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Abstract The tumor microenvironment (TME) cells interact with each other and play a pivotal role in tumor progression and treatment response. A comprehensive characterization of cell and intercellular crosstalk in the TME is essential for understanding tumor biology and developing effective therapies. However, current cell infiltration analysis methods only partially describe the TME's cellular landscape and overlook cell‐cell crosstalk. Here, this approach, CITMIC, can infer the cell infiltration of TME by simultaneously measuring 86 different cell types, constructing an individualized cell‐cell crosstalk network based on functional similarities between cells, and using only gene transcription data. This is a novel approach to estimating the relative cell infiltration levels, which are shown to be superior to the current methods. The TME cell‐based features generated by analyzing melanoma data are effective in predicting prognosis and treatment response. Interestingly, these features are found to be particularly effective in assessing the prognosis of high‐stage patients, and this method is applied to multiple high‐stage adenocarcinomas, where more significant prognostic performance is also observed. In conclusion, CITMIC offers a more comprehensive description of TME cell composition by considering cell‐cell crosstalk, providing an important reference for the discovery of predictive biomarkers and the development of new therapeutic strategies.

Because the upper-stage separation of a lifting-body rocket is difficult under the low-altitude and high-speed flight environments, an upper-stage separation scheme based on the separation spring is proposed. The integration of ADAMS and MATLAB realizes the multi-body dynamics simulation analysis of upper-stage separation. The experimental design method is used to carry out the target simulation and calculation of the upper-stage separation process, with the separation condition deviation and the separation spring deviation considered at the same time, thus ensuring the reliability of the separation scheme. In order to further optimize the separation scheme, an upper-stage separation optimization model is established with the Isight software, and the mass of separation spring is optimized with the multi-island genetic algorithm and significantly reduced by 48.87% under the condition that the upper-stage separation process satisfies all constraints, thereby effectively improving the performance of the lifting-body rocket.

In recent years, an increasing number of viruses have triggered outbreaks that pose a severe threat to both human and animal life, as well as caused substantial economic losses. It is crucial to understand the genomic structure and epidemiology of these viruses to guide effective clinical prevention and treatment strategies. Nanopore sequencing, a third-generation sequencing technology, has been widely used in genomic research since 2014. This technology offers several advantages over traditional methods and next-generation sequencing (NGS), such as the ability to generate ultra-long reads, high efficiency, real-time monitoring and analysis, portability, and the ability to directly sequence RNA or DNA molecules. As a result, it exhibits excellent applicability and flexibility in virus research, including viral detection and surveillance, genome assembly, the discovery of new variants and novel viruses, and the identification of chemical modifications. In this paper, we provide a comprehensive review of the development, principles, advantages, and applications of nanopore sequencing technology in animal and human virus research, aiming to offer fresh perspectives for future studies in this field.

MicroRNAs (miRNAs) are important posttranscriptional regulators of metabolism and energy homeostasis. Dysregulation of certain miRNAs in the liver has been shown to contribute to the pathogenesis of Type 2 diabetes (T2D), in part by impairing hepatic insulin sensitivity. By small RNA-sequencing analysis, we identified seven hepatic miRNAs (including miR-29b) that are consistently aberrantly expressed across five different rodent models of metabolic dysfunction that share the feature of insulin resistance (IR). We also showed that hepatic miR-29b exhibits persistent dysregulation during disease progression in a rat model of diabetes, UCD-T2DM. Furthermore, we observed that hepatic levels of miR-29 family members are attenuated by interventions known to improve IR in rodent and rhesus macaque models. To examine the function of the miR-29 family in modulating insulin sensitivity, we used locked nucleic acid (LNA) technology and demonstrated that acute in vivo suppression of the miR-29 family in adult mice leads to significant reduction of fasting blood glucose (in both chow-fed lean and high-fat diet-fed obese mice) and improvement in insulin sensitivity (in chow-fed lean mice). We carried out whole transcriptome studies and uncovered candidate mechanisms, including regulation of DNA methyltransferase 3a (Dnmt3a) and the hormone-encoding gene Energy homeostasis associated (Enho). In sum, we showed that IR/T2D is linked to dysregulation of hepatic miR-29b across numerous models and that acute suppression of the miR-29 family in adult mice leads to improved glycemic control. Future studies should investigate the therapeutic utility of miR-29 suppression in different metabolic disease states.Enho; insulin resistance; liver; microRNA-29 (miR-29); UCD-T2DM.

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused huge economic losses for the global pig industry, but its origins and evolution remain a mystery. In 2018, the genome sequences of seven arteriviruses isolated from rodents were determined, and here we publish new analysis showing that they may be ancestors of PRRSV. The sequence similarity of these viruses to PRRSV was ~60%, with shared genome organization and other characteristics, such as slippery sequences and C-rich motifs in nsp2, and a transactivated protein sequence in nsp1β. Codon usage basis analysis showed that PRRSV was closer to these rodent arteriviruses than lactate dehydrogenase-elevating virus (LDV) and they were both under pressure of natural selection. Evolutionary analysis revealed that four of the rodent arteriviruses shared the same genus with PRRSV, and were more closely related to PRRSV-2 than PRRSV-1. In addition to this, they all appeared earlier than PRRSV according to evolutionary modeling, and we speculate that they represent an intermediate step in the origin of PRRSV by arterivirus transmission from rodents to swine. Our in-depth analysis furthers our understanding of arteriviruses, and will serve as the basis for subsequent exploration of the evolution of PRRSV and other arteriviruses.

The quality of traditional sMDT(single-centered multi-disciplinary treatment team) teaching model will be affected by the centerlocation, leve of heathcare service, performance habits, dominant disciplines, and superior technologies, which will directly affect the depth and breadth of students' knowledge learning. Based on the traditional sMDT teaching, the new multi-centered MDT (mMDT) teaching model establishes cooperative teaching relationships with multiple hospitals and disciplines, cocultivates undergraduate and graduate students, and regularly conducts mMDT teaching, which effectively avoids the defects of the traditional sMDT teaching model and meets the needs of students at different levels. Through the mMDT teaching mode, students can learn the advanced clinical reasoning and techniques in different disciplines or hospitals, have a deeper understanding of the concept of comprehensive diagnosis and treatment of tumors, and improve the comprehensive quality of clinical research.

In the construction industry, the combination of Industry Foundation Classes (IFC) and semantic web technologies emerges as a promising approach for project information management. However, semantic web technologies are unfamiliar to construction industry practitioners, and there is an absence of useable tools to automate semantic web-based create, read, update, and delete (CRUD) operations on Building Information Modeling (BIM) data. Moreover, the query results from some SPARQL Protocol and RDF Query Language (SPARQL)-based information retrieval methods typically cannot be postprocessed. To overcome these issues, this paper initially proposes a browser/server (B/S) architecture platform prototype to mitigate the operational complexity of the developed system. Subsequently, the core submodules of this platform prototype are developed via Apache Jena and Java Database Connectivity (JDBC) APIs, thereby supporting automatic CRUD operations and result-analyzable SPARQL queries. Furthermore, by leveraging the developed CRUD systems, we propose a feasible method for implementing the soft-coded Shapes Constraint Language (SHACL)-based validation with variable thresholds, and subsequently develop an information compliance checking service for weld size. Eventually, the effectiveness of the developed CRUD system functions and the compliance checking service is validated by conducting case tests. In short, this study proposes a viable approach for the automatic execution of semantic web-based CRUD operations and constraint validation on Resource Description Framework (RDF)-represented information converted from the IFC model. This work contributes to the application of IFC and semantic web technologies within construction project management. [ABSTRACT FROM AUTHOR]

The Microbial Prospecting for Oil and Gas (MPOG) is an exploration method based on the seepage of light gaseous hydrocarbons from oil/gas reservoirs to the surface and their utilization by hydrocarbon oxidizing bacteria. By studying the abnormal characteristics of oil and gas microorganisms in Xinhe area of the Tarim Basin, this project provides a solid scientific basis for oil and gas prediction and the validation and application of oil and gas microbial exploration technology in this area. Soil samples were collected to investigate prospects for hydrocarbon exploration. The amount of cultivable soil microorganisms in different soil samples were analyzed using the agar plating method. High-throughput sequencing has been used directly to study the composition of microbial population in soil samples. Based on the data from Xinhe area, an abnormal pattern of oil and gas microorganisms has been established. By using this pattern, five abnormal microbial areas were identified in the Xinhe and Sandaoqiao area. Combined with the results of structural traps and the abnormal number of hydrocarbon microorganisms, five potential favorable exploration target areas were identified.

Amyloid beta (Aβ) monomers aggregate to form fibrils and amyloid plaques, which are critical mechanisms in the pathogenesis of Alzheimer’s disease (AD). Given the important role of Aβ1-42 aggregation in plaque formation, leading to brain lesions and cognitive impairment, numerous studies have aimed to reduce Aβ aggregation and slow AD progression. The diphenylalanine (FF) sequence is critical for amyloid aggregation, and magnetic fields can affect peptide alignment due to the diamagnetic anisotropy of aromatic rings. In this study, we examined the effects of a moderate-intensity rotating magnetic field (RMF) on Aβ aggregation and AD pathogenesis. Results indicated that the RMF directly inhibited Aβ amyloid fibril formation and reduced Aβ-induced cytotoxicity in neural cells in vitro. Using the AD mouse model APP/PS1, RMF restored motor abilities to healthy control levels and significantly alleviated cognitive impairments, including exploration and spatial and non-spatial memory abilities. Tissue examinations demonstrated that RMF reduced amyloid plaque accumulation, attenuated microglial activation, and reduced oxidative stress in the APP/PS1 mouse brain. These findings suggest that RMF holds considerable potential as a non-invasive, high-penetration physical approach for AD treatment. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine (NAC); however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field (SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAPinduced oxidative stress, free radicals, and liver damage, resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione (GSH). During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24 h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose. Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses. [ABSTRACT FROM AUTHOR]

Background: Total neoadjuvant therapy (TNT) is a new strategy combining neoadjuvant therapy and chemotherapy to enhance tumor shrinkage and systemic control. Its effectiveness remains debated. Objectives: This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess TNTs impact and provide high-quality evidence for rectal cancer treatment decisions. Method: We searched China National Knowledge Infrastructure, VIP Database, Wanfang Database, China biomedical literature database, PubMed database, Embase database, and The Cochrane Library for RCTs comparing TNT with neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. The included trials were screened and assessed for quality based on inclusion and exclusion criteria, and meta-analysis was performed using RevMan 5.3 software. Results: A total of 11 RCTs reported in 14 articles, with 1,624 cases in the TNT group and 1,541 cases in the CRT group. The results of the meta-analysis showed that compared with the CRT group, the TNT group had a higher pathological complete response rate (risk ratio [RR] = 1.65, 95% confidence interval [CI]: [1.40, 1.94], p <0.00001), higher T0 downstaging rate (RR = 1.51, 95% CI: [1.29, 1.77], p <0.00001), higher 3-year overall survival (hazard ratio [HR] = 0.81, 95% CI: [0.67, 0.98], p = 0.03), and higher 3-year disease-free survival (HR = 0.82, 95% CI: [0.70, 0.95], p = 0.008). However, there was no statistically significant difference between the two groups in terms of R0 resection rate (RR = 1.02, 95% CI: [0.99, 1.05], p = 0.14), sphincter preservation rate (RR = 0.94, 95% CI: [0.88, 1.01], p = 0.12), anastomotic leakage rate (RR = 1.42, 95% CI: [0.85, 2.38], p = 0.18), and grade 3 or higher adverse events (RR = 1.21, 95% CI: [0.95, 1.54], p = 0.13). Conclusions: In the treatment of locally advanced rectal cancer, TNT offers greater survival benefits compared to neoadjuvant CRT and does not significantly increase the incidence of adverse events. However, further data and studies with long-term outcomes are still required. [ABSTRACT FROM AUTHOR]

Abstract Background Livestock production aims to provide meats of high and consistent eating quality. Insufficient intramuscular (IM) fat and excessive subcutaneous (SC) fat are paramount pork quality challenges. IM fat and SC fat, which are modulated by the adipogenesis of IM and SC adipocytes, play key roles in pork quality. Galectin-12 (LGALS12) was proven to be an important regulator of fat deposition in porcine. However, the current knowledge of the transcriptome-wide role of LGALS12 in adipocytes is still limited. This study was aimed to discover the different regulatory mechanisms of LGALS12 in porcine IM and SC adipocyte. Results The siRNA-mediated knockdown of the expression of LGALS12 identified 1075 and 3016 differentially expressed genes (DEGs) in IM and SC adipocytes, respectively. Among these, 585 were up- and 490 were downregulated in the IM adipocytes, while 2186 were up- and 830 were downregulated in the SC adipocytes. Moreover, 418 DGEs were observed only in the IM adipocytes, 2359 DGEs only in the SC adipocytes, and 657 DGEs in both types of adipocytes. According to Gene Ontology (GO) analysis, DEGs in both IM and SC adipocytes were mainly enriched in categories related to lipids or fat cell differentiation. Pathway analysis of the DEGs revealed 88 changed signaling pathways in the IM adipocytes and 86 in the SC adipocytes. The signaling pathways present in only one type of adipocyte were identified from among the top 50 signaling pathways in each type of adipocyte. Four signaling pathways, encompassing PI3K-AKT, cardiac muscle contraction, fatty acid metabolism and Ras, were significantly enriched in the IM adipocytes. On the other hand, four different signaling pathways, encompassing TNF, WNT, cGMP-PKG and NF-kappa B, were greatly enriched in the SC ones. The pathway changes were confirmed by chemical inhibition assays. Conclusions Our data reveals that LGALS12 knockdown alters the expression of numerous genes involved in key biological processes in the development of adipocytes. These observations provide a global view of the role of LGALS12 in porcine IM and SC adipocytes; thus, improving our understanding of the regulatory mechanisms by which this gene acts in fat development.