Mineralised collagen regulated the secretion of adrenomedullin by macrophages to activate the PI3K/AKT signalling pathway to promote bone defect repair.

Biomaterials can affect the osteogenic process by regulating the function of macrophages and transforming the bone immune microenvironment. Mineralised collagen (MC) is an artificial bone that is highly consistent to the microstructure of the native osseous matrix. The studies have confirmed that MC can achieve effective regeneration of bone defects, but the potential mechanism of MC regulating osteogenesis is still unclear. This study confirmed that MC regulate the high expression of adrenomedullin (ADM) in macrophages and promote the osteogenic differentiation, proliferation and migration of BMSCs. Moreover, ADM activated the PI3K/Akt pathway, while the inhibition of PI3K/Akt hindered the proliferation, migration and osteogenic differentiation of BMSCs promoted by ADM. Additionally, the rat mandibular defect model confirmed that ADM promote the repair of mandibular defects, and the inhibition of PI3K/Akt pathway hinders the osteogenic effect of ADM. Our study suggests that MC regulates ADM secretion by macrophages, creates an ideal bone immune microenvironment, activates the PI3K/AKT signalling pathway, and promotes osteogenesis.

M3YOLOv5: Feature enhanced YOLOv5 model for mandibular fracture detection.

BACKGROUND: It is very important to detect mandibular fracture region. However, the size of mandibular fracture region is different due to different anatomical positions, different sites and different degrees of force. It is difficult to locate and recognize fracture region accurately. METHODS: To solve these problems, M3YOLOv5 model is proposed in this paper. Three feature enhancement strategies are designed, which improve the ability of model to locate and recognize mandibular fracture region. Firstly, Global-Local Feature Extraction Module (GLFEM) is designed. By effectively combining Convolutional Neural Network (CNN) and Transformer, the problem of insufficient global information extraction ability of CNN is complemented, and the positioning ability of the model to the fracture region is improved. Secondly, in order to improve the interaction ability of context information, Deep-Shallow Feature Interaction Module (DSFIM) is designed. In this module, the spatial information in the shallow feature layer is embedded to the deep feature layer by the spatial attention mechanism, and the semantic information in the deep feature layer is embedded to the shallow feature layer by the channel attention mechanism. The fracture region recognition ability of the model is improved. Finally, Multi-scale Multi receptive-field Feature Mixing Module (MMFMM) is designed. Deep separate convolution chains are used in this modal, which is composed by multiple layers of different scales and different dilation coefficients. This method provides richer receptive field for the model, and the ability to detect fracture region of different scales is improved. RESULTS: The precision rate, mAP value, recall rate and F1 value of M3YOLOv5 model on mandibular fracture CT data set are 97.18%, 96.86%, 94.42% and 95.58% respectively. The experimental results show that there is better performance about M3YOLOv5 model than the mainstream detection models. CONCLUSION: The M3YOLOv5 model can effectively recognize and locate the mandibular fracture region, which is of great significance for doctors' clinical diagnosis.

Macrophage exosomes modified by miR-365-2-5p promoted osteoblast osteogenic differentiation by targeting OLFML1.

In the bone immune microenvironment, immune cells can regulate osteoblasts through a complex communication network. Macrophages play a central role in mediating immune osteogenesis, exosomes derived from them have osteogenic regulation and can be used as carriers in bone tissue engineering. However, there are problems with exosomal therapy alone, such as poor targeting, and the content of loaded molecules cannot reach the therapeutic concentration. In this study, macrophage-derived exosomes modified with miR-365-2-5p were developed to accelerate bone healing. MC3T3-E1 cells were incubated with the culture supernatants of M0, M1 and M2 macrophages, and it was found that the culture medium of M2 macrophages had the most significant effects in contributing to osteogenesis. High-throughput sequencing identified that miR-365-2-5p was significantly expressed in exosomes derived from M2 macrophages. We incubated MC3T3-E1 with exosomes overexpressing or knocking down miR-365-2-5p to examine the biological function of exosome miR-365-2-5p on MC3T3-E1 differentiation. These findings suggested that miR-365-2-5p secreted by exosomes increased the osteogenesis of MC3T3-E1. Moreover, miR-365-2-5p had a direct influence over osteogenesis for MC3T3-E1. Sequencing analysis combined with dual luciferase detection indicated that miR-365-2-5p binded to the 3'-UTR of OLFML1. In summary, exosomes secreted by M2 macrophages targeted OLFML1 through miR-365-2-5p to facilitate osteogenesis.

CCGL-YOLOV5:A cross-modal cross-scale global-local attention YOLOV5 lung tumor detection model.

BACKGROUND: Multimodal medical image detection is a key technology in medical image analysis, which plays an important role in tumor diagnosis. There are different sizes lesions and different shapes lesions in multimodal lung tumor images, which makes it difficult to effectively extract key features of lung tumor lesions. METHODS: A Cross-modal Cross-scale Clobal-Local Attention YOLOV5 Lung Tumor Detection Model (CCGL-YOLOV5) is proposed in this paper. The main works are as follows: Firstly, the Cross-Modal Fusion Transformer Module (CMFTM) is designed to improve the multimodal key lesion feature extraction ability and fusion ability through the interactive assisted fusion of multimodal features; Secondly, the Global-Local Feature Interaction Module (GLFIM) is proposed to enhance the interaction ability between multimodal global features and multimodal local features through bidirectional interactive branches. Thirdly, the Cross-Scale Attention Fusion Module (CSAFM) is designed to obtain rich multi-scale features through grouping multi-scale attention for feature fusion. RESULTS: The comparison experiments with advanced networks are done. The Acc, Rec, mAP, F1 score and FPS of CCGL-YOLOV5 model on multimodal lung tumor PET/CT dataset are 97.83%, 97.39%, 96.67%, 97.61% and 98.59, respectively; The experimental results show that the performance of CCGL-YOLOV5 model in this paper are better than other typical models. CONCLUSION: The CCGL-YOLOV5 model can effectively use the multimodal feature information. There are important implications for multimodal medical image research and clinical disease diagnosis in CCGL-YOLOV5 model.

MicroRNA-21a-5p-modified macrophage exosomes as natural nanocarriers promote bone regeneration by targeting GATA2.

Bone immune responses based on macrophages are critical in the osteogenesis of bone abnormalities. In general, M2 macrophage facilitate the promotion of osteogenesis, as well, M1 macrophage play an important role in early bone healing, as confirmed by previous studies. However, it is not clear how M1 macrophage are involved in the bone immune response. MiR-21a-5p is a highly expressed microRNA in M1 macrophage in contrast to M2. Therefore, the current work sought to ascertain the influence of M1 macrophage on bone healing via exosomal miR-21a-5p and the probable mechanism. We discovered that injecting M1 macrophage exosomes overexpressing miR-21a-5p into bone defect locations enhanced bone regeneration in vivo. Furthermore, by directly targeting GATA2, miR-21a-5p accelerated MC3T3-E1 osteogenic differentiation. Our findings showed that exosomal miR-21a-5p from M1 macrophage may be transported to osteoblasts and target GATA2 to enhance bone defect healing.

CaP-coated Zn-Mn-Li alloys regulate osseointegration via influencing macrophage polarization in the osteogenic environment.

Immune response is an important factor in determining the fate of bone replacement materials, in which macrophages play an important role. It is a new idea to design biomaterials with immunomodulatory function to reduce inflammation and promote bone integration by regulating macrophages polarization. In this work, the immunomodulatory properties of CaP Zn-Mn-Li alloys and the specific mechanism of action were investigated. We found that the CaP Zn0.8Mn0.1Li alloy promoted the polarization of macrophages toward M2 and reduced inflammation, which could effectively upregulate osteogenesis-related factors and promote new bone formation, indicating the important role of macrophages polarization in biomaterial induction of osteogenesis. In vivo studies further demonstrated that CaP Zn0.8Mn0.1Li alloy could stimulate osteogenesis better than other Zn-Mn-Li alloys implantations by regulating macrophages polarization and reducing inflammation. In addition, transcriptome results showed that CaP Zn0.8Mn0.1Li played an important regulatory role in the life process of macrophages, activating Toll-like receptor signaling pathway, which participated in the activation and attenuation of inflammation, and accelerated bone integration. Thus, by preparing CaP coatings on the surface of Zn-Mn-Li alloys and combining the bioactive ingredient with controlled release, the biomaterial will be imbibed with beneficial immunomodulatory properties that promote bone integration.

Fabrication and evaluation of 3D printed poly(l-lactide) copolymer scaffolds for bone tissue engineering.

The application of poly(L-lactic acid) (PLLA) in tissue engineering is limited due to its brittleness and uncontrollable degradation rate. In this study, the flexible p-dioxanone (PDO) and highly reactive glycolide (GA) units were introduced into PLLA segments by chemical modification to prepare poly(l-lactide-ran-p-dioxanone-ran-glycolide) (PLPG) copolymers. The copolymers were then processed into the PLPG scaffold by a 3D printing technology. The physicochemical properties of the PLPG copolymers were studied by NMR, DSC, XRD, GPC, and SEM. Furthermore, the mechanical properties, degradation properties, and biocompatibility of the PLPG scaffolds were also studied. The results showed that introducing PDO and GA units disrupted the regularity of PLLA, decreasing the crystallinity of the PLPG copolymers. However, introducing PDO and GA units could effectively improve the mechanical and degradation properties of the PLLA scaffolds. In vitro cell culture experiments indicated that the PLPG scaffolds supported proliferation, growth, and differentiation of MC3T3-E1 cells. The PLPG scaffolds reported herein, with controllable degradation rates and mechanical performance, may find applications in bone tissue engineering.

Fine mapping of qAHPS07 and functional studies of AhRUVBL2 controlling pod size in peanut (Arachis hypogaea L.).

Cultivated peanut (Arachis hypogaea L.) is an important oil and cash crop. Pod size is one of the major traits determining yield and commodity characteristic of peanut. Fine mapping of quantitative trait locus (QTL) and identification of candidate genes associated with pod size are essential for genetic improvement and molecular breeding of peanut varieties. In this study, a major QTL related to pod size, qAHPS07, was fine mapped to a 36.46 kb interval on chromosome A07 using F2 , recombinant inbred line (RIL) and secondary F2 populations. qAHPS07 explained 38.6%, 23.35%, 37.48%, 25.94% of the phenotypic variation for single pod weight (SPW), pod length (PL), pod width (PW) and pod shell thickness (PST), respectively. Whole genome resequencing and gene expression analysis revealed that a RuvB-like 2 protein coding gene AhRUVBL2 was the most likely candidate for qAHPS07. Overexpression of AhRUVBL2 in Arabidopsis led to larger seeds and plants than the wild type. AhRUVBL2-silenced peanut seedlings represented small leaves and shorter main stems. Three haplotypes were identified according to three SNPs in the promoter of AhRUVBL2 among 119 peanut accessions. Among them, SPW, PW and PST of accessions carrying Hap_ATT represent 17.6%, 11.2% and 26.3% higher than those carrying Hap_GAC，respectively. In addition, a functional marker of AhRUVBL2 was developed. Taken together, our study identified a key functional gene of peanut pod size, which provides new insights into peanut pod size regulation mechanism and offers practicable markers for the genetic improvement of pod size-related traits in peanut breeding.

Evaluating the effect of PD-1 inhibitors on left ventricular function in lung cancer with noninvasive myocardial work.

Background: The treatment of advanced lung cancer has been revolutionized by immune checkpoint inhibitors (ICIs) in recent years, largely driven by programmed cell death-1 (PD-1) inhibitors. However, patients with lung cancer who are treated with PD-1 inhibitors are prone to immune-related adverse events (irAEs), especially cardiac adverse events. Noninvasive myocardial work is a novel technique used to assess left ventricular (LV) function, which can effectively predict myocardial damage. Here, noninvasive myocardial work was used to evaluate changes in LV systolic function during PD-1 inhibitor therapy and to assess ICIs-related cardiotoxicity. Methods: From September 2020 to June 2021, 52 patients with advanced lung cancer in the Second Affiliated Hospital of Nanchang University were prospectively enrolled. In total, 52 patients underwent PD-1 inhibitor therapy. The cardiac markers, noninvasive LV myocardial work, and conventional echocardiographic parameters were measured at pretherapy (T0) and posttreatment after the first (T1), second (T2), third (T3), and fourth (T4) cycles. Following this, the trends of the above parameters were analyzed using analysis of variance with repeated measures and the Friedman nonparametric test. Furthermore, the relationships between disease characteristics (tumor type, treatment regimen, cardiovascular risk factors, cardiovascular drugs, and irAEs) and noninvasive LV myocardial work parameters were assessed. Results: Throughout the follow-up, the cardiac markers and conventional echocardiographic parameters showed no significant changes. Based on the normal reference ranges, patients with PD-1 inhibitor therapy had increased values of LV global waste work (GWW) and decreased global work efficiency (GWE) that began at T2. Compared with T0, GWW increased from T1 to T4 (42%, 76%, 87%, and 87%, respectively), while global longitudinal strain (GLS), global work index (GWI), and global constructive work (GCW) decreased in varying degrees (P<0.001). Most of the disease characteristics had no effect on the LV myocardial work parameters; however, the numbers of irAEs were closely associated with GLS (P=0.034), GWW (P<0.001), and GWE (P<0.001). Patients with 2 or more irAEs had higher values of GWW and lower GLS and GWE. Conclusions: Noninvasive myocardial work can accurately reflect myocardial function and energy utilization in patients with lung cancer who are undergoing PD-1 inhibitor treatment and may thus benefit the management of patients with ICIs-related cardiotoxicity.

Highly Efficient and Stable Perovskite Solar Cells: Competitive Crystallization Strategy and Synergistic Passivation.

Defects of perovskite (PVK) films are one of the main obstacles to achieving high-performance perovskite solar cells (PSCs). Here, the authors fabricated highly efficient and stable PSCs by introducing prolinamide (ProA) into the PbI2 precursor solution, which improves the performance of PSCs by the competitive crystallization and efficient defect passivation of perovskite. The theoretical and experimental results indicate that ProA forms an adduct with PbI2 , competes with free I- to coordinate with Pb2+ , leads to the increase of the energy barrier of crystallization, and slows down the crystallization rate. Furthermore, the dual-site synergistic passivation of ProA is revealed by density functional theory (DFT) calculations and experimental results. ProA effectively reduces non-radiative recombination in the resultant films to improve the photovoltaic performance of PSCs. Notably, ProA-assisted PSCs achieve 24.61% power conversion efficiency (PCE) for the champion device and the stability of PSCs devices under ambient and thermal environments is improved.

Genome-wide characterization of the PP2C gene family in peanut (Arachis hypogaea L.) and the identification of candidate genes involved in salinity-stress response.

Plant protein phosphatase 2C (PP2C) play important roles in response to salt stress by influencing metabolic processes, hormone levels, growth factors, etc. Members of the PP2C family have been identified in many plant species. However, they are rarely reported in peanut. In this study, 178 PP2C genes were identified in peanut, which were unevenly distributed across the 20 chromosomes, with segmental duplication in 78 gene pairs. AhPP2Cs could be divided into 10 clades (A-J) by phylogenetic analysis. AhPP2Cs had experienced segmental duplications and strong purifying selection pressure. 22 miRNAs from 14 different families were identified, targeting 57 AhPP2C genes. Gene structures and motifs analysis exhibited PP2Cs in subclades AI and AII had high structural and functional similarities. Phosphorylation sites of AhPP2C45/59/134/150/35/121 were predicted in motifs 2 and 4, which located within the catalytic site at the C-terminus. We discovered multiple MYB binding factors and ABA response elements in the promoter regions of the six genes (AhPP2C45/59/134/150/35/121) by cis-elements analysis. GO and KEGG enrichment analysis confirmed AhPP2C-A genes in protein binding, signal transduction, protein modification process response to abiotic stimulus through environmental information processing. Based on RNA-Seq data of 22 peanut tissues, clade A AhPP2Cs showed a varying degree of tissue specificity, of which, AhPP2C35 and AhPP2C121 specifically expressed in seeds, while AhPP2C45/59/134/150 expressed in leaves and roots. qRT-PCR indicated that AhPP2C45 and AhPP2C134 displayed significantly up-regulated expression in response to salt stress. These results indicated that AhPP2C45 and AhPP2C134 could be candidate PP2Cs conferring salt tolerance. These results provide further insights into the peanut PP2C gene family and indicate PP2Cs potentially involved in the response to salt stress, which can now be further investigated in peanut breeding efforts to obtain cultivars with improved salt tolerance.

Cerium-Doped Indium Oxide as a Top Electrode of Semitransparent Perovskite Solar Cells.

Semitransparent perovskite solar cells (ST-PSCs) play a very important role in high-efficiency tandem solar cells and building integrated photovoltaics (BIPV). One of the main challenges for high-performance ST-PSCs is to obtain suitable top-transparent electrodes by appropriate methods. Transparent conductive oxide (TCO) films, as the most widely used transparent electrodes, are also adopted in ST-PSCs. However, the possible ion bombardment damage during the TCO deposition and the relatively high postannealing temperature usually required for high-quality TCO films is not conducive to improving the performance of the perovskite solar cells with low ion bombardment and temperature tolerances. Herein, cerium-doped indium oxide (ICO) thin films are prepared by reactive plasma deposition (RPD) at substrate temperatures below 60 °C. A high carrier mobility of 50.26 cm2 V-1 s-1, a low resistivity of 7.18 × 10-4 Ω·cm, and an average transmittance of 86.53% in the wavelength range of 400-800 nm and 87.37% in the wavelength range of 800-1200 nm are achieved. The RPD-prepared ICO film is used as a transparent electrode on top of the ST-PSCs (band gap ∼1.68 eV), and photovoltaic conversion efficiency (PCE) of 18.96% is achieved on the champion device.

Rectal ectopic pregnancy after in vitro fertilization and embryo transfer: A case report.

RATIONALE: Rectal ectopic pregnancy is an extremely rare abdominal pregnancy. This article presents a female underwent an unsuccessful in vitro fertilization which was misdiagnosed by serum beta-human chorionic gonadotropin (ß-hCG) test and transvaginal ultrasonography. Twenty days later, a ruptured rectal ectopic pregnancy was confirmed by laparoscopy then the gestational tissue removed successfully. PATIENT CONCERNS: A 32-year-old Chinese female was admitted to our hospital with complaining of symptoms, like gradual worsening of lower abdominal pain and dysuria. The abdominal ultrasonography revealed a sac-like mass in the posterior area to the uterus and a moderate amount of free fluid in the pelvic cavity. Forty days ago, she underwent a frozen embryo transfer. Twenty days ago, her serum ß-hCG level was <5 mIU/mL and neither intrauterine nor ectopic pregnancy was detected by transvaginal ultrasonography. Then the procedure was thought to have resulted in biochemical pregnancy failure. DIAGNOSIS: The primary rectal ectopic pregnancy. INTERVENTIONS: The mass was removed laparoscopic surgery. OUTCOMES: The patient recovered well. LESSONS: When the history of in vitro fertilization combined with an inappropriate rise of serum ß-hCG and no visible evidence of an intra-uterine pregnancy, physicians should consider the possibility of abdominal pregnancy. Early diagnosis of abdominal pregnancy can effectively save the life of the pregnant woman.

Alginate Fiber-Enhanced Poly(vinyl alcohol) Hydrogels with Superior Lubricating Property and Biocompatibility.

The design of a novel interpenetrating network hydrogel inspired by the microscopic architecture of natural cartilage based on a supramolecular sodium alginate (SA) nanofibril network is reported in this paper. The mechanical strength and toughness of the poly(vinyl alcohol) (PVA) hydrogel were significantly improved after being incorporated with the alginate nanofibril network. The multiple hydrogen bonds between PVA chains and alginate fibers provided an efficient energy dissipation, thus leading to a significant increase in the mechanical strength of the PVA/SA/NaCl hydrogel. The PVA/SA/NaCl hydrogel demonstrated superior water-lubrication and load-bearing performance due to noncovalent interactions compared with pure PVA hydrogels. Moreover, the bioactivity of the PVA/SA/NaCl hydrogel was proved by the MC3T3 cell proliferation and viability assays over 7 days. Therefore, alginate fiber-enhanced hydrogels with high strength and low friction properties are expected to be used as novel biomimetic lubrication materials.

Development of biodegradable Zn-Mn-Li and CaP coatings on Zn-Mn-Li alloys and cytocompatibility evaluation for bone graft.

Zn-based alloys are considered as new kind of potential biodegradable implanted biomaterials recently. The difficulty of metal implanted biomaterials and bone tissue integration seriously affects the applications of metal implanted scaffolds in bone tissue-related fields. Herein, we self-designed Zn0.8Mn and Zn0.8Mn0.1Li alloys and CaP coated Zn0.8Mn and Zn0.8Mn0.1Li alloys, then evaluated the degradation property and cytocompatibility. The results demonstrated that the Zn0.8Mn0.1Li alloys had profoundly modified the degradation property and cytocompatibility, but Zn0.8Mn0.1Li alloys had particularly adverse effects on the surface morphology of osteoblasts. The results furtherly showed that the CaP-coated Zn0.8Mn and Zn0.8Mn0.1Li alloys scaffold had better biocompatibility, which would further guarantee the biosafety of this new kind of biodegradable Zn-based alloys implants for future clinical applications.

Microporous structures on mineralized collagen mediate osteogenesis by modulating the osteo-immune response of macrophages.

It is a new hot pot in tissue engineering and regenerative medicine to study the effects of physicochemical properties of implanted biomaterials on regulating macrophage polarization to promote bone regeneration. In this study, we designed and fabricated mineralized collagen (MC) with different microporous structures via in vitro biomimetic mineralization method. The microporous structures, mechanical properties, shore hardness and water contact angle measurements were tested. Live/dead cell staining, CCK-8 assay, phalloidine staining, staining of focal adhesions were used to detect cell behavior. ELISA, qRT-PCR, ALP, and alizarin red staining (ARS) were performed to appraise osteogenic differentiation and investigated macrophage response and their subsequent effects on the osteogenic differentiation. The results showed that RAW264.7 and MC3T3-E1 cells were able to survive on the MC. MC with the microporous structure of approximately 84 µm and 70%-80% porosity could promote M2 macrophage polarization and increase the expression level of TGF-ß and VEGF. Moreover, the gene expression of the osteogenic markers ALP, COL-1, and OCN increased. Therefore, MC with different microporous structures mediated osteoimmunomodulation in bone regeneration. These data will provide a new idea of biomaterials inducing bone repair and direct the optimal design of novel immune biomaterials, development, and rational usage.

Quantitative assessment of left ventricular systolic function in patients with systemic lupus erythematosus: a non-invasive pressure-strain loop technique.

Background: Systemic lupus erythematosus (SLE) is associated with a variety of cardiovascular diseases, even in the early stage of disease development. The purpose of this study was to quantitatively evaluate left ventricular (LV) systolic function in patients with SLE using a novel non-invasive pressure-strain loop (PSL) technique. Methods: This prospective case-control study included 132 patients with SLE and 99 normal controls, all of whom underwent traditional transthoracic echocardiography. The LV myocardial work was evaluated with the PSL technique based on speckle tracking and brachial artery blood pressure. The differences among groups were compared, and the correlations between myocardial work, laboratory data, and disease activity were analyzed in the SLE group. Results: Compared with the normal group, SLE patients had significantly higher global wasted work {GWW; SLE: 109 [82-150] mmHg%; controls: 66 [45-109] mmHg%; P<0.001} and impaired global work efficiency [GWE; SLE: 95% (94-97%); controls: 97% (96-98%); P<0.001]. Global work index (GWI) and global constructive work (GCW) did not show significant differences (P>0.05). Further subdivision analysis found that the increase of GWW and the damage of GWE were more obvious in SLE patients with high disease activity or severe diastolic dysfunction. Multivariate analysis revealed that increased erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-phospholipid antibodies, peak strain dispersion, and SLE Disease Activity Index (SLEDAI) were independently associated with increased GWW (ß=0.189, 0.230, 0.444, 0.111, and 0.180, respectively; all P<0.05) and damaged GWE (ß=-0.184, -0.130, -0.468, -0.149, and -0.191, respectively; all P<0.05). Conclusions: The non-invasive PSL can quantitatively evaluate the LV systolic function in SLE patients. This technique may provide a new method for monitoring cardiac function in chronic diseases.

Collecting and deactivating TGF-ß1 hydrogel for anti-scarring therapy in post-glaucoma filtration surgery.

Scar formation can lead to glaucoma filtration surgery (GFS) failure, wherein transforming growth factor (TGF)-ß is the core regulator. To reducing scar formation, this paper presents our study on the design of hydrogels to deactivate TGF-ß1. We hypothesized that excess TGF-ß1 can be removed from aqueous humor through the addition of oxidized hyaluronic acid (O-HA) hydrogels that are seeded with decorin (O-HA â€‹+ â€‹D). Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were performed to demonstrate the adsorption properties of O-HA â€‹+ â€‹D hydrogel, thus reducing the TGF-ß1 concentration in aqueous humor. In the light that collagen contraction in human Tenon's capsule fibroblasts (HTFs) and the angiogenesis of human umbilical vein endothelial cells (HUVECs) can be activated by TGF-ß1 and ß2, we performed the quantitative analysis of polymerase chain reaction to determine the effect of O-HA â€‹+ â€‹D on the type I collagen, fibronectin, and angiogenesis. Our results illustrate that O-HA â€‹+ â€‹D can inhibit the increase of α-SMA expression in HTF induced by TGF-ß1 and that O-HA â€‹+ â€‹D can inhibit the production of collagen I and fibronectin in HTF treated with TGF-ß1. Furthermore, we performed in vivo studies by employing a rabbit model, where rabbits were treated with hydrogels post GFS. Our results demonstrate that, as compared with other groups, the rabbits treated with O-HA â€‹+ â€‹D had the greatest reduction in inflammatory cells with reduced level of collagen in wounds. Taken together, the present study paves the way toward the treatment of post-glaucoma fibrosis following surgery.

Genome-Wide Identification of Auxin Response Factors in Peanut (Arachis hypogaea L.) and Functional Analysis in Root Morphology.

Auxin response factors (ARFs) play important roles in plant growth and development; however, research in peanut (Arachis hypogaea L.) is still lacking. Here, 63, 30, and 30 AhARF genes were identified from an allotetraploid peanut cultivar and two diploid ancestors (A. duranensis and A. ipaensis). Phylogenetic tree and gene structure analysis showed that most AhARFs were highly similar to those in the ancestors. By scanning the whole-genome for ARF-recognized cis-elements, we obtained a potential target gene pool of AhARFs, and the further cluster analysis and comparative analysis showed that numerous members were closely related to root development. Furthermore, we comprehensively analyzed the relationship between the root morphology and the expression levels of AhARFs in 11 peanut varieties. The results showed that the expression levels of AhARF14/26/45 were positively correlated with root length, root surface area, and root tip number, suggesting an important regulatory role of these genes in root architecture and potential application values in peanut breeding.

Structural basis for the tethered peptide activation of adhesion GPCRs.

Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes1-6. Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence7-12. Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with Gs: GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an α-helical-bulge-ß-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W6.53 and the constitution of a hydrogen-bond network formed by Q7.49/Y7.49 and the P6.47/V6.47φφG6.50 motif (φ indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and Gs coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common Gs-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with Gs. Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their Gs coupling.