Immunogenicity and safety of a self-assembling ZIKV nanoparticle vaccine in mice.

Zika virus (ZIKV) is a mosquito-borne flavivirus that highly susceptibly causes Guillain-Barré syndrome and microcephaly in newborns. Vaccination is one of the most effective measures for preventing infectious diseases. However, there is currently no approved vaccine to prevent ZIKV infection. Here, we developed nanoparticle (NP) vaccines by covalently conjugating self-assembled 24-subunit ferritin to the envelope structural protein subunit of ZIKV to achieve antigen polyaggregation. The immunogenicityof the NP vaccine was evaluated in mice. Compared to monomer vaccines, the NP vaccine achieved effective antigen presentation, promoted the differentiation of follicular T helper cells in lymph nodes, and induced significantly greater antigen-specific humoral and cellular immune responses. Moreover, the NP vaccine enhanced high-affinity antigen-specific IgG antibody levels, increased secretion of the cytokines IL-4 and IFN-γ by splenocytes, significantly activated T/B lymphocytes, and improved the generation of memory T/B cells. In addition, no significant adverse reactions occurred when NP vaccine was combined with adjuvants. Overall, ferritin-based NP vaccines are safe and effective ZIKV vaccine candidates.

The combined effect of MTHFR C677T and A1298C polymorphisms on the risk of digestive system cancer among a hypertensive population.

BACKGROUND AND PURPOSE: The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in directing folate species towards nucleotide synthesis or DNA methylation. The MTHFR polymorphisms C677T and A1298C have been linked to cancer susceptibility, but the evidence supporting this association has been equivocal. To investigate the individual and joint associations between MTHFR C677T, A1298C, and digestive system cancer in a Chinese hypertensive population, we conducted a population-based case-control study involving 751 digestive system cancer cases and one-to-one matched controls from the China H-type Hypertension Registry Study (CHHRS). METHODS: We utilized the conditional logistic regression model to evaluate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of digestive system cancer. RESULTS: The analysis revealed a significantly lower risk of digestive system cancer in individuals with the CT genotype (adjusted OR: 0.71; 95% CI 0.52, 0.97; P = 0.034) and TT genotype (adjusted OR: 0.57; 95% CI 0.40, 0.82; P = 0.003; P for trend = 0.003) compared to those with the 677CC genotype. Although A1298C did not show a measurable association with digestive system cancer risk, further stratification of 677CT genotype carriers by A1298C homozygotes (AA) and heterozygotes (AC) revealed a distinct trend within these subgroups. CONCLUSION: These findings indicate a potential protective effect against digestive system cancer associated with the T allele of MTHFR C677T. Moreover, we observed that the presence of different combinations of MTHFR polymorphisms may contribute to varying susceptibilities to digestive system cancer.

Federated attention consistent learning models for prostate cancer diagnosis and Gleason grading.

Artificial intelligence (AI) holds significant promise in transforming medical imaging, enhancing diagnostics, and refining treatment strategies. However, the reliance on extensive multicenter datasets for training AI models poses challenges due to privacy concerns. Federated learning provides a solution by facilitating collaborative model training across multiple centers without sharing raw data. This study introduces a federated attention-consistent learning (FACL) framework to address challenges associated with large-scale pathological images and data heterogeneity. FACL enhances model generalization by maximizing attention consistency between local clients and the server model. To ensure privacy and validate robustness, we incorporated differential privacy by introducing noise during parameter transfer. We assessed the effectiveness of FACL in cancer diagnosis and Gleason grading tasks using 19,461 whole-slide images of prostate cancer from multiple centers. In the diagnosis task, FACL achieved an area under the curve (AUC) of 0.9718, outperforming seven centers with an average AUC of 0.9499 when categories are relatively balanced. For the Gleason grading task, FACL attained a Kappa score of 0.8463, surpassing the average Kappa score of 0.7379 from six centers. In conclusion, FACL offers a robust, accurate, and cost-effective AI training model for prostate cancer pathology while maintaining effective data safeguards.

Direct single-molecule detection of CoA-SH and ATP by the membrane proteins TMEM120A and TMEM120B.

Membrane proteins are vital resources for developing biosensors. TMEM120A is a membrane protein associated with human pain transmission and lipid metabolism, and recent studies have demonstrated its ability to transport ions and bind to coenzyme A (COA-SH), indicating its potential to develop into a single-molecule sensor based on electrical methods. In this study, we investigated the ion transport properties of TMEM120A and its homolog TMEM120B on an artificial lipid bilayer using single-channel recording. The results demonstrate that both proteins can fuse into the lipid bilayer and generate stable ion currents under a bias voltage. Based on the stable ion transport capabilities of TMEM120A and TMEM120B, as well as the feature of TMEM120A binding with COA-SH, we developed these two proteins into a single-molecule sensor for detecting COA-SH and structurally similar molecules. We found that both COA-SH and ATP can reversibly bind to single TMEM120A and TMEM120B proteins embedded in the lipid bilayer and temporarily block ion currents during the binding process. By analyzing the current blocking signal, COA-SH and ATP can be identified at the single-molecule level. In conclusion, our work has provided two single-molecule biosensors for detecting COA-SH and ATP, offering insights for exploring and developing bio-inspired small molecule sensors.

Direct and Continuous Monitoring of Multicomponent Antibiotic Gentamicin in Blood at Single-Molecule Resolution.

Point-of-care monitoring of small molecules in biofluids is crucial for clinical diagnosis and treatment. However, the inherent low degree of recognition of small molecules and the complex composition of biofluids present significant obstacles for current detection technologies. Although nanopore sensing excels in the analysis of small molecules, the direct detection of small molecules in complex biofluids remains a challenge. In this study, we present a method for sensing the small molecule drug gentamicin in whole blood based on the mechanosensitive channel of small conductance in Pseudomonas aeruginosa (PaMscS) nanopore. PaMscS can directly detect gentamicin and distinguish its main components with only a monomethyl difference. The 'molecular sieve' structure of PaMscS enables the direct measurement of gentamicin in human whole blood within 10 min. Furthermore, a continuous monitoring device constructed based on PaMscS achieved continuous monitoring of gentamicin in live rats for approximately 2.5 h without blood consumption, while the drug components can be analyzed in situ. This approach enables rapid and convenient drug monitoring with single-molecule level resolution, which can significantly lower the threshold for drug concentration monitoring and promote more efficient drug use. Moreover, this work also lays the foundation for the future development of continuous monitoring technology with single-molecule level resolution in the living body.

Increased serum SGLT2 and its potential diagnostic and prognostic value in patients with acute ischemic stroke.

BACKGROUND: Recently acquired data suggests that sodium-glucose cotransporter-2 (SGLT2) may be a therapeutic target for cerebral ischemia. The specific impact of SGLT2 in acute ischemic stroke (AIS) remains unknown. We aimed to explore the levels of SGLT2 in AIS patients and its association with functional prognosis. METHODS: In this study, 132 AIS patients and 44 healthy controls were recruited prospectively to determine serum SGLT2 levels. Logistic regression analysis was employed to assess the association between serum SGLT2 level and stroke risk as well as 3-month outcome. Receiver operating characteristic (ROC) curves were utilized to evaluate predictive values for blood biomarkers. RESULTS: Serum SGLT2 levels were significantly higher (P =.000) in AIS patients (47.1 (interquartile range [IQR]: 42.4-50.9) ng/mL) than healthy controls (35.7 (IQR: 28.6-39.5) ng/mL). The optimal SGLT2 cutoff point for diagnosing AIS was 39.55 ng/mL, with a sensitivity of 90.2 % and specificity of 77.3 %. Serum levels of SGLT2 were negatively correlated with the onset time of AIS (linear fit R2 = 0.056, P =.006), but were not associated with National Institutes of Health Stroke Scale (NIHSS) scores (r = 0.007, P >.05) and lesion volume (r = -0.151, P >.05). SGLT2 was not remarkably different between patients with unfavorable and favorable outcomes (46.7 (IQR: 41.9-49.6) ng/mL vs 47.6 (IQR: 42.5-51.9) ng/mL; P =.321). CONCLUSIONS: The serum SGLT2 concentration may be a potential biomarker for the diagnosis of AIS. However, it does not exhibit any association with disease severity or functional prognosis.

Layered hybrid PAM-DMT for IM/DD OWC systems.

Traditional pulse-amplitude-modulated discrete multitone modulation (PAM-DMT) suffers from poor overall performance of spectral and power efficiencies in optical wireless communication (OWC) systems. We propose layered hybrid PAM-DMT (LHPAM-DMT) to utilize more subcarriers to improve the performance. The real part of frequency domain signal is divided into several layers and symmetry biases are added in time domain to generate real-valued and nonnegative signals for intensity modulation with direct detection (IM/DD) OWC systems. By appropriately designing the orthogonality between the signals in lower layers and signals & added biases in higher layers, we further propose an iterative receiver to recover the transmitted information. Theoretical derivation proves that LHPAM-DMT has higher spectral efficiency than PAM-DMT and lower complexity than layered PAM-DMT. Numerical results suggest that LHPAM-DMT is more power efficient than PAM-DMT as well as direct-current (DC) biased optical OFDM (DCO-OFDM), one of the most popular schemes.

LncRNA like NMRK2 mRNA functions as a key molecular scaffold to enhance mitochondrial respiration of NONO-TFE3 rearranged renal cell carcinoma in an NAD+ kinase-independent manner.

BACKGROUND: NONO-TFE3 rearranged renal cell carcinoma (NONO-TFE3 rRCC) is one of a subtype of TFE3 rRCCs with high malignancy and poor prognosis. Compared with clear cell RCC, NONO-TFE3 rRCC shows a preference for mitochondrial respiration. We recently identified that the upregulation of nicotinamide ribokinase 2 (NMRK2) was associated with enhanced mitochondrial respiration and tumor progression in TFE3 rRCC. METHODS: A tumor-bearing mouse model was established to verify the pro-oncogenic effect of NMRK2 on NONO-TFE3 rRCC. Then the expression of NMRK2 RNA and protein was detected in cell lines and patient specimens. The NMRK2 transcripts were Sanger-sequenced and blasted at NCBI website. We constructed dCas13b-HA system to investigate the factors binding with NMRK2 RNA. We also used molecular experiments like RIP-seq, IP-MS, FISH and fluorescence techniques to explore the mechanisms that long non-coding RNA (lncRNA) like NMRK2 mRNA promoted the mitochondrial respiration of NONO-TFE3 rRCC. The efficacy of the combination of shRNA (NMRK2)-lentivirus and metformin on NONO-TFE3 rRCC was assessed by CCK-8 assay. RESULTS: In this study, we confirmed that NMRK2 showed transcriptional-translational conflict and functioned as lncRNA like mRNA in the NONO-TFE3 rRCC. Furthermore, we revealed the molecular mechanism that NONO-TFE3 fusion suppressed the translation of NMRK2 mRNA. Most importantly, three major pathways were shown to explain the facilitation effects of lncRNA like NMRK2 mRNA on the mitochondrial respiration of NONO-TFE3 rRCC in an NAD+ kinase-independent manner. Finally, the efficacy of combination of shRNA (NMRK2)-lentivirus and metformin on NONO-TFE3 rRCC was demonstrated to be superior than either agent alone. CONCLUSIONS: Overall, our data comprehensively demonstrated the mechanisms for the enhanced mitochondrial respiration in NONO-TFE3 rRCC and proposed lncRNA like NMRK2 mRNA as a therapy target for NONO-TFE3 rRCC.

The relationship between school climate and general teachers' attitude toward inclusion in China: the mediation effect of teachers' efficacy.

The prosperity of inclusion of students with disabilities largely rest on the attitudes of mainstream teachers. Few studies explore the relationship among school climate, teachers' attitude on inclusion and teachers' efficacy in China. This study surveyed 266 general teachers in China to understand the role of teachers' efficacy on inclusive education between school climate and teachers' attitude. The results indicated that teachers hold positive attitudes towards inclusion on average, especially in the dimension of affection. Additionally, school climate, teachers' efficacy and teachers' attitude were significantly associated, and the mediating effect of teachers' efficacy between school climate and teachers' attitude were proved by mediation analyses. The findings suggested that creating more inclusive school climate and improving general teachers' knowledge and skills on inclusive education, especially the skills on collaboration with others, which could contribute to promote more positive attitude on inclusive education of general teachers.

Correlation Between Oncostatin M and Acute Ischemic Stroke: A Case-Control Study.

BACKGROUND: The expression of oncostatin M (OSM) has been studied in various diseases related to inflammatory response, but its implementation in acute ischemic stroke (AIS) remains to be explored.  Objective: The objective of this study is to assess the correlation between serum OSM expression and various aspects of AIS in a clinical setting. MATERIALS AND METHOD: A single-centered case-control study was performed in the First Affiliate Hospital of Chongqing Medical University from October 2020 to March 2021. A total of 134 patients were enrolled in the AIS group and 34 healthy individuals were enrolled in the control group. Physical examinations were performed and venous blood samples were collected. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum OSM. Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, National Institutes of Health Stroke Scale (NIHSS) score, magnetic resonance imaging (MRI) scan, and modified Rankin scale (mRS) were used to assess the classification, etiology, severity, and prognosis of the AIS group. Assessments were done to analyze serum OSM expression based on sensitivity, etiology, severity, prognosis, and several risk factors of AIS. Regression models, correlation, and sensitivity tests were performed to explore the correlation of OSM expression with various aspects of AIS. RESULTS: There was a statistically significant elevation of serum OSM expression in the AIS group (P<0.001). All AIS subgroups showed elevation in OSM level and statistically significant results were reflected in three subgroups. The area under the curve to differentiate AIS patients and control by serum OSM level was 0.747 (P<0.001), with the optimal cut-off value showing sensitivity at 58.82% and specificity at 75.37%. The elevation of serum OSM expression was proportional with severity, not proportional to the volume of infarct, and less elevated in the favorable outcome group. Serum OSM correlation with several risk factors of AIS was statistically significant in age, low-density lipoprotein, non-high-density lipoprotein, prothrombin time, and systolic blood pressure. CONCLUSION: Serum OSM was expressed differently in correlation with various aspects of AIS. Our findings supported the initial hypothesis that OSM is correlated with various aspects of AIS in humans.

[Expression of SCD1 in TFE3-rRCC and its effect on proliferation and migration].

OBJECTIVE: To investigate the expression of SCD1 in TFE3-rRCC and its effect on the proliferation and migration of TFE3-rRCC cells. METHODS: GEPIA database was used to analyze the expression level of SCD1 in different tumors and its effect on the prognosis of patients. The expression levels of SCD1 in TFE3-rRCC patients and cell lines UOK109 and UOK120 were detected by QPCR and Western blot. Liposomal shRNA was used to knock down SCD1 expression in cell lines. The changes of cell proliferation and migration ability before and after SCD1 knockdown were detected by CCK-8 and Transwell experiments. RESULTS: SCD1 expression levels were higher in all three common renal cancers, and patients with high SCD1 expression had shorter survival and worse prognosis (Logrank P<0.001). The mRNA and protein levels of SCD1 were also significantly increased in renal cancer tissues of patients with high expression of TFE3 and in TFE3-rRCC cell lines UOK109 and UOK120. After SCD1 knockdown, the proliferation and migration ability of UOK109 and UOK120 cells decreased significantly. CONCLUSION: SCD1 is highly expressed in TFE3-rRCC and can promote the proliferation and migration of TFE3-rRCC cell lines, which may be a key molecule in promoting the development of TFE3-rRCC.

Experimental study on underwater continuous-variable quantum key distribution with discrete modulation.

We experimentally demonstrated the feasibility of an underwater continuous-variable quantum key distribution (CV-QKD) system based on four-state protocol, which is promising to guarantee the unconditionally secure underwater wireless optical communication. CV-QKD parameter estimation is performed after transmitting quantum coherent signal from Alice to Bob through a water tank. The secure key rate under collective attack of the demonstrated CV-QKD system is estimated as 22.9 kbits/s at a channel loss of 12.4 dB. In addition, the performance is also investigated with various water types and the maximum underwater transmission distance of the demonstrated CV-QKD system is estimated as 148.7 m in the pure sea water.

RCMNet: A deep learning model assists CAR-T therapy for leukemia.

Acute leukemia is a type of blood cancer with a high mortality rate. Current therapeutic methods include bone marrow transplantation, supportive therapy, and chemotherapy. Although a satisfactory remission of the disease can be achieved, the risk of recurrence is still high. Therefore, novel treatments are demanding. Chimeric antigen receptor-T (CAR-T) therapy has emerged as a promising approach to treating and curing acute leukemia. To harness the therapeutic potential of CAR-T cell therapy for blood diseases, reliable cell morphological identification is crucial. Nevertheless, the identification of CAR-T cells is a big challenge posed by their phenotypic similarity with other blood cells. To address this substantial clinical challenge, herein we first construct a CAR-T dataset with 500 original microscopy images after staining. Following that, we create a novel integrated model called RCMNet (ResNet18 with Convolutional Block Attention Module and Multi-Head Self-Attention) that combines the convolutional neural network (CNN) and Transformer. The model shows 99.63% top-1 accuracy on the public dataset. Compared with previous reports, our model obtains satisfactory results for image classification. Although testing on the CAR-T cell dataset, a decent performance is observed, which is attributed to the limited size of the dataset. Transfer learning is adapted for RCMNet and a maximum of 83.36% accuracy is achieved, which is higher than that of other state-of-the-art models. This study evaluates the effectiveness of RCMNet on a big public dataset and translates it to a clinical dataset for diagnostic applications.

Fluorescent concentrator based MISO-NOMA for visible light communications.

The experimental realization of multiple-input single-output (MISO) in visible light communication (VLC) has always been difficult due to dynamic channels, complex alignment, and limited capacity. We designed a quantum dot (QD) fluorescent concentrator combined with power domain multiplexing of a non-orthogonal multiple access (NOMA) scheme to provide an estimation-free MISO system. The system supports a large detection area of over 4 cm2 and a sum rate up to 120 Mbps over 2.3-m free space, providing a promising connection for the Internet of things (IoT). The concentrator was further implemented in an underwater environment under insufficient incident power. A record data rate of 120 Mbps has been achieved in a 1.5-m underwater MISO system, with a mean bit error rate of 3.24 × 10-3, which is below the forward error correction criterion.

ZooME: Efficient Melanoma Detection Using Zoom-in Attention and Metadata Embedding Deep Neural Network.

Melanoma detection is a crucial yet hard task for both dermatologists and computer-aided diagnosis (CAD). Many traditional machine learning algorithms including deep learning-based methods are employed for melanoma classification. However, more and more complex network architectures do not harvest a leap in model performance. In this paper, we aim to enhance the credibility of CAD approach for melanoma by paying more attention to clinically important information. We propose a Zoom-in Attention and Metadata Embedding (ZooME) melanoma detection network by: 1) introducing a Zoom-in Attention model to better extract and utilize unique pathological information of dermoscopy images; 2) embedding patients' demographic information including age, gender, and anatomic body site, to provide well-rounded information for better prediction. We apply a ten-fold cross-validation on the latest ISIC-2020 dataset with 33,126 dermoscopy images. The proposed ZooME achieved state-of-the-art results with 92.23% in AUC score, 84.59% in accuracy, 85.95% in sensitivity, and 84.63% in specialty, respectively.

The regulation of DKGA2ox1 and miR171f_3 in scion dwarfing with Diospyros kaki Thunb. cv. 'Nan-tong-xiao-fang-shi' as interstocks.

MAIN CONCLUSION: High-throughput sequencing and yeast one and two-hybrid library screening reveal that DKGA2ox1 and miR171f_3 are involved in the regulation of scion dwarfing with 'Nan-tong-xiao-fang-shi' as interstocks. Diospyros kaki Thunb. cv. Nan-tong-xiao-fang-shi ('Nan-tong-xiao-fang-shi') interstocks play a critical role in the scion dwarfing. However, the understanding of the molecular signaling pathways that regulate the scion dwarfing with 'Nan-tong-xiao-fang-shi' as interstocks remain unclear. In this work, the regulatory network in the scion dwarfing with 'Nan-tong-xiao-fang-shi' as interstocks was identified. Using a yeast one-hybrid library screening, luciferase activity analysis, luciferase complementation imaging assays and GFP signal detection, a SPL transcription factor named Diospyros kaki SPL (DKSPL), potentially functioning as a transcriptional activator of the Diospyros kaki GA2ox1 (DKGA2ox1) gene, was identified as a key stimulating factor in the persimmon growth and development. The DKSPL was found in the nucleus, and might play a role in the transcriptional regulation system. A microRNA named miR171f_3 was identified, which might act as a negative regulator of Diospyros kaki SCR (DKSCR) in persimmon. The interactions between DKSCR and seven proteins were experimentally validated with a yeast two-hybrid library screening. Compared to the non-grafted wildtype persimmon, the tissue section of graft union healed well due to the increased expression of cinnamyl-alcohol dehydrogenase. These results indicate that DKGA2ox1 and miR171f_3 may co-promote the scion dwarfing by plant hormone signal transduction pathways.

The regulatory role of gibberellin related genes DKGA2ox1 and MIR171f_3 in persimmon dwarfism.

'Nantongxiaofangshi' (Diospyros kaki Thunb., D. kaki Thunb.) is a local cultivar of persimmon with dwarf-like traits in Jiangsu, China. Closely spaced planting afforded by dwarfism is usually one of the most important ways to promote fruit cultivation and production. However, the understanding of dwarfism in D. kaki Thunb. is very limited at the molecular level, which hinders the further increase of the fruit production. In this work, a persimmon transgenic system was successfully established, and the field experiments of grafting phenotype were carried out. The results showed that D. kaki Thunb. could be used as an interstock to induce dwarfing in grafted scions, and the dwarf character was better when interstock lengths were between 20 and 25 cm. Furthermore, the key genes related to dwarfism in D. kaki Thunb. were screened and verified, and subsequently, the regulatory role of related genes in persimmon dwarfism was figured out. It was found that the gene encoding gibberellin 2-oxidase-1 (DkGA2ox1) involved in GA biosynthesis was associated with the dwarfing in D. kaki Thunb. Overexpression of DkGA2ox1 in Diospyros lotus resulted in a typical dwarf phenotype. Meanwhile, the microRNA data showed that the miR171f_3 demonstrated the active involvement in GA pathway response in persimmon dwarfism. DkGA2ox1 and MIR171f_3, as two highly expressed genes in D. kaki Thunb. interstock, could be used as stimulus signals to affect the content of GA in scion, however, the specific transmission mechanism still needs to be further explored. Ultimately, the bioactive GA level was decreased, resulting in the scion dwarfism.

Full-duplex high-speed indoor optical wireless communication system based on a micro-LED and VCSEL array.

We built a full-duplex high-speed optical wireless communication (OWC) system based on high-bandwidth micro-size devices, for which micro-LED and VCSEL arrays are implemented to establish downlink and uplink, respectively. The high-capacity downlink based on a single-pixel quantum dot (QD) micro-LED can reach a data rate of 2.74 Gbps with adaptive orthogonal frequency division multiplexing (OFDM). VCSEL-based line-of-sight (LOS) and non-line-of-sight (NLOS) uplinks are designed with lens-free receiving functions for a 2.2-m communication distance. Experimental results have been demonstrated and confirmed that both downlink and uplinks are capable of providing sufficient bandwidth for a multi-gigabit OWC. Besides, the lens-free uplink receiver can alleviate requirements for aligning and improve the mobility of the transmitter. The VCSELs implemented for both systems work with low driving currents of 140-mA and 190-mA under consideration of the human eye safety. For non-return-to-zero on-off keying (NRZ-OOK), both uplinks can achieve 2.125 Gbps with bit-error-rate (BER) lower than the forward error correction (FEC) threshold of 3.8×10-3 for Ethernet access.

Ethylene-regulated asymmetric growth of the petal base promotes flower opening in rose (Rosa hybrida).

Flowers are the core reproductive structures and key distinguishing features of angiosperms. Flower opening to expose stamens and gynoecia is important in cases where pollinators much be attracted to promote cross-pollination, which can enhance reproductive success and species preservation. The floral opening process is accompanied by the coordinated movement of various floral organs, particularly petals. However, the mechanisms underlying petal movement and flower opening are not well understood. Here, we integrated anatomical, physiological, and molecular approaches to determine the petal movement regulatory network using rose (Rosa hybrida) as a model. We found that PETAL MOVEMENT-RELATED PROTEIN1 (RhPMP1), a homeodomain transcription factor (TF) gene, is a direct target of ETHYLENE INSENSITIVE3, a TF that functions downstream of ethylene signaling. RhPMP1 expression was upregulated by ethylene and specifically activated endoreduplication of parenchyma cells on the adaxial side of the petal (ADSP) base by inducing the expression of RhAPC3b, a gene encoding the core subunit of the Anaphase-Promoting Complex. Cell expansion of the parenchyma on the ADSP base was subsequently enhanced, thus resulting in asymmetric growth of the petal base, leading to the typical epinastic movement of petals and flower opening. These findings provide insights into the pathway regulating petal movement and associated flower-opening mechanisms.�.

Controlled growth factor delivery system with osteogenic-angiogenic coupling effect for bone regeneration.

OBJECTIVE: Bone regeneration involves a coordinated cascade of events that are regulated by several cytokines and growth factors, among which bone morphogenic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) play important roles. In this study, we investigated the effects of dual release of the three growth factors on bone regeneration in femur defects. METHODS: A composite consisting of Gelatin microparticles loaded with VEGF/FGF-2 and poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH) microparticles loaded with BMP-2 encapsulated in a nano hydroxyapatite-poly actic-co-glycolic acid (nHA-PLGA) scaffold was prepared for the dual release of the growth factors. RESULTS: On the 14th day, decreased release rate of BMP-2 compared with FGF-2 and VEGF was observed. However, after 14 days, compared to FGF-2 and VEGF, BMP-2 showed an increased release rate. Controlled dual release of BMP-2 and VEGF, FGF-2 resulted in a significant osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Moreover, effects of the composite scaffold on functional connection of osteoblast-vascular cells during bone development were evaluated. The synergistic effects of dual delivery of growth factors were shown to promote the expression of VEGF in BMSCs. Increased secretion of VEGF from BMSCs promoted the proliferation and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) in the co-culture system. At 12 weeks after implantation, blood vessel and bone formation were analyzed by micro-CT and histology. The composite scaffold significantly promoted the formation of blood vessels and new bone in femur defects. CONCLUSIONS: These findings demonstrate that dual delivery of angiogenic factors and osteogenic factors from Gelatin and PLGA-PEG-COOH microparticles-based composite scaffolds exerted an osteogenic-angiogenic coupling effect on bone regeneration. This approach will inform on the development of appropriate designs of high-performance bioscaffolds for bone tissue engineering.