Long noncoding RNAs and mRNAs profiling in ovary during laying and broodiness in Taihe Black-Bone Silky Fowls (Gallus gallus Domesticus Brisson).

BACKGROUND: Broodiness significantly impacts poultry egg production, particularly notable in specific breeds such as the black-boned Silky, characterized by pronounced broodiness. An understanding of the alterations in ovarian signaling is essential for elucidating the mechanisms that influence broodiness. However, comparative research on the characteristics of long non-coding RNAs (lncRNAs) in the ovaries of broody chickens (BC) and high egg-laying chickens (GC) remains scant. In this investigation, we employed RNA sequencing to assess the ovarian transcriptomes, which include both lncRNAs and mRNAs, in eight Taihe Black-Bone Silky Fowls (TBsf), categorized into broody and high egg-laying groups. This study aims to provide a clearer understanding of the genetic underpinnings associated with broodiness and egg production. RESULTS: We have identified a total of 16,444 mRNAs and 18,756 lncRNAs, of which 349 mRNAs and 651 lncRNAs exhibited significantly different expression (DE) between the BC and GC groups. Furthermore, we have identified the cis-regulated and trans-regulated target genes of differentially abundant lncRNA transcripts and have constructed an lncRNA-mRNA trans-regulated interaction network linked to ovarian follicle development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses have revealed that DE mRNAs and the target genes of DE lncRNAs are associated with pathways including neuroactive ligand-receptor interaction, CCR6 chemokine receptor binding, G-protein coupled receptor binding, cytokine-cytokine receptor interaction, and ECM-receptor interaction. CONCLUSION: Our research presents a comprehensive compilation of lncRNAs and mRNAs linked to ovarian development. Additionally, it establishes a predictive interaction network involving differentially abundant lncRNAs and differentially expressed genes (DEGs) within TBsf. This significantly contributes to our understanding of the intricate interactions between lncRNAs and genes governing brooding behavior.

Identification and functional analysis of ovarian lncRNAs during different egg laying periods in Taihe Black-Bone Chickens.

Introduction: Long non-coding RNA (lncRNA) refers to a category of non-coding RNA molecules exceeding 200 nucleotides in length, which exerts a regulatory role in the context of ovarian development. There is a paucity of research examining the involvement of lncRNA in the regulation of ovary development in Taihe Black-Bone Chickens. In order to further investigate the egg laying regulation mechanisms of Taihe Black-Bone Chickens at different periods, transcriptome analysis was conducted on the ovarian tissues at different laying periods. Methods: This study randomly selected ovarian tissues from 12 chickens for RNA-seq. Four chickens were selected for each period, including the early laying period (102 days, Pre), the peak laying period (203 days, Peak), and the late laying period (394 days, Late). Based on our previous study of mRNA expression profiles in the same ovarian tissue, we identified three differentially expressed lncRNAs (DE lncRNAs) at different periods and searched for their cis- and trans-target genes to draw an lncRNA-mRNA network. Results and discussion: In three groups of ovarian tissues, we identified 136 DE lncRNAs, with 8 showing specific expression during the early laying period, 10 showing specific expression during the peak laying period, and 4 showing specific expression during the late laying period. The lncRNA-mRNA network revealed 16 pairs of lncRNA-target genes associated with 7 DE lncRNAs, and these 14 target genes were involved in the regulation of reproductive traits. Furthermore, these reproductive-related target genes were primarily associated with signaling pathways related to follicle and ovary development in Taihe Black-Bone Chickens, including cytokine-cytokine receptor interaction, TGF-beta signaling pathway, tyrosine metabolism, ECM-receptor interaction, focal adhesion, neuroactive ligand-receptor interaction, and cell adhesion molecules (CAMs). This study offers valuable insights for a comprehensive understanding of the influence of lncRNAs on poultry reproductive traits.

8-Br-cGMP suppresses tumor progression through EGFR/PLC γ1 pathway in epithelial ovarian cancer.

BACKGROUND: Cyclic guanosine monophosphate (cGMP)-dependent protein kinase I (PKG-I), a serine/threonine kinase, is important in tumor development. The present study determines that the cGMP/PKG I pathway is essential for promoting cell proliferation and survival in human ovarian cancer cells, whereas cGMP analog has been shown to lead to growth inhibition and apoptosis of various cancer cells. The role of cGMP/PKG I pathway in epithelial ovarian cancer (EOC), therefore, remains controversial. We investigated the effect of cGMP/PKG I pathway and the underlying mechanism in EOC. METHODS AND RESULTS: The results showed that exogenous 8-Bromoguanosine-3', 5'-cyclic monophosphate (8-Br-cGMP) (cGMP analog) could antagonize the effects by EGF, including suppressing proliferation, invasion and migration of EOC cells. In vivo, 8-Br-cGMP hampered the growth of the xenograft tumor. Additionally, the expressions of epidermal growth factor receptor (EGFR), matrix metallopeptidase 9 (MMP9), proliferating cell nuclear antigen and Ki67 in xenograft tumor were decreased after 8-Br-cGMP intervention. Further research demonstrated that 8-Br-cGMP decreased the phosphorylation of EGFR (Y992) and downstream proteins phospholipase Cγ1 (PLC γ1) (Y783), calmodulin kinase II (T286) and inhibited cytoplasmic Ca2+ release as well as PKC transferring to cell membrane. It's worth noting that the inhibition was 8-Br-cGMP dose-dependent and 8-Br-cGMP showed similar inhibitory effect on EOC cells compared with U-73122, a specific inhibitor of PLC γ1. CONCLUSIONS: The activation of endogenous PKG I by addition of exogenous 8-Br-cGMP could inhibit EOC development probably via EGFR/PLCγ1 signaling pathway. 8-Br-cGMP/PKG I provide a new insight and strategy for EOC treatment.

Myricetin suppresses TGF-ß-induced epithelial-to-mesenchymal transition in ovarian cancer.

Background: Ovarian cancer (OC) is the second most common gynecological malignancy and has a high mortality rate. The current chemotherapeutic drugs have the disadvantages of drug resistance and side effects. Myricetin, a kind of natural compound, has the advantages of easy extraction, low price, and fewer side effects. Multiple studies have demonstrated the anti-cancer properties of myricetin. However, its impact on OC is still unknown and needs further investigation. Therefore, this study aimed to elucidate the mechanism by which myricetin suppresses transforming growth factor-ß (TGF-ß) -induced epithelial-to-mesenchymal transition (EMT) in OC through in vivo and in vitro experiments. Methods: In vitro experiments were conducted to evaluate the effects of myricetin on cell proliferation and apoptosis using CCK8 assay, plate clonal formation assay, and flow cytometry. Western blot was employed to evaluate the expression levels of caspase-3, PARP, and the MAPK/ERK and PI3K/AKT signaling pathways. Wound healing, transwell, western blot and immunofluorescence assay were used to detect TGF-ß-induced cell migration, invasion, EMT and the levels of Smad3, MAPK/ERK, PI3K/AKT signaling pathways. Additionally, a mouse xenograft model was established to verify the effects of myricetin on OC in vivo. Results: Myricetin inhibited OC proliferation through MAPK/ERK and PI3K/AKT signaling pathways. Flow cytometry and western blot analyses demonstrated that myricetin promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase-3 and the ratio of Bax/Bcl-2 in OC. Furthermore, myricetin suppressed the TGF-ß-induced migration and invasion by transwell and wound healing assays. Mechanistically, western blot indicated that myricetin reversed TGF-ß-induced metastasis through Smad3, MAPK/ERK and PI3K/AKT signaling pathway. In vivo, myricetin significantly repressed OC progression and liver and lung metastasis. Conclusion: Myricetin exhibited inhibitory effects on OC progression and metastasis both in vivo and in vitro. And it also reversed TGF-ß-induced EMT through the classical and non-classical Smad signaling pathways.

TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer.

BACKGROUND: Tetraspanin 8 (TSPAN8), a transmembrane glycoprotein, is implicated in various pathological conditions including human malignancies. However, the roles and underlying mechanisms of TSPAN8 in promoting gastric cancer(GC) progression are yet to be fully understood. METHODS AND RESULTS: Our study found that TSPAN8 expression was significantly elevated in GC tissues. We also observed a positive correlation between high TSPAN8 expression and various clinicopathological characteristics of GC, including tumor differentiation, invasion depth, lymph node metastasis, and clinical stage. Moreover, the elevated TSPAN8 expression was indicative of poor prognosis. Functionally, we observed that knockdown of TSPAN8 significantly attenuated while overexpression of TSPAN8 promoted GC cell migration and invasion. In vivo experiments, knockdown of TSPAN8 suppressed lung metastasis in nude mice. We further explored the underlying mechanisms of TSPAN8 and found that it regulated EGFR expression in GC cells by accelerating phosphorylation of EGFR and AKT. CONCLUSIONS: Our study reveals that TSPAN8 plays a significant role in promoting tumor metastasis by activating the EGFR/AKT pathway, indicating that it may serve as a promising therapeutic target of gastric cancer.

B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer.

B7-H3 is an attractive target for immunotherapy because of its high expression across multiple solid tumors, including prostate cancer, and restricted expression in normal tissues. Among various types of tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematological tumors. However, the potency of CAR-T cell therapy in solid tumors is still limited. Here, we examined the expression of B7-H3 in prostate cancer tissues and cells and developed a second-generation CAR that specifically targets B7-H3 and CD28 as costimulatory receptor to explore its tumoricidal potential against prostate cancer in vitro and in vivo. The high expression of B7-H3 was detected on both the surface of PC3, DU145 and LNCaP cells and prostate cancer tissues. B7-H3 CAR-T cells efficiently controlled the growth of prostate cancer in an antigen-dependent manner in vitro and in vivo. Moreover, tumor cells could induce the proliferation of CAR-T cells and the release of high levels of cytokines of IFN-γ and TNF-α in vitro. Results demonstrated that B7-H3 is a potential target for prostate cancer therapy that supports the clinical development of B7-H3 specific CAR-T cells for prostate cancer.

ORP8 inhibits renal cell carcinoma progression by accelerating Stathmin1 degradation and microtubule polymerization.

ORP8 has been reported to suppress tumor progression in various malignancies. However, the functions and underlying mechanisms of ORP8 are still unknown in renal cell carcinoma (RCC). Here, decreased expression of ORP8 was detected in RCC tissues and cell lines. Functional assays verified that ORP8 suppressed RCC cell growth, migration, invasion, and metastasis. Mechanistically, ORP8 attenuated Stathmin1 expression by accelerating ubiquitin-mediated proteasomal degradation and led to an increase in microtubule polymerization. Lastly, ORP8 knockdown partly rescued microtubule polymerization, as well as aggressive cell phenotypes induced by paclitaxel. Our findings elucidated that ORP8 suppressed the malignant progression of RCC by increasing Stathmin1 degradation and microtubule polymerization, thus suggesting that ORP8 might be a novel target for the treatment of RCC.

Passive Backscatter Communication Scheme for OFDM-IM with Dynamic Carrier Activation.

Multicarrier backscattering has been proposed to improve the communication rate, but the complex circuit structure of multicarrier backscattering devices requires more power consumption, resulting in devices far away from the radio frequency (RF) source without enough power to maintain communication, which greatly reduces the limited communication range in backscattering. To solve this problem, this paper introduces carrier index modulation (IM) into orthogonal frequency division multiplexing (OFDM) backscattering and proposes a dynamic subcarrier activated OFDM-IM uplink communication scheme suitable for passive backscattering devices. When the existing power collection level of the backscatter device is detected, only a subset of carrier modulation is activated using part of the circuit modules to reduce the power threshold required for device activation. The activated subcarriers are mapped by a block-wise combined index using the look-up table method, which can not only transmit information using traditional constellation modulation but also carry additional information through the frequency domain carrier index. Monte Carlo experiments show that this scheme can effectively increase the communication distance and improve the spectral efficiency of low-order modulation backscattering when the power of the transmitting source is limited.

p53 regulates the effects of DAPT on Rac1 activation and migration of non-small-cell lung cancer cells.

The use of γ-secretase inhibitors to inhibit the activation of Notch receptors can effectively inhibit the malignant process of tumors. Here, we demonstrate that p53 can modulate the effect of DAPT (a γ-secretase inhibitor) on the activation of small GTPase Rac1, thereby affecting cell migration of non-small-cell lung cancer H1299 and A549 cells. After treatment with 20 µM DAPT, activation of Rac1 was increased in H1299 cells but not in A549 cells. We further found that the migration ability of H1299 cells was increased, whereas that of A549 cells was reduced. The effect of DAPT on H1299 migration was repressed by Rac1-T17N, a dominant inactivated mutant of Rac1. H1299 is a p53-deficient cell line. When p53 protein was overexpressed in H1299 cells with a pEGFP-p53 plasmid, DAPT treatment no longer activated Rac1 and increased migration ability. Moreover, DAPT promoted the migration of H1299 cells by increasing the activity of Rac1 through the non-canonical Notch pathway. Taken together, these results indicate that the expression of p53 protein in lung cancer cells regulates the effect of DAPT on cell migration by modulating the activation of Rac1, suggesting that p53 may affect the therapeutic effects of Notch inhibitors in lung cancer patients.

Trimer structures formed by target-triggered AuNPs self-assembly inducing electromagnetic hot spots for SERS-fluorescence dual-signal detection of intracellular miRNAs.

Accurate quantitative, in situ and temporal tracking imaging of tumor-associated miRNAs in living cells could provide a basis for cancer diagnosis and prognosis. In this strategy, a surface-enhanced Raman scattering (SERS)-fluorescence (FL) dual-spectral sensor (DSS) was constructed based on the nanoscale photophysical properties of AuNPs, mediated by functionalized DNA, to achieve rapid imaging of FL and accurate SERS quantification of intracellular miRNAs. The dual-spectrum sensor in the strategy is highly sensitive, specific and reproducibly stable. The LOD values of the dual spectra were 3.58 pM (SERS) as well as 11.8 pM (FL) with RSD values less than 2.69%. The bispectral sensor self-assembled into a trimer by the lapidation of Y-type DNA under the excitation of the target, generating a stable enhanced electric field coupling; and selected adenine located in the enhanced electric field as the reporter molecule, simplifying the labeling process and variables of the Raman reporter molecule, distinguishing it from other traditional methods. This strategy successfully achieved accurate tracking and quantification of miR-21 in cancer cells and showed good stability in the cells. The reported probes are potential tools for reliable monitoring of biomolecular dynamics in living cells.

Increased endogenous PKG I activity attenuates EGF-induced proliferation and migration of epithelial ovarian cancer via the MAPK/ERK pathway.

The type I cGMP-dependent protein kinase (PKG I) is recognized as a tumor suppressor, but its role in EGFR regulated epithelial ovarian cancer (EOC) progression remains unclear. We evaluated the in vivo and in vitro effects of activated PKG I in EGF-induced EOC cell proliferation, migration, and invasion. The expressions of EGFR and PKG I were elevated, but the activated PKG I was decreased in EOC tissues of patients and cells lines. The addition of 8-Br-cGMP, a specific PKG I activator, attenuated the EGF-induced EOC cell proliferation, migration, and invasion in vitro. Similarly, activated PKG I also attenuated EOC progression in vivo using an EOC xenograft nude mouse model. The activated PKG I interacted with EGFR, causing increased threonine (693) phosphorylation and decreased tyrosine (1068) phosphorylation of EGFR, which resulted in disrupted EGFR-SOS1-Grb2 combination. Subsequently, the cytoplasmic phosphorylation of downstream proteins (c-Raf, MEK1/2, and ERK1/2) were declined, impeding the phosphorylated ERK1/2's nucleus translocation, and this reduction of phosphorylated tyrosine (1068) EGFR and ERK1/2 were also abolished by Rp-8-Br-cGMPS. Our results suggest that the activation of PKG I attenuates EGF-induced EOC progression, and the 8-Br-cGMP-PKG I-EGFR/MEK/ERK axis might be a potential target for EOC therapy.

Construction of a novel nano-enzyme for ultrasensitive glucose detection with surface-enhanced Raman scattering.

Fabricating more sensitive, stable and low-cost nanomaterials for the detection of glucose is important for the disease diagnosis and monitoring. Herein, we established a nanocomposite (polypyrrole bridging GO@Au@MnO2) as a novel surface-enhanced Raman scattering (SERS) nanoprobe for the quantitative detection of glucose in trace serum. Each component in the nanocomposites played an irreplaceable role in SERS detection of glucose. Polypyrrole (PPy) could act as Raman signal and extra SERS signal molecules didn't need to be introduced; Graphene oxide (GO) and gold nanoparticles (Au NPs) could enhance Raman signal of PPy; Au NPs also acted as glucose oxidase, which can oxidize glucose to produce gluconic acid and hydrogen peroxide(H2O2); Manganese oxide (MnO2) further enhanced Raman signal of PPy and responded to hydrogen peroxide, which will induce the decrease of Raman intensity of PPy. Thus, glucose can be quantified according to Raman signal output of PPy, which displayed a liner range from 1 to 10 µM, with detectable limit of 0.114 µM. Because of the merits in sensitivity, convenience and versatility, the novel method shows large potential space for disease-related substance detection in the future.

Changes in Quality and Collagen Properties of Cattle Rumen Smooth Muscle Subjected to Repeated Freeze-Thaw Cycles.

This study revealed changes in the quality, structural and functional collagen properties of cattle rumen smooth muscle (CSM) during F-T cycles. The results showed that thawing loss, pressing loss, ß-galactosidase, ß-glucuronidase activity, ß-sheet content, emulsifying activity index (EAI), emulsion stability index (ESI), surface hydrophobicity, and turbidity of samples were significantly (p < 0.05) increased by 108.12%, 78.33%, 66.57%, 76.60%, 118.63%, 119.57%, 57.37%, 99.14%, and 82.35%, respectively, with increasing F-T cycles. Meanwhile, the shear force, pH, collagen content, α-helix content, thermal denaturation temperature (Tmax), and enthalpy value were significantly (p < 0.05) decreased by 30.88%, 3.19%, 33.23%, 35.92%, 10.34% and 46.51%, respectively. Scanning electron microscopy (SEM) and SDS-PAGE results indicated that F-T cycles induced an increase in disruption of CSM muscle microstructure and degradation of collagen. Thus, repeated F-T cycles promoted collagen degradation and structural disorder in CSM, while reducing the quality of CSM, but improving the functional collagen properties of CSM. These findings provide new data support for the development, processing, and quality control of CSM.

Underwater Acoustic Target Recognition Based on Attention Residual Network.

Underwater acoustic target recognition is very complex due to the lack of labeled data sets, the complexity of the marine environment, and the interference of background noise. In order to enhance it, we propose an attention-based residual network recognition method (AResnet). The method can be used to identify ship-radiated noise in different environments. Firstly, a residual network is used to extract the deep abstract features of three-dimensional fusion features, and then a channel attention module is used to enhance different channels. Finally, the features are classified by the joint supervision of cross-entropy and central loss functions. At the same time, for the recognition of ship-radiated noise in other environments, we use the pre-training network AResnet to extract the deep acoustic features and apply the network structure to underwater acoustic target recognition after fine-tuning. The two sets of ship radiation noise datasets are verified, the DeepShip dataset is trained and verified, and the average recognition accuracy is 99%. Then, the trained AResnet structure is fine-tuned and applied to the ShipsEar dataset. The average recognition accuracy is 98%, which is better than the comparison method.

Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway.

Ovarian cancer is one of the most common gynecological malignancies in women worldwide with a poor survival rate. Cinnamaldehyde (CA), a bioactive substance isolated from cinnamon bark, is a natural drug and has shown that it can inhibit the progression of other tumors. However, the role of CA in ovarian cancer and its mechanism is poorly understood. In this study, wound healing assays, plate cloning, CCK-8, and transwell assays were used to determine cell proliferation and invasion. Western blot and flow cytometry were used to detect apoptosis levels. Western blot and immunofluorescence were used to detect changes in cellular EMT levels. The Western blot was used to detect levels of the PI3K/AKT signaling pathway. In vivo, we established a subcutaneous transplantation tumor model in nude mice to verify the role of CA in the progression and metastasis of ovarian cancer. Our data showed that in vitro CA was able to inhibit the cell viability of ovarian cancer. The results of scratch assay and transwell assay also showed that CA inhibited the proliferation and invasion ability of A2780 and SKOV3 cells. In addition, CA promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase 3 in ovarian cancer cells. Mechanistically, we found that CA inhibited the EGF-induced PI3K/AKT signaling pathway and reduced the phosphorylation levels of mTOR, PI3K, and AKT. The EGF-induced EMT process was also abolished by CA. The EMT process induced by AKT-specific activator SC79 was also suppressed by CA. Furthermore, in in vivo, CA significantly repressed the progression of ovarian cancer as well as liver metastasis. In all, our results suggest that CA inhibits ovarian cancer progression and metastasis in vivo and in vitro and inhibits EGF-induced EMT processes through the PI3K/AKT signaling pathway.

ADAM10-cleaved ephrin-A5 contributes to prostate cancer metastasis.

A disintegrin and metalloprotease-10(ADAM10) promotes the metastasis of prostate cancer (PCa), but the specific mechanism is indistinct. Herein, DU145 cell lines with stable overexpression and knockdown of ADAM10 were constructed. We found that ectopic expression of ADAM10 not only significantly facilitated cell proliferation, migration, invasion, and inhibited apoptosis, but also could specifically hydrolyze ephrin-A5 and release the ephrin-A5 soluble ectodomain into extracellular media in vitro. These effects were reversed by ADAM10 depletion or treatment of GI254023X. Meanwhile, the co-location and physical interaction among EphA3, ephrin-A5, and ADAM10 were observed in PCa cells using immunofluorescence and immunoprecipitation techniques. Interestingly, overexpression of EphA3 exerted opposite effects in DU145 (ephrin-A5 + ) cells and PC-3 (ephrin-A5 ± ) cells. In addition, the pro-tumor function of EphA3 was reversed by the treatment with the exogenous ephrin-A5-Fc, which increased the phosphorylation level of EphA3 in PC-3 (ephrin-A5 ± ) cells. In nude mice, ADAM10 accelerated growth of the primary tumor, decreased the level of ephrin-A5 in the tumor tissue, but increased the level of ephrin-A5 in the peripheral blood, accompanied with an increase in the expression of CD31 and VEGF (vascular endothelial growth factor) in the tissue. What is more, the serum ephrin-A5 content of patients with metastatic PCa was significantly higher than that of the non-metastatic group (P < 0.05). The receiver operating characteristic curve(ROC) showed that the area under the curve(AUC) of serum ephrin-A5 as a marker of PCa metastasis was 0.843, with a sensitivity of 93.5% and a specificity of 75%. It is concluded that ADAM10-mediated ephrin-A5 shedding promotes PCa metastasis via transforming the role of EphA3 from ligand-dependent tumor suppressor to ligand-independent promoter, and ephrin-A5 in the blood can be used as a new biomarker for PCa metastasis.

The Development of Filler Morphology in Dental Resin Composites: A Review.

Dental resin composites (DRCs) with diverse fillers added are widely-used restorative materials to repair tooth defects. The addition of fillers brings an improvement in the mechanical properties of DRCs. In the past decade, diverse fillers have emerged. However, the change of emerging fillers mainly focuses on the chemical composition, while the morphologic characteristics changes are often ignored. The fillers with new morphologies not only have the advantages of traditional fillers (particles, fibrous filler, etc.), but also endow some additional functional characteristics (stronger bonding ability to resin matrix, polymerization resistance, and wear resistance, drug release control ability, etc.). Moreover, some new morphologies are closely related to the improvement of traditional fillers, porous filler vs. glass particles, core-sheath fibrous vs. fibrous, etc. Some other new morphology fillers are combinations of traditional fillers, UHA vs. HA particles and fibrous, tetrapod-like whisker vs. whisker and fibrous filler, mesoporous silica vs. porous and silica particles. In this review, we give an overall description and a preliminary summary of the fillers, as well as our perspectives on the future direction of the development of novel fillers for next-generation DRCs.

Target-Triggered Nanomaterial Self-Assembly Induced Electromagnetic Hot-Spot Generation for SERS-Fluorescence Dual-Mode In Situ Monitoring MiRNA-Guided Phototherapy.

A multifunctional theranostic nanosystem that integrates dynamic monitoring and therapeutic functions is necessary for precision tumor medicine. Herein, an entropy-driven self-assembly nanomachine is developed that overcomes the mechanism differences of different diagnostic modes and is applied to miRNA surface-enhanced Raman scattering (SERS)-fluorescence dual-mode dynamic monitoring and synergy phototherapy. It is worth noting that the activated dual-mode theranostic nanosystem (DTN) is capable of tumor in situ fluorescence imaging and SERS absolute quantification of the target. After being internalized into tumor cells, the DTN nanosystem is activated by the DNA cascade chain displacement of the target miR-21, resulting in the secondary release of fluorophores and the assembly of core-satellite structures (CS structures). The coupling of localized surface plasmon resonances (LSPRs) in the CS structure results in the formation of numerous enhanced electric fields (hot spot) in the nanogap of the CS structure. Then the DTN nanosystem greatly improves the sensitivity and repeatability of Raman detection by converting trace targets into numerous adenines residing in the electromagnetic hot spot of the CS structure. Meanwhile, the CS structure and the loaded photosensitizer are used for synergy phototherapy under the guidance of fluorescence imaging. This proposed strategy is confirmed by in vivo and in vitro results, and it provides new ideas for tumor SERS-fluorescence dual-mode diagnosis and effective tumor therapy.

The utility of competency-oriented clinical laboratory teaching combined with case-based learning (CBL).

OBJECTIVES: This study aimed to evaluate the effectiveness and efficiency of competency-oriented clinical laboratory teaching combined with case-based learning (CBL) and improve the examination of students' competence of laboratory medicine. METHODS: A total of 107 medical laboratory medicine interns at the Affiliated Hospital of Xuzhou Medical University from June 2017 to July 2019 volunteered to participate in the study and were randomly assigned into a control group with training of the traditional teacher-centered method, and an experimental group under a CBL teaching program. Student basic theory tests and skill assessment were designed to evaluate what the students gained from their internship when they completed their studies at the Affiliated Hospital of Xuzhou Medical University. RESULTS: Compared to students in the control group taught with the teacher-centered method, those in the CBL teaching program had significantly higher theory test scores and skill assessment scores on average. Competencies with particularly significant improvement included identification and processing of instrument alarm information, analysis of test results, identification and solution of the problem, as well as identification and reporting of the critical value and clinical communication. CONCLUSIONS: The competency-oriented teaching method combined with CBL is an effective method for improving students' professional knowledge, increasing language expression, and enhancing interpersonal relationship and teamwork, which is worthy of being promoted in laboratory medicine teaching.

Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT.

BACKGROUND: Ephrin-A2, a member of the Eph receptor subgroup, is used in diagnosing and determining the prognosis of prostate cancer. However, the role of ephrin-A2 in prostate cancer is remains elusive. METHODS: We established stable clones overexpressing or silencing ephrin-A2 from prostate cancer cells. Then, CCK-8 was used in analyzing the proliferation ability of cells. CD31 staining was used in evaluating angiogenesis. Migration and invasion assay were conducted in vivo and in vitro. The expression of EMT-related markers was evaluated in prostate cancer cells through Western blotting. RESULTS: We revealed that the ectopic expression of ephrin-A2 in prostate cancer cells facilitated cell migration and invasion in vitro and promoted tumor metastasis and angiogenesis in vivo and that the silencing of ephrin-A2 completely reversed this effect. Although ephrin-A2 did not affect tumor cell proliferation in vitro, ephrin-A2 significantly promoted primary tumor growth in vivo. Furthermore, to determine the biological function of ephrin-A2, we assayed the expression of EMT-related markers in stable-established cell lines. Results showed that the overexpression of ephrin-A2 in prostate cancer cells down-regulated the expression of epithelial markers (ZO-1, E-cadherin, and claudin-1) and up-regulated the expression of mesenchymal markers (N-cadherin, ß-catenin, vimentin, Slug, and Snail), but the knocking out of ephrin-A2 opposed the effects on the expression of EMT markers. CONCLUSIONS: These findings indicate that ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT and may be a potentially therapeutic target in metastatic prostate cancer.