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Optical devices play an important role in different fields, such as refractive index detection in food processing and the biochemical industry. In our work, a novel nanoscale optical structure, composed of a metal-insulator-metal waveguide with a stub and a horizontal number eight-shape cavity (HNEC), is presented. The transmission properties of this structure are investigated in detail by using finite element method The effects of geometric parameters on sensing performance are studied in detail. Moreover, the influences of an asymmetric resonator caused by shifting central rectangular cavity of HNEC on transmission spectrum are discussed. The changing parameters of HNEC resonator have different effects on different resonance dips. Then, when the parameters of this presented structure are fixed as a of 540 nm, b of 340 nm, S of 0, l of 70 nm and g of 10 nm, this intriguing structure can serve as a refractive index sensor, whose maximum sensitivity can reach 1,500 nm/refractive index unit with a figure of merit of 75. Therefore, this structure will contribute to the development of miniaturization of optical devices.

Carbon dioxide and methane are the two most important greenhouse gases and are closely related to global warming and extreme weather events. To master their spatial and temporal variations, the CO2 and CH4 concentration data monitored by the GOSAT satellite in 2020 and 2021 were used to map and analyse the annual, seasonal and monthly changes in CO2 and CH4 concentrations in the world and major countries/regions. The results demonstrate that (1) in 2021, the average annual CO2 concentration over the global land area was 412.74 ppm, an increase in 0.64% compared with the same period last year, and there were spatial differences in the distribution of CO2 concentration, with high values mostly concentrated in the middle latitudes of the Northern Hemisphere; (2) compared with 2020, the CO2 concentration in China, the United States, India, the European Union and other countries/regions increased significantly; (3) in 2020 and 2021, the quarterly CO2 trend of the global and major countries/regions was the same, which was higher in the first (January, February, March) and second (April, May, June) quarters, significantly lower in the third (July, August, September) quarter, and gradually increased in the fourth (October, November, December) quarter. Further work on long time series and validation needs to be conducted.

Cell senescence is one of the most important forms of injury induced by cardiovascular and other ischemic diseases. Fibroblasts are important participants in tissue repair after ischemic injury and the main source of IL11 secretion. However, the roles of oxygen–glucose deprivation (OGD) and IL11 in promoting fibroblast senescence and their regulatory mechanisms remain unclear. This study selected the NIH3T3 and L929 fibroblast cell lines as research objects. We found that OGD could induce the expression of p53, P16, p21, and collagen in fibroblasts. In the condition of OGD, when IL11 intervened, fibroblasts’ senescence and collagen expression were changed. Some studies have found that changes in kynurenine (KYN) metabolism are related to aging diseases, and indoleamine 2,3-dioxygenase 1 (IDO1) is a key rate-limiting enzyme in the KYN metabolic pathway. We found that KYN secretion decreased after OGD increased fibroblast senescence, and inhibition of IL11 promoted IDO1 and increased KYN secretion. These results suggest that OGD may promote fibroblast senescence and collagen expression via IL11 inhibition of the IDO1/KYN metabolic pathway. Therefore, the revealed mechanism of OGD-promoted fibroblast senescence could provide an effective theoretical basis for the clinical treatment of aging-related ischemic diseases.

Multiple-input–multiple-output (MIMO) communication systems utilize multiple transmitters to send different pieces of information in parallel. This offers a promising way to communicate at a high data rate over bandwidth-limited underwater acoustic channels. However, underwater acoustic MIMO communication not only suffers from serious inter-symbol interference, but also critical co-channel interference (CoI), both of which degrade the communication performance. In this paper, we propose a new framework for underwater acoustic MIMO communications. The proposed framework consists of a CoI-cancellation-based channel estimation method and channel-estimation-based decision feedback equalizer (CE-DFE) with CoI cancellation functionalities for underwater acoustic MIMO communication. We introduce a new channel estimation model that projects the received signal to a specific subspace where the interference is free; therefore, the CoI is cancelled. We also introduce a CE-DFE with CoI cancellation by appending some filters from traditional CE-DFE. In addition, the traditional direct adaptive decision feedback equalization (DA-DFE) method and the proposed method are compared in terms of communication performance and computational complexity. Finally, the sea trial experiment demonstrates the effectiveness and merits of the proposed method. The proposed method achieves a more than 1 dB of output SNR over traditional DA-DFE, and is less sensitive to parameters. The proposed method provides a new approach to the design of robust underwater acoustic MODEM.

Bacillus amyloliquefaciens NCPSJ7 showed potential fungicidal activities for the effective control of fungal infection. From the PCR test, the key genes (srfAA, sfp, fenD, bmyB, ituD, and ituC) were detected in B. amyloliquefaciens NCPSJ7. These genes were closely related to the lipopeptides (LPs) synthesis. Next, three LPs families were identified with liquid chromatography–mass spectrometry (LC/MS), including iturin A, fengycin A, and surfactin. After purification with C18, the main active antifungal compound was proven to be C14-iturin A by ESI-HRMS, which has significant activities against fungi. These results proved that C14-iturin A played an important role in inhibiting the growth of fungi for B. amyloliquefaciens NCPSJ7. Furthermore, the isolated LP could inhibit mycelial growth and conidia germination at 30 μg/mL. SEM allowed us to observe that mycelial morphology and conidia germination were also affected. The mycelial ultrastructure TEM observations showed that the external electron-dense outer layer cell wall, which mainly consisted of glycoproteins, was affected. Furthermore, swollen mitochondria, enriched glycogen, and increased vacuoles were also found. LP also affected the intact wall and membranes, leading to their increased permeability, which was proved by propidium iodide (PI) staining and conductivity measurements. Meanwhile, the ergosterol, which has an affinity for iturin A, also increased. These results indicated that LP caused fungal dysfunction and membrane permeability increase, leading to fungal inhibition. Identifying and studying LPs is important in exploring the fungicidal activities of B. amyloliquefaciens, which promotes the use of B. amyloliquefaciens NCPSJ7 as a potential candidate for biocontrol.

BackgroundAdiposity and adipokines are associated with metabolic disorders, but little is known regarding that whether adiposity measurements link metabolic syndrome (MetS) through circulating neuregulin 4 (Nrg4) and adipsin levels.Materials and MethodsA total of 1212 subjects with a waist circumference greater than 90 cm for men or 80 cm for women were enrolled from a Chinese community. Circulating Nrg4 and adipsin levels were measured using commercial kits. Mediation analyses of circulating Nrg4 and adipsin were performed in the study using linear and logistic regression.ResultsSubjects with MetS had higher waist circumference, visceral fat level, and circulating adipsin level, and lower levels of circulating Nrg4 and muscle mass to visceral fat (MVF) ratio (all P < 0.05). In multivariable logistic regression analyses, after adjusting for confounding variables, per standard deviation (SD) increase in waist circumference and visceral fat level were significantly associated with increased odds of MetS [OR (95% CI), 1.42 (1.22–1.64); 2.20 (1.62–2.99); respectively]; and per SD reduction in MVF ratio was significantly associated with reduced odds of MetS [OR (95% CI), 0.65 (0.55–0.77)]. In the mediation analyses, both circulating Nrg4 and adipsin levels mediated the association between waist circumference (8.31% and 18.35%, respectively), visceral fat level (7.50% and 9.98%, respectively), and MVF ratio (5.80% and 9.86%, respectively) and MetS after adjustments.ConclusionThese findings indicate that adiposity measurements and MetS are linked through circulating Nrg4 and adipsin levels in obese adults, suggesting that circulating Nrg4 and adipsin levels might be potential predictors for management of MetS.

BackgroundMyasthenia gravis (MG) is the most common paraneoplastic syndromes of thymoma and closely related to thymus abnormalities. Timely detecting of the risk of MG would benefit clinical management and treatment decision for patients with thymoma. Herein, we developed a 3D DenseNet deep learning (DL) model based on preoperative computed tomography (CT) as a non-invasive method to detect MG in thymoma patients.MethodsA large cohort of 230 thymoma patients in a hospital affiliated with a medical school were enrolled. 182 thymoma patients (81 with MG, 101 without MG) were used for training and model building. 48 cases from another hospital were used for external validation. A 3D-DenseNet-DL model and five radiomic models were performed to detect MG in thymoma patients. A comprehensive analysis by integrating machine learning and semantic CT image features, named 3D-DenseNet-DL-based multi-model, was also performed to establish a more effective prediction model.FindingsBy elaborately comparing the prediction efficacy, the 3D-DenseNet-DL effectively identified MG patients and was superior to other five radiomic models, with a mean area under ROC curve (AUC), accuracy, sensitivity, and specificity of 0.734, 0.724, 0.787, and 0.672, respectively. The effectiveness of the 3D-DenseNet-DL-based multi-model was further improved as evidenced by the following metrics: AUC 0.766, accuracy 0.790, sensitivity 0.739, and specificity 0.801. External verification results confirmed the feasibility of this DL-based multi-model with metrics: AUC 0.730, accuracy 0.732, sensitivity 0.700, and specificity 0.690, respectively.InterpretationOur 3D-DenseNet-DL model can effectively detect MG in patients with thymoma based on preoperative CT imaging. This model may serve as a supplement to the conventional diagnostic criteria for identifying thymoma associated MG.

Exosomes, a key element of the central nervous system microenvironment, mediate intercellular communication via horizontally transferring bioactive molecules. Emerging evidence has implicated exosomes in the regulation of neurogenesis. Recently, we compared the neurogenic potential of exosomes released from primary mouse embryonic neural stem cells (NSCs) and astrocyte-reprogrammed NSCs, and observed diverse neurogenic potential of those two exosome populations in vitro. However, the roles of NSC-derived exosomes on NSC differentiation and the underlying mechanisms remain largely unknown. In this study, we firstly demonstrated that NSC-derived exosomes facilitate the differentiation of NSCs and the maturation of both neuronal and glial cells in defined conditions. We then identified miR-9, a pro-neural miRNA, as the most abundantly expressed miRNA in NSC-derived exosomes. The silencing of miR-9 in exosomes abrogates the positive effects of NSC-derived exosomes on the differentiation of NSCs. We further identified Hes1 as miR-9 downstream target, as the transfection of Hes1 siRNA restored the differentiation promoting potential of NSC-derived exosomes after knocking down exosomal miR-9. Thus, our data indicate that NSC-derived exosomes facilitate the differentiation of NSCs via transferring miR-9, which sheds light on the development of cell-free therapeutic strategies for treating neurodegeneration.

Anticancer bioactive peptide (ACBP), a novel bioactive peptide isolated from spleens of goats immunized with tumor extracts in our lab, can inhibit the proliferation of CRC in vitro and vivo. However, it remains unclear how the proliferation of CRC is inhibited by ACBP at the molecular level. Here, we provide evidences showing that ACBP significantly inhibits the expression of Wnt/β-catenin related genes (cyclin D1, met and c-myc) through pharmacotranscriptomic and qRT-PCR analysis in CRCs. Active β-catenin, a key protein within Wnt pathway, was compromised remarkably by ACBP in three CRCs, including HCT116, RKO and HT29. Thus nuclear accumulation of active β-catenin was retarded and finally lead to the decreased expression of oncogenes cyclin D1, met, and c-myc. In addition, we proved that active β-catenin reduction was mainly due to the inhibition of phospho-LRP6 and stimulation of phospho-β-catenin by ACBP. Based on the detection of Met and C-Myc in CRC tumor tissue without prior radiotherapy or chemotherapy, our results demonstrated that ACBP can act as a promising anticancer agent for CRC by targeting Wnt/β-catenin pathway, especially active β-catenin.

Abstract Background Recent studies suggested that miR-17~106 family was involved in the regulation of neural stem/progenitor cells (NPCs). However, distinct function of each family member was reported in regulating stem cells within and without the brain. Hence, to investigate the roles of individual miRNAs in miR-17~106 family and mechanisms underlying their effects on neurogenesis is important to extend our understanding in the CNS development. Methods Here, we examined the influence of miR-106a/b on the proliferation, differentiation, and survival of embryonic NPCs using specific mimics and inhibitor. The targets of miR-106a/b were identified from miRNA target prediction database and confirmed by luciferase assay. Specific siRNAs were utilized to erase the effects of miR-106a/b on the expression levels of target genes. Results A positive correlation was observed between the temporal reduction of miR-106a/b expression levels and the decline of NPC pools in vivo and in vitro. The perturbation of miR-106’s function approaches revealed that miR-106b, but not miR-106a, facilitated the maintenance of NPCs and repressed the generation of both neuronal and glial cells, without preference to a particular lineage. No effect was observed for miR-106a/b in NPCs’ survival. The influence of miR-106b on NPCs’ proliferation and differentiation is likely achieved by directly inhibiting the expression of Tp53inp1 and Cdkn1a, key components of Tp53inp1-Tp53-Cdkn1a axis. Conclusion Our study demonstrated a novel axis, miR-106b-Tp53inp1-Tp53-Cdkn1a, in regulating the proliferation and differentiation of NPCs.

Abstract Background The quantity of metastases lesions is an important reference when it comes to making a more informed treatment decision for patients with colorectal cancer liver metastases. However, the molecular alterations in patients with different numbers of lesions have not been systematically studied. Methods We investigated somatic alterations and microsatellite instability (MSI) of liver metastases from patients with single, multiple or diffuse metastasis lesions. A new algorithm “Pathway Damage Score” was developed to comprehensively assess the functional impact of somatic alterations at the pathway level. Pathogenic pathways of different metastasis were identified and their prognosis effects were evaluated. Furthermore, the subnetworks and affected phenotypes of the altered genes in each pathogenic pathway were analyzed. Results Somatic alterations and altered genes occurred sporadically as well as in MSI state in different metastasis types, although MSS patients had more metastatic lesions than that of the MSI patients. Every metastasis group has their own pathogenic pathways and damaged “Cargo recognition for clathrin‐mediated endocytosis” is significantly associated with poor prognosis (P

The present study aims to investigate the effect of Longan Arillus extract (ELA) on oral absorption of bioactive peptides (cationic P1: VEGNLQVLRPR, anionic P2: HNLDTQTESDV) derived from defatted walnut meal hydrolysates (DWMH). Oral co-delivery of ELA with DWMH led to a significantly higher maximum blood concentration of P2 in rats than delivering DWMH alone. Endocytosis pathway of P2 in intestinal epithelia cells was altered by ELA, probably resulting from formation of uniform microparticles by mixing of P2 and ELA. Results of isothermal calorimetry proved strong binding between molecules of P2 and ELA at a molar ratio of 1:1. On the contrary, the absorption of cationic P1 remained unchanged after co-delivery of ELA, probably resulting from the complicated patterns of binding between ELA and P1 molecules. In conclusion, we found the enhancing effect of polysaccharides on absorption of peptides by formation of microparticles, which could be predicted by molecule binding.

Base editors can efficiently produce single nucleotide alterations without requiring a double-strand break. Here the authors show base editing at multiple sites simultaneously in pigs.

Abstract Background Systemic alterations in coagulation are associated with complications of acute pancreatitis (AP). D-dimer, a fibrin degradation product, was recently described as a marker of pancreatitis outcome. Early prediction is essential for reducing mortality in AP. The present study aims to assess the relationship between elevated serum D-dimer levels and the severity of AP. Methods We performed an observational retrospective study with data from 3451 enrolled patients with AP. Serum D-dimer levels were measured upon admission, after 24 h and during the week after admission by immunoturbidimetry. Univariate and multivariate analyses were used to determine whether elevated D-dimer levels were independently associated with the severity of AP. Results Of the 3451 AP patients, 2478 (71.8%) had serum D-dimer levels measured within 24 h of hospital admission; 1273 of these patients had D-dimer levels ≤2.5 mg/L, and 1205 had D-dimer levels > 2.5 mg/L (934 patients had mild AP (MAP); 1086, moderately severe AP (MSAP); and 458, severe AP (SAP)). Patients with D-dimer levels > 2.5 mg/L (n = 1205) had higher incidences of SAP (75.5% vs. 24.5%), acute peripancreatic fluid collection (APFC) (53.3% vs. 46.7%), acute necrotic collection (ANC) (72.4% vs. 27.6%), pancreatic necrosis (PN) (65.2% vs. 34.8%), infected pancreatic necrosis (IPN) (77.7% vs. 22.8%), organ failure (OF) (68.5% vs. 31.5%), persistent organ failure (POF) (75.5% vs. 24.5%), ICU requirement (70.2% vs. 29.8%), and mortality (79.2% vs. 20.8%) than did patients with D-dimer levels ≤2.5 mg/L (n = 1273). The multivariate analysis showed that patients with higher serum D-dimer levels had poorer prognoses that worsened over time. Conclusion The measurement of D-dimer levels at admission may be useful for risk stratification of AP.

Abstract Background Cell surface display of recombinant proteins has become a powerful tool for biotechnology and biomedical applications. As a model eukaryotic microorganism, Saccharomyces cerevisiae is an ideal candidate for surface display of heterologous proteins. However, the frequently used commercial yeast surface display system, the a-agglutinin anchor system, often results in low display efficiency. Results We initially reconstructed the a-agglutinin system by replacing two anchor proteins with one anchor protein. By directly fusing the target protein to the N-terminus of Aga1p and inserting a flexible linker, the display efficiency almost doubled, and the activity of reporter protein α-galactosidase increased by 39%. We also developed new surface display systems. Six glycosylphosphatidylinositol (GPI) anchored cell wall proteins were selected to construct the display systems. Among them, Dan4p and Sed1p showed higher display efficiency than the a-agglutinin anchor system. Linkers were also inserted to eliminate the effects of GPI fusion on the activity of the target protein. We further used the newly developed Aga1p, Dan4p systems and Sed1p system to display exoglucanase and a relatively large protein β-glucosidase, and found that Aga1p and Dan4p were more suitable for immobilizing large proteins. Conclusion Our study developed novel efficient yeast surface display systems, that will be attractive tools for biotechnological and biomedical applications

In the process of gear fault feature extraction， empirical mode decomposition （EMD） has the problem of modal aliasing， intrinsic mode function（IMF） screening difficulty， and Wigner-Ville distribution（WVD） has cross-terms interference. So， a gear fault diagnosis method combining ensemble empirical mode decomposition（EEMD） decomposition and Choi-Williams distribution（CWD） is proposed. Firstly， the collected signal is decomposed by EEMD and decomposed into the combination of single component intrinsic mode functions. Then， the false components are removed and IMFs are screened through the correlation coefficient and Shannon entropy. Finally， the selected IMF components are expressed in CWD time frequency graph， and the gear fault features are extracted with the characteristics of frequency and isochronous impact exhibited in the time-frequency domain. Through simulation and experimental analysis， the applicability and effectiveness of this proposed method in gearbox gear fault diagnosis are verified.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a cause of male infertility. Here the authors identify homozygous nonsense mutations of the glutamine rich 2 (QRICH2) gene in two MMAF patients from 2 consanguineous families and show using QRICH2 knockout mice that the protein is required for sperm flagellar formation and motility.

We recently reported that siRNA-knockdown of delta-5-desaturase (D5D), the rate-limiting enzyme converting upstream ω − 6 dihomo-γ-linolenic acid (DGLA) to arachidonic acid, promoted formation of the anti-cancer byproduct 8-hydroxyoctanoic acid (8-HOA) from COX-2-catalyzed DGLA peroxidation, consequently suppressing pancreatic cancer cell growth, migration and invasion. In this study, we have further investigated the anti-tumor effects of D5D-knockdown and the resulting intensified COX-2-catalyzed DGLA peroxidation in subcutaneous xenograft tumors. Four-week old female nude mice (Jackson Laboratory, J:Nu-007850) were injected with human pancreatic cancer cell line BxPC-3 or its D5D knockdown counterpart (via shRNA), followed by 4-week treatments of: vehicle control, DGLA supplementation (8 mg/mouse, twice a week), gemcitabine (30 mg/kg, twice a week), and a combination of DGLA and gemcitabine. In D5D-knockdown tumors, DGLA supplementation promoted 8-HOA formation to a threshold level (> 0.3 µg/g) and resulted in significant tumor reduction (30% vs. control). The promoted 8-HOA not only induced apoptosis associated with altered expression of Bcl-2, cleaved PARP, procaspase 3 and procaspase 9, but also suppressed the tumor metastatic potential via altering MMP-2 and E-cadherin expression. DGLA supplementation resulted in similar anti-tumor effects to those of gemcitabine in our experiments, while the combined treatment led to most significant inhibitory effect on D5D-knockdown tumor growth (70% reduction vs. control). Compared to conventional COX-2 inhibition in cancer treatment, our new strategy that takes advantage of overexpressed COX-2 in cancer cells and tumors, and of abundant ω − 6 fatty acids in the daily diet, should lead us to develop a better and safer anti-pancreatic cancer therapy for patients. Keywords: COX-2 catalyzed DGLA peroxidation, Delta-5-desaturase knockdown, Pancreatic cancer growth and migration, Xenograft tumor

Chlamydia trachomatis is an important human pathogen responsible for a variety of important diseases. pORF5, a plasmid protein in C. trachomatis, has been reported to contribute to chlamydial pathogenesis. Apoptosis and autophagy are two important cellular processes, which also participate in the pathological and the physiological processes in C. trachomatis infection. The present study aimed to explore the effects of pORF5 protein on autophagy and apoptosis in HeLa cells. Stable pORF5-HeLa and vector-HeLa cell lines that were transduced with pORF5 recombination lentivirus and control lentivirus, respectively, were constructed. Immunofluorescence was used to observe the cells. Western blotting was carried out to detect expression of target proteins. Real-time polymerase chain reaction was used to determine the mRNA expression. Flow cytometry, TUNEL assay and Hoechst staining were employed to detect apoptosis. pORF5 sensitized HeLa cells to autophagy that was induced by nutrient deprivation. In addition, pORF5 increased the ratio of LC3-II/LC3-I and Beclin-1 expression, down-regulated the expression of Bax and Caspase-3 and up-regulated Bcl-2 expression to suppress apoptosis induced by TNF-α. Autophagy inhibitor 3-MA elevated apoptotic rate significantly in pORF5-HeLa cells. The study preliminarily confirms that plasmid protein pORF5 mediates the crosstalk between autophagy and apoptosis, which may contribute to persistent C. trachomatis infection in host cells.

While underwater acoustic (UWA) communication offers a practical way to establish a wireless link with underwater vehicles, designing a UWA communication system onboard a small autonomous underwater vehicle (AUV) still poses significant challenges. As the adoption of the low-complexity, robust noncoherent communication technology is limited by low bandwidth efficiency and a low data rate, coherent UWA communication requires Doppler mitigation and channel equalization measures to achieve a relatively high data rate in a moving state. Due to the strict constraints of a small-scale AUV in terms of resources and energy consumption, it is not appropriate to use high-complexity Doppler/multipath compensation technology from the prospect of system implementation. In this paper, an efficient and low-complexity UWA differential binary phase-shift keying (DBPSK) system onboard a small AUV is proposed by simplifying the Doppler and multipath compensation. Specifically, for Doppler, the delay of the adjacent DBPSK symbols is calculated according to the Doppler estimate to facilitate delay-tuning Doppler correction. For multipath, low-complexity LMS channel equalization is incorporated with error correction coding to enable multipath mitigation. With a simple structure and low computational complexity, the proposed scheme facilitates the practical hardware implementation and system integration in the small AUV platform. The numerical simulations are conducted to assess the validity of the proposed scheme under different channel conditions and the effectiveness of the proposed scheme is further verified by two UWA communication field tests, which are performed at a practical shallow water sea and lake, respectively.

Intrauterine adhesions (IUAs) have caused serious harm to women’s reproductive health. Although emerging evidence has linked intrauterine microbiome to gynecological diseases, the association of intrauterine microbiome with IUA, remains unknown. We performed metagenome-wide association, metabolomics, and transcriptomics studies on IUA and non-IUA uteri of adult rats to identify IUA-associated microbial species, which affected uterine metabolites and endometrial transcriptions. A rat model was used with one side of the duplex uterus undergoing IUA and the other remaining as a non-IUA control. Both 16S rRNA sequencing and metagenome-wide association analysis revealed that instead of Mycoplasmopsis specie in genital tract, murine lung pathogen Mycoplasmopsispulmonis markedly increased in IUA samples and displayed a distinct positive interaction with the host immune system. Moreover, most of the IUA-enriched 58 metabolites positively correlate with M.pulmonis, which inversely correlates with a mitotic progression inhibitor named 3-hydroxycapric acid. A comparison of metabolic profiles of intrauterine flushing fluids from human patients with IUA, endometritis, and fallopian tube obstruction suggested that rat IUA shared much similarity to human IUA. The endometrial gene Tenascin-N, which is responsible for extracellular matrix of wounds, was highly up-regulated, while the key genes encoding parvalbumin, trophectoderm Dkkl1 and telomerase involved in leydig cells, trophectoderm cells, activated T cells and monocytes were dramatically down-regulated in rat IUA endometria. Treatment for rat IUA with estrogen (E2), oxytetracycline (OTC), and a traditional Chinese patent medicine GongXueNing (GXN) did not reduce the incidence of IUA, though inflammatory factor IL-6 was dramatically down-regulated (96–86%) with all three. Instead, in both the E2 and OTC treated groups, IUA became worse with a highly up-regulated B cell receptor signaling pathway, which may be associated with the significantly increased proportions of Ulvibacter or Staphylococcus. Our results suggest an association between intrauterine microbiota alterations, certain uterine metabolites, characteristic changes in endometrial transcription, and IUA and the possibility to intervene in IUA formation by targeting the causal factors, microbial infection, and Tenascin-like proteins.

Avian metapneumovirus subgroup C (aMPV/C) is highly pathogenic to various avian species with acute respiratory tract clinicopathology and/or drops in egg production. Nucleolin (NCL), an important nucleolar protein, has been shown to regulate multiple viral replication and serve as a functional receptor for viral entry and internalization. Whether NCL is involved in aMPV/C pathogenesis is not known. In this study, we found that aMPV/C infection altered the subcellular localization of NCL in cultured cells. siRNA-targeted NCL resulted in a remarkable decline in aMPV/C replication in Vero cells. DF-1 cells showed a similar response after CRISPR/Cas9-mediated knock out of NCL during aMPV/C infection. Conversely, NCL overexpression significantly increased aMPV/C replication. Pretreatment with AS1411-a aptamer, a guanine (G)-rich oligonucleotide that forms four-stranded structures and competitively binding to NCL, decreased aMPV/C replication and viral titers in cultured cells. Additionally, we found that the aMPV/C fusion (F) protein specifically interacts with NCL through its central domain and that AS1411 disrupts this interaction, thus inhibiting viral replication. Taken together, these results reveal that the aMPV/C F protein interacts with NCL, which is employed by aMPV/C for efficient replication, thereby highlighting the strategic potential for control and therapy of aMPV/C infection.

In order to improve the corrosion resistance of the automotive AM60B-Mg alloy, a nano-SiO2/MAO composite coating was prepared on the surface of the alloy. The electrochemical properties were studied in an 80 °C corrosion environment using potentiodynamic polarization tests. Local Electrochemical Impedance Spectroscopy (LEIS) was used to study the corrosion mechanisms of coating defect zone. The microstructure and phase of the samples were observed by confocal laser microscopy, scanning electron microscopy (SEM) and X-ray diffraction (XRD). Macroscopic electrochemical test results showed that the impedance of the nano-SiO2/MAO coating was much higher than that of the MAO coating, by about 433 times. Local electrochemical test results showed that the minimum impedance of the nano-SiO2/MAO coating was 1–2 orders of magnitude higher than the maximum impedance of the MAO coating. The defective SiO2/MAO coating still had high corrosion resistance compared to the defective MAO coating. A physical model of local corrosion mechanisms was proposed.

Abstract Background We previously demonstrated that knockdown of delta-5-desaturase via siRNA transfection together with dihomo-γ-linolenic acid supplementation inhibited colon cancer cell growth and migration, by promoting the production of the anti-cancer byproduct 8-hydroxyoctanoic acid from Cyclooxygenase-2-catalyzed dihomo-γ-linolenic acid peroxidation. Here, we extend our study to investigate the effects of delta-5-desaturase-knockdown and the resulting intensified dihomo-γ-linolenic acid peroxidation in xenograft tumor mice model. Methods Four-week old nude mice bearing the human colon cancer cell HCA-7/C29 vs. its delta-5-desaturase knockdown analog (via shRNA transfection) were subject to 4-week treatments of: vehicle control, dihomo-γ-linolenic acid supplementation, 5-Fluorouracil, and combination of dihomo-γ-linolenic acid and 5-Fluorouracil. Tumor growth was monitored during the treatment. At the endpoint, the mice were euthanized and the tumor tissues were collected for further mechanism analysis. Results Delta-5-desaturase knockdown (shRNA) together with dihomo-γ-linolenic acid supplementation increased 8-hydroxyoctanoic acid production to a threshold level in xenograft tumors, which consequently induced p53-dependent apoptosis and reduced tumors significantly. The promoted 8-hydroxyoctanoic acid formation was also found to suppress the tumors’ metastatic potential via regulating MMP-2 and E-cadherin expressions. In addition, our in vivo data showed that delta-5-desaturase knockdown along with dihomo-γ-linolenic acid supplementation resulted in anti-tumor effects comparable to those of 5-Fluorouracil. Conclusions We have demonstrated that our paradigm-shifting strategy of knocking down delta-5-desaturase and taking advantage of overexpressed Cyclooxygenase-2 in tumor cells can be used for colon cancer suppression. Our research outcome will lead us to develop a better and safer anti-cancer therapy for patients.

Background Epicardial adipose tissue may be associated with the pathogenesis of coronary artery disease (CAD), but its effect on obstructive CAD risk is uncertain. Therefore, we aimed to examine the relationship between epicardial adipose tissue and obstructive CAD in Chinese patients with suspected CAD. Methods and Results The present study enrolled 194 consecutive inpatients with suspected CAD who underwent both noncontrast computed tomography and coronary angiography. We measured epicardial fat volume (EFV) and evaluated its association with obstructive CAD, which was defined as coronary stenosis severity ≥70%. Overall, 44.3% patients had obstructive CAD and tend to have higher EFV. Age, body mass index, triglycerides, incidence of hypertension, and hyperlipidemia were higher across tertiles of EFV (P for trend

Herein, an ultra compact plasmonics-based refractive index nanosensor is designed consisting of a metal–insulator-metal (MIM) waveguide with a silver-bar and a triangle stub, coupled with a half-ring resonator which can excite Fano resonance. The finite element method (FEM) is used to analyze the transmission spectra of the proposed design. The transmission spectra showed that there were typical Fano resonance line shapes, which roots in a coupling between the broadband state of triangle stub and the narrowband sta te of the half-ring. The effects of structural parameters of the whole system on transmission properties were analyzed, respectively. And the maximum sensitivity (S) of the system obtains 1723 nm/RIU, and figure of merit (FOM) can obtain 51. The proposed system has promising applications for integrated circuits, especially in nanophotonic sensors.

Leukocyte invasion (neutrophils and monocytes/macrophages) is closely related to the severity of acute pancreatitis (AP) and plays an important role in the systemic inflammatory response and other organ injuries secondary to AP. Increased and sustained activation of neutrophils are major determinants of pancreatic injury and inflammation. After the onset of AP, the arrival of the first wave of neutrophils occurs due to a variety of triggers and is critical for the exacerbation of inflammation. In this review, we summarize the functional characteristics of neutrophils, elastase, and heparin-binding proteins in granules, the mechanisms of neutrophil recruitment and the role of neutrophil extracellular traps (NETs) in AP.

Amino acid metabolism plays an important role in controlling blood pressure by regulating the production of NO and ROS. The present study examined amino acid levels in the serum of Dahl SS rats and SS.13BN rats fed a low or high salt diet. We observed that 8 of 27 amino acids responded to a high salt diet in SS rats. Thus, we hypothesized that a defect in amino acids may contribute to the development of salt-induced hypertension. L-phenylalanine was used to treat SS rats with a low or high salt diet. The results demonstrated that L-phenylalanine supplementation significantly enhanced the serum nitrite levels and attenuated the high salt-induced hypertension in SS rats. Low levels of BH4 and nitrite and the impaired vascular response to acetylcholine were rescued by L-phenylalanine supplementation. Moreover, increased GTP cyclohydrolase (GCH1) mRNA, levels of BH4 and nitrite, and reduced superoxide production were observed in the kidneys of hypertensive SS rats with L-phenylalanine. The antihypertensive effects of L-phenylalanine might be mediated by enhancing BH4 biosynthesis and decreasing superoxide production from NO synthase, thereby protecting vascular and kidney function with reduced ROS and elevated NO levels. The present study demonstrated that L-phenylalanine supplementation restored vascular function, suggesting L-phenylalanine represented a potential target to attenuate high salt-sensitive hypertension through GCH1-BH4.

In the electroosmosis method, when the distance between the opposite electrode and the same electrode is equal, the two-dimensional effect of electroosmotic consolidation is significant, and the use of one-dimensional model will overestimate the potential gradient, making the calculated pore pressure value too large. Aiming at this problem, according to the electrode arrangement rule and the minimum composition, a punctiform electrode unit model is proposed, and electroosmotic experiments are carried out on the symmetric and asymmetric unit models. The two-dimensional electroosmotic consolidation governing equation of the punctiform electrode unit is established. The electric potential field of the electrode unit and the finite element form of the electroosmotic consolidation equation are given by the Galerkin method. The PyEcFem finite-element numerical library is developed using Python programming to calculate. The research results show the following: (1) The two-dimensional effect of the potential field distribution of the punctiform electrode unit is significant. The reduction of spacing of the same nature electrode in the symmetrical unit can make the potential distribution close to a uniform electric field. The asymmetry prevents the electric potential field distribution from being reduced to a one-dimensional model. (2) The number of anodes will affect the electroosmosis effect of the soil. The more the anodes, the better the electroosmosis reinforcement effect of the soil, and the distribution of negative excess pore water pressure will be more uniform. (3) In the early stage of electroosmosis, the more the drainage boundaries, the faster the generation of negative pore pressure, but in the middle and late stages of electroosmosis, the potential value becomes the decisive factor, and the amplitude of negative pore water pressure in asymmetric units is higher than that in symmetric units. The potential distribution will not affect the degree of consolidation but will affect the extreme pore water pressure.

As part of the inner ear, the vestibular system is responsible for sense of balance, which consists of three semicircular canals, the utricle, and the saccule. Increasing evidence has indicated that the noncanonical Wnt/PCP signaling pathway plays a significant role in the development of the polarity of the inner ear. However, the role of canonical Wnt signaling in the polarity of the vestibule is still not completely clear. In this study, we found that canonical Wnt pathway-related genes are expressed in the early stage of development of the utricle and change dynamically. We conditionally knocked out β-catenin, a canonical Wnt signaling core protein, and found that the cilia orientation of hair cells was disordered with reduced number of hair cells in the utricle. Moreover, regulating the canonical Wnt pathway (Licl and IWP2) in vitro also affected hair cell polarity and indicated that Axin2 may be important in this process. In conclusion, our results not only confirm that the regulation of canonical Wnt signaling affects the number of hair cells in the utricle but also provide evidence for its role in polarity development.

To study the effect of the lime-soil compaction pile on the collapsible loess foundation and the influence of water-heat-force characteristics on the soil during compaction, the field test of lime-soil compaction pile treatment of collapsible loess foundation is carried out. This paper monitors the process of soil temperature, water, and soil pressure change in the process of pile forming. According to the macroprocess and micromechanism of lime-soil compaction pile treatment of collapsible loess foundation, the qualitative law of water-heat-force change in the process of pile forming is obtained. Meanwhile, the influence of soil damage is introduced in the process of compaction expansion. The model of pore expansion under linear damage conditions in the plastic zone is established. The formula of radial stress distribution under damage conditions is given. The influence of different damage factors on the expansion process is analyzed.

Intensive and massive coal mining causes a series of geological hazards and environmental problems, especially surface subsidence. At present, two major types of subsidence control technology are applied: backfilling technology and partial mining technology. However, the cost of backfill mining is high and partial mining has a low recovery ratio. Therefore, the backfill-strip mining is used to solve the problems of high cost and shortage of filling materials in coal mines at present. A subsidence control design method of backfill-strip mining was proposed in this paper based on the subsidence control effects and economic benefits. First, the stability of the composite support pillar of the filling body and coal pillars in the backfill-strip mining is analyzed, and the values of the main subsidence influencing factors that include the filling material, the size of the backfilling working face, caving mining face, and residual coal pillar are preliminarily determined. Then, the surface movement and deformation are predicted based on the equivalent superposition probability integral method (PIM). The subsidence influencing factors are optimized and determined by comparing the requirements of the safety fortification index of the antideformation ability of surface buildings, resource recovery rate, and coal mining cost. Finally, the mining scheme design parameters of the backfill-strip mining technology are determined. This method is applied in the subsidence control design of backfill-strip mining in the Ezhuang coal mine. Research results show that backfill-strip mining can ensure the safety of surface buildings, increase the resource recovery rate, and reduce coal mining costs through the reasonable design of this method. This study can provide scientific guidance for subsidence disaster control, prevention, and engineering design in backfill-strip mining.

Extremely broken phyllite is widely distributed and is easily seen in engineering construction. Aiming at the problem that the empirical strength parameters of extremely broken surrounding rock have intense subjectivity and significant difference, based on the characteristics of the existence of particle group state in the highly broken surrounding rock, the fractal theory and large-scale direct shear test are used, the fractal description of polar broken phyllite samples with different pile numbers in fault fracture zone of Qinyu Tunnel is carried out, and the fractal dimensions and empirical strength parameters of each sample are determined. Based on a fractal description and large shear test, the functional relationship between fractal dimension and empirical strength parameter of extremely broken phyllite in fault fracture zone is established, and the quantitative value method of empirical strength parameter determined by fractal dimension of extremely broken phyllite is given, which provides ideas for the quantitative value of empirical strength parameter of the similar extremely broken surrounding rock.

The microRNA-200 (miR-200) family has been reported to be vital for the inhibition of epithelial-to-mesenchymal transition (EMT) in tumor cells. The miR-200 family represents a complex multi-factorial regulatory network which has not been well described in breast cancer. This study aimed to clarify the underlying regulatory association between IL-8 and miR-200 family in the process of EMT in breast cancer cell. In estrogen-receptor (ER) positive breast cancer cell line MCF-7, IL-8 overexpression cells were performed by lentivirus transfection as endogenous regulation with additional exogenous IL-8 stimulation. Transient overexpressions of miR-200 family were performed after endogenous or exogenous IL-8 overexpression in MCF-7 cells. IL-8 knockdown cells were constructed via siRNA and shRNA transfection in triple negative breast cancer cell line MDA-MB-231. N-cadherin, vimentin and ZEB2 were down-regulated and E-cadherin was up-regulated in IL-8 knockdown group compared with control group. On the other hand, N-cadherin, vimentin and ZEB2 were up-regulated and E-cadherin was down-regulated in IL-8 overexpression group compared with control group. This indicated IL-8 promotes EMT in breast cancer cells. Transwell assay showed that IL-8 increased the migration and invasiveness of tumor cells. Furthermore, we performed transient overexpression of miR-200 family after endogenous or exogenous IL-8 overexpression in MCF-7 cells, which showed that the miR-200 family could inhibit EMT induced by IL-8. IL-8 promoted EMT via downregulation of miR-200 family expression in breast cancer cells and increases tumor cell migration and invasion.

Natural biomaterials, such as collagen, gelatin, and chitosan, are considered as promising candidates for use in tissue regeneration treatment, given their similarity to natural tissues regarding components and structure. Nevertheless, only receiving a crosslinking process can these biomaterials exhibit sufficient strength to bear high tensile loads for use in skeletal system regeneration. Recently, genipin, a natural chemical compound extracted from gardenia fruits, has shown great potential as a reliable crosslinking reagent, which can reconcile the crosslinking effect and biosafety profile simultaneously. In this review, we briefly summarize the genipin extraction process, biosafety, and crosslinking mechanism. Subsequently, the applications of genipin regarding aiding skeletal system regeneration are discussed in detail, including the advances and technological strategies for reconstructing cartilage, bone, intervertebral disc, tendon, and skeletal muscle tissues. Finally, based on the specific pharmacological functions of genipin, its potential applications, such as its use in bioprinting and serving as an antioxidant and anti-tumor agent, and the challenges of genipin in the clinical applications in skeletal system regeneration are also presented.

Angiogenesis and osteogenesis have been considered as inseparable and critical processes for bone formation and fracture healing. One promising strategy to improve the capability of angiogenesis and osteogenesis on a titanium (Ti) surface involves the fabrication of stable multifunctional release interfaces. This study developed a combined sequential bio-interfacial release system with basic fibroblast growth factor (bFGF) and bone morphogenetic protein 2 (BMP-2) using a polydopamine (PDA) coating on the Ti surface to enhance angiogenesis and osteogenesis. Their surfaces were characterized and their biological properties were evaluated to provide sufficient supporting evidence for successfully fabricating the combined release system. The novel bio-interface demonstrated a significant improvement in surface hydrophilicity; highly effective growth factor adsorption; and moderate, sustained release on the surface of modified Ti substrates. Furthermore, this system surpassingly promoted the initial proliferation, migration and late angiogenic and osteogenic differentiation of HUVECs and MC3T3-E1 in vitro while also augmenting the osseointegration between the implant surface and the surrounding host tissues in vivo. All these results suggest that the fabrication of this novel bio-interface is a practical modification strategy for Ti implants to stimulate angiogenesis and osteogenesis and further optimize its clinical performance.

Flowering is an important link in the life process of angiosperms, and it is also an important sign of the transformation of plants from vegetative to reproductive growth. Although the flowering regulation network of Arabidopsis is well-understood, there has been little research on the molecular mechanisms of perennial woody plant flower development regulation. Populus tomentosa is a unique Chinese poplar species with fast growth, strong ecological adaptability, and a long lifecycle. However, it has a long juvenile phase, which seriously affects its breeding process. Nuclear factor-Y (NF-Y) is an important type of transcription factor involved in the regulation of plant flowering. However, there are few reports on PtoNF-Y gene flowering regulation, and the members of the PtNF-YC subfamily are unknown. In this study, four key genes were cloned and analyzed for sequence characteristics, gene structure, genetic evolution, expression patterns, and subcellular localization. The plant expression vector was further constructed, and transgenic Arabidopsis and P. tomentosa plants were obtained through genetic transformation and a series of molecular tests. The flowering time and other growth characteristics were analyzed. Finally, the expression level of flowering genes was detected by quantitative PCR, the interaction between PtoNF-YC and PtoCOL proteins was measured using the yeast two-hybrid system to further explain the flowering regulation mechanism, and the molecular mechanisms by which PtNF-YC6 and PtNF-YC8 regulate poplar flowering were discussed. These results lay the foundation for elucidating the molecular regulation mechanism of PtoNF-YC in flowering and furthering the molecular design and breeding of poplar, while providing a reference for other flowering woody plants.

High-throughput sequencing of ribosome footprints precisely maps and quantifies in vivo mRNA translation. The ribosome footprint sequencing has undergone continuing development since its original report. Here we provide a detailed protocol for construction of high-quality ribosome footprint library of rice. Rice total polysomes are isolated with a modified low ionic polysome extraction buffer. After nuclease digestion, rice ribosome footprints are extracted using SDS method followed by column purification. High-quality rice ribosome footprint library with peak reads of approximately 28-nucleotide (nt) length and strong 3-nt periodicity is constructed via key steps including rRNA depletion, end repair, 3’ adapter ligation, reverse transcription, circularization, PCR enrichment and several rounds of purification. Biological significance of rice ribosome footprint library is further revealed by the comparison of transcriptomic and translatomic responses to salt stress and the utilization for novel open reading frame (ORF) identification. This improved protocol for rice ribosome footprint library construction will facilitate the global comprehension and quantitative measurement of dynamic translation in rice.

Androgen receptor (AR) is essential for maintaining normal spermatogenesis and male fertility, and its mutation can cause complete or partial androgen insensitivity syndrome (CAIS or PAIS) in patients. We established an induced pluripotent stem cell line (SKLRMi001-A) from a PAIS patient with AR mutation (c.2710G > A; p. V904M). The iPSC line expressed pluripotency markers, retained normal karyotype, carried the mutation, showed capability of differentiating into three germ layers and was absence of mycoplasma infection. The iPSC line will help to further elucidate the pathogenic mechanisms of AR mutation, and benefit treatment for PAIS in the future.

Helicobacter pylori (H. pylori) infection is the greatest known risk factor for gastric cancer (GC). Long non-coding RNAs (lncRNAs) are implicated in multiple biological processes. However, their contribution in H. pylori-associated GC remains largely unknown. We performed transcriptome sequencing to investigate differential lncRNA and mRNA expression profiles in gastric AGS cells infected with the H. pylori strain 7.13 or 43504. We identified significantly differentially expressed (SDE) mRNAs and lncRNAs following H. pylori infection. A co-expression network of lncRNAs and mRNAs was constructed via WGCNA analysis. Moreover, several of the most significantly upregulated genes were selected for further validation by qRT-PCR analysis in H. pylori-infected gastric cells and transgenic INS-GAS mice. We finally evaluated these genes in human GC tissues. A total of 158442 genes were identified between uninfected and infected cells. Of these, 298 mRNAs and 73 lncRNAs were consistently differentially expressed following infection with the H. pylori 7.13 and 43504 strains, respectively. The expression levels of most upregulated mRNAs (DDIT4, NDRG1, CHAC1, IL32, RELB, CTH, and SLC7A1) and lncRNAs (lncRNA36068, lncRNA51663, lncRNA49853, lncRNA49852, and FLJ46906) were validated by qRT-PCR analysis. We found that H. pylori infection significantly induced the transcript levels of the coding genes RELB and SLC7A11 in in vitro and in vivo assays, which was supported by their high expression levels in GC tissues. In addition, lncRNA51663 and FLJ46906 were remarkably increased in H. pylori-infected cells and consistently overexpressed in human GC tissues compared to adjacent normal tissues. Our study identified mRNA and lncRNA expression profiles related to H. pylori infection. These results may provide important insights regarding lncRNAs in H. pylori-induced gastric carcinogenesis.

In December 2017, an influenza A(H9N2) virus (B51) was isolated from migratory waterfowl in Hubei Province, China. Phylogenetic analysis demonstrated that B51 is a novel reassortant influenza virus containing segments from human H7N4 virus and North American wild bird influenza viruses. This suggest that B51 has undergone multiple reassortment events.

Cerebral ischemia induces a robust neuroinflammatory response that is largely mediated by the activation of CNS resident microglia. Activated microglia produce pro-inflammatory molecules to cause neuronal damage. Identifying regulators of microglial activation bears great potential in discovering promising candidates for neuroprotection post cerebral ischemia. Previous studies demonstrate abnormal elevation of glutaminase 1 (GLS1) in microglia in chronic CNS disorders including Alzheimer's disease and HIV-associated neurocognitive disorders. Ectopic expression of GLS1 induced microglia polarization into pro-inflammatory phenotype and exosome release in vitro. However, whether GLS1 is involved in neuroinflammation in acute brain injury remains unknown. Here, we observed activation of microglia, elevation of GLS1 expression, and accumulation of pro-inflammatory exosomes in rat brains 72 h post focal cerebral ischemia. Treatment with CB839, a glutaminase inhibitor, reversed ischemia-induced microglial activation, inflammatory response, and exosome release. Furthermore, we found that the application of exosome secretion inhibitor, GW4869, displayed similar anti-inflammatory effects to that of CB839, suggesting GLS1-mediated exosome release may play an important role in the formation of neuroinflammatory microenvironment. Therefore, GLS1 may serve as a key mediator and promising target of neuroinflammatory response in cerebral ischemia.

Accurate RNA quantification at the single-cell level is critical for understanding the dynamics of gene expression and regulation across space and time. Single molecule FISH (smFISH), such as RNAscope, provides spatial and quantitative measurements of individual transcripts, therefore, can be used to explore differential gene expression among a heterogeneous cell population if combined with cell identify information. However, such analysis is not straightforward, and existing image analysis pipelines cannot integrate both RNA transcripts and cellular staining information to automatically output cell type-specific gene expression. We developed an efficient and customizable analysis method, Single-Molecule Automatic RNA Transcription Quantification (SMART-Q), to enable the analysis of gene transcripts in a cell type-specific manner. SMART-Q efficiently infers cell identity information from multiplexed immuno-staining and quantifies cell type-specific transcripts using a 3D Gaussian fitting algorithm. Furthermore, we have optimized SMART-Q for user experiences, such as flexible parameters specification, batch data outputs, and visualization of analysis results. SMART-Q meets the demands for efficient quantification of single-molecule RNA and can be widely used for cell type-specific RNA transcript analysis.

Chitosan (CS) has been extensively studied as a natural polymer, in the field of wound repair, due to its useful properties, which include a lack of toxicity and stimulation, excellent biological affinity, degradability, and promotion of collagen deposition. However, inferior mechanical strength and moderate antibacterial properties are the drawbacks restricting its further clinical application. Many researchers have adopted the use of nanotechnology, in particular metallic nanoparticles (MNPs), in order to improve the mechanical strength and specific antibacterial properties of chitosan composites, with promising results. Furthermore, chitosan naturally functions as a reducing agent for MNPs, which can also reduce cytotoxicity. Thus, CS, in combination with MNPs, exhibits antibacterial activity, excellent mechanical strength, and anti-inflammatory properties, and it has great potential to accelerate the process of wound healing. This review discusses the current use of CS and MNPs in wound healing and emphasises the synergy and the advantages for various applications in wound healing.

At present, there are few relevant studies on the intensive sea use, and few scholars have provided qualitative and quantitative research examples on the interaction and interaction coupling relationship between intensive sea use and the marine economy. This study constructs comprehensive evaluation indicator systems using the Liaoning Coastal Economic Belt as the research object. The set pair analysis method is used to obtain comprehensive results, and the coupling coordination degree model is employed to carry out an in-depth analysis of the spatiotemporal characteristics of the interaction between intensive sea use and the marine economy. The results show the following. (1) The six cities in the Liaoning Coastal Economic Belt exhibited a fluctuating upward trend in the composite index for intensive sea use, but the intensive sea use level differed among the cities. The intensive sea use level of Huludao was the lowest among the six cities. (2) All cities in the Liaoning Coastal Economic Belt witnessed an upward trend in the marine economy development index, and the gaps between the cities gradually narrowed. The marine economy development index was ranked from top to bottom as follows: Jinzhou, Panjin, Dalian, Yingkou, Dandong, and Huludao. (3)The coupling coordination degree between intensive sea use and marine economy development was relatively stable in Dalian, Jinzhou, Yingkou, and Panjin, ranging approximately from 0.76 to 0.96, which indicates that the four cities witnessed good coordination between sea area utilization and marine economy development. The coupling coordination degree of Dandong and Huludao were relatively low, and Huludao consistently witnessed a low value.

Chitosan (CS) is a natural polymer with applications in wound restorations and coatings for artificial implants. However, the lack of antimicrobial activity restricts its further application. Thus, the purpose of this study is to prepare CS/AuNPs film by adding gold nanoparticles (AuNPs) to modify chitosan. Through transmission electron microscopy, we found that the presence of CS can effectively prevent the agglomeration of nanoparticles. Furthermore, through the CCK experiment, we found that AuNPs at a certain concentration can improve the adhesion and proliferation of cells, which has also been proved in animal experiments, including gross appearance, histological observations, and immunofluorescence staining. Such findings support the feasibility of using the film as a promising candidate for tissue engineering of skin in a near future.

Inorganic ceramic membranes have attracted much attention due to their advantages of long life, acid and alkali corrosion resistance, and easy cleaning, but they have not been widely used due to the high cost. In order to obtain a ceramic membrane with low cost and good performance, in this paper, loess-based ceramic membrane support was prepared by using loess as raw material, bauxite as aluminum source, dolomite as pore-forming agent and talc as plasticizer. Response surface optimization was used to determine the optimal addition parameters of ingredients. In addition, the factors affecting the performance of the supports were analyzed in terms of material composition, microscopic morphology, and porosity. The results show that the addition of talc conduced to avoid the negative impact of the pore-forming effect of dolomite on the mechanical strength of the support, and the optimum proportioning parameters are 48.85 wt% of bauxite, 9.93 wt% of dolomite and 8 wt% of talc. Under this condition, the bending strength was 42.24 MPa, the pure water flux was 8323.73 l·m ^−2 ·h ^−1 ·MPa ^−1 , and the average pore throat radius was 5.15 μ m. The performance of the best sample reaches the application performance of porous ceramic supports, which provides a theoretical basis for the wide application of low-cost ceramic membrane supports.

Inorganic ceramic membranes have received a lot of attention due to their resistance to acid and alkali corrosion and ease of cleaning and utilisation, however, their high cost has limited their widespread use. To obtain lower-cost ceramic membranes with better performance, in this paper, single-channel tubular ceramic membrane supports were prepared using natural loess and solid waste fly ash as raw materials. This paper firstly investigated the effects of various additives (including carboxymethyl cellulose (CMC), graphite, calcium carbonate, copper oxide, magnesium oxide, and manganese dioxide,) on the pore size distribution, pure water flux, and flexural strength of the supports to select the appropriate additives; secondly, the response surface methodology was used to determine the amount of each parameter to be added. The results showed that CMC was more viscous and malleable compared to graphite and CaCO _3 , thus increasing the density and pure water flux of the supports. MnO _2 improved both the pure water flux and flexural strength of the supports compared to CuO and MgO. The best sample was obtained when the contents of CMC, MnO _2 , and kaolinite were 9.85 wt%, 10.62 wt%, and 4.8 wt%, respectively, the best sample obtained exhibited a pure water flux of 4985.52 L·m ^−2 ·h ^−1 ·MPa ^−1 and a flexural strength of 45.4 MPa. The support obtained meets the conditions for the application of porous ceramic carriers and provides a viable pathway for the wide application of low-cost ceramic membrane carriers.

Dilated cardiomyopathy (DCM) is an important cause of sudden death and heart failure with an unknown etiology. Recent studies have suggested that long non-coding RNA (lncRNA) can interact with microRNA (miRNA) and indirectly interact with mRNA through competitive endogenous RNA (ceRNA) activities. However, the mechanism of ceRNA in DCM remains unclear. In this study, a miRNA array was first performed using heart samples from DCM patients and healthy controls. For further validation, we conducted real-time quantitative reverse transcription (RT)-PCR using samples from DCM patients and a doxorubicin-induced rodent model of cardiomyopathy, revealing that miR-144-3p and miR-451a were down-regulated, and miR-21-5p was up-regulated. Based on the ceRNA theory, we constructed a global triple network using data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) and our miRNA array. The lncRNA-miRNA-mRNA network comprised 22 lncRNA nodes, 32 mRNA nodes, and 11 miRNA nodes. Hub nodes and the number of relationship pairs were then analyzed, and the results showed that two lncRNAs (NONHSAT001691 and NONHSAT006358) targeting miR-144/451 were highly related to DCM. Then, cluster module and random walk with restart for the ceRNA network were analyzed and identified four lncRNAs (NONHSAT026953/NONHSAT006250/NONHSAT133928/NONHSAT041662) targeting miR-21 that were significantly related to DCM. This study provides a new strategy for research on DCM or other diseases. Furthermore, lncRNA-miRNA pairs may be regarded as candidate diagnostic biomarkers or potential therapeutic targets of DCM.