High-yield extracellular vesicle production from HEK293T cells encapsulated in 3D auxetic scaffolds with cyclic mechanical stimulation for effective drug carrier systems.

Extracellular vesicles (EVs) show promise in drug loading and delivery for medical applications. However, the lack of scalable manufacturing processes hinders the generation of clinically suitable quantities, thereby impeding the translation of EV-based therapies. Current EV production relies heavily on non-physiological two-dimensional (2D) cell culture or bioreactors, requiring significant resources. Additionally, EV-derived ribonucleic acid cargo in three-dimensional (3D) and 2D culture environments remains largely unknown. In this study, we optimized the biofabrication of 3D auxetic scaffolds encapsulated with human embryonic kidney 293 T (HEK293 T) cells, focusing on enhancing the mechanical properties of the scaffolds to significantly boost EV production through tensile stimulation in bioreactors. The proposed platform increased EV yields approximately 115-fold compared to conventional 2D culture, possessing properties that inhibit tumor progression. Further mechanistic examinations revealed that this effect was mediated by the mechanosensitivity of YAP/TAZ. EVs derived from tensile-stimulated HEK293 T cells on 3D auxetic scaffolds demonstrated superior capability for loading doxorubicin compared to their 2D counterparts for cancer therapy. Our results underscore the potential of this strategy for scaling up EV production and optimizing functional performance for clinical translation.

Effect of dorsal capsular imbrication on intraoperative DRUJ instability following arthroscopic TFCC repair surgery.

BACKGROUND: To assess the clinical outcomes and identify the ideal indication for implementing dorsal distal radioulnar joint (DRUJ) capsular imbrication after triangular fibrocartilage complex (TFCC) repair in cases of DRUJ instability. METHODS: We conducted a retrospective study on patients who underwent arthroscopic TFCC repair between 2016 and 2021. Inclusion criteria comprised a symptomatic ulna fovea sign for over 6 months and dorsal DRUJ subluxation on magnetic resonance imaging. A total of 225 patients were divided into two groups: Group 1 (135 cases) with a negative ballottement test after "Cross-form TFCC repair" (CR) and Group 2 (90 cases) with a positive ballottement test after "Cross-form TFCC repair" and augmented DRUJ stability through dorsal DRUJ capsular imbrication (CR + DCI). Pain visual analog scale score (VAS), grip strength, modified Mayo Wrist Score (MMWS), wrist range of motion (ROM), and patient-reported outcomes (PROMs) were assessed for a minimum of 3 years postoperatively. RESULTS: Both groups showed significant improvements in pain VAS score, grip strength, wrist ROM, MMWS, and PROMs between the preoperative and postoperative periods (all P < 0.05). Recurrent DRUJ instability occurred in 3.7% and 1.1% of patients in the "CR" and "CR + DCI" groups, respectively, with a significant difference. Despite the "CR + DCI" group initially exhibiting inferior ROM compared with the "CR" group, subsequently, no significant difference was noted between them. CONCLUSIONS: Dorsal DRUJ capsular imbrication effectively reduces postoperative DRUJ instability rates, enhances grip strength, and maintains wrist ROM in patients with a positive intra-operative ballottement test after arthroscopic TFCC repair.

A quality grade classification method for fresh tea leaves based on an improved YOLOv8x-SPPCSPC-CBAM model.

In light of the prevalent issues concerning the mechanical grading of fresh tea leaves, characterized by high damage rates and poor accuracy, as well as the limited grading precision through the integration of machine vision and machine learning (ML) algorithms, this study presents an innovative approach for classifying the quality grade of fresh tea leaves. This approach leverages an integration of image recognition and deep learning (DL) algorithm to accurately classify tea leaves' grades by identifying distinct bud and leaf combinations. The method begins by acquiring separate images of orderly scattered and randomly stacked fresh tea leaves. These images undergo data augmentation techniques, such as rotation, flipping, and contrast adjustment, to form the scattered and stacked tea leaves datasets. Subsequently, the YOLOv8x model was enhanced by Space pyramid pooling improvements (SPPCSPC) and the concentration-based attention module (CBAM). The established YOLOv8x-SPPCSPC-CBAM model is evaluated by comparing it with popular DL models, including Faster R-CNN, YOLOv5x, and YOLOv8x. The experimental findings reveal that the YOLOv8x-SPPCSPC-CBAM model delivers the most impressive results. For the scattered tea leaves, the mean average precision, precision, recall, and number of images processed per second rates of 98.2%, 95.8%, 96.7%, and 2.77, respectively, while for stacked tea leaves, they are 99.1%, 99.1%, 97.7% and 2.35, respectively. This study provides a robust framework for accurately classifying the quality grade of fresh tea leaves.

Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer.

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.

Spatial distribution, source identification, and transportation paths of plutonium in the Beibu Gulf, South China Sea.

To investigate the spatial distribution and source of plutonium isotopes in the Beibu Gulf, surface sediments were collected and analyzed using sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). The activities of 239+240Pu in surface sediments ranged from 0.012 to 0.451 mBq/g (mean: 0.171 ± 0.138 mBq/g, n = 36), indicating a decreasing trend in a counterclockwise direction from the southern bay mouth. The counterclockwise decreasing trend in the south of the bay mouth is similar to the current in the Beibu Gulf. The 240Pu/239Pu atom ratios in surface sediments ranged from 0.156 to 0.283 (mean: 0.236 ± 0.031, n = 36), slightly higher than that of the global fallout value of 0.18. This suggests that the Pu in the Beibu Gulf was a combination of global fallout and Pacific Proving Ground (PPG). The average contribution of the plutonium (Pu) derived from the PPG in the sediment was estimated to be 52 % ± 24 %.

Effect of intraoperative hand-grip position on surgical outcome of thumb carpometacarpal arthrodesis.

BACKGROUND: A variety of surgical techniques had been developed over the past few decades for treating thumb carpometacarpal joint (CMCJ) osteoarthritis (OA). However, there are currently no accepted consensus on the ideal treatment for thumb CMCJ OA. Arthrodesis was one of the widely popular treatment methods; however, studies have showed that non-union rates were as high as 50%, with higher complications such as osteoarthritis of neighbouring joints and higher revision surgeries required as compared to other surgical methods. Patients with arthrodesis were also reported to have decreased thumb range of motion and loss of opponens function. Currently, there are numerous intraoperative positioning techniques for arthrodesis which could be confusing for young surgeons. With recent developments of fixation plates and better understanding of the wrist anatomy, this retrospective review aimed to evaluate the efficacy of our intraoperative hand-grip positioning method for arthrodesis of thumb CMCJ OA. What are the postoperative functional outcomes of (1) T-hook plates and (2) our intraoperative hand-grip positioning method for Eaton III thumb CMCJ OA arthrodesis by evaluating pain visual analogue scale (VAS) score, Disabilities of the Arm, Shoulder and Hand questionnaires (DASH), Mayo Wrist scores, capability of thumb opposition (Kapandji score), and comparing pre- and postoperative grip and pinch strength? METHODS: Twenty patients with CMCJ OA underwent arthrodesis using our intraoperative hand-grip positioning method and T-hook plates and screws (Acumed, USA). Patients were evaluated preoperatively and at 1, 3, 6 and 12 months postoperatively. Radiologic assessment including fusion evaluation, evaluation of radial and palmar abduction angles was done on hand X-rays. RESULTS: Twenty patients with a minimum follow-up duration of 12 months were included in this study. 100% fusion rate was achieved with only 1 case of complication involving radial sensory nerve neuropathy which was resolved after removal of implant and neurolysis. Significant improvement in pain and Mayo Wrist scores were noted 3 months postoperatively, whilst DASH score exhibited significant improvements after 6 months of follow-up (p < 0.05). Even though there were no significant differences observed between preoperative and postoperative grip strength, pinch strength and Kapandji scores, positive recovery trends were noted for all parameters with these functions surpassing preoperative levels after 12 months of follow-up. Significant improvements on hand X-rays were also noted for both postoperative radial and palmar abduction angles. CONCLUSIONS: There is currently no consensus on the ideal treatment method for thumb CMCJ OA. In this study, we would like to propose a simple intraoperative hand-grip positioning method with T-hook plates for arthrodesis. As seen from our results, our technique was able to provide satisfactory and replicable postoperative results and thus we would like to propose our hand-grip positioning method with T-hook plates fixation for subsequent treatment of patients with Eaton stage III thumb CMCJ OA.

The exosomal secretomes of mesenchymal stem cells extracted via 3D-printed lithium-doped calcium silicate scaffolds promote osteochondral regeneration.

The development of surface modification techniques has brought about a major paradigm shift in the clinical applications of bone tissue regeneration. Biofabrication strategies enable the creation of scaffolds with specific microstructural environments and biological components. Lithium (Li) has been reported to exhibit anti-inflammatory, osteogenic, and chondrogenic properties by promoting several intracellular signaling pathways. Currently, research focuses on fabricating scaffolds with simultaneous dual bioactivities to enhance osteochondral regeneration. In this study, we modified the surface of calcium silicate (CS) scaffolds with Li using a simple immersion technique and evaluated their capabilities for bone regeneration. The results showed that Li ions could be easily coated onto the surfaces of CS scaffolds without affecting the microstructural properties of CS itself. Furthermore, the modifications did not affect the printing capabilities of the CS, and porous scaffolds could be fabricated via extrusion. Moreover, the presence of Li improved the surface roughness and hydrophilicity, thus leading to enhanced secretion of osteochondral-related regeneration factors, such as alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen II (Col II) proteins. Subsequent in vivo studies, including histological and micro-CT analyses, confirmed that the Li-modified CS scaffolds promoted osteochondral regeneration. The transcriptome analysis suggested that the enhanced osteochondrogenic capabilities of our scaffolds were influenced by paracrine exosomes. We hope this study will inspire further research on osteochondral regeneration.

3D-biofabricated chondrocyte-laden decellularized extracellular matrix-contained gelatin methacrylate auxetic scaffolds under cyclic tensile stimulation for cartilage regeneration.

Three-dimensional (3D) hydrogel constructs can mimic features of the extracellular matrix (ECM) and have tailorable physicochemical properties to support and maintain the regeneration of articular cartilage. Various studies have shown that mechanical cues affect the cellular microenvironment and thereby influence cellular behavior. In this study, we fabricated an auxetic scaffold to investigate the effect of 3D tensile stimulation on chondrocyte behavior. Different concentrations of decellularized extracellular matrix (dECM) were mixed with fish gelatin methacrylate (FGelMa) and employed for the preparation of dECM/FGelMa auxetic bio-scaffolds using 3D biofabrication technology. We show that when human chondrocytes (HCs) were incorporated into these scaffolds, their proliferation and the expression of chondrogenesis-related markers increased with dECM content. The function of HC was influenced by cyclic tensile stimulation, as shown by increased production of the chondrogenesis-related markers, collagen II and glycosaminoglycans, with the involvement of the yes-associated protein 1 signaling pathway. The biofabricated auxetic scaffold represents an excellent platform for exploring interactions between cells and their mechanical microenvironment.

Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics.

Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient-specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient-derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung-cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co-clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care.

Progress in use of pigs as model animals / 中国实验动物学报

Animal models of human diseases include experimental animals and related materials established during biomedical research,which in turn play a vital role in medical research.Pigs and humans are similar in terms of their anatomy,physiology,immunology,and genetics.Pigs are thus suitable model animals for biomedical research and have various advantages compared with other model animals.Recent advances in biotechnology,such as genetic engineering,have contributed to a rapid increase in the use of pig models for human disease research.In addition to serving as xenotransplant organ donors and as tools in drug-design studies,pigs can also be used as model animals to study human developmental processes,congenital diseases,and disease-response mechanisms,thus making important contributions to improving human health.This review considers the current status and future applications of pigs as research models for studies of human cardiovascular diseases,cancer,ophthalmology,craniofacial,musculoskeletal,and skin research,reproductive and fetal development,nutrition,microbiome research,brain and neurodegenerative diseases,diabetes,infectious diseases,and vaccine design,as well as for xenotransplantation.

Research progress of circadian rhythm and circadian clock gene regulation in the development of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

With the development of society, the incidence of myopia and the population of myopia has increased year by year, which has become a major public health problem. Therefore, the research on the pathogenesis and prevention and control measures of myopia is imminent. In recent years, the role of the biological clock in the development of myopia has gradually attracted scholars interest. Now the author starts from the impact of the biological clock on the axial length, retina and choroid in the development of myopia. In order to provide new ideas for the study of prevention and control measures and the pathogenesis of myopia, a brief review is made from the perspective of contemporary society and disrupted body clock.

Synergistic Effect of Static Magnetic Fields and 3D-Printed Iron-Oxide-Nanoparticle-Containing Calcium Silicate/Poly-ε-Caprolactone Scaffolds for Bone Tissue Engineering.

In scaffold-regulated bone regeneration, most three-dimensional (3D)-printed scaffolds do not provide physical stimulation to stem cells. In this study, a magnetic scaffold was fabricated using fused deposition modeling with calcium silicate (CS), iron oxide nanoparticles (Fe3O4), and poly-ε-caprolactone (PCL) as the matrix for internal magnetic sources. A static magnetic field was used as an external magnetic source. It was observed that 5% Fe3O4 provided a favorable combination of compressive strength (9.6 ± 0.9 MPa) and degradation rate (21.6 ± 1.9% for four weeks). Furthermore, the Fe3O4-containing scaffold increased in vitro bioactivity and Wharton's jelly mesenchymal stem cells' (WJMSCs) adhesion. Moreover, it was shown that the Fe3O4-containing scaffold enhanced WJMSCs' proliferation, alkaline phosphatase activity, and the osteogenic-related proteins of the scaffold. Under the synergistic effect of the static magnetic field, the CS scaffold containing Fe3O4 can not only enhance cell activity but also stimulate the simultaneous secretion of collagen I and osteocalcin. Overall, our results demonstrated that Fe3O4-containing CS/PCL scaffolds could be fabricated three dimensionally and combined with a static magnetic field to affect cell behaviors, potentially increasing the likelihood of clinical applications for bone tissue engineering.

Knockdown of RAD51AP1 suppressed cell proliferation and invasion in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is a common malignant tumor of digestive tract with esophageal squamous cell carcinoma (ESCC) being the main histological subtype. This study aimed to identify potential hub gene associated with the pathophysiology of ESCC through bioinformatics analysis and experiment validation. METHODS: Three microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. The overlapping differentially expressed genes (DEGs) were analyzed by GEO2R tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway analyses were performed to predict the potential functions of DEGs. Nine hub genes were identified using protein-protein interaction (PPI) network and Cytoscape software. We selected RAD51-associated protein 1 (RAD51AP1) for further research because of its poor prognosis and it has not been sufficiently studied in ESCC. The effects of RAD51AP1 on proliferation, apoptosis, migration and invasion of ESCC cells were determined by in vitro functional assays. RESULTS: RAD51AP1 expression was significantly upregulated in ESCC tissues compared with normal tissues by using The Cancer Genome Atlas (TCGA) database. High expression of RAD51AP1 was associated with worse survival in ESCC patients. RAD51AP1 expression was positively associated with the enrichment of Th2 cells and T helper cells. Furthermore, CCK-8 and colony formation assays showed knockdown of RAD51AP1 inhibited the proliferation of ESCC cells. Flow cytometry analysis indicated knockdown of RAD51AP1 induced cell cycle arrest and apoptosis in ESCC cells. Transwell assay revealed knockdown of RAD51AP1 suppressed the migration and invasion of ESCC cells. CONCLUSIONS: Finally, our results demonstrated that RAD51AP1 silencing significantly inhibited cell proliferation and invasion in ESCC, thereby highlighting its potential as a novel target for ESCC treatment.

Three-Dimensional Printing and Fracture Mapping in Pelvic and Acetabular Fractures: A Systematic Review and Meta-Analysis.

Three-dimensional printing and fracture mapping technology is gaining popularity for preoperative planning of fractures. The aim of this meta-analysis is to further understand for the effects of 3D printing and fracture mapping on intraoperative parameters, postoperative complications, and functional recovery on pelvic and acetabular fractures. The PubMed, Embase, Cochrane and Web of Science databases were systematically searched for articles according to established criteria. A total of 17 studies were included in this study, of which 3 were RCTs, with a total of 889 patients, including 458 patients treated by traditional open reduction and internal fixation methods and 431 patients treated using 3D printing strategies. It was revealed that three-dimensional printing and fracture mapping reduced intraoperative surgical duration (RoM 0.74; 95% CI; 0.66-0.83; I2 = 93%), and blood loss (RoM 0.71; 95% CI; 0.63-0.81; I2 = 71%). as compared to traditional surgical approaches. In addition, there was significantly lower exposure to intraoperative imaging (RoM 0.36; 95% CI; 0.17-0.76; I2 = 99%), significantly lower postoperative complications (OR 0.42; 95% CI; 0.22-0.78; I2 = 9%) and significantly higher excellent/good reduction (OR 1.53; 95% CI; 1.08-2.17; I2 = 0%) in the three-dimensional printing and fracture mapping group. Further stratification results with only prospective studies showed similar trends. Three-dimensional printing and fracture mapping technology has potential in enhancing treatment of complex fractures by improving surgical related factors and functional outcomes and therefore could be considered as a viable tool for future clinical applications.

Combined Effects of Polydopamine-Assisted Copper Immobilization on 3D-Printed Porous Ti6Al4V Scaffold for Angiogenic and Osteogenic Bone Regeneration.

Numerous studies have demonstrated that biological compounds and trace elements such as dopamine (DA) and copper ions (Cu) could be modified onto the surfaces of scaffolds using a one-step immersion process which is simple, inexpensive and, most importantly, non-cytotoxic. The development and emergence of 3D printing technologies such as selective laser melting (SLM) have also made it possible for us to fabricate bone scaffolds with precise structural designs using metallic compounds. In this study, we fabricated porous titanium scaffolds (Ti) using SLM and modified the surface of Ti with polydopamine (PDA) and Cu. There are currently no other reported studies with such a combination for osteogenic and angiogenic-related applications. Results showed that such modifications did not affect general appearances and microstructural characteristics of the porous Ti scaffolds. This one-step immersion modification allowed us to modify the surfaces of Ti with different concentrations of Cu ions, thus allowing us to fabricate individualized scaffolds for different clinical scenarios. The modification improved the hydrophilicity and surface roughness of the scaffolds, which in turn led to promote cell behaviors of Wharton's jelly mesenchymal stem cells. Ti itself has high mechanical strength, therefore making it suitable for surgical handling and clinical applications. Furthermore, the scaffolds were able to release ions in a sustained manner which led to an upregulation of osteogenic-related proteins (bone alkaline phosphatase, bone sialoprotein and osteocalcin) and angiogenic-related proteins (vascular endothelial growth factor and angiopoietin-1). By combining additive manufacturing, Ti6Al4V scaffolds, surface modification and Cu ions, the novel hybrid 3D-printed porous scaffold could be fabricated with ease and specifically benefited future bone regeneration in the clinic.

Point cloud registration method for maize plants based on conical surface fitting-ICP.

Reconstructing three-dimensional (3D) point cloud model of maize plants can provide reliable data for its growth observation and agricultural machinery research. The existing data collection systems and registration methods have low collection efficiency and poor registration accuracy. A point cloud registration method for maize plants based on conical surface fitting-iterative closest point (ICP) with automatic point cloud collection platform was proposed in this paper. Firstly, a Kinect V2 was selected to cooperate with an automatic point cloud collection platform to collect multi-angle point clouds. Then, the conical surface fitting algorithm was employed to fit the point clouds of the flowerpot wall to acquire the fitted rotation axis for coarse registration. Finally, the interval ICP registration algorithm was used for precise registration, and the Delaunay triangle meshing algorithm was chosen to triangulate the point clouds of maize plants. The maize plant at the flowering and kernel stage was selected for reconstruction experiments, the results show that: the full-angle registration takes 57.32 s, and the registration mean distance error is 1.98 mm. The measured value's relative errors between the reconstructed model and the material object of maize plant are controlled within 5%, the reconstructed model can replace maize plants for research.

The effects of a 3D-printed magnesium-/strontium-doped calcium silicate scaffold on regulation of bone regeneration via dual-stimulation of the AKT and WNT signaling pathways.

Numerous studies have demonstrated that calcium silicate (CS) can be doped with various trace metal elements such as strontium (Sr) or magnesium (Mg). These studies have confirmed that such modifications promote bone regeneration. However, the development and emergence of 3D printing have further made it possible to fabricate bone grafts with precise structural designs using multi-bioceramics so as to better suit specific clinical requirements. We fabricated scaffolds using Mg-doped CS as the outer layer with Sr-doped CS in the center. In addition, PCL was used to improve printability of the scaffolds. This enhanced Mg and Sr architecture prevented premature degradation of the scaffolds during immersion while enabling the release of ions in a sustained manner in order to achieve the desired therapeutic goals. Even the capabilities of stem cells were shown to be enhanced when cultured on these scaffolds. Furthermore, the hybrid scaffolds were found to up-regulate the expression of bone-related proteins such as factors leading to differentiation-inducing pathways, including PI3K/Akt, Wnt, and TRPM7. The in vivo performance of the proposed scaffolds was assessed using micro-CT. The histological results revealed that the hybrid scaffolds were able to further enhance bone regeneration as compared to uni-bioceramics. By combining 3D printing, multi-ceramics, and trace metal elements, a novel hybrid scaffold could be fabricated with ease and specifically suited to future bone tissue engineering applications.

Genome-wide association study identifies quantitative trait loci affecting cattle temperament.

Cattle temperament is an interesting trait due to its correlation with production efficiency, labor safety, and animal welfare. To date, however, its genetic basis is not clearly understood. Here, we performed a genome-wide association study for a series of temperament traits in cattle, assessed with via open field and novel object tests, using autosomal single nucleotide polymorphisms (SNPs) derived from the whole-genome sequence. We identified 37 and 29 genome-wide significant loci in the open field and novel object tests, respectively. Gene set analysis revealed the most significant pathway was the neuroactive ligand-receptor interaction pathway, which may be essential for emotional control in cattle. Analysis of the expression levels of 18 tissue-specific genes based on transcriptomic data showed enrichment in the brain, with some candidate genes involved in psychiatric and neurodegenerative diseases in humans. Based on principal component analysis, the first principal component explained the largest variance in the open field and novel object test data, and the most significant loci were assigned to SORCS3 and SESTD1, respectively. Our findings should help facilitate cattle breeding for sound temperament by pyramiding favorable alleles to further improve cattle production.

[Research progress on chemical constituents and biological activities of Arisaematis Rhizoma].

Arisaematis Rhizoma included in the Chinese Pharmacopoeia is the dried tuber of Arisaema erubescens, A. heterophyllum or A. amurense in the family Araceae. This paper mainly focuses on the classification and summary of the chemical components and structures reported in recent years in the above three varieties of this medicinal material included in the pharmacopoeia, including alkaloids, flavonoids, phenylpropanoids, lignans and benzene ring derivatives, steroids and terpenes, glycosides and esters, etc. Then we reviewed the reported biological activities of these chemical components, including cytotoxicity, antitumor activity, antibacterial activity, nematicidal activity, etc. Although there have been reports on the review of the chemical composition of the medicinal material, the structure and classification of the chemical composition in these reviews are not clear enough. This review provides a basis for the later study of the chemical composition of this medicinal material, especially the identification of the chemical structures. And most of the current reviews on the biological activity of this medicinal material are mainly for the crude extract. This paper mainly summarized the biological activity of related monomer compounds and expected to lay a foundation for the development of novel high-efficiency and low-toxicity active leading compounds from Arisaematis Rhizoma.

Additive Manufacturing of Caffeic Acid-Inspired Mineral Trioxide Aggregate/Poly-ε-Caprolactone Scaffold for Regulating Vascular Induction and Osteogenic Regeneration of Dental Pulp Stem Cells.

Mineral trioxide aggregate (MTA) is a common biomaterial used in endodontics regeneration due to its antibacterial properties, good biocompatibility and high bioactivity. Surface modification technology allows us to endow biomaterials with the necessary biological targets for activation of specific downstream functions such as promoting angiogenesis and osteogenesis. In this study, we used caffeic acid (CA)-coated MTA/polycaprolactone (PCL) composites and fabricated 3D scaffolds to evaluate the influence on the physicochemical and biological aspects of CA-coated MTA scaffolds. As seen from the results, modification of CA does not change the original structural characteristics of MTA, thus allowing us to retain the properties of MTA. CA-coated MTA scaffolds were shown to have 25% to 55% higher results than bare scaffold. In addition, CA-coated MTA scaffolds were able to significantly adsorb more vascular endothelial growth factors (p < 0.05) secreted from human dental pulp stem cells (hDPSCs). More importantly, CA-coated MTA scaffolds not only promoted the adhesion and proliferation behaviors of hDPSCs, but also enhanced angiogenesis and osteogenesis. Finally, CA-coated MTA scaffolds led to enhanced subsequent in vivo bone regeneration of the femur of rabbits, which was confirmed using micro-computed tomography and histological staining. Taken together, CA can be used as a potently functional bioactive coating for various scaffolds in bone tissue engineering and other biomedical applications in the future.