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Abstract Objective To construct the deep learning convolution neural network (CNN) model and machine learning support vector machine (SVM) model of bone remodeling of chronic maxillary sinusitis (CMS) based on CT image data to improve the accuracy of image diagnosis. Methods Maxillary sinus CT data of 1000 samples in 500 patients from January 2018 to December 2021 in our hospital was collected. The first part is the establishment and testing of chronic maxillary sinusitis detection model by 461 images. The second part is the establishment and testing of the detection model of chronic maxillary sinusitis with bone remodeling by 802 images. The sensitivity, specificity and accuracy and area under the curve (AUC) value of the test set were recorded, respectively. Results Preliminary application results of CT based AI in the diagnosis of chronic maxillary sinusitis and bone remodeling. The sensitivity, specificity and accuracy of the test set of 93 samples of CMS, were 0.9796, 0.8636 and 0.9247, respectively. Simultaneously, the value of AUC was 0.94. And the sensitivity, specificity and accuracy of the test set of 161 samples of CMS with bone remodeling were 0.7353, 0.9685 and 0.9193, respectively. Simultaneously, the value of AUC was 0.89. Conclusion It is feasible to use artificial intelligence research methods such as deep learning and machine learning to automatically identify CMS and bone remodeling in MSCT images of paranasal sinuses, which is helpful to standardize imaging diagnosis and meet the needs of clinical application.

This paper presents a surrogate modeling approach for predicting ground surface settlement caused by synchronous grouting during shield tunneling process. The proposed method combines finite element simulations with machine learning algorithms and introduces an intelligent optimization algorithm to invert geological parameters and synchronous grouting variables, thereby predicting ground surface settlement without conducting numerous finite element analyses. Two surrogate models based on the random forest algorithm are established. The first is a parameter inversion surrogate model that combines an artificial fish swarm algorithm with random forest, taking into account the actual number and distribution of complex soil layers. The second model predicts surface settlement during synchronous grouting by employing actual cover-diameter ratio, inverted soil parameters, and grouting variables. To avoid changes to input parameters caused by the number of overlying soil layers, the dataset of this model is generated by the finite element model of the homogeneous soil layer. The surrogate modeling approach is validated by the case history of a large-diameter shield tunnel in Beijing, providing an alternative to numerical computation that can efficiently predict surface settlement with acceptable accuracy.

Abstract Clarifying the principles of proportioning optimization for brittle transparent rock-like specimens with differential fracture structures is crucial for the visualization study of the internal fracture and seepage evolution mechanisms in rock masses. This study, utilizing orthogonal experimental methods, uncovers the influence mechanisms, extents, and patterns by which the ratios of resin, hardener, and accelerator, along with the freezing duration, impact the mechanical characteristics of transparent rock-like specimens. Notably, it was observed that as the accelerator ratio and freezing time are increased, there’s a general decline in the uniaxial compressive strength, tensile strength, and elastic modulus of the specimens. In contrast, an increase in the hardener ratio initially leads to an enhancement in these mechanical properties, followed by a subsequent decrease. Under uniaxial compressive loading, the specimens exhibit four typical modes of failure: bursting failure, splitting failure, single inclined plane failure, and bulging failure. As the hardener and accelerator ratios increase, the mode of failure gradually shifts from bulging to bursting, with freezing time having a minor overall impact on the evolution of failure modes. The study proposes a method for inducing random three-dimensional closed fractures within the specimens and further clarifies the principles for optimizing the proportions of specimens with different fracture structures, such as intact, embedded regular, and random three-dimensional fractures. This research facilitates the in-depth application of transparent rock-like materials in various scenarios and provides theoretical guidance and technical support for visualizing the evolution of fracture and seepage characteristics within the fractured rock mass.

Abstract Endogenous retroviruses (ERVs) are ancient retroviral remnants integrated in host genomes, and commonly deleted through unequal homologous recombination, leaving solitary long terminal repeats (solo-LTRs). This study, analysing the genomes of 362 bird species and their reptilian and mammalian outgroups, reveals an unusually higher level of solo-LTRs formation in birds, indicating evolutionary forces might have purged ERVs during evolution. Strikingly in the order Passeriformes, and especially the parvorder Passerida, endogenous retrovirus K (ERVK) solo-LTRs showed bursts of formation and recurrent accumulations coinciding with speciation events over past 22 million years. Moreover, our results indicate that the ongoing expansion of ERVK solo-LTRs in these bird species, marked by high transcriptional activity of ERVK retroviral genes in reproductive organs, caused variation of solo-LTRs between individual zebra finches. We experimentally demonstrated that cis-regulatory activity of recently evolved ERVK solo-LTRs may significantly increase the expression level of ITGA2 in the brain of zebra finches compared to chickens. These findings suggest that ERVK solo-LTRs expansion may introduce novel genomic sequences acting as cis-regulatory elements and contribute to adaptive evolution. Overall, our results underscore that the residual sequences of ancient retroviruses could influence the adaptive diversification of species by regulating host gene expression.

Purposes The Hutuo Group belongs to the Early Proterozoic strata. As one of the most typical Paleoproterozoic strata in North China, the timing redefinition of the Hutuo Group is of great significance to the establishment of the early Precambrian stratigraphic chronology framework, the discussion of the early Precambrian geological evolution process in North China and the study of plate assembly. Methods This article conducts a detailed study of the Dongye Subgroup strata of the Hutuo Group, collecting 24 detrital zircon samples from the Jian'ancun Formation of the Hutuo Group. From 23 similar age detrital zircons, we define the weighted average age of the bottom boundary of the Hutuo Group is 2 469 Ma, and regional tectonic movements occurred in the Wutai area around 1 855 Ma. According to the 1 109 zircon ages in Hutuo Group from previous studies, we considered that the ages of >2.5 Ga are from underlying Gaofan subgroup and the maximum depositional age of Hutuo Group was early Paleoproterozoic. Findings The results show that the crust of the Wutai area was unstable at 2 376, 2 170, 2 066, 1 988, and 1 825 Ma, resulting in multiple magmatic events. The 1 825 Ma zircon age can further indicate the occurrence of the Lyuliang movement, and provide a basis for the early Proterozoic North China Craton integration.

Bioabsorbable zinc (Zn)-based materials for bone defect repair have received increasing attention. Based on 3D printing technology, this study innovatively designed and manufactured pure Zn and Ti6Al4V porous scaffolds. The pore size of the scaffold was 700 μm and the porosity was 70%. Compared with the traditional Ti6Al4V scaffolds, it was found that the Zn scaffolds had a larger deformation, the ultimate compressive stress was 18 MPa, but the ultimate strain could exceed 20%, while Ti6Al4V was only 6%. The elastic modulus of the Zn scaffolds was also lower than that of Ti6Al4V, which was 0.25 GPa, which can meet bone repair requirements in the non-weight-bearing area. However, Zn scaffolds had better strain capacity and lower elastic modulus, so they had less stress-shielding effect on bone. Degradation experiments also proved that the Zn scaffold had good degradation performance. Further in vivo and in vitro experiments showed that the Zn scaffolds had better osteogenic ability than the Ti6Al4V scaffolds. The findings of our study underscore the potential of integrating pure Zn into 3D printed scaffolds for their application in orthopedic scenarios.

The matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) diagnostic tool was used to rapidly detect and identify three foodborne pathogens, Salmonella, Staphylococcus aureus and Bacillus cereus in ready-to-eat bulk foods in this study. The best method was identified by optimizing and screening various experimental conditions such as spot sampling method, pre-treatment method, different media and culture time, and its detection limit and stability were evaluated. Meanwhile, the established method was compared with multiplex PCR and the other biochemical identification methods such as VITEK 2 to contrast the consistency of the three identification results. Finally, batch food sample testing was carried out to explore the applicability of using MALDI-TOF MS to test ready-to-eat bulk foods. Results indicated that all the identification scores of the three bacteria were higher than 95% for the same batch and different passages, with a coefficient of variation of less than 2%. It demonstrated that the established method had good repeatability and stability, and the detection limit was 105 CFU/mL. The results of strain identification by MALDI-TOF MS were highly consistent with those of multiplex PCR and biochemical identification methods. Moreover, the MALDI-TOF MS method was more specific and efficient. Regarding spot sampling, the three covering methods showed higher average identification scores than the sandwich and mixed methods, all of which scored 99.9%. The 1 μL+1 μL covering method spot sampling approach obtained higher average peak numbers, and more complex and stronger characteristic peaks. Regarding pre-treatment, the formic-acid-acetonitrile method obtained a higher peak volume and peak intensity than other bacterial treatment methods, with an average identification score of 98% or higher. At the same time, the matching degree with the database spectrum was higher. In summary, MALDI-TOF MS method was not only sensitive, specific, accurate and rapid in foodborn pathogen identification, but also had simple operation and intuitive in results. As a powerful supplement to the national standard method, it provided a viable alternative for analysing, identifying and typing foodborne pathogens.

Three-dimensional (3D) printing is emerging as an innovative technology, which is widely used in cardiovascular disease at bench and bedside. During the last decade, with the development of 3D printing industry, many 3D printed models have been used in clinic, because it can provide the advantage of haptic feedback, direct manipulation, and enhanced doctors’ understanding of cardiovascular anatomy and underlying pathologies. In addition to the preparation of 3D printed models, 3D printing technology also shows great application potential in cardiovascular regenerative medicine because it has the advantages of integrating cells, cytokines and materials. Although cardiovascular regenerative medicine application still has a gap between bench and bedside, this gap is gradually narrowing with the development of new materials and new technology of 3D printing recently. In this review, we firstly analyze the characteristics and clinical needs of cardiovascular diseases, and introduce the concept and category of 3D printing technology. Secondly, we summarize the application of 3D printed models, stents, vascular graft, vascular network, and heart organs at bench and bedside. In the end, we discuss the challenges and future perspectives of 3D printing in cardiovascular diseases.

Accurately determining the modulus of cement stabilized macadam is a crucial and essential task for effectively calculating the mechanical response or evaluating the performance of semi-rigid asphalt pavement. However, there is currently still no standardized or widely acknowledged method for determining the modulus of cement stabilized macadam, which makes pavement response calculation and performance evaluation more challenging. Therefore, this study first outlines the features of several typical approaches that have been utilized to date to determine the modulus of cement-stabilized macadam while also highlighting the drawbacks of these approaches. Then, based on these analyses and summaries, proposes a new method that uses bending beam test to simultaneously determine the dynamic resilient modulus in compression and tension for cement stabilized macadam. Afterwards, in order to verify the proposed method, this study conducts three different types of dynamic resilient modulus tests for cement stabilized macadam, and compares the test results of these three types of methods to figure out the differences in their mechanical mechanisms. Finally, based on these tests and analysis, some reasonable recommendations about dynamic resilient modulus testing of cement stabilized macadam are provided.

Constructing infrastructure on soft soils demands the implementation of ground improvement. This study proposed an eco-friendly method of stabilizing marine soil using a calcium carbide residue (CCR)-activated coal gangue (CG) geopolymer derived from industrial waste. Laboratory experiments were conducted to investigate the mechanical properties, durability performance, and stabilization mechanisms of stabilized marine soils under multiple wetting-dry cycles. The results highlighted the effectiveness of CG-CCR geopolymer by a content of 15% to achieve satisfactory strength gain over the engineering requirements. However, the largest decrease in strength (71.89%) was observed when the initial water content was beyond 1.5 times the liquid limit (LL). The optimum solution was proposed to have a geopolymer content of 15% or an initial water content of 1.25·LL to exhibit the highest resistance to strength decay after 12 cycles. Compared with water intrusion, mass loss had a more significant effect on soil strength deterioration. The formation of noncrystalline or amorphous-phase reaction products effectively filled intergranular pores and reduced the void space between soil particles, improving the mechanical properties. The CG-CCR geopolymer was demonstrated to offer a promising solution for soil improvement in geotechnical engineering and waste reduction in industry as a soil stabilizer.

ObjectivesThe objective of this network meta-analysis is to systematically compare the efficacy of diverse progestin-based combination regimens in treating patients diagnosed with endometrial cancer or atypical endometrial hyperplasia. The primary goal is to discern the optimal combination treatment regimen through a comprehensive examination of their respective effectiveness.MethodsWe systematically searched four prominent databases: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials, for randomized controlled trials addressing the efficacy of progestins or progestin combinations in the treatment of patients with endometrial cancer or atypical endometrial hyperplasia. The search spanned from the inception of these databases to December 2023. Key outcome indicators encompassed survival indices, criteria for assessing efficacy, as well as pregnancy and relapse rate. This study was registered in PROSPERO (CRD42024496311).ResultsFrom the 1,558 articles initially retrieved, we included 27 studies involving a total of 5,323 subjects in our analysis. The results of the network meta-analysis revealed that the mTOR inhibitor+megestrol acetate (MA)+tamoxifen regimen secured the top rank in maintaining stable disease (SD) (SUCRA=73.4%) and extending progression-free survival (PFS) (SUCRA=72.4%). Additionally, the progestin combined with tamoxifen regimen claimed the leading position in enhancing the partial response (PR) (SUCRA=75.2%) and prolonging overall survival (OS) (SUCRA=80%). The LNG-IUS-based dual progestin regimen emerged as the frontrunner in improving the complete response (CR) (SUCRA=98.7%), objective response rate (ORR) (SUCRA=99.1%), pregnancy rate (SUCRA=83.7%), and mitigating progression (SUCRA=8.0%) and relapse rate (SUCRA=47.4%). In terms of safety, The LNG-IUS-based dual progestin regimen had the lowest likelihood of adverse events (SUCRA=4.2%), while the mTOR inhibitor regimen (SUCRA=89.2%) and mTOR inbitor+MA+tamoxifen regimen (SUCRA=88.4%) had the highest likelihood of adverse events.ConclusionsPatients diagnosed with endometrial cancer or atypical endometrial hyperplasia exhibited the most favorable prognosis when undergoing progestin combination therapy that included tamoxifen, mTOR inhibitor, or LNG-IUS. Notably, among these options, the LNG-IUS-based dual progestin regimen emerged as particularly promising for potential application.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42024496311.

Continuous fiber-reinforced silicon carbide composites have received significant attention due to their high-temperature mechanical stability. However, their widespread implementation has been hindered by intricate fracture mechanisms and limited toughness. This study presents a real-time approach for identifying damage type in 2.5D SiCf/SiC composites and highlights the significant impact of minor eccentric loading angle on the fracture behavior and mechanical properties using acoustic emission (AE). Even a slight degree of eccentric loading angle can significantly alter the fracture behaviors, leading to a significant increase in fracture toughness. The fracture damage evolution law of 2.5D SiCf/SiC under varying eccentric loading angles was investigated with the help of the AE damage identification, fracture morphology and finite element analysis. These findings provide valuable insights for multi-axis stress analysis of 2.5D high-performance composites.

The fabrication of zinc (Zn) parts devoid of inherent defects through Powder Bed Fusion-Laser Beam (PBF-LB) remains a formidable challenge. This study focuses on the optimization of process parameters and the implementation of tailored heat treatment to achieve high-performance PBF-LB fabricated (PBF-LBed) pure Zn bulk and scaffolds. Microstructural analysis, residual stress assessment, mechanical property testing, electrochemical experiments, immersion tests, in vitro and in vivo evaluations were conducted. The research results revealed that, under optimized process parameters and subsequent annealing, the yield strength, ultimate tensile strength, and ductility of PBF-LBed parts exhibit remarkable enhancements. Concurrently, the grain size was refined to 3 μm, accompanied by a notable improvement in biocompatibility. It could be roughly concluded that the microstructure refinement obtained through the heat treatment could significantly enhance their mechanical and electrochemical performances. Meanwhile, an appropriate Zn ion release rate achieved through grain refinement might created a more conducive microenvironment for new bone formation. Consequently, heat-treated PBF-LBed pure Zn scaffolds exhibits superior performance and application potential compared to untreated scaffolds.

Abstract Molecular folding regulation with environmental stimuli is critical in living and artificial molecular machine systems. Herein, we described a macrocycle, cyclo[4] (1,3-(4,6-dimethyl)benzene)[4](1,3-(4,6-dimethyl)benzene)(4-pyridine). Under 298 K, it has three stable stiff atropisomers with names as 1 (C s symmetry), 2 (C s symmetry), and 3 (C 4v symmetry). At 393 K, 1 can reversibly transform into 2, but at 473 K, it can irrevocably transform into 3. At 338 K, 3 and (PhCN)2PdCl2 complex to produce the metal-organic cage 4. Only at 338 K does the combination of 1 or 2 and (PhCN)2PdCl2 create a gel-like structure. Heating both gels to 473 K transforms them into 4. In addition to offering a thermally accelerated method for modifying self-assembled systems using macrocyclic building blocks, this study also has the potential to develop the nanoscale transformation material with a thermal response.

The lattice square degree, denoted by the c/a value, is a crucial factor that influences the slip mode of α-Ti alloys and thereby affects their plasticity. However, the relationship between the c/a value and the plasticity of α-Ti alloys has not been fully clarified. In this study, the powder metallurgy method (PM) was used to prepare Ti alloys with different square degrees by introducing interstitial O and substitutional Si solutes into α-Ti crystal. Then the mechanical properties, particularly plasticity, and lattice parameters of the resulted alloys were measured. By combining first-principles calculation with experimental studying, a plastic criterion based on the square degree was established. Subsequently, the mechanism of strength and plasticity was investigated by means of the density of states and charge density difference. Finally, the composition of α-Ti alloys with both O and Si solution atoms was designed, whose c/a values were calculated by the first-principles calculation and accorded with the proposed square degree criterion, and then the reliability of this criterion was verified by the experimental results. As a result, a high strength and plasticity α-Ti alloy with tensile strength 1106 MPa and elongation 23.2 % was successfully prepared. The findings of this research offer new insights into the alloying design of α-Ti alloys with high strength and moderate plasticity.

In this work study, a comparative analysis was undertaken to investigate investigation into the cavitation erosion (CE) and corrosion behavior of laser powder bed fusion (LPBF) TC4 and as-cast TC4 in 0.6 mol/L NaCl solution. Relevant results indicated that LPBF TC4 revealed a rectangular checkerboard-like pattern with a more refined grain size compared to as-cast TC4. Meanwhile, LPBF TC4 surpassed its as-cast counterpart in CE resistance, demonstrating approximately 2.25 times lower cumulative mass loss after 8 h CE. The corrosion potential under alternating CE and quiescence conditions demonstrated that both LPBF TC4 and as-cast TC4 underwent a rapid potential decrease at the initial stages of CE, while a consistent negative shift in corrosion potential was observed with the continuously increasing CE time, indicative of a gradual decline in repassivation ability. The initial surge in corrosion potential during the early CE stages was primarily attributed to accelerated oxygen transfer. As CE progressed, the significant reduction in corrosion potential for both LPBF TC4 and as-cast TC4 was attributed to the breakdown of the passive film. The refined and uniform microstructure in LPBF TC4 effectively suppresses both crack formation and propagation, underscoring the potential of LPBF technology in enhancing the CE resistance of titanium alloys. This work can provide important insights into developing high-quality, reliable, and sustainable CE-resistant materials via LPBF technology.

The seismic damage investigations indicated the high probability for the pile-supported structure to suffer further destruction due to the effects of strong aftershocks, but the seismic fragility assessment of pile-supported structures considering aftershocks rarely attracted notice. In this study, the seismic fragility of a pile-supported structure under the mainshock-aftershock sequence is systematically assessed through the simulation results based on a solid-fluid coupling finite element model. Firstly, the numerical model is validated by the test date got from a centrifuge model in order to check its effectiveness. Then the strong motion records recorded at liquefied sites are selected for synthesizing the seismic sequences through scaling and combination. And the Engineering Demand Parameter (EDP) is dertemined as the residual displacement, representing the cumulative damage caused by seismic sequences. Additionally, the quantitative limit states of EDP corresponding to four damage states considering pile-soil interaction is defined by a push-over analysis. Furthermore, since the choice of optimal Intensity Measures for seismic sequences is beneficial for enhancing the credibility, 24 sets of Intensity Measures are assessed from three sides including efficiency, practicality, and proficiency. Finally, the mainshock-aftershock fragility surfaces with two Intensity Measures are proposed, considering the random uncertainty. And the results indicate that mainshock aftershock sequences could induce higher exceedance probabilities of a limit state when comparing to under the excitation of mainshock only. The research results could offer a basis for the seismic performance evaluation of the kind of pile-supported structure.

BackgroundObservational studies have indicated a potential association between education and cardiovascular diseases (CVDs). However, uncertainties regarding the causal relationship persist. Therefore, this study aimed to investigate whether higher levels of education causally reduce the risks of CVDs.MethodsEmploying a two-sample Mendelian randomization (MR) design, our study examined the relationship between education and ten different CVDs. Utilizing data from the IEU Open GWAS database, relevant single nucleotide polymorphisms (SNPs) were identified through stringent screening criteria. Causality was assessed using the inverse-variance weighted (IVW), ME-Egger regression, and weighted median methods. Sensitivity analyses, including heterogeneity and pleiotropy tests, were conducted to ensure the robustness of our findings.ResultsOur study identified a genetic predisposition associated with an additional 3.6 years of education, which significantly reduced the risk of various CVDs. Specifically, this genetic factor was found to lower the risk of type 2 diabetes by 46.5%, coronary heart disease by 37.5%, ischemic stroke by 35.4%, cardiac-related mortality by 28.6%, heart failure by 28.2%, transient ischemic attack by 24%, atrial fibrillation by 15.2%, peripheral artery disease by 0.3%, and hypertension by 0.3%. However, no significant evidence revealed a causal relationship between education and pulmonary embolism.ConclusionOur study provides robust evidence supporting the role of higher educational attainment in reducing the incidence of various cardiovascular diseases, including type 2 diabetes, coronary heart disease, ischemic stroke, cardiac-related mortality, heart failure, transient ischemic attack, atrial fibrillation, peripheral artery disease, and hypertension. However, the impact of education on pulmonary embolism remains inconclusive.

Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are becoming more common in younger women. Solute carrier family 39 member 4 (SLC39A4) produces a zinc ion transporter involved in metastasis and invasion of tumors. Methods: The Cancer Genome Atlas RNA-seq data was used to investigate the expression of SLC39A4 and its prognostic potential. The assessment of the effect of SLC39A4 on cell growth and migration in CESC was conducted using MTT, colony formation, and Transwell assays. SLC39A4 was studied in vivo using a xenograft mouse model, and its functional involvement in oncogenesis was investigated by identifying the associated differentially expressed genes (DEGs). We evaluated the relationships among SLC39A4 levels, chemosensitivity, radiosensitivity and immune infiltration. Results: SLC39A4 was upregulated in CESC samples, and individuals with greater SLC39A4 mRNA expression had shorter overall survival. SLC39A4 has been identified to be a regulator of tumor cell metastasis and proliferation in vivo and in vitro, with an area under the curve of 0.874 for diagnosing CESC. In total, 948 DEGs were discovered to be enriched in key CESC progression-related signaling pathways. Additionally, intratumoral immune checkpoint and infiltration activity were associated with SLC39A4 expression. High SLC39A4 expression exhibited poor chemosensitivity and radiosensitivity profiles. Conclusion: In conclusion, SLC39A4 is a key regulator of CESC development, prognosis, and the composition of the tumor immune microenvironment. SLC39A4 could be used as a prognostic or diagnostic screening tool and as a potential target for CESC treatment.

BackgroundThe pathogenesis of silicosis is complex and treatment methods are limited. SiO2-induced increase of transforming growth factor-β1 (TGF-β1) can activate fibroblasts to promote collagen deposition, ultimately leading to fibrosis. Previous studies have confirmed that lipid metabolism plays an important role in the progression of silicosis. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) mediates mitochondrial dysfunction and lipid metabolism pathways in diabetic models, but its role in silicosis has not been elucidated. ObjectiveTo investigate the effect of PGC1α on lipid metabolism disorder of macrophages induced by SiO2 and its effect on the progression of silicosis fibrosis. Methods(1) Macrophages were divided into four groups by transfecting and silencing PGC1α and its control sequence in macrophages and followed by SiO2 stimulation: negative control group (transfected with si-NC for 48 h), si-PGC1α group (transfected with si-PGC1α for 48 h), SiO2 stimulation group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-NC for 48 h), and si-PGC1α+SiO2 group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-PGC1α for 48 h). Western blot and cell immunofluorescence were used to test PGC1α expression, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) and total cholesterol (TC) and free cholesterol (FC) kits were used to test lipid accumulation, and the Oroboros2k-Oxygraph respiratory test system (O2K) was used to assess the effects of PGC1α on mitochondrial respiratory chain. ELISA kits were used to test TGF-β1 expressed in the macrophage supernatant. (2) Lung fibroblasts were divided into the same four groups as above, and stimulated with the supernatant of macrophages in the above groups. The expression of collagen Ι (COL Ι), E-cadherin (Eca), and fibronectin (FN) were detected by cell immunofluorescence and Western blot to further evaluate the effect of silencing PGC1α on fibrosis. ResultsThe protein expression level of PGC1α stimulated by SiO2 was decreased, and the relative expression level of PGC1α was 0.78 times that of the control group (P

Abstract Background Energy homeostasis is essential for the adaptation of animals to their environment and some wild animals keep low metabolism adaptive to their low-nutrient dietary supply. Giant panda is such a typical low-metabolic mammal exhibiting species specialization of extremely low daily energy expenditure. It has low levels of basal metabolic rate, thyroid hormone, and physical activities, whereas the cellular bases of its low metabolic adaptation remain rarely explored. Results In this study, we generate a single-nucleus transcriptome atlas of 21 organs/tissues from a female giant panda. We focused on the central metabolic organ (liver) and dissected cellular metabolic status by cross-species comparison. Adaptive expression mode (i.e., AMPK related) was prominently displayed in the hepatocyte of giant panda. In the highest energy-consuming organ, the heart, we found a possibly optimized utilization of fatty acid. Detailed cell subtype annotation of endothelial cells showed the uterine-specific deficiency of blood vascular subclasses, indicating a potential adaptation for a low reproductive energy expenditure. Conclusions Our findings shed light on the possible cellular basis and transcriptomic regulatory clues for the low metabolism in giant pandas and helped to understand physiological adaptation response to nutrient stress.

The present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma.

Background This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score and renal venous Doppler waveform (RVDW) pattern in predicting acute kidney injury (AKI) in critically ill patients and establish prediction models.Methods This prospective observational study included 234 critically ill patients. Renal ultrasound was measured within 24 h after intensive care unit admission. The main outcome was the highest AKI stage within 5 days after admission according to the Kidney Disease Improving Global Outcomes criteria.Results Patients in the AKI stage 3 group had significantly higher RRI, RVDW pattern and lower PDU score (p

ABSTRACTObjective: To explore the feasibility, safety and cost effectiveness of the use of peripherally inserted central catheter (PICC) in children with hemophilia A and inhibitors who underwent ITI treatment.Method: This retrospective cohort study evaluated the effect of PICC placement and ITI on bleeding rates, costs, and parents’ satisfaction before and within 6 months after PICC placement in children with hemophilia A and inhibitors.Results: A total of 20 children with hemophilia A and high-titer inhibitors were included, with a success rate for PICC placement of 100%, at a cost of ¥6730.50. Parents’ satisfaction with PICC was 100%, and the total length of catheter indwelling was 6055 days. In terms of curative effect, the success rate of ITI treatment was 75%, and the annualized bleeding rate was decreased from 10.90 ± 12.16 times before placement to 2.10 ± 3.32 times (p

ObjectiveTo investigate the clinical effect of prolonging predilated transverse cervical flap with stepwise pressure packing for neck and chest lesions in children.MethodsA retrospective review of children with large cervicothoracic lesions admitted to our department from January 2011 to June 2021 was conducted to compare stepwise pressure packing with normal dressing in the surgical method of transverse cervical pedicled flaps after expansion. Among 58 included children, 22 (14 males and 8 females) were allocated to the extended and expanded transverse cervical flap with stepwise compression dressing group, and 36 (19 males and 17 females) to the transverse cervical flap group. The causes of skin defects were: scars (37 cases) and giant nevus (21 cases). The course of the disease ranged from 0.5 to 8 years. The two groups were compared in terms of child satisfaction, the occurrence of infection, recurrence of the contracture, secondary operation, and repaired area.ResultsIn 22 cases of extended transverse cervical flaps, 8 cases were embedded with two expanders, resulting in a total of 30 expanded flaps, which were successfully transferred to the neck and chest without necrosis at the distal end of compression, with good effect. Comparison of pedicled transverse cervical flaps with stepwise pressure packing and pedicled transverse cervical flaps alone revealed no significant difference in child satisfaction, the occurrence of infection, recurrence of the contracture, and secondary surgery (all P > 0.05). Yet, there was a significant difference in the repair area between two groups (P

Trimethyltin chloride (TMT) is a highly toxic organotin compound often used in plastic heat stabilizers, chemical pesticides, and wood preservatives. TMT accumulates mainly through the environment and food chain. Exposure to organotin compounds is associated with disorders of glucolipid metabolism and obesity. The mechanism by which TMT damages pancreatic tissue is unclear. For this purpose, a subacute exposure model of TMT was designed for this experiment to study the mechanism of damage by TMT on islet. The fasting blood glucose and blood lipid content of mice exposed to TMT were significantly increased. Histopathological and ultrastructural observation and analysis showed that the TMT-exposed group had inflammatory cell infiltration and necrosis. Then, mouse pancreatic islet tumour cells (MIN-6) were treated with TMT. Autophagy levels were detected by fluorescence microscopy. Real-time quantitative polymerase chain reaction and Western blotting were used for verification. A large amount of autophagy occurred at a low concentration of TMT but stagnated at a high concentration. Excessive autophagy activates apoptosis when exposed to low levels of TMT. With the increase in TMT concentration, the expression of necrosis-related genes increased. Taken together, different concentrations of TMT induced apoptosis and necrosis through autophagy disturbance. TMT impairs pancreatic (islet β cell) function.

Abstract Nuclear decoupling and softening are the main cellular mechanisms to resist mechanical stress-induced nuclear/DNA damage, however, its molecular mechanisms remain much unknown. Our recent study of Hutchinson-Gilford progeria syndrome (HGPS) disease revealed the role of nuclear membrane protein Sun2 in mediating nuclear damages and cellular senescence in progeria cells. However, the potential role of Sun2 in mechanical stress-induced nuclear damage and its correlation with nuclear decoupling and softening is still not clear. By applying cyclic mechanical stretch to mesenchymal stromal cells (MSCs) of WT and Zmpset24−/− mice (Z24−/−, a model for HGPS), we observed much increased nuclear damage in Z24−/− MSCs, which also featured elevated Sun2 expression, RhoA activation, F-actin polymerization and nuclear stiffness, indicating the compromised nuclear decoupling capacity. Suppression of Sun2 with siRNA effectively reduced nuclear/DNA damages caused by mechanical stretch, which was mediated by increased nuclear decoupling and softening, and consequently improved nuclear deformability. Our results reveal that Sun2 is greatly involved in mediating mechanical stress-induced nuclear damage by regulating nuclear mechanical properties, and Sun2 suppression can be a novel therapeutic target for treating progeria aging or aging-related diseases.

Plastic film mulching, widely used in agriculture, leads to microplastic (MP) pollution in soils. While biodegradable polybutylene adipate terephthalate (PBAT) films may offer a solution, their impacts on subsurface soils and microorganisms remain unclear. To investigate the effects of conventional non-biodegradable polyethylene (PE) and biodegradable PBAT MPs on the properties of sub-surface soils and microbial communities, MPs were added at varying doses in a field experiment and incubated for 160 days. Physicochemical characteristics, nutrient dynamics, and microbial composition, diversity, and networks of soils were analyzed using standard techniques and 16S rRNA/ITS gene sequencing. Correlations between soil properties and microbes were assessed. Both MP types significantly altered soil characteristics, with PBAT-MP elevating pH and the levels of available phosphorus and potassium more than PE-MP. Microbial composition shifts occurred, with low-addition PBAT-MP promoting plastic-degrading genera. The assessment of α/β-diversity indicated that PBAT-MP predominantly influenced fungi while PE-MP impacted bacteria. An examination of microbial co-occurrence networks highlighted that PE-MP primarily disrupted fungal interactions, whereas PBAT-MP streamlined network complexity. Correlation analyses revealed that PBAT-MP promoted fungal diversity/network resilience correlating to nutrients. PE-MP and PBAT-MP significantly altered native soil/microbe relationships. PBAT-MP may exert greater, yet unknown, impacts over time through its biodegradation into newer and smaller fragments. Future research needs to integrate multi-omics and stable isotope science to elucidate the deep mechanistic impacts of degraded film-derived MPs on microbial ecological functions and biogeochemical cycles. Attention should also be paid to the long-term accumulation/transport of MPs in agricultural soils. Overall, this work deepens the impact and understanding of MPs from plastic film on sub-surface soil ecology. Furthermore, it provides a theoretical foundation for managing ‘white pollution’ in the film-covered farmlands of arid and semi-arid regions in China.

Object detection in remote sensing scenarios plays an indispensable and significant role in civilian, commercial, and military areas, leveraging the power of convolutional neural networks (CNNs). Remote sensing images, captured by crafts and satellites, exhibit unique characteristics including complicated backgrounds, limited features, distinct density, and varied scales. The contextual and comprehensive information in an image can make a detector precisely localize and classify targets, which is extremely valuable for object detection in remote sensing scenarios. However, CNNs, restricted by the essence of the convolution operation, possess local receptive fields and scarce contextual information, even in large models. To address this limitation and improve detection performance by extracting global contextual information, we propose a novel plug-and-play attention module, named Convolution with Transformer Attention Module (CTAM). CTAM is composed of a convolutional bottleneck block and a simplified Transformer layer, which can facilitate the integration of local features and position information with long-range dependency. YOLOv8n, a superior and faster variant of the YOLO series, is selected as the baseline. To demonstrate the effectiveness and efficiency of CTAM, we incorporated CTAM into YOLOv8n and conducted extensive experiments on the DIOR dataset. YOLOv8n-CTAM achieves an impressive 54.2 mAP@50-95, surpassing YOLOv8n (51.4) by a large margin. Notably, it outperforms the baseline by 2.7 mAP@70 and 4.4 mAP@90, showcasing its superiority with stricter IoU thresholds. Furthermore, the experiments conducted on the TGRS-HRRSD dataset validate the excellent generalization ability of CTAM.

Abstract Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death worldwide. Clinical research results have provided more treatment opportunities for CRC patients, showing that an optimal combination of existing drugs and new drugs is needed to mitigate the burden of this disease. In this review, we have summarized recent advances in drug clinical research for CRC in 2022, including chemotherapy, targeted therapy, and immunotherapy, to find opportunities for substantial improvements in drug discovery and clinical development methods.

Abstract Background The maximum likelihood activity and attenuation (MLAA) reconstruction algorithm has been proposed to jointly estimate tracer activity and attenuation at the same time, and proven to be a promising solution to the CT attenuation correction (CT-AC) artifacts in PET images. This study aimed to perform a quantitative evaluation and clinical validation of the MLAA method. Methods A uniform cylinder phantom filled with 18F-FDG solution was scanned to optimize the reconstruction parameters for the implemented MLAA algorithm. 67 patients who underwent whole-body 18F-FDG PET/CT scan were retrospectively recruited. PET images were reconstructed using MLAA and clinical standard OSEM algorithm with CT-AC (CT-OSEM). The mean and maximum standardized uptake values (SUVmean and SUVmax) in regions of interest (ROIs) of organs, high uptake lesions and areas affected by metal implants and respiration motion artifacts were quantitatively analyzed. Results In quantitative analysis, SUVs in patient’s organ ROIs between two methods showed R 2 ranging from 0.91 to 0.98 and k ranging from 0.90 to 1.06, and the average SUVmax and SUVmean differences between two methods were within 10% range, except for the lung ROI, which was 10.5% and 16.73% respectively. The average SUVmax and SUVmean differences of a total of 117 high uptake lesions were 7.25% and 7.10% respectively. 20 patients were identified to have apparent respiration motion artifacts in the liver in CT-OSEM images, and the SUVs differences between two methods measured at dome of the liver were significantly larger than measured at middle part of the liver. 10 regions with obvious metal artifacts were identified in CT-OSEM images and the average SUVmean and SUVmax differences in metal implants affected regions were reported to be 52.90% and 56.20% respectively. Conclusions PET images reconstructed using MLAA are clinically acceptable in terms of image quality as well as quantification and it is a useful tool in clinical practice, especially when CT-AC may cause respiration motion and metal artifacts. Moreover, this study also provides technical reference and data support for the future iteration and development of PET reconstruction technology of SUV accurate quantification.

Abstract Emerging evidence showed that epigenetic regulation plays important role in the pathogenesis of HCC. N4-acetocytidine (ac4C) was an acetylation chemical modification of mRNA, and NAT10 is reported to regulate ac4C modification and enhance endoplasmic reticulum stress (ERS) in tumor metastasis. Here, we report a novel mechanism by which NAT10-mediated mRNA ac4C-modified HSP90AA1 regulates metastasis and tumor resistance in ERS of HCC. Immunohistochemical, bioinformatics analyses, and in vitro and in vivo experiments, e.g., acRIP-Seq, RNA-Seq, and double luciferase reporter experiment, were employed to investigate the effect of NAT10 on metastasis and drug resistance in HCC. The increased expression of NAT10 was associated with HCC risk and poor prognosis. Cell and animal experiments showed that NAT10 enhanced the metastasis ability and apoptosis resistance of HCC cells in ERS and ERS state. NAT10 could upregulate the modification level of HSP90AA1 mRNA ac4C, maintain the stability of HSP90AA1, and upregulate the expression of HSP90AA1, which further promotes the metastasis of ERS hepatoma cells and the resistance to apoptosis of Lenvatinib. This study proposes a novel mechanism by which NAT10-mediated mRNA ac4C modification regulates tumor metastasis. In addition, we demonstrated the regulatory effect of NAT10-HSP90AA1 on metastasis and drug resistance of ERS in HCC cells.

In order to study the quality and development value of nanofiltration liquid (sugarcane plant water, SPW) by the No-added brown sugar from membrane processing, red peel fruit sugarcane and ROC 22 were used as materials to evaluate the nutritional quality with the method of index of nutritional quality (INQ), which could be obtained by comparing and calculating the physical indexes, chemical indexes, nutritional indexes and volatile aroma components of SPW with 250 u roll membrane nanofiltration concentration on the basis of two-stage ceramic membranes (800 nm and 50 nm). Results showed that SPW of two different varieties contained no sucrose and both had the characteristic fragrance of sugarcane juice. The volatile components shared with sugarcane juice accounted for 50.00% and 60.61% of the total volatile components in sugarcane juice. Alcohols were the most abundant, and the relative high contents of 2-ethylhexanol, 2-heptanol, 1-penten-3-ol, hexanol and (-)-isocedarol were higher. More than 14 kinds of free amino acids were detected in SPW, among which 7 kinds were essential amino acids for human body, accounting for more than 66% of the total free amino acids, threonine was the most important amino acid with the content in two SPW was 474.67 and 118.11 mg/L, respectively. The SPW contained 7 mineral elements such as potassium, sodium and calcium, among which the content of potassium was the highest, reaching 907 and 525 mg/L, respectively. The INQ of potassium and copper was above 40 and 14, respectively, which was a high-quality source of potassium and copper supplement for human body. In general, nanofiltration SPW based on No-added membrane brown sugar process was a kind of pure natural plant-flavor drinking water rich in nutrients, which had a good value of development and utilization.

This paper presents a case study of deep excavation adjacent to an existing bridge in karst region of Guangzhou city, China. The movements of retaining structures, settlements of surrounding ground and pipelines, and the responses of bridge piles were measured and evaluated. A sudden surge of groundwater was recorded at the north pit when excavated halfway. Soil-cement columns using the Metro Jet System (MJS) method was employed along the outer perimeters of the diaphragm wall where water inflow occurred, for the sake of blocking the flow channels. The measured maximum wall deflection δhm in this case ranged from 0.13 %H to 0.3 %H, with a mean value of 0.2 %H (H is the excavation depth), which agreed well with the empirical prediction in mixed ground. During the MJS treatment, the wall and surrounding soils experienced notable lateral deflection and settlement. The bridge piles experienced significant settlement since the excavation commenced, which might be attributed to the inherent deficiency in geological condition and pile length. The soil disturbance induced by the adjacent deep excavation accelerated bridge settlement. The finite element analysis revealed that the excessive settlement of the bridge piles and ground surface resulted from confined-water withdrawal in sand layers.

ABSTRACT As an RNA virus, severe acute respiratory coronavirus 2 (SARS-CoV-2) is known for frequent substitution mutations, and substitutions in important genome regions are often associated with viral fitness. However, whether indel mutations are related to viral fitness is generally ignored. Here we developed a computational methodology to investigate indels linked to fitness occurring in over 9 million SARS-CoV-2 genomes. Remarkably, by analyzing 31,642,404 deletion records and 1,981,308 insertion records, our pipeline identified 26,765 deletion types and 21,054 insertion types and discovered 65 indel types with a significant association with Pango lineages. We proposed the concept of featured indels representing the population of specific Pango lineages and variants as substitution mutations and termed these 65 indels as featured indels. The selective pressure of all indel types is assessed using the Bayesian model to explore the importance of indels. Our results exhibited higher selective pressure of indels like substitution mutations, which are important for assessing viral fitness and consistent with previous studies in vitro. Evaluation of the growth rate of each viral lineage indicated that indels play key roles in SARS-CoV-2 evolution and deserve more attention as substitution mutations. IMPORTANCE The fitness of indels in pathogen genome evolution has rarely been studied. We developed a computational methodology to investigate the severe acute respiratory coronavirus 2 genomes and analyze over 33 million records of indels systematically, ultimately proposing the concept of featured indels that can represent specific Pango lineages and identifying 65 featured indels. Machine learning model based on Bayesian inference and viral lineage growth rate evaluation suggests that these featured indels exhibit selection pressure comparable to replacement mutations. In conclusion, indels are not negligible for evaluating viral fitness.

ABSTRACT Foamy viruses (FVs) are a class of complex retroviruses that could lead to persistent infections in specific species. FVs have two evolutionary characteristics: the first is co-evolution with the host, and the second is difficulty going through the endogenization process. To date, in mammals, only a few species (aye-aye, sloths, and cape golden mole) have been found to have endogenous forms of FVs. In this study, we identified a novel endogenous FV named TraEFV in the genomes of two species of even-toed ungulate chevrotain (genus Tragulus, family Tragulidae) known as mouse-deer. Phylogenetic analysis clustered TraEFVs with an exogenous FV isolated from feline but not with those isolated from cow and horse, and such inconsistent virus-host relationships reflect their complex evolutionary history. Interestingly, TraEFVs could be divided into two lineages, suggesting that TraEFV invaded these hosts at least twice during ancient times. Finally, the molecular clock estimates that TraEFV is approximately 20 million years old, suggesting its ancient nature. Our findings enrich the host taxonomy of spumaretroviruses. IMPORTANCE Foamy viruses (FV) are complex retroviruses that generally codiverge with their hosts. We identified a novel endogenous FV in the genomes of two mouse-deer species, the first endogenous FV found in Artiodactyla. The phylogenetic inconsistency of viruses and hosts suggested that the viruses might have emerged from cross-species transmission in the past. These findings indicate that ancient FVs may have had a wider range of hosts that remain to be expanded.

Abstract On 21 May 2021 (local time), an Mw 6.1 earthquake struck the Yangbi County, Yunnan Province, China. The finite fault stochastic simulation approach is usually used to simulate ground motions in high‐frequency band (f > 1 Hz). Model parameters needed for earthquake ground motion simulation mainly include source, path, and site. In the high‐frequency ground motion simulation program widely used in earthquake engineering, the reciprocal of corner frequency is typically used to define the source rise time; however, the complete step‐wise derivation process is unavailable. In deriving the static corner frequency f0, source rise time is typically estimated to be the time required for the rupture to reach 50% of the final location, and the source rise time then can be obtained as 0.27/f0, which is consistent with the hypothesis of corner frequency and rupture velocity, and the correlation and integrity between parameters are established. This study also focuses on the influence of different source rise times and path durations on the simulation results, such as Fourier acceleration spectrum, pseudo‐spectral acceleration, and peak ground acceleration. The results show that the source rise time recommended in this simulation can improve the accuracy of near‐fault ground motion simulations. This study provides suggestions for a reasonable selection of path duration in different engineering applications.

This study aimed to determine whether the abnormal deep layer of dartos fascia plays an important role in buried penis. Forty-nine patients with buried penis were treated with anatomical resection of the deep layer of dartos fascia under a microscope. Penile length was measured before and after completely resecting the deep layer to investigate the role of this layer in penile retraction. The superficial and deep layers of dartos fascia were collected from 49 patients with buried penis, the normal superficial layers were collected from 25 children/adults who underwent circumcision for nonmedical reasons, and the normal deep layers were collected from 20 adult cadavers. The penile fascia samples were stained with hematoxylin-eosin, Masson's trichrome, Sirius red, and Verhoeff's Van Gieson, and subjected to immunohistochemical examination and scanning electron microscopy. The penile shaft (mean ± standard deviation) was found to be significantly elongated after resecting the deep layer compared with that before resection (6.8 ± 1.9 cm vs 6.0 ± 1.6 cm, P < 0.001). An abnormal deep layer of dartos fascia characterized by disordered and fragmented elastic fibers was observed in 87.8% (43/49) of buried penis samples, whereas no abnormal deep layer was observed in normal penises from cadavers (0/20, P < 0.001). Thus, the abnormal deep layer of dartos fascia plays an important role in the buried penis. Its resection is helpful for avoiding recurrence.

Benefiting from the large stock of raw materials and the support of policies, China’s biomass utilization get rapid development in recent years. In particular, the Chinese government advocates the transformation of energy utilization from coal power to renewable energy power generation, of which biomass power generation will be play an important role. Therefore, it is necessary to get the actual situation of China’s biomass power generation industry at present. The latest storage and distribution of biomass resources data in China is collected and the technological development of biomass power plants in China is described in this paper. The installed capacity and power generation of biomass power generation in China are illustrated since 2012. This paper also counts policies related to biomass power generation since 2006 and analyzes future policy trends. Some recommendations with practical problems are put forward in this paper.

Fluid slosh caused by residual acceleration in microgravity is a common problem encountered in space engineering. To solve this problem, the ground-based experiment research on the influence of gravity jitter and gravitational tilt on the thermocapillary convection (TCC) transition behaviour of non-axisymmetric liquid bridge has become an important issue in microgravity fluid management. Based on a mesoscale liquid bridge experimental platform which can realize gravitational tilt, the effect of gravitational tilt on TCC by using a high-speed camera equipped with a near-focus lens and a self-developed interface image recognition package. The results show that the spatio-temporal evolution of TCC by the influence of gravitational tilt is still divided into steady and oscillatory flow. In the stable TCC, the vortex core distortion of cellular flow caused by the imbalance left and right interface curvature invites cellular flow close to the free surface, and it shrinks to the intermediate height. As gravitational tilt increases, the transverse/longitudinal velocity peaks are significantly reduced, peak velocity has been reduced by 26%–27%. Meanwhile, the longitudinal velocity gradient at the free interface increases significantly. Therefore, gravitational tilt plays an important role in improving the surface flow velocity. In the oscillatory TCC, the position of vortex core is closer to the free interface at the hot/cold corner as the periodic mutual occupation of the left and right cellular flows. The TCC is obviously inhibited due to the gravitational tilt. The critical temperature difference is increased by 25% and the onset of temperature oscillation at the hot corner is delayed by 20% compared with conventional gravity condition.

Mer and c-Met kinases, which are commonly overexpressed in various tumors, are ideal targets for the development of antitumor drugs. This study focuses on the design, synthesis, and evaluation of several 2-substituted aniline pyrimidine derivatives as highly potent dual inhibitors of Mer and c-Met kinases for effective tumor treatment. Compound 18c emerged as a standout candidate, demonstrating robust inhibitory activity against Mer and c-Met kinases, with IC50 values of 18.5 ± 2.3 nM and 33.6 ± 4.3 nM, respectively. Additionally, compound 18c displayed good antiproliferative activities on HepG2, MDA-MB-231, and HCT116 cancer cells, along with favorable safety profiles in hERG testing. Notably, it exhibited exceptional liver microsomal stability in vitro, with a half-life of 53.1 min in human liver microsome. Compound 18c also exhibited dose-dependent cytotoxicity and hindered migration of HCT116 cancer cells, as demonstrated in apoptosis and migration assays. These findings collectively suggest that compound 18c holds promise as a dual Mer/c-Met agent for cancer treatment.

ARGONAUTE (AGO) proteins are key components of the RNA-induced silencing complex (RISC) that mediates gene silencing in eukaryotes. Small-RNA (sRNA) cargoes are selectively loaded into different members of the AGO protein family and then target complementary sequences to in-duce transcriptional repression, mRNA cleavage, or translation inhibition. Previous reviews have mainly focused on the traditional roles of AGOs in specific biological processes or on the molecular mechanisms of sRNA sorting. In this review, we summarize the biological significance of canonical sRNA loading, including the balance among distinct sRNA pathways, cross-regulation of different RISC activities during plant development and defense, and, especially, the emerging roles of AGOs in sRNA movement. We also discuss recent advances in novel non-canonical functions of plant AGOs. Perspectives for future functional studies of this evolutionarily conserved eukaryotic protein family will facilitate a more comprehensive understanding of the multi-faceted AGO proteins.

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease worldwide, without any Food and Drug Administration-approved pharmacological intervention in clinic. Trim38, as an important member of the TRIM (tripartite motif-containing) family, was largely reported to be involved in the regulation of innate immune and inflammatory responses. However, the functional roles of TRIM38 in NAFLD remain largely unknown. Here, the expression of TRIM38 was first detected in liver samples of both NAFLD mice model and patients diagnosed with NAFLD. We found that TRIM38 expression was downregulated in NAFLD liver tissues compared with normal liver tissues. Genetic Trim38-KO in vivo showed that TRIM38 depletion deteriorated the high-fat diet and high fat and high cholesterol diet-induced hepatic steatosis and high fat and high cholesterol diet-induced liver inflammation and fibrosis. In particular, we found that the effects of hepatocellular lipid accumulation and inflammation induced by palmitic acid and oleic acid were aggravated by TRIM38 depletion but mitigated by TRIM38 overexpression in vitro. Mechanically, RNA-Seq analysis demonstrated that TRIM38 ameliorated nonalcoholic steatohepatitis progression by attenuating the activation of MAPK signaling pathway. We further found that TRIM38 interacted with transforming growth factor-β-activated kinase 1 binding protein 2 and promoted its protein degradation, thus inhibiting the transforming growth factor-β-activated kinase 1-MAPK signal cascades. In summary, our study revealed that TRIM38 could suppress hepatic steatosis, inflammatory, and fibrosis in NAFLD via promoting transforming growth factor-β-activated kinase 1 binding protein 2 degradation. TRIM38 could be a potential target for NAFLD treatment.

Case studies show that earthquake-induced soil liquefaction can cause large lateral deformation of piles, leading to bridge damage. In this study, an iron and steel manufacturing by-product, slag powder, was utilized for the first time to mitigate soil liquefaction, thereby reducing the lateral deformation of piles during earthquakes. First, the liquefaction resistance of soil improved by slag powder was analyzed by cyclic triaxial tests. The results indicate that as the slag powder content increased, the soil liquefaction resistance increased. When the cyclic stress ratio is 0.2, the number of liquefaction cycles of the reinforced soil increases by 30 compared with that of the unreinforced soil. Second, a numerical modeling method of slag powder reinforced sand was proposed and validated by the cyclic triaxial test results. Third, the seismic response of piles in liquefiable soils enhanced by slag powder was evaluated using finite element analyses, and slag powder was determined to be effective in decreasing the lateral deformation of piles in liquefiable soils, the maximum displacement of the pile was reduced by 45 %. Last, an empirical formula that can easily evaluate the mitigation effect of slag powder on the lateral deformation of piles is proposed and verified by the results of finite element analysis.

Venous malformation (VM) results from the abnormal growth of the vasculature; however, the detailed molecular mechanism remains unclear. As a glycosyltransferase, UDP-glucose ceramide glucosyltransferase (UGCG) is localized to the Golgi body and is a key enzyme in the first step of glycosphingolipid synthesis. Here, we aimed to explore the relationship between UGCG and the development of VM. First, investigations using RT-qPCR and Western blotting on the diseased vasculature of VM patients and normal vascular tissues revealed that UGCG expression was markedly elevated in the diseased vessels. Subsequently, immunofluorescence assay showed that UGCG was co-localized with CD31, an endothelial cell marker, in tissues from patients with VM and healthy subjects. Then, we established TIE2-L914F-mutant human umbilical vein endothelial cells (HUVECs) by lentivirus transfection. Next, Western blotting revealed that UGCG expression was considerably higher in HUVECsTIE2-L914F. In addition, we established a UGCG-overexpressing HUVECs line by plasmid transfection. With the CCK8 cell proliferation experiment, wound healing assay, and tube formation assay, we found that UGCG could promote the proliferation, migration, and tube formation activity of HUVECs, whereas the inhibition of UGCG could inhibit the proliferation, migration, and tube formation activity of HUVECsTIE2-L914F. Finally, Western blotting revealed that UGCG regulates the AKT/mTOR pathway in HUVECs. These data demonstrated that UGCG can affect the activity of vascular endothelial cells and regulate the AKT/mTOR signaling pathway; this is a potential mechanism underlying VM pathogenesis.

Abstract In recent years, the mobile Internet of Things (MIoT) for online English education has quickly become an important means and main tool for people to learn and communicate English due it has characteristics and advantages such as high efficiency and no geographical restrictions. However, most MIoT for online English education is vulnerable to security attacks because of the online learning device's weak security protection measures and their communication channels with open wireless nature. To address these issues, herein, a novel secure authentication scheme in 6G‐enabled MIoT for online English education is proposed. The proposed authentication scheme does not rely on the ideal tamper‐proof device. In this scheme, the certificate and key are updated in real‐time to resist side‐channel attacks, and pseudonym seeds are used to generate pseudonyms to hide user's identity information and realise identity privacy protection. The scheme allows the attacker to continuously obtain private key information. Detailed security analysis proves that the authors’ scheme is unforgeable to adaptive selection message attacks and can satisfy the security requirements of 6G‐enabled MIoT for online English education. In addition, compared with other related studies, the proposed scheme achieves better performance in terms of computation and communication costs.

Abstract Background Transurethral resection of the bladder tumor (TURBT) is one of the most established urological procedures for the treatment of the primary non-muscle-invasive bladder cancer (NMIBC). The aim of the study is to evaluate the efficacy and safety of 980 nm diode laser as a treatment for primary NMIBC. Methods Eighty-eight patients with NMIBC were treated by en bloc transurethral resection with 980 nm diode laser, and 76 patients were treated by plasmakinetic transurethral resection from May 2016 to July 2019 at the Department of Urology, Tangdu Hospital, Air Force Medical University. The clinical data were collected and compared between the two groups. Results The bladder irrigation time was shortened in 980 nm diode laser group compared to that of plasmakinetic transurethral resection group (4.1 ± 0.6 vs 13.1 ± 3.1 h, p < 0.001). A total of 13.2% (10/76) patients experienced obturator nerve reflex, and 5.3% (4/76) experienced delayed bleeding in plasmakinetic transurethral resection group, while no obturator nerve reflex and delayed bleeding cases were observed in 980 nm diode laser group (p < 0.05). The postoperative catheterization and hospitalization time showed no significant difference between the two groups. The median follow-up time was 27 months (13–38 months). No significant difference in the recurrence rate was observed between the two groups. Conclusions The 980 nm diode laser is an effective and safe tool in transurethral resection of NMIBC using en bloc technique. It has less perioperative complications and shortened bladder irrigation time.