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Question-asking is essential for reasoning, understanding, and investigating scientific problems within and beyond traditional classrooms. Nevertheless, questions generated in formal and informal learning environments can be infrequent and unsophisticated. This study explores museum visitors' question-asking quality by considering their interactions with two different modes of a question-asking mobile app (Ask or Game Mode) in two different museum environments (linear non-interactive or non-linear interactive exhibits). Results showed that visitors' question-asking quality was influenced by app modes and by museum environments. Specifically, we found that visitors' question-asking quality was significantly higher when using the gamified version of the app (Game Mode) compared to a non-gamified version (Ask Mode) in a linear non-interactive exhibit. Findings also revealed that question-asking performance could be significantly influenced by instrumental factors (such as app performance in answering questions) and socio-contextual factors (such as visitor group inquiry frequency). The study provides fundamental and comprehensive insights for designing active learning environments by considering the influential factors of question-asking.

BackgroundThe successful implementation of assisted ventilation depends on matching the patient’s effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient’s inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient’s effort during ventilator support.MethodsIn this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to −1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure–time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient’s inspiratory effort.ResultsA total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10–12) to 5 (4–6) cm H2O (p

Ferroptosis is an emerging mode of programmed cell death fueled by iron buildup and lipid peroxidation. Recent evidence points to the function of ferroptosis in the aetiology and development of cancer and other disorders. Consequently, harnessing iron death for disease treatment has diverted the interest of the researchers in the field of basic and clinical research. The ubiquitin-proteasome system (UPS) represents a primary protein degradation pathway in eukaryotes. It involves labelling proteins to be degraded by ubiquitin (Ub), followed by recognition and degradation by the proteasome. Dysfunction of the UPS can contribute to diverse pathological processes, emphasizing the importance of maintaining organismal homeostasis. The regulation of protein stability is a critical component of the intricate molecular mechanism underlying iron death. Moreover, the intricate involvement of the UPS in regulating iron death-related molecules and signaling pathways, providing valuable insights for targeted treatment strategies. Besides, it highlights the potential of ferroptosis as a promising target for cancer therapy, emphasizing the combination between ferroptosis and the UPS. The molecular mechanisms underlying ferroptosis, including key regulators such as glutathione peroxidase 4 (GPX4), cysteine/glutamate transporter (system XC-), and iron metabolism, are thoroughly examined, alongside the role of the UPS in modulating the abundance and activity of crucial proteins for ferroptotic cell death, such as GPX4, and nuclear factor erythroid 2–related factor 2 (NRF2). As a pivotal regulatory system for macromolecular homeostasis, the UPS substantially impacts ferroptosis by directly or indirectly modulating iron death-related molecules or associated signaling pathways. This review explores the involvement of the UPS in regulating iron death-related molecules and signaling pathways, providing valuable insights for the targeted treatment of diseases associated with ferroptosis.

Lysosomes-associated membrane proteins (LAMPs), a family of glycosylated proteins and major constituents of the lysosomal membranes, play a dominant role in various cellular processes, including phagocytosis, autophagy and immunity in mammals. However, their roles in aquatic species remain poorly known. In the present study, three lamp genes were cloned and characterized from Micropterus salmoides. Subsequently, their transcriptional levels in response to different nutritional status were investigated. The full-length coding sequences of lamp1, lamp2 and lamp3 were 1251bp, 1224bp and 771bp, encoding 416, 407 and 256 amino acids, respectively. Multiple sequence alignment showed that LAMP1-3 were highly conserved among the different fish species, respectively. 3-D structure prediction, genomic survey, and phylogenetic analysis were further confirmed that these genes are widely existed in vertebrates. The mRNA expression of the three genes was ubiquitously expressed in all selected tissues, including liver, brain, gill, heart, muscle, spleen, kidney, stomach, adipose and intestine, lamp1 shows highly transcript levels in brain and muscle, lamp2 displays highly expression level in heart, muscle and spleen, but lamp3 shows highly transcript level in spleen, liver and kidney. To analyze the function of the three genes under starvation stress in largemouth bass, three experimental treatment groups (fasted group and refeeding group, control group) were established in the current study. The results indicated that the expression of lamp1 was significant induced after starvation, and then returned to normal levels after refeeding in the liver. The expression of lamp2 and lamp3 exhibited the same trend in the liver. In addition, in the spleen and the kidney, the transcript level of lamp1 and lamp2 was remarkably increased in the fasted treatment group and slightly decreased in the refed treatment group, respectively. Collectively, our findings suggest that three lamp genes may have differential function in the immune and energetic organism in largemouth bass, which is helpful in understanding roles of lamps in aquatic species.

Purpose: The aim of this study is to investigate abdominal aortic aneurysm (AAA), a disease characterised by inflammation and progressive vasodilatation, for novel gene-targeted therapeutic loci. Methods: To do this, we used weighted co-expression network analysis (WGCNA) and differential gene analysis on samples from the GEO database. Additionally, we carried out enrichment analysis and determined that the blue module was of interest. Additionally, we performed an investigation of immune infiltration and discovered genes linked to immune evasion and mitochondrial fission. In order to screen for feature genes, we used two PPI network gene selection methods and five machine learning methods. This allowed us to identify the most featrue genes (MFGs). The expression of the MFGs in various cell subgroups was then evaluated by analysis of single cell samples from AAA. Additionally, we looked at the expression levels of the MFGs as well as the levels of inflammatory immune-related markers in cellular and animal models of AAA. Finally, we predicted potential drugs that could be targeted for the treatment of AAA. Results: Our research identified 1249 up-regulated differential genes and 3653 down-regulated differential genes. Through WGCNA, we also discovered 44 genes in the blue module. By taking the point where several strategies for gene selection overlap, the MFG (ITGAL and SELL) was produced. We discovered through single cell research that the MFG were specifically expressed in T regulatory cells, NK cells, B lineage, and lymphocytes. In both animal and cellular models of AAA, the MFGs' mRNA levels rose. Conclusion: We searched for the AAA novel targeted gene (ITGAL and SELL), which most likely function through lymphocytes of the B lineage, NK cells, T regulatory cells, and B lineage. This analysis gave AAA a brand-new goal to treat or prevent the disease.

A new Cu-1.5Ni-0.7Co-0.7Si-0.3Fe-0.1Mg alloy with low cobalt content was designed. Multi-stage thermo-mechanical treatment (MTT) was used to produce the high-performance alloy with hardness of 286 HV, yield strength of 858 MPa, tensile strength of 910 MPa and electrical conductivity of 45.4 % IACS. The addition of 0.3 wt% Fe element dissolved in (Ni,Co)2Si resulted in the formation of the orthorhombic δ-(Ni,Co,Fe)2Si. During MTT, the δ-(Ni,Co,Fe)2Si, (Ni,Co)2Si, β-Ni3Si, and Fe2Si precipitated successively near the deformation microstructure. Transmission electron microscope observations indicated that the δ-(Ni,Co,Fe)2Si precipitates showed disc-like and rod-like shapes at different orientations, respectively. A new resource-saving, high-strength and medium-conductivity Cu-Ni-Co-Si-Fe-Mg alloy was prepared by replacing an equal amount of Co element with 0.3 wt% Fe element, reducing the amount of scarce metal Co in the alloy.

Thin coatings are subject to scratch and wear damage in tribological applications. Scratch hardness numbers are used to evaluate scratch and abrasive wear resistance. Few studies have measured the scratch hardness of thin films, and a proper scratch hardness measurement method for thin coatings is still lacking. In this study, the scratch hardness of these DLC coatings was measured at both micro-scale and nano-scale, respectively. The micro-scratch test using a 200 µm tip is an inapplicable method because the substrate effect has dominated the scratch hardness measurement. On the other hand, a nano-scratch hardness test using a sharper tip is an effective method to measure the scratch hardness of thin coatings. Although the scratch hardness introduces a lateral force compared with the indentation hardness, it well correlates with the nano-indentation hardness. The ratio of the scratch hardness to the indentation hardness is close to 1 for DLC coatings due to the amorphous structure. It proves that the tangential force induced by scratching does not influence the hardness property. In addition, a simple approach is proposed to obtain the scratch hardness of DLC coatings qualitatively without width measurement.

Staphylococcus (S.) aureus infection is a serious, worldwide health concern, particularly in many communities and hospitals. Understanding the S. aureus pathogenetic regulatory network will provide significant insights into diagnostic target screening to improve clinical treatment of diseases caused by S. aureus. We screened differentially expressed genes between normal mice and S. aureus-infected mice. We used the Gene Expression Omnibus (GEO) DataSets database for functional analysis (GO-analysis) and the DAVID and KEGG databases for signaling pathway analyses. We next integrated the gene and pathway analyses with Transcriptional Regulatory Element Database (TRED) to build an antimicrobial resistance gene regulatory network of S. aureus. We performed association analysis of network genes and diseases using DAVID online annotation tools. We identified a total of 437 virulence genes and 15 transcription factors (TFs), as well as 444 corresponding target genes, in the S. aureus TF regulatory network. We screened seven key network nodes (Met, Mmp13, Il12b, Il4, Tnf, Ptgs2, and Ctsl), four key transcription factors (Jun, C3, Spil, and Il6) and an important signaling pathway (TNF). We hypothesized that the cytokine activity and growth factor activity of S. aureus are combinatorically cross-regulated by Met, Mmp13, Il12b, Il4, Tnf, Ptgs2, and Ctsl genes, the TFs Jun, C3, Spi1, and Il6, as well as the immune response, cellular response to lipopolysaccharide, and inflammatory response. Our study provides information and reference values for the molecular understanding of the S. aureus pathogenetic gene regulatory network.

IntroductionChimeric antigen receptor natural killer (CAR-NK) cells have been found to be successful in treating hematologic malignancies and present potential for usage in solid tumors.MethodsIn this study, we created CD276-targeted CAR-expressing NK cells from pluripotent stem cells (iPSC CD276-targeted CAR-NK cells) and evaluated their cytotoxicity against esophageal squamous cell carcinoma (ESCC) using patient-specific organoid (PSO) models comprising of both CD276-positive and CD276-negative adjacent epithelium PSO models (normal control PSO, NC PSO) as well as primary culture of ESCC cell models. In addition, in vitro and in vivo models such as KYSE-150 were also examined. iPSC NK cells and NK-free media were used as the CAR-free and NK-free controls, respectively.ResultsThe positive CD276 staining was specifically detected on the ESCC membrane in 51.43% (54/105) of the patients of all stages, and in 51.35% (38/74) of stages III and IV. The iPS CD276-targeted CAR-NK cells, comparing with the iPS NK cells and the NK-free medium, exhibited specific and significant cytotoxic activity against CD276-positive ESCC PSO rather than CD276-negative NC PSO, and exhibited significant cytotoxicity against CD276-expressing cultured ESCC cells, as well as against CD276-expressing KYSE-150 in vitro and in BNDG mouse xenograft.DiscussionThe efficacy of the iPSC CD276-targeted CAR-NK cells demonstrated by their successful treatment of CD276-expressing ESCC in a multitude of pre-clinical models implied that they hold tremendous therapeutic potential for treating patients with CD276-expressing ESCC.

Abstract Myocardial infarction (MI) is the most prevalent non‐communicable disease worldwide. Nanotheranostics have made significant progress in the biomedical field, presenting an avenue to overcome the limitations of conventional approaches towards MI, in which personalized interventions have enhanced nanotherapeutic efficacy. The pharmacokinetics and pharmacodynamics of nanoscale materials have been modified through alteration of their physical and chemical properties such as structure, size, and surface, thereby improving target sensitivity and specificity. This revolutionary technology has also been accomplished through precision therapeutics in MI. In this review, we discuss advanced nanoparticle designs utilized in the diagnosis and treatment of MI that could be applied to deliver personalized treatment and improve patient outcomes.

IntroductionTo analyze public perceptions of active aging in China on mainstream social media platforms to determine whether the “14th Five Year Plan for the Development of the Aging Career and Older Adult Care System” issued by the CPC in 2022 has fully addressed public needs.MethodsThe original tweets posted on Weibo between January 1, 2020, and June 30, 2022, containing the words “aging” or “old age” were extracted. A bidirectional encoder representation from transformers (BERT)-based model was used to generate themes related to this perception. A qualitative thematic analysis and an independent review of the theme labels were conducted by the researchers.ResultsThe findings indicate that public perceptions revolved around four themes: (1) health prevention and protection, (2) convenient living environments, (3) cognitive health and social integration, and (4) protecting the rights and interests of the older adult.DiscussionOur study found that although the Plan aligns with most of these themes, it lacks clear planning for financial security and marital life.

The human cytomegalovirus major immediate early gene (CMV) promoter is currently the most preferred promoter for recombinant therapeutic proteins (RTPs) production in CHO cells. To enhance the production of RTPs, five synthetic enhancers including multiple transcription factor regulatory elements (TFREs) were evaluated to enhance recombinant protein level in transient and stably transfected CHO cells. Compared with the control, four elements can enhance the report genes expression under both two transfected states. Further, the function of these four enhancers on human serum albumin (HSA) were investigated. We found that the transient expression can increase by up to 1.5 times, and the stably expression can maximum increase by up to 2.14 times. The enhancement of transgene expression was caused by the boost of their corresponding mRNA levels. Transcriptomics analysis was performed and found that transcriptional activation and cell cycle regulation genes were involved. In conclusion, optimization of enhancers in the CMV promoter could increase the production yield of transgene in transfected CHO cells, which has significance for developing high-yield CHO cell expression system.

ObjectiveThis multi-center cross-sectional study aimed to delineate latent profiles of benefit finding (BF) in individuals undergoing maintenance hemodialysis (MHD) in Shanghai and examine associations between these BF profiles, social support, and coping style.MethodsA total of 384 individuals undergoing MHD (mean age = 57.90, SD = 13.36) were assessed using the Benefit Finding Scale, Simplified Coping Style Questionnaire, and Perceived Social Support Scale. Latent profile analysis (LPA) identified distinct BF categories. Analysis of variance (ANOVA) evaluated the correlation between BF groups and demographic variables, while the relationship between BF, social support, and coping style was tested through correlation and multiple regression analyses.ResultsLPA identified three BF groups: rich BF (54.17%), moderate BF (41.14%), and poor BF (4.69%). Regression analyses indicated that positive coping and social support are protective factors for BF. Additionally, older age and heightened understanding of MHD correlated with higher BF levels.ConclusionThe findings highlighted the importance of recognizing different BF profiles in individuals on MHD and working toward promoting BF levels in the rich BF and moderate BF groups, while helping the poor BF group to identify and address their challenges. Medical professionals should consider interventions tailored to individual psychological profiles to improve mental health and quality of life outcomes in this population.

In this paper, the structural, electronic, and elastic properties of Fe3SnC were calculated based on local density approximation (LDA) and generalized gradient approximation (GGA) in density functional theory (DFT). Compared with GGA, LDA underestimates lattice constants and overestimates binding energy and elastic constants. The calculated lattice constants are 3.76 Å (LDA) and 3.83 Å (GGA), respectively, and the latter is closer to the experimental values. With U correction in GGA and LDA, the magnetic properties of the system are shown in the band structure. The GGA calculation results are more accurate, and the calculated magnetic moment of Fe3SnC is 5.74μB. The band structure indicates that Fe3SnC is a metallic compound. The elastic constants show that Fe3SnC has a large elastic constant and bulk modulus, in which the C11 calculated by GGA is as high as 463.81GPa, and the Young's modulus is as high as 350.72GPa. This indicates that Fe3SnC is a potential cermet due to a strong deformation resistance. At the same time, with the minimum thermal conductivity of 1.65 W/mK calculated by the Cahill model.

BiNiO3 is a perovskite material with potential applications in various fields. In this paper, the crystal structure, electronic structure and elastic constants of monoclinic BiNiO3 under different pressure have been studied by first-principles. The results show that applying pressure causes changes in bond length between atoms and crystal structure, and can cause electrons to transfer between atoms. In particular, the valence states of Bi and Ni may change. These changes may lead to the transformation of the material from a monoclinic structure to an orthorhombic structure. Under the action of pressure, the magnetic moment decreases from 1.00 μB to about 0.50 μB, and the decrease is the largest in the range of 5 ∼ 15 GPa, which indicates that the pressure has an effective modulation effect on the magnetic moment. In addition, the influence of pressure on the elastic constant is studied. The results show that pressure has a significant effect on the elastic constants along the matrix diagonal, and the elastic constant increases with the increase of pressure. Finally, the changes of sound velocity on the crystal planes [100], [010] and [001] of monoclinic crystal structure under pressure are also studied, and it is found that pressure can effectively regulate sound velocity. This study shows that the crystal structure and electromagnetic properties of BiNiO3 can be regulated by pressure.

Abstract Over the past few decades, there has been a significant interest in the study of essential genes, which are crucial for the survival of an organism under specific environmental conditions and thus have practical applications in the fields of synthetic biology and medicine. An increasing amount of experimental data on essential genes has been obtained with the continuous development of technological methods. Meanwhile, various computational prediction methods, related databases and web servers have emerged accordingly. To facilitate the study of essential genes, we have established a database of essential genes (DEG), which has become popular with continuous updates to facilitate essential gene feature analysis and prediction, drug and vaccine development, as well as artificial genome design and construction. In this article, we summarized the studies of essential genes, overviewed the relevant databases, and discussed their practical applications. Furthermore, we provided an overview of the main applications of DEG and conducted comprehensive analyses based on its latest version. However, it should be noted that the essential gene is a dynamic concept instead of a binary one, which presents both opportunities and challenges for their future development.

IntroductionThe clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined. MethodsWe assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC in vitro using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and in vivo by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively.ResultsMUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells in vitro, in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. ConclusionThe MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.

We propose and experimentally demonstrate an ultra-broadband metamaterial absorber based on photonic topological transition by using metals with large real part of permittivity (ε′). The simulation results show that the absorptivity is larger than 0.9 in the wavelength range from 400 nm to 2832 nm. The simulation results also show that the absorption effect is insensitive to the incident angle and polarization. According to the effective medium theory, the ultra-broad bandwidth is originated from the photonic topological transition. In addition, the analyses reveal that the absorption bandwidths can be extended by manipulating the wavelengths of photonic topological transition (PTT) points with large-ε′ metals. Furthermore, an ultra-broadband metamaterial absorber with multilayer films is fabricated by using standard film deposition techniques. The measured results show that the absorptivity is larger than 0.9 under normal incidence over the measured wavelength range of 400–2500 nm. This metamaterial absorber is expected to be potential candidate for various applications, such as thermal photovoltaic energy conversion, detectors, and solar cells.

ABSTRACT: Growth performance and carcass traits may be retarded by low nutrient density diets. Organic chromium propionate (CrProp) can improve growth, carcass traits, and meat quality in farmed lambs, white broilers, and fish. Limited data regarding CrProp's impacts on yellow-feathered broilers are available. Eight hundred yellow-feathered male broilers (1-day old) were randomly allocated to 4 dietary groups and reared for 56 d. The trial was a 2 (dietary nutrient density) ×2 (CrProp) factorial arrangement with 4 diets: regular nutrient diet and low nutrient density (LND, reduction in metabolizable energy by 81 kcal and crude protein by 0.43%) diet supplemented with or without 200 mg/kg CrProp. Broilers were euthanized at d 56 after blood collection. The results indicated that the LND diet led to greater average daily feed intake (ADFI) from d 1 to 42 and feed conversion ratio (FCR) from d 22 to 42 (P < 0.05). Supplementation of CrProp improved body weight (BW) from d 1 to 56, average daily gain (ADG), and FCR during d 1 to 42 but reduced ADFI during d 1 to 21, as well as lowered abdominal fat percentage (P < 0.05). Supplementation with CrProp to regular and LND diets reduced ADFI but improved FCR from d 1 to 21 (P < 0.05). The LND diet lowered total antioxidant capacity (T-AOC) concentration and total superoxide dismutase (T-SOD) activity in the jejunal mucosa. CrProp elevated T-AOC levels and glutathione peroxidase activity (GSH-Px, P < 0.05). Dietary CrProp upregulated (P < 0.05) the expression of fatty acid transporter (FABP1) gene and peptide transporter (Pept1) gene. CrProp administration increased jejunal FABP1 expression and lowered cooking loss of breast meat (P < 0.05) in the LND group while reducing shear force (P = 0.009) of broilers treated by regular diet. In summary, CrProp administration to the LND diet can improve growth performance in the starter period and meat quality on d 56, possibly through upregulated nutrient transporter gene expression in the jejunum and enhanced antioxidant capability.

A pregnant woman had a normal second-trimester anatomic survey at 22 weeks gestation. She was revealed to have a fetal oral mass with polyhydramnios and invisible stomach bubble by ultrasound at 28 weeks. A 50 mm × 36 mm × 42 mm, solid mass was found in the fetal mouth, filling the entire oral cavity. Fetal magnetic resonance imaging showed a homogeneous solid mass in the oral cavity compressing the hypopharynx. At 33 weeks, preterm labor occurred because of the continuation of increased amniotic fluid volume, and a female infant was vaginally delivered. The infant died shortly after tracheal intubation attempt failed. Autopsy confirmed the prenatal sonographic finding. The final pathologic diagnosis was oral immature teratoma. Our study indicates that although oral teratomas are rare, they are readily apparent at prenatal sonographic examinations. Respiratory compromise is the frequent complication of oral teratomas, which is associated with high perinatal mortality.