulated to form different protein/energy ratios of 84, 88, 90, 93, 95, 96, 99, and 103 mg/kcal (P/E84, P/E88, P/E90, P/E93, P/E95, P/E96, P/E99, and P/E103), respectively. These diets contain different levels of gross energy (GE), ranging from 4.13 to 4.76 kcal g-1. Seven hundred and twenty healthy fish (17.15±0.02 g) were randomly dispersed into 24 rectangular fiberglass tanks with 8 treatments in triplicate groups. The fish fed a P/E ratio of 95 mg/kcal demonstrated the best growth and feed utilization. A significant (P

In lepidopteran insects, dichotomous spermatogenesis produces eupyrene spermatozoa, which are nucleated, and apyrene spermatozoa, which are anucleated. Both sperm morphs are essential for fertilization, as eupyrene sperm fertilize the egg, and apyrene sperm is necessary for the migration of eupyrene sperm. In Drosophila, Prmt5 acts as a type II arginine methyltransferase that catalyzes the symmetrical dimethylation of arginine residues in the RNA helicase Vasa. Prmt5 is critical for the regulation of spermatogenesis, but Vasa is not. To date, functional genetic studies of spermatogenesis in the lepidopteran model Bombyx mori has been limited. In this study, we engineered mutations in BmPrmt5 and BmVasa through CRISPR/Cas9-based gene editing. Both BmPrmt5 and BmVasa loss-of-function mutants had similar male and female sterility phenotypes. Through immunofluorescence staining analysis, we found that the morphs of sperm from both BmPrmt5 and BmVasa mutants have severe defects, indicating essential roles for both BmPrmt5 and BmVasa in the regulation of spermatogenesis. Mass spectrometry results identified that R35, R54, and R56 of BmVasa were dimethylated in WT while unmethylated in BmPrmt5 mutants. RNA-seq analyses indicate that the defects in spermatogenesis in mutants resulted from reduced expression of the spermatogenesis-related genes, including BmSxl, implying that BmSxl acts downstream of BmPrmt5 and BmVasa to regulate apyrene sperm development. These findings indicate that BmPrmt5 and BmVasa constitute an integral regulatory module essential for spermatogenesis in B. mori.

The HIV-1 Rev response element (RRE) is a cis-acting RNA element that facilitates the nuclear export of mRNA-containing introns by binding specifically to the Rev protein, enabling a critical step in the viral replication cycle. This study aims to determine the subtype-specific loci of HIV-1 subtype B RRE circulating in China and to analyze their effects on Rev-RRE function and HIV-1 replication. We amplified 71 HIV-1 subtype B RRE full-length sequences from the HIV patients’ blood samples collected in China, analyzed the subtype-specific loci on them by comparing them with subtype B in the United States, and predicted their RNA secondary structures. Rev-RRE activity assay was used to test the binding activity of Rev and different RREs. Infectious clones were mutated to test the effect of the subtype-specific loci on replication capacity. In this study, two sites were determined to be the subtype-specific loci of HIV-1 subtype B RRE circulating in China. Both site 186 and site 56-57insAAC can significantly increase the viral mRNA transcription and Rev-RRE activity, but only the site 186 can significantly improve viral replication ability. Collectively, the subtype-specific loci of subtype B RRE circulating in China have a significant effect on the Rev-RRE activity and viral replication. This study investigates the subtype-specific loci of RRE, which are unique to retroviruses and essential for viral replication, and will help to explore the reasons why subtype B circulating in China is more widespread and persistent than American subtype B in China at the genetic level, and will provide theoretical support for the development of more inclusive detection and treatment methods for subtype B circulating in China. At the same time, it will also provide insight into the impact of different subtype HIV-1 genetic characteristics on viral replication.

In order to promote the ecological environment protection and ecological disaster control of Yellow Sea, this paper analyzed the background of ecological environment and problems, and put forward suggestions for the construction of regional monitoring system based on the collection of historical data. The results showed that climate change and nutrient changes were the important factors affecting plankton community. The red tide, green tide and jellyfish bloom were the main ecological disasters of the Yellow Sea Large Marine Ecosystem (YSLME). The regional monitoring system of the YSLME should be established by strengthening various forms of monitoring and cooperation continuously.

The Special Issue contains eleven accepted and published submissions to a Special Issue of the MDPI journal Axioms on the subject of “Nonlinear Dynamical Systems with Applications” [...]

Nowadays, the output of light crude oil is approaching its peak, which has shifted the attentions of petroleum industry to a large quantity of heavy oil and bitumen in order to offset the growing demand of energy and fuels. The heavy oil and bitumen are usually characterized by high viscosity, high density/low API gravity, low yield of low boiling point fuel fraction, and high heteroatom content in comparison with the light oil, requiring in situ upgrading to improve the mobility of heavy oil. before recovery it. One of the methods for upgrading is to add catalysts to the underground reservoir.This paper firstly reviewed various kinds of catalysts, including mineral, water-soluble, oil-soluble, solid acid, ionic liquid (IL) catalysts, and dispersed and super-dispersed catalysts that reported in domestic and foreign literatures, and secondly described their effectiveness in underground catalytic cracking and upgrading of heavy oil. This critical review suggests that it is necessary to develop the catalytic cracking catalysts of low-cost, high activity, high selectivity, and wide adaptability in order to accommodate a wide range of heavy oil with different properties, especially the ultra-dispersed nano-catalysts. The in situ upgrading technology by injecting super-dispersed nano-catalysts is a promising method to improve the quality of the lowest grade heavy oil components and enhance the recovery of heavy oil reservoirs. Moreover, further research is needed to explore the optimal process of catalyst synthesis, catalytic working conditions and the actual mechanisms of heavy oil with catalysts.

Concrete-filled rectangular steel tubular (CFRST) composite truss bridge is a new type of structure composed of a CFRST truss and concrete deck slab. This new type of bridge has the advantages of high structural force-transferring efficiency, rapid assembly construction speed and excellent total life cycle, which meets the construction concept of green, recyclable and sustainable development. Due to the broad application prospects, experiment on the flexural behavior of CFRST composite truss bridge in the negative moment region was reported by authors previously. This paper thus presents a finite element analysis (FEA) modelling verified by the reported test data to further investigate the detailed analytical behavior of this structure. The structural response and failure mechanism of CFRST composite truss beam in the negative moment region are studied. In addition, the important structural design parameters on the flexural performance of the CFRST composite truss beam are also investigated, including the height to span ratio, the brace-to-chord wall thickness ratio, the reinforcement ratio of steel reinforcements and prestressed tendons and the strength grade of concrete infill in chords. Finally, the reasonable structural design parameters range are proposed for the optimum design of the CFRST composite truss bridge.

Adipose tissue is composed of a number of adipocytes and a number of other cells including immune cells. Here the authors use single-cell sequencing of murine brown adipose tissue immune cells and describe multiple macrophage and monocyte subsets and show that monocytes contribute to brown adipose tissue expansion.

Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-β bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes were primarily engulfed by alveolar macrophages (AMs), which were reprogrammed to become less responsive to TGF-β and reduce TGF-β bioavailability through secretion of the TGF-β antagonist decorin. In untreated recipients, high airway TGF-β activity stimulated AMs to express CCL2, leading to CCR2+ monocyte-driven BOS development. Moreover, we found TGF-β receptor 2–dependent differentiation of CCR2+ monocytes was required for the generation of monocyte-derived AMs, which in turn promoted BOS by expanding tissue-resident memory CD8+ T cells that inflicted airway injury through Blimp-1–mediated granzyme B expression. Thus, through studying the effects of ECP, we have identified an AM functional plasticity that controls a TGF-β–dependent network that couples CCR2+ monocyte recruitment and differentiation to alloimmunity and BOS.

CD36 mediates the uptake of long-chain fatty acids (FAs), a major energy substrate for the myocardium. Under excessive FA supply, CD36 can cause cardiac lipid accumulation and inflammation while its deletion reduces heart FA uptake and lipid content and increases glucose utilization. As a result, CD36 was proposed as a therapeutic target for obesity-associated heart disease. However, more recent reports have shown that CD36 deficiency suppresses myocardial flexibility in fuel preference between glucose and FAs, impairing tissue energy balance, while CD36 absence in tissue macrophages reduces efferocytosis and myocardial repair after injury. In line with the latter homeostatic functions, we had previously reported that CD36–/– mice have chronic subclinical inflammation. Lipids are important for the maintenance of tissue homeostasis and there is limited information on heart lipid metabolism in CD36 deficiency. Here, we document in the hearts of unchallenged CD36–/– mice abnormalities in the metabolism of triglycerides, plasmalogens, cardiolipins, acylcarnitines, and arachidonic acid, and the altered remodeling of these lipids in response to an overnight fast. The hearts were examined for evidence of inflammation by monitoring the presence of neutrophils and pro-inflammatory monocytes/macrophages using the respective positron emission tomography (PET) tracers, 64Cu-AMD3100 and 68Ga-DOTA-ECL1i. We detected significant immune cell infiltration in unchallenged CD36–/– hearts as compared with controls and immune infiltration was also observed in hearts of mice with cardiomyocyte-specific CD36 deficiency. Together, the data show that the CD36–/– heart is in a non-homeostatic state that could compromise its stress response. Non-invasive immune cell monitoring in humans with partial or total CD36 deficiency could help evaluate the risk of impaired heart remodeling and disease.

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.

Raw materials for making dried shrimp (a type of foodstuff) are mostly from farmed shrimp and preliminary findings indicated that head copper (Cu) concentrations in some commercial dried shrimp products exceeded the safe limit specified in pollution-free aquatic products (50 mg/kg), which may influence food safety. Therefore, a 63-day feeding trial was conducted to explore effects of dietary Cu concentrations on accumulation of Cu in tissues, growth performance, immune response and antioxidant status of Pacific white shrimp (Litopenaeus vannamei). Moderating effect of myo-inositol (MI, adding 200 mg/kg diet) on the adverse impacts caused by excessive dietary Cu was also investigated. 600 shrimp (initial weight: 0.89 ± 0.00 g) were divided into five groups: 37.08 mg Cu/kg diet group (control group), 62.57 mg Cu/kg diet group, 125.99 mg Cu/kg diet group, 63.41 mg Cu/kg diet group (supplemented with MI) and 119.19 mg Cu/kg diet group (supplemented with MI). The results showed that dietary Cu concentrations increased from 37.08 to over 62.57 mg/kg, hepatopancreas Cu concentrations raised from 29.04 to 233.43–263.65 mg/kg, and muscle Cu concentrations only increased from 6.22 to 6.99–8.39 mg/kg. Report to control group, excessive Cu concentration (125.99 mg/kg) didn’t significantly affect growth performance, but it notably reduced whole body lipid content and immune response, induced oxidative stress and damaged the hepatopancreas structure, which was ameliorated by MI supplementation. The results suggested that consuming shrimp head and its processed products weren’t recommended. Cu concentrations of commercial feeds for Pacific white shrimp should be controlled below 62.57 mg/kg. Additionally, MI supplementation mitigated the negative impacts induced by excessive dietary Cu.

Rehmanniae Radix (RR, the dried tuberous roots of Rehmannia glutinosa (Gaertn.) DC.) is an important traditional Chinese medicine distributed in Henan, Hebei, Inner Mongolia, and Northeast in China. RR is frequently used to treat diabetes mellitus, cardiovascular disease, osteoporosis and aging-related diseases in a class of prescriptions. The oligosaccharides and catalpol in RR have been confirmed to have neuroprotective effects. However, there are few studies on the anti-Alzheimer’s disease (AD) effect of oligosaccharides in Rehmanniae Radix (ORR). The chemical components and pharmacological effects of dried Rehmannia Radix (DRR) and prepared Rehmannia Radix (PRR) are different because of the different processing methods. ORR has neuroprotective potential, such as improving learning and memory in rats. Therefore, this study aimed to prove the importance of oligosaccharides in DRR (ODRR) and PRR (OPRR) for AD based on the Caenorhabditis elegans (C. elegans) model and the different roles of ODRR and OPRR in the treatment of AD. In this study, we used paralysis assays, lifespan and stress resistance assays, bacterial growth curve, developmental and behavioral parameters, and ability of learning and memory to explore the effects of ODRR and OPRR on anti-AD and anti-aging. Furthermore, the accumulation of reactive oxygen species (ROS); deposition of Aβ; and expression of amy-1, sir-2.1, daf-16, sod-3, skn-1, and hsp-16.2 were analyzed to confirm the efficacy of ODRR and OPRR. OPRR was more effective than ODRR in delaying the paralysis, improving learning ability, and prolonging the lifespan of C. elegans. Further mechanism studies showed that the accumulation of ROS, aggregation, and toxicity of Aβ were reduced, suggesting that ORR alleviated Aβ-induced toxicity, in part, through antioxidant activity and Aβ aggregation inhibiting. The expression of amy-1 was downregulated, and sir-2.1, daf-16, sod-3, and hsp-16.2 were upregulated. Thus, ORR could have a possible therapeutic effect on AD by modulating the expression of amy-1, sir-2.1, daf-16, sod-3, and hsp-16.2. Furthermore, ORR promoted the nuclear localization of daf-16 and further increased the expression of sod-3 and hsp-16.2, which significantly contributed to inhibiting the Aβ toxicity and enhancing oxidative stress resistance. In summary, the study provided a new idea for the development of ORR.

During the operational phase of a bridge, the crossbeam, acting as a supporting member, plays an important role in keeping the cross-sectional shape constant in addition to resisting against various lateral and longitudinal loads and distributing the dead and the live loads to the adjacent main girders. The complex functional requirements lead to a complex internal force composition of the crossbeam. When subjected to torque, the two main beams of the twin I-girder bridge will have deformation in opposite longitudinal directions (known as warping deformation) to counteract the torque. The existing research has not considered the impact of main beam warping deformation on the internal force of the crossbeam. Based on the existing research, this article further considers the impact of main beam warping deformation on the internal force of the crossbeam, making the calculation of the internal force of the crossbeam more accurate. The results show that the torsional characteristics of the continuous twin I-girder bridge can be calculated using Vlasov’s theory of thin-walled structures combined with the displacement method. As for the effect of the crossbeam on the torsional stiffness of the structure, it can be managed by making the crossbeam stiffness continuous; however, in general, the equivalent stiffness is small compared to the stiffness of the main beam and it can be ignored. The crossbeam can be simplified to a bar with two solid ends for the internal force calculation whose formula is proposed in this paper, based on the existing frame model, and it can further consider the influence of warping deformation of the main beam on the internal force of the beam, and the calculation accuracy is high.

In order to accurately calculate the sunshine-induced temperature effect of an ultra-high bridge pylon, a refined numerical simulation model for the 3D bridge temperature field was established based on the proposed automatic sunshine shadow recognition method and pylon-height-related convection modification method. A suspension bridge H-shaped pylon with a height of 280 m was taken as an example, and the temperature field and corresponding thermal stress and deformation were calculated under typical meteorological conditions in spring, summer, autumn, and winter. The results show that the maximum temperature differences between the outer surfaces of the pylon can reach 19 °C and 16 °C for north–south walls and east–west walls, respectively, and exceed the recommended value of ±5 °C in the Chinese Specification. The maximum displacements can reach 370 mm and 110 mm at the top of the bridge pylon in the longitudinal and transverse directions of the bridge, respectively. After the modification of the convective coefficient of the outer surfaces with different wind speeds at different pylon heights, the temperature gradually decreased from the top to the bottom of the pylon, with a temperature difference of 8 °C. The significant influence of the sunshine shadow was shown on the temperature field and temperature effect of the bridge pylon. By considering the shadow effect, the maximum temperature difference can reach 12 °C between adjacent sunlit and shaded areas and can reach 14 °C between two pylon columns. A significant mutation of thermal stress existed in the shaded area, and the maximum stress could be reduced by 13 MPa compared with the adjacent sunlit area. Obvious asynchronous deformation was shown between two pylon columns, and the maximum asynchronous displacement at the top of the pylon can reach 18 mm and 45 mm in the longitudinal and transverse directions, respectively.

In terms of load transfer, the design of the joints in concrete-filled steel tubular (CFST) arch bridges is more critical than that in buildings due to the higher likelihood of steel–concrete-interface debonding. To improve the contact at the steel–concrete interface, a novel arch rib was manufactured by longitudinally welding perfobond-rib-shear connectors to the inner surface of a steel tube and then filling the tube with concrete. In this study, extensive numerical and analytical investigations on the mechanism of introducing loads into CFST arch ribs through perfobond-rib-shear connectors were carried out. A deck CFST arch bridge, namely, the Shuangbao Bridge in China, was selected as a typical application location. The design parameters, including the geometric dimensions of the perfobond-rib-shear connector and the arrangement of the perfobond rib along the cross-section and longitudinal section of the arch rib, were evaluated. The design flow for the joint with perfobond-rib-shear connectors between the vertical columns and the CFST arch ribs was proposed. To improve the load-transfer efficiency, the design scheme of the joint in the Shuangbao Bridge was optimized by replacing the weld studs with perfobond ribs. Significant increases of 1.84–4.02 in the shear resistance were found for the perfobond ribs compared to the welded studs. Additionally, the fabrication of the perfobond ribs was more convenient compared to that of the welded studs.

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.

This paper predicts the tension strength of Concrete-filled Branch Plate-to-Rectangular Hollow (CBPRH) joint by conducting experimental and theoretical analysis. A total of 46 X-joints with different geometric parameters were investigated, in which 4 specimens were tested under ultimate tension and 42 specimens were numerically analyzed. The joint�s strength, failure mode and load-displacement curve were obtained. Perfobond Leister Rib (PBR) was welded in part of the specimens to investigate its effect on joint�s tensile performance. It is shown that the ultimate strength of transverse CBPRH joint benefit from grouting of chord and installation of PBR. The ultimate strength of CBPRH joint with PBR is larger than the counterpart without PBR. Tension strength equations were proposed for both CBPRH joints with and without PBR by nonlinear regression. The chord axial stress reduction factor was discussed and a modified equation originated from hollow joint was recommended for CBPRH joint. Connection efficiency was presented and compared among branch plate-to-rectangular hollow (BPRH) joint, CBPRH joint and CBPRH joint with PBR.

Background and objective Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease. Methods From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted. Results 297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%). Conclusion Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.

Objective: This study aimed to evaluate the clinical and angiographic outcomes of aneurysms that were completely or near-completely embolized and ascertain whether complete embolization is important in the stent-assisted coiling (SAC) of intracranial aneurysms. Methods: This retrospective study enrolled 390 patients (417 aneurysms). Among them, complete (100%) or near-complete (>90%) angiographic obliteration of the aneurysms on immediate angiography was accomplished. Baseline characteristics, complications, angiography follow-up results, and clinical outcomes were analyzed. Results: Cumulative adverse events occurred in 30 patients (7.7%), including thromboembolic complications in 17 (4.4%), intraoperative rupture in 10 (2.6%), and others in 3 (0.8%). Statistical analyses revealed an increased intraprocedural rupture rate in the initial completely occluded aneurysms (5.6% compared with 1.0%). The incidence of cumulative adverse events was higher in patients with completely occluded aneurysms (11.1%) than in those with near-completely occluded aneurysms (5.5%). Angiography follow-up was available for 173 aneurysms. Aneurysm occlusion status at follow-up was correlated with stent placement (p ​= ​0.000, odds ratio ​= ​5.847), size (p ​= ​0.000, odds ratio ​= ​6.446 for tiny aneurysms; and p ​= ​0.001, odds ratio ​= ​5.616 for small aneurysms), and initial aneurysm occlusion status (p ​= ​0.001, odds ratio ​= ​3.436). Complete occlusion at follow-up was seen in 82.6% of the initial complete occlusion group versus 63.0% of the initial near-complete occlusion group. The incidence of complete occlusion at follow-up was higher in the initial completely occluded aneurysms with SAC (100%) than in the initial completely occluded aneurysms with non-SAC (65.2%). Conclusions: Initial complete treatment may lead to higher complication rates and good clinical outcomes at follow-up. Stent placement may enhance progressive aneurysm occlusion. Initial complete occlusion with SAC can provide durable closure at follow-up.

Seawater acidification and warming have been found to affect the early life of many marine organisms, but their effects on the microbial community in the environment related to the early development stage of aquaculture species have been rarely investigated. To understand how seawater acidification and warming impact the microbial community in aquaculture systems, we designed four microcosms to monitor and characterize the microbial composition on the corrugated plates in the Apostichopus japonicus culture tanks during its post-settlement stage. High-throughput 16S rRNA sequencing revealed that the bacterial community composition varied significantly in different periods of incubation. The bacterial diversity and community composition were obviously changed by seawater acidification and warming in the early period and then tended to revert to the level of the control group. Acidification significantly increased the relative abundance of dominant families Rhodobacteraceae and Flavobacteriaceae in the early period, suggesting that microbiota could increase the abundance of predominant taxa to adapt to increased CO2 concentration and reconstruct a stable community structure. No interaction effect of both factors was observed in the combined group. Results reveal that the microbial communities on the corrugated plates in A. japonicus culture tank were affected in the early period of incubation, and could then acclimatize to the increased CO2 and temperature. This study provides new insights into the variation and adaptation responses of the microbiota in aquaculture systems to seawater acidification and warming.

An 8-week feeding experiment was conducted to investigate whether diet supplementation of lutein could result in similar growth performance, antioxidant capacity, and immunity of Litopenaeus vannamei when compared to dietary astaxanthin. Juvenile L. vannamei (initial body weight: 0.64 ± 0.04 g) were fed with one of five isonitrogen and isolipids diets with/without lutein or astaxanthin [control group (C); the lutein (L) groups contained 0, 62.5, 75, 87.5 ppm lutein, respectively, the astaxanthin (A) group contained 50 ppm astaxanthin]. Results showed that dietary supplementation of lutein ranging from 62.5 to 75 ppm resulted in similar growth performance (WGR, SGR, FCR, and SR) of L. vannamei compared with the A group (P > 0.05). Apart from that, no statistical difference was observed in antioxidant parameters (hemolymph T-AOC, hemolymph MDA, and RNA expression level of GSH-PX, CAT), anti-inflammatory ability (Relish, Rho, and HSP70) and apoptosis-related gene expression (Caspase3) among lutein treatments ranging from 62.5 to 87.5 ppm and the A group (P > 0.05). These results indicate that a dose of 62.5–75 ppm of lutein was suitable in the diet of L. vannamei for substituting dietary astaxanthin.

Abstract Background Endosperm-trait related genes are associated with grain yield or quality in maize. There are vast numbers of these genes whose functions and regulations are still unknown. The biolistic system, which is often used for transient gene expression, is expensive and involves complex protocol. Besides, it cannot be used for simultaneous analysis of multiple genes. Moreover, the biolistic system has little physiological relevance when compared to cell-specific based system. Plant protoplasts are efficient cell-based systems which allow quick and simultaneous transient analysis of multiple genes. Typically, PEG-calcium mediated transfection of protoplast is simple and cost-effective. Notably, starch granules in cereal endosperm may diminish protoplast yield and integrity, if the isolation and transfection conditions are not accurately measured. Prior to this study, no PEG-calcium mediated endosperm protoplast system has been reported for cereal crop, perhaps, because endosperm cells accumulate starch grains. Results Here, we showed the uniqueness of maize endosperm-protoplast system (EPS) in conducting endosperm cell-based experiments. By using response surface designs, we established optimized conditions for the isolation and PEG-calcium mediated transfection of maize endosperm protoplasts. The optimized conditions of 1% cellulase, 0.75% macerozyme and 0.4 M mannitol enzymolysis solution for 6 h showed that more than 80% protoplasts remained viable after re-suspension in 1 ml MMG. The EPS was used to express GFP protein, analyze the subcellular location of ZmBT1, characterize the interaction of O2 and PBF1 by bimolecular fluorescent complementation (BiFC), and simultaneously analyze the regulation of ZmBt1 expression by ZmMYB14. Conclusions The described optimized conditions proved efficient for reasonable yield of viable protoplasts from maize endosperm, and utility of the protoplast in rapid analysis of endosperm-trait related genes. The development of the optimized protoplast isolation and transfection conditions, allow the exploitation of the functional advantages of protoplast system over biolistic system in conducting endosperm-based studies (particularly, in transient analysis of genes and gene regulation networks, associated with the accumulation of endosperm storage products). Such analyses will be invaluable in characterizing endosperm-trait related genes whose functions have not been identified. Thus, the EPS will benefit the research of cereal grain yield and quality improvement.

Concrete-filled steel tube (CFST) has been widely applied in bridges due to its excellent structural and constructional performance. In CFST bridges, temperature action is not only an important but also a special load that must be considered in bridge design, construction and structural evaluation. This paper presents an overview on current researches of the temperature action and effect of CFST bridges. The historical and spatial characteristics as well as corresponding influencing factors of temperature distributions are summarized, and classifications of temperature actions are also reviewed. Results show that in-depth investigations of the contributions of temperature influencing factors can help to effectively reduce the adverse temperature effects on CFST bridges in the design stage. Due to the lack of long-term measurements and insufficient use of historical meteorological data, research on the representative value along with correlation analysis of CFST temperature actions and meteorological parameters have to be further carried out. In the meanwhile, a decomposition method of temperature distribution is proposed based on structural effects of CFST bridges in this paper. The decomposed temperature actions can be used for more accurate effect calculation than traditional temperature action classification method, especially for CFST truss bridges. At last, specific temperature action patterns still need to be investigated in some of the special problems, such as longitudinal temperature differences along the CFST arch rib and thermal debonding in the CFST interface. Further investigations are required on the accurate simulation of temperature distribution of CFST bridges considering the shading effects of components and terrain. Keywords: Bridge engineering, CFST bridge, Temperature action, Temperature effect, Thermal debonding

Abstract Background There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance. Methods We used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database. Results A total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients. Conclusions This study confirmed the expansion CRF65_cpx in China. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.

Abstract Background Anhui Province in China is facing a severe HIV epidemic with an increasing number of newly diagnosed cases. Methods In this study, HIV genetic characteristics in the province were investigated. Newly reported HIV-positive individuals from 15 districts of Anhui Province were enrolled and interviewed. Total viral RNA was extracted from plasma isolated from blood samples. We amplified and sequenced an HIV pol fragment of the 1062 bp. The sequences were used for determination of HIV subtypes and the presence of drug resistance mutations. Transmission networks were constructed to explore possible relationships. And all of assembled partial pol genes were submitted to the Stanford HIV Drug Resistance Database website to find the transmitted drug resistance. Results Partial pol gene sequences were obtained from 486 cases. The results showed that MSM was the most dominant transmission route (253, 52.06%), followed by heterosexual transmission (210, 43.21%) and blood-borne transmission (1, 0.21%). Many subtypes were identified, including CRF01_AE (226, 46.50%), CRF07_BC (151, 31.07%), subtype B (28, 5.76%), CRF08_BC (20, 4.12%), CRF55_01B (15, 3.09%), CRF68_01B (7, 1.44%), CRF67_01B (3, 0.62%), CRF57_BC (2, 0.41%), CRF59_01B (2, 0.41%), CRF79_0107 (2, 0.41%), subtype C (2, 0.41%), CRF64_BC (1, 0.21%), and circulating recombinant forms (URFs) (27, 5.55%). Four transmission subnetworks containing high transmission risk individuals (with degree ≥4) were identified based on CRF01_AE and CRF07_BC sequences, including two CRF01_AE transmission subnetworks constituted by elderly people with average ages of 67.9 and 61.5 years. Infection occurred most likely through heterosexual transmission, while the other two CRF07_BC transmission subnetworks consist mainly of MSMs with average ages of 31.73 and 34.15. The level of HIV-transmitted drug resistance is 3.09%. Conclusions The simultaneous spread of multiple HIV subtypes in Anhui province underscores that close surveillance of the local HIV epidemic is necessary. Furthermore, the elderly people were frequently involved, arguing for behaviour intervention in this specific population besides the MSM risk group.

Curved composite twin-girder bridges are suitable for mountainous areas, due to their advantages of light self-weight, excellent mechanical performance, and fewer construction requirements. It has been found that many composite twin-girder bridges collapsed due to fatigue failure. However, the literature review showed no relevant studies on the fatigue performance of curved composite twin-girder bridges. Because of this, the specimen of 1:2 scale curved composite twin-girder bridge in accordance with the design scheme of Xizhen Bridge in China was designed and tested. Three possible fatigue details were selected: cruciform connections, transverse attachments, and transverse splices named Class I, Class II, and Class III. For the test data of nominal stress (NS), equations were proposed to convert the strain value into the internal force of the fatigue detail position. The stress caused by torsion accounts for 2.8% of the total stress, which is almost negligible. The fatigue evaluation process based on the hot spot stress (HSS) S-N curve method is presented. The HSS method is more conservative than the NS S-N curve method in predicting the fatigue life of complex structures with high-stress concentrations.

The shear bond performance between steel tube and concrete is the basis of a synergistic effect between two materials. When a concrete-filled steel tube structure is damaged by freeze and thaw cycles, the shear bond performance will deteriorate, which will inevitably affect the safety of the structure. In this paper, the effects of the numbers of freeze–thaw cycles, section type of steel tube, and concrete strength on the failure mode, bond strength, and peak slip of concrete-filled steel tube are investigated. In addition, the load–slip curve, the shear bond strength calculation formula, and the peak slip calculation formula are obtained. The results show that the shear bond performance decreases with the increase in freeze and thaw cycles; after 20 freeze and thaw cycles, the shear bond strength of the round steel tube specimen with 30 MPa decreases by 33.33%, while that of peak slip increases by 11.49%; the shear bond strength increases with the increase in concrete strength, while the degree of decrease in shear bond strength after freeze–thaw cycles is reduced; the shear bond strength of the round steel tube push-out specimen is higher than that of square steel tube push-out specimen, and after 20 freeze and thaw cycles, the shear bond strength of the round steel tube push-out specimen with 30 MPa/45 MPa is 0.86 MPa/1.62 MPa, while that of square steel tube push-out specimen with 30 MPa/45 MPa is 0.40 MPa/0.50 MPa.