Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration.

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

Pulmo-protection of long-term swimming exercise via improving insulin sensitivity in monocrotaline-induced pulmonary hypertensive rats.

Exercise has been recognized as an effective intervention in the treatment of pulmonary arterial hypertension (PAH), supported by numerous studies. However, the precise effects of exercise on pulmonary function remain to be fully elucidated. In this study, using a rat model of swimming exercise training and monocrotaline-induced PAH, we aimed to explore its impact on pulmonary morphology and function. Our investigations revealed that MCT-treated rats exhibited augmented mean pulmonary arterial pressure (MPAP) and pulmonary vascular remodeling, which can be attenuated by 4 weeks of swimming exercise training (60 min/day, 5 days/week). Notably, MCT-treated rats showed impaired pulmonary function, as manifested by decreased tidal volume and dynamic compliance, which were reversed by exercise training. Assessment of pulmonary substrate in PAH rats indicated a prominent pro-inflammatory substrate, evidenced by macrophage accumulation through quantitative immunohistological analysis of macrophage-like cell expression (CD68), and extracellular matrix remodeling, evaluated by Masson staining. Importantly, both the pro-inflammatory substrate and extracellular matrix remodeling were ameliorated by swimming exercise training. Additionally, serum biochemical analysis demonstrated elevated levels of low-density lipoprotein cholesterol and Apolipoprotein B following MCT treatment, which were reduced with exercise intervention. Moreover, exercise enhanced systemic insulin sensitivity in both MCT-treated and untreated rats. Notably, MCT and exercise treatment both decreased fasting blood glucose (FBG) levels in rats, whereas exercise training reinstated FBG levels to normal in MCT-treated rats. In summary, our study suggests that swimming exercise confers a pulmonary protective effect in MCT-induced PAH rats, highlighting the potential importance of exercise-based rehabilitation in the management of PAH.

BiTSC 2: Bayesian inference of tumor clonal tree by joint analysis of single-cell SNV and CNA data.

The rapid development of single-cell DNA sequencing (scDNA-seq) technology has greatly enhanced the resolution of tumor cell profiling, providing an unprecedented perspective in characterizing intra-tumoral heterogeneity and understanding tumor progression and metastasis. However, prominent algorithms for constructing tumor phylogeny based on scDNA-seq data usually only take single nucleotide variations (SNVs) as markers, failing to consider the effect caused by copy number alterations (CNAs). Here, we propose BiTSC$^2$, Bayesian inference of Tumor clonal Tree by joint analysis of Single-Cell SNV and CNA data. BiTSC$^2$ takes raw reads from scDNA-seq as input, accounts for the overlapping of CNA and SNV, models allelic dropout rate, sequencing errors and missing rate, as well as assigns single cells into subclones. By applying Markov Chain Monte Carlo sampling, BiTSC$^2$ can simultaneously estimate the subclonal scCNA and scSNV genotype matrices, subclonal assignments and tumor subclonal evolutionary tree. In comparison with existing methods on synthetic and real tumor data, BiTSC$^2$ shows high accuracy in genotype recovery, subclonal assignment and tree reconstruction. BiTSC$^2$ also performs robustly in dealing with scDNA-seq data with low sequencing depth and variant missing rate. BiTSC$^2$ software is available at https://github.com/ucasdp/BiTSC2.

The functional study of a novel MKRN3 missense mutation associated with familial central precocious puberty.

Central precocious puberty (CPP) refers to a syndrome of early puberty initiation with a characteristic increase in the release of gonadotropin-releasing hormone (GnRH); therefore, it is also called GnRH-related precocious puberty. About a quarter of idiopathic central precocious puberty (ICPP) may be familial. Studies suggest that mutations of makorin ring finger protein 3 (MKRN3) can cause familial central precocious puberty (FCPP). In this report, we describe a Chinese female patient carrying a novel MKRN3 variant (c.980G>A/p.Arg327His) and presenting the CPP phenotype. This novel variant attenuated its own ubiquitination, degradation, and inhibition on the transcriptional and translational activity of GNRH1, which was verified through functional tests. We can consider this variant as a loss-of-function mutation, which subsides the inhibition of GnRH1-related signaling and gives rise to GnRH-related precocious puberty.

Involvement of PI3K/AKT Pathway in the Rapid Antidepressant Effects of Crocetin in Mice with Depression-Like Phenotypes.

The current first-line antidepressants have the drawback of slow onset, which greatly affects the treatment of depression. Crocetin, one of the main active ingredients in saffron (Crocus sativus L.), has been demonstrated to have antidepressant activities, but whether it has a rapid antidepressant effect remains unclear. This study aimed to investigate the onset, duration, and mechanisms of the rapid antidepressant activity of crocetin (20, 40 and 80 mg/kg, intraperitoneal injection) in male mice subjected to chronic restraint stress (CRS). The results of behavioral tests showed that crocetin exerted rapid antidepressant-like effect in mice with depression-like phenotypes, including rapid normalization of depressive-like behaviors within 3 h, and the effects could be maintained for 2 days. Hematoxylin-eosin (HE) and Nissl staining showed that crocetin ameliorated hippocampal neuroinflammation and nerve injuries in mice with depression-like phenotypes. The levels of inflammatory factors, corticosterone and pro brain-derived neurotrophic factor in crocetin-administrated mice serum were significantly reduced compared with those in the CRS group, as well as the levels of inflammatory factors in hippocampus. What's more, Western blot analyses showed that, compared to CRS-induced mice, the relative levels of mitogen-activated kinase phosphatase 1 and toll-like receptor 4 were significantly reduced after the administration of crocetin, and the relative expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP-response element binding protein, phosphorylated phosphoinositide 3 kinase (p-PI3K)/PI3K, phosphorylated protein kinase B (p-AKT)/AKT, phosphorylated glycogen synthase kinase 3ß (p-GSK3ß)/GSK3ß, phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR were markedly upregulated. In conclusion, crocetin exerted rapid antidepressant effects via suppressing the expression of inflammatory cytokines and the apoptosis of neuronal cells through PI3K/AKT signaling pathways. The rapid antidepressant effect of crocetin (40 mg/kg) could be maintained for at least 2 days after single treatment.

Transformation of Metal-Organic Framework from Kinetic to Thermodynamic Product for Controlled Delivery of Vitamin C.

A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5. Furthermore, precise control over VC release can be achieved by introducing surface modifications involving SiO2 onto the structure of VC@HSCT-5, while simultaneously adjusting environmental factors such as pH and temperature conditions. Preliminary cell culture experiments and cytotoxicity assays highlight the biocompatibility of HSTC-5, suggesting that it is a promising platform for sustained drug delivery and diverse biomedical applications.

Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms.

Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research.

Proangiogenic effect and underlying mechanism of holmium oxide nanoparticles: a new biomaterial for tissue engineering.

BACKGROUND: Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue "tracking" labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs. RESULTS: In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced. CONCLUSION: Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.

Omentin-1 drives cardiomyocyte cell cycle arrest and metabolic maturation by interacting with BMP7.

Mammalian cardiomyocytes (CMs) undergo maturation during postnatal heart development to meet the increased demands of growth. Here, we found that omentin-1, an adipokine, facilitates CM cell cycle arrest and metabolic maturation. Deletion of omentin-1 causes mouse heart enlargement and dysfunction in adulthood and CM maturation retardation in juveniles, including delayed cell cycle arrest and reduced fatty acid oxidation. Through RNA sequencing, molecular docking analysis, and proximity ligation assays, we found that omentin-1 regulates CM maturation by interacting directly with bone morphogenetic protein 7 (BMP7). Omentin-1 prevents BMP7 from binding to activin type II receptor B (ActRIIB), subsequently decreasing the downstream pathways mothers against DPP homolog 1 (SMAD1)/Yes-associated protein (YAP) and p38 mitogen-activated protein kinase (p38 MAPK). In addition, omentin-1 is required and sufficient for the maturation of human embryonic stem cell-derived CMs. Together, our findings reveal that omentin-1 is a pro-maturation factor for CMs that is essential for postnatal heart development and cardiac function maintenance.

Differential expression of ASIP transcripts reveals genetic mechanism underpinning black-tail independence from body plumage in yellow-bodied chickens.

The genetic foundation of chicken body plumage color has been extensively studied. However, little attention has been paid to the inheritance patterns and molecular mechanisms underlying the formation of distal feather colors (tail and wingtip). Differences in these colors are common; for example, the Chinese Huiyang Beard chicken has black tail feathers, but yellow body plumage. Here, the hybrid offspring of Huiyang Beard and White Leghorn chickens were used to study the inheritance patterns of tail-feather color. The expression levels of pigment genes in differently colored feather follicles were analyzed using quantitative real-time PCR. The results showed that genetic regulation of tail-feather color was independent of body-plumage color. The Dominant White locus inhibited eumelanin synthesis in tail feathers without affecting the formation of yellow body plumage, whereas the Silver locus had the opposite effect. The expression of agouti signaling protein (ASIP) gene class 1 transcripts was significantly lower in black tail-feather follicles than in yellow body follicles, whereas tyrosinase-related protein 1 (TYRP1) gene expression was significantly higher in black tail feathers. These differentially expressed genes were confirmed to exert an effect on eumelanin and pheomelanin formation in feathers, thus influencing the regulation of chicken tail-feather color. In conclusion, this study lays the foundation for further research on the genetic mechanisms of regional differences in feather color, contributing to a better understanding of plumage pigmentation in chickens.

Taraxerone exerts antipulmonary fibrosis effect through Smad signaling pathway and antioxidant stress response in a Sirtuin1-dependent manner.

Idiopathic pulmonary fibrosis treatments are limited, often with severe side effects, highlighting the need for novel options. Taraxerone has diverse biomedical properties, but its mechanism remains unclear. This study investigates taraxerone's impact and the mechanisms involved in bleomycin-induced pulmonary fibrosis in mice. After establishing a pulmonary fibrosis mouse model, taraxerone was intraperitoneally injected continuously for 14-28 days. The in vivo antifibrotic and antioxidative stress effects of taraxerone were assessed. In vitro, the influence of taraxerone on transforming growth factor-ß1-induced myofibroblast transformation and oxidative stress was investigated. Subsequently, quantitative polymerase chain reaction screened the histone deacetylase and Sirtuin family, and taraxerone's effects on SIRT1 were assessed. After SIRT1 siRNA treatment, changes in myofibroblast transformation and antioxidant capacity in response to taraxerone were observed. Acetylation and phosphorylation levels of Smad3 were evaluated. We also examined the binding levels of SIRT1 with Pho-Smad3 and Smad3, as well as the nuclear localization of Smad2/3. EX527 confirmed SIRT1's in vivo action in response to taraxerone. In vitro experiments suggested that taraxerone inhibited myofibroblast differentiation by activating SIRT1 and reducing oxidative stress. We also observed a new interaction between SIRT1 and the Smad complex. Taraxerone activates SIRT1, enabling it to bind directly to Smad3. This leads to reduced Smad complex phosphorylation and limited nuclear translocation. As a result, the transcription of fibrotic factors is reduced. In vivo validation confirms taraxerone's SIRT1-mediated antifibrotic effectiveness. This suggests that targeting SIRT1-mediated inhibition of myofibroblast differentiation could be a key strategy in taraxerone-based therapy for pulmonary fibrosis.

Electron Impact with the Liquid-Vapor Interface.

Reaction dynamics in the liquid-vapor interface is one of the crucial physical sciences but is still starving for in-depth exploration. It is challenging to selectively detect the interfacial species or the yields of chemical reaction therein, meanwhile shielding or reducing the interference from the vapor and liquid bulk. Mass spectrometry is a straightforward method but is also frustrated in such a selective detection. Using a liquid microjet in combination with a pulsed electron beam, a linear time-of-flight mass spectrometer, and a quadrupole mass filter, we recently innovated time-delayed mass spectrometry for investigations of the liquid-vapor interface. In this Account, we illustrate how this unique method succeeds in disentangling different sources, i.e., the vapor and liquid-vapor interface, of the ionic yields of the electron impacts with a liquid beam of alcohol in vacuum. These achievements are basically attributed to the application of an onion-peeling strategy in the ion detection. Concretely, the microsecond time scale of molecular volatilization can be resolved well by tuning the delay time between the nanosecond pulses of incident electron bunch and ion attractor. First, the specific orientation of the interfacial molecule, i.e., a well-known fact about the hydrophobic hydrocarbon groups pointing outside the liquid surface of alcohol, is validated again. More importantly, the dynamic features of time-delayed mass spectra, in particular, for the ionic yields from the liquid-vapor interface, are rationalized explicitly. Moreover, we demonstrate evidence of in situ molecular dimers in the liquid-vapor interface of 1-propanol. As the first example of electron-induced reaction in the liquid-vapor interface, dimethyl ether can be synthesized in the liquid methanol interface due to local interfacial acidification by high-energy electron impacts. On the contrary, the low energy electron can lead to local basicity through dissociative electron attachment (DEA). Besides the primary low-energy electrons, the low-energy secondary and inelastically scattered electrons in the higher-energy impacts of the primary electrons can also participate in the DEA process. In contrast to the gas- or solid-phase DEAs, that in the liquid-vapor interface shows distinct differences in both the types and efficiencies of anionic products. With these and efforts in the future, we develop a molecular-level understanding of how the chemical reactions happen in the liquid-vapor interface.

Communications between macrophages and cardiomyocytes.

The heart is a muscular organ that pumps blood throughout the body and is one of the most vital organs in human body. While cardiomyocytes are essential for maintaining the normal function of the heart, a variety of cardiovascular diseases such as coronary artery occlusion, arrhythmia, and myocarditis can lead to cardiomyocyte death, resulting in deterioration of heart function. The adult mammalian heart is incapable of regenerating sufficient cardiomyocytes following cardiac injuries, eventually leading to heart failure and death. Cardiac macrophages are ubiquitously distributed in the healthy heart and accumulated at the site of injury. Macrophages play essential roles in regulating homeostasis and proliferation of cardiomyocyte, promoting electrical conduction, and removing dead cardiomyocytes and debris through direct and indirect cell-cell crosstalk. In this review, we summarize the latest insights into the role of macrophages in maintaining cardiac homeostasis and the macrophage-cardiomyocyte crosstalk in both healthy and injured scenarios. Video Abstract.

Application of molecular dynamics simulation in the field of food enzymes: improving the thermal-stability and catalytic ability.

Enzymes can produce high-quality food with low pollution, high function, high acceptability, and medical aid. However, most enzymes, in their native form, do not meet the industrial requirements. Sequence-based and structure-based methods are the two main strategies used for enzyme modification. Molecular Dynamics (MD) simulation is a sufficiently comprehensive technology, from a molecular perspective, which has been widely used for structure information analysis and enzyme modification. In this review, we summarize the progress and development of MD simulation, particularly for software, force fields, and a standard procedure. Subsequently, we review the application of MD simulation in various food enzymes for thermostability and catalytic improvement was reviewed in depth. Finally, the limitations and prospects of MD simulation in food enzyme modification research are discussed. This review highlights the significance of MD simulation and its prospects in food enzyme modification.

Bioparameter-directed nanoformulations as MRI CAs enable the specific visualization of hypoxic tumour.

A malignant tumour has hypoxic cells of varying degrees. The more severe the hypoxic degree, the more difficult the prognosis of the tumour and the higher the recurrence rate. Therefore, tumour hypoxia imaging is crucial. Magnetic resonance imaging (MRI) shows its strength in high resolution, depth of penetration and noninvasiveness. However, it needs more excellent contrast agents (CAs) to combat the complex tumour microenvironment (TME) and increased targeting of tumours to enhance clinical safety. Many research studies have focused on developing hypoxia-responsive MRI CAs that take advantage of the unique characteristics of hypoxic tumours. The low oxygen pressure, acidic TME, and up-regulated redox molecule levels found in hypoxic tumours serve as biological stimuli for nanoformulations that can accurately image the hypoxic region. This review highlights the importance of developing bioparameter-directed nanoformulations as MRI CAs for accurate tumour diagnosis. The design strategies and mechanisms of tumour-hypoxia imaging with nanoformulations are exemplified, with a focus on pH-responsiveness, redox-responsiveness, and p(O2)-responsiveness. The promising future of bioparameter-responsive nanoformulations for accurate tumour diagnosis and personalised cancer treatment is discussed.

Pathway and Cost-Benefit Analysis to Achieve China's Zero Hydrofluorocarbon Emissions.

Global hydrofluorocarbon (HFC) cumulative emissions will be more than 20 Gt CO2-equiv during 2020-2060 and have a non-negligible impact on global warming even in full compliance with the Kigali Amendment (KA). Fluorochemical manufacturers (including multinationals) in China have accounted for about 70% of global HFC production since 2015, of which about 60% is emitted outside China. This study built an integrated model (i.e., DECAF) to estimate both territorial and exported emissions of China under three scenarios and assess the corresponding climate effects as well as abatement costs. Achieving near-zero territorial emissions by 2060 could avoid 23 ± 4 Gt CO2-equiv of cumulative territorial emissions (compared to the 2019 Baseline scenario) during 2020-2060 at an average abatement cost of 9 ± 6 USD/t CO2-equiv. Under the near-zero emission (including territorial and abroad) pathway, radiative forcing from HFCs will peak in 2037 (60 ± 6 mW/m2) with a 33% peak reduction and 8 years in advance compared to the path regulated by the KA, and the radiative forcing by 2060 will be lower than that in 2019. Accelerated phase-out of HFC production in China could provide a possibility for rapid global HFC abatement and achieve greater climate benefits.

Crocetin confers neuroprotection and is anti-inflammatory in rats with induced glaucoma.

BACKGROUND: Crocetin is a bioactive ingredient in saffron, derived from the Crocus sativus stigmas of the Iridaceae family. As a chemically carotenoid derivative, crocetin exhibites effects like anti-inflammatory, antioxidant, neuroprotective, etc. However, the protective effect of crocetin on glaucoma and its mechanism remains unclear. The current study assesed the neuroprotective and anti-inflammatory effects of crocetin on retinal neurons in glaucoma rats which were induced by 0.3% carbomer injection into the anterior chamber. METHODS AND RESULTS: The pathological structures on the retina and optic nerve were observed and examined by H&E staining and transmission electron microscopy. Immunohistochemical staining was used to detect the expression of TNF-α, IL-1ß, and IL-6 of the retina and the expression of a brain-derived neurotrophic factor (BDNF) in the primary visual cortex (PVC). Western blot was carried out to detect the expression of PI3K, Akt, and NF-κB in the retina. It was found that crocetin ameliorated the pathological changes of the retina and ON and reduced the number of apoptotic retinal ganglion cells. Immunohistochemical staining showed that crocetin could decrease the contents of TNF-α, IL-1ß, and IL-6 and increase the contents of BDNF. Western blot showed that crocetin was found to suppress the expression of PI3K, Akt, and NF-κB. CONCLUSION: The results obtained in this study have indicated that crocetin showes neuroprotective effects on retinal ganglion cells in glaucoma rats and inhibits retinal dysfunction. Meanwhile, crocetin exerted an anti-inflammatory effect to protect the retina by inhibiting the expression of the PI3K/Akt/NF-κB signaling pathway. This work provides substantial evidence that crocetin may be a potential drug for the treatment of glaucoma.

Telestration with augmented reality improves surgical performance through gaze guidance.

BACKGROUND: In minimally invasive surgery (MIS), trainees need to learn how to interpret the operative field displayed on the laparoscopic screen. Experts currently guide trainees mainly verbally during laparoscopic procedures. A newly developed telestration system with augmented reality (iSurgeon) allows the instructor to display hand gestures in real-time on the laparoscopic screen in augmented reality to provide visual expert guidance (telestration). This study analysed the effect of telestration guided instructions on gaze behaviour during MIS training. METHODS: In a randomized-controlled crossover study, 40 MIS naive medical students performed 8 laparoscopic tasks with telestration or with verbal instructions only. Pupil Core eye-tracking glasses were used to capture the instructor's and trainees' gazes. Gaze behaviour measures for tasks 1-7 were gaze latency, gaze convergence and collaborative gaze convergence. Performance measures included the number of errors in tasks 1-7 and trainee's ratings in structured and standardized performance scores in task 8 (ex vivo porcine laparoscopic cholecystectomy). RESULTS: There was a significant improvement 1-7 on gaze latency [F(1,39) = 762.5, p < 0.01, ηp2 = 0.95], gaze convergence [F(1,39) = 482.8, p < 0.01, ηp2 = 0.93] and collaborative gaze convergence [F(1,39) = 408.4, p < 0.01, ηp2 = 0.91] upon instruction with iSurgeon. The number of errors was significantly lower in tasks 1-7 (0.18 ± 0.56 vs. 1.94 ± 1.80, p < 0.01) and the score ratings for laparoscopic cholecystectomy were significantly higher with telestration (global OSATS: 29 ± 2.5 vs. 25 ± 5.5, p < 0.01; task-specific OSATS: 60 ± 3 vs. 50 ± 6, p < 0.01). CONCLUSIONS: Telestration with augmented reality successfully improved surgical performance. The trainee's gaze behaviour was improved by reducing the time from instruction to fixation on targets and leading to a higher convergence of the instructor's and the trainee's gazes. Also, the convergence of trainee's gaze and target areas increased with telestration. This confirms augmented reality-based telestration works by means of gaze guidance in MIS and could be used to improve training outcomes.

Estimation of genetic parameters and single-step genome-wide association studies for milk urea nitrogen in Holstein cattle.

The main objectives of this study were to estimate genetic parameters for milk urea nitrogen (MUN) in Holstein cattle and to conduct a single-step (ss)GWAS to identify candidate genes associated with MUN. Phenotypic measurements from 24,435 Holstein cows were collected from March 2013 to July 2019 in 9 dairy farms located in the Beijing area, China. A total of 2,029 cows were genotyped using the Illumina 150K Bovine Bead Chip, containing 121,188 SNP. A single-trait repeatability model was used to evaluate the genetic background of MUN. We found that MUN is a trait with low heritability (0.06 ± 0.004) and repeatability (0.12). Considering similar milk production levels, a lower MUN concentration indicates higher nitrogen digestibility. The genetic correlations between MUN and milk yield, net energy concentration, fat percentage, protein percentage, and lactose percentage were positive and ranged from 0.02 to 0.26. The genetic correlation between MUN and somatic cell score (SCS) was negative (-0.18), indicating that animals with higher MUN levels tend to have lower SCS. Both ssGWAS and pathway enrichment analyses were used to explore the genetic mechanisms underlying MUN. A total of 18 SNP (located on BTA11, BTA12, BTA14, BTA17, and BTA18) were found to be significantly associated with MUN. The genes CFAP77, CAMSAP1, CACNA1B, ADGRB1, FARP1, and INTU are considered to be candidate genes for MUN. These candidate genes are associated with important biological processes such as protein and lipid metabolism and binding to specific proteins. This set of candidate genes, metabolic pathways, and their functions provide a better understanding of the genomic architecture and physiological mechanisms underlying MUN in Holstein cattle.

Global development and future trends of artificial sweetener research based on bibliometrics.

Artificial sweeteners have sparked a heated debate worldwide due to their ambiguous impacts on public and environmental health and food safety and quality. Many studies on artificial sweeteners have been conducted; however, none scientometric studies exist in the field. This study aimed to elaborate on the knowledge creation and development of the field of artificial sweeteners and predict the frontiers of knowledge based on bibliometrics. In particular, this study combined VOSviewer, CiteSpace, and Bibliometrix to visualize the mapping of knowledge production, covered 2389 relevant scientific publications (1945-2022), and systematically analyzed articles and reviews (n = 2101). Scientific publications on artificial sweeteners have been growing at an annual rate of 6.28% and globally attracting 7979 contributors. Susan J. Brown with total publications (TP) of 17, average citation per article (AC) of 36.59, and Hirsch (h)-index of 12 and Robert F. Margolskee (TP = 12; AC = 2046; h-index = 11) were the most influential scholars. This field was clustered into four groups: eco-environment and toxicology, physicochemical mechanisms, public health and risks, and nutrition metabolism. The publications about environmental issues, in particular, "surface water," were most intensive during the last five years (2018-2022). Artificial sweeteners are gaining importance in the monitoring and assessment of environmental and public health. Results of the dual-map overlay showed that the future research frontiers tilt toward molecular biology, immunology, veterinary and animal sciences, and medicine. Findings of this study are conducive to identifying knowledge gaps and future research directions for scholars.