Narrow-linewidth and low RIN Tm/Ho co-doped fiber laser based on self-injection locking.

A narrow-linewidth and low relative intensity noise (RIN) Tm/Ho co-doped fiber laser based on a saturable absorber and self-injection locking was demonstrated for the first time. Utilizing self-injection locking technology, the frequency noise power spectral density is remarkably reduced by more than 17.1 dB from 1.21 × 106 Hz2/Hz to 7.30 × 103 Hz2/Hz when the frequency is approximately 1 kHz. Furthermore, a laser with a linewidth compressed to a quarter of the original linewidth from 44.386 kHz to 2.850 kHz, a RIN of less than -127.74 dB/Hz, and an optical signal-to-noise ratio of more than 71.6 dB can be obtained. Using a delay fiber, the relaxation oscillation peak frequencies move to lower frequencies, from 27.9 kHz to 15.8 kHz. The proposed laser is highly competitive in advanced coherent light detection fields, including coherent Doppler wind lidar, high-speed coherent optical communication, and precise absolute distance coherent measurement.

Equalization system of low differential mode delay few-mode fibers based on the neural network MIMO algorithm.

In recent years, with the development of information networks, higher requirements for transmission capacity have been recommended. Yet, at the same time, the capacity of single-mode fiber is rapidly approaching the theoretical limit. The multidimensional multiplexing technique is an effective way to solve this problem. Since the high differential mode delay (DMD) of transmission fiber increases the complexity of demultiplexing in equalization algorithms, we use an intelligent design method to optimize the trench-assisted gradient refractive index structure in this paper. The maximum DMD of the optimized optical fiber structure is 19.6 ps/km. A least mean squares-feedforward neural network constant modulus algorithm (LMS-FNNCMA) is also designed by using the theory of the least mean squares (LMS), constant modulus algorithm (CMA), and the multiple input multiple output (MIMO) neural networks. In order to verify the accuracy of the algorithm, a polarization division multiplexing-wavelength division multiplexing-mode division multiplexing (PDM-WDM-MDM) optical transmission system is constructed through simulation. The algorithm successfully realizes the de-crosstalk over a transmission distance of 1200 km at a rate of 1.2 Tbps under simulation conditions.

Metabolomic profiles predict clinical severity in patients with obstructive sleep apnea hypopnea syndrome.

STUDY OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSAHS) poses a significant health hazard, as intermittent hypoxia inflicts damage throughout the body and is considered a critical risk factor for metabolic disorders. The aim of this study was to establish a metabolic profile for patients with OSAHS using nontargeted metabolomics detection techniques, providing a basis for OSAHS diagnosis and novel biological marker identification. METHODS: Forty-five patients with OSAHS composed the OSAHS group, and 44 healthy volunteers composed the control group. Nontargeted metabolomics technology was used to analyze participants' urinary metabolites. Differentially abundant metabolites were screened and correlated through hierarchical clustering analysis. We constructed a composite metabolite diagnostic model using a random forest model. Simultaneously, we analyzed the relationships between 20 metabolites involved in model construction and OSAHS severity. RESULTS: The urinary metabolomics pattern of the OSAHS group exhibited significant changes, demonstrating noticeable differences in metabolic products. Urinary metabolite analysis revealed differences between the mild-moderate OSAHS and severe OSAHS groups. The composite metabolite model constructed in this study demonstrated excellent diagnostic performance not only in distinguishing healthy control participants from patients with mild-moderate OSAHS (AUC = 0.78) and patients with severe OSAHS (AUC = 0.78), but also in discriminating between patients with mild-moderate and severe OSAHS (AUC = 0.71). CONCLUSIONS: This study comprehensively analyzed the urinary metabolomic characteristics of patients with OSAHS. The established composite metabolite model provides robust support for OSAHS diagnosis and severity assessment. Twenty metabolites associated with OSAHS disease severity offer a new perspective for diagnosis.

Insights into heterogeneous surface induced bubble nucleation mechanisms in cellulose reinforced polylactic acid foams.

As the most abundant natural homo-polymer, cellulose has the potential to enhance polymer properties reducing the cost of raw materials. In this work, the carboxylate cellulose nanofiber (CNF-C) was selected to modify polylactic acid (PLA) foams, and the density functional theory was constructed to help analyze the foaming mechanism quantitatively. The theoretical results showed that the ordered structure, the carboxyl and the hydroxyl of CNF-C were more conducive to providing much stronger CO2 adsorption for bubble nucleation, where the predicted critical bubble size decreased and the cell density increased with the addition of CNF-C. The experimental results revealed that the CNF-C promoted the rheological properties and crystallization behaviors of PLA samples, the PLA/CNF-C foams were characterized with uniform structures, the average cell size decreased from 21.39 µm to 0.19 µm, and the cell number density increased from 2.65×1010cell/cm3 to 2.30×1014cell/cm3. Those improvements resulted in an increase of 394.0 % for the compressive strength of the prepared foams. Generally, the high-performance PLA/CNF-C foams were fabricated successfully without compromising the properties of bio-based and biodegradable, the foaming mechanism was analyzed combining theoretical results with experimental data, and it was believed to provide a guide for cellulose reinforcing biodegradable polymer materials.

Characterization of biliary and duodenal microbiota in patients with primary and recurrent choledocholithiasis.

Purpose: To explore the biliary and duodenal microbiota features associated with the formation and recurrence of choledocholithiasis (CDL). Methods: We prospectively recruited patients with primary (P-CDL, n = 29) and recurrent CDL (R-CDL, n = 27) for endoscopic retrograde cholangiopancreatography (ERCP). Duodenal mucosa (DM), bile and bile duct stones (BDS) samples were collected in P- and R-CDL patients. DM samples were also collected in 8 healthy controls (HC). The microbiota profile analysis was performed with 16S rRNA gene sequencing. Results: Short-course antibiotic application before ERCP showed no significant effects in alpha and beta diversities of the biliary and duodenal microbiota in CDL. Alpha diversity showed no difference between DM and bile samples in CDL. The duodenal microbial richness and diversity was lower in both P- and R-CDL than HC. The biliary microbiota composition showed a high similarity between P- and R-CDL. Fusobacterium and Enterococcus were higher abundant in DM, bile, and BDS samples of R-CDL than P-CDL, as well as Escherichia and Klebsiella in bile samples of R-CDL. The enriched duodenal and biliary bacteria in CDL were closely associated with cholecystectomy, inflammation and liver dysfunction. The bile-associated microbiota of R-CDL expressed enhanced capacity of D-glucuronide and D-glucuronate degradation, implicating an elevated level of ß-glucuronidase probably produced by enriched Escherichia and Klebsiella in bile. Conclusions: The duodenal microbiota was in an imbalance in CDL. The duodenal microbiota was probably the main source of the biliary microbiota and was closely related to CDL formation and recurrence. Enterococcus, Fusobacterium, Escherichia and Klebsiella might contribute to CDL recurrence. Clinical trials: The study was registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/index.html, ChiCTR2000033940). Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00267-2.

The evolution of Earth's surficial Mg cycle over the past 2 billion years.

The surficial cycling of Mg is coupled with the global carbon cycle, a predominant control of Earth's climate. However, how Earth's surficial Mg cycle evolved with time has been elusive. Magnesium isotope signatures of seawater (δ26Mgsw) track the surficial Mg cycle, which could provide crucial information on the carbon cycle in Earth's history. Here, we present a reconstruction of δ26Mgsw evolution over the past 2 billion years using marine halite fluid inclusions and sedimentary dolostones. The data show that δ26Mgsw decreased, with fluctuations, by about 1.4‰ from the Paleoproterozoic to the present time. Mass balance calculations based on this δ26Mgsw record reveal a long-term decline in net dolostone burial (NDB) over the past 2 billion years, due to the decrease in dolomitization in the oceans and the increase in dolostone weathering on the continents. This underlines a previously underappreciated connection between the weathering-burial cycle of dolostone and the Earth's climate on geologic timescales.

Genomic characterization and pathogenicity of a novel fowl adenovirus serotype 11 isolated from chickens with inclusion body hepatitis in China.

Fowl adenovirus serotype 11 (FAdV-11) is one of the primary causative agents of inclusion body hepatitis (IBH), which causes substantial economic losses in the world poultry industry. In this study, we characterized the genome of the fowl adenovirus serotype 11 (FAdV-11) isolate FJSW/2021. The full genome of FJSW/2021 was 44, 154 base pairs (bp) in length and had a similar organization to that of previously reported FAdV-11 isolates. Notably, compared with those of other reported FAdV-11 strains, the preterminal protein (pTP) of FAdV-11 FJSW/2021 has six amino acid (aa) insertions (S-L-R-I-I-C) between 470 and 475 and one aa mutation of L476F; moreover, the tandem repeat (TR) regions of TR1 and TR2 were 33 bp (1 repeat) and 1,080 bp (8 repeats) shorter than those of the Canadian nonpathogenic isolate ON NP2, respectively. The pathogenicity of FJSW/2021 was studied in 10-day-old specific pathogen-free chicken embryos following allantoic cavity inoculation and in 1-day-old, 1-wk-old and 2-wk-old SPF chickens following intramuscular inoculation with 107 TCID50 of the virus. The results showed that FJSW/2021 can induce typical severe IBH in chicks less than 2 wk old. These findings highlighted the genetic differences between the pathogenic and non-pathogenic FAdV-11 isolates. The data will provide guidance for identifying the virulence factors of FAdV-11 strains. The animal challenge model developed in our study will allow precise evaluation of the efficacy of potential FAdV-11 vaccine candidates.

DSG-GAN:A dual-stage-generator-based GAN for cross-modality synthesis from PET to CT.

PET/CT devices typically use CT images for PET attenuation correction, leading to additional radiation exposure. Alternatively, in a standalone PET imaging system, attenuation and scatter correction cannot be performed due to the absence of CT images. Therefore, it is necessary to explore methods for generating pseudo-CT images from PET images. However, traditional PET-to-CT synthesis models encounter conflicts in multi-objective optimization, leading to disparities between synthetic and real images in overall structure and texture. To address this issue, we propose a staged image generation model. Firstly, we construct a dual-stage generator, which synthesizes the overall structure and texture details of images by decomposing optimization objectives and employing multiple loss functions constraints. Additionally, in each generator, we employ improved deep perceptual skip connections, which utilize cross-layer information interaction and deep perceptual selection to effectively and selectively leverage multi-level deep information and avoid interference from redundant information. Finally, we construct a context-aware local discriminator, which integrates context information and extracts local features to generate fine local details of images and reasonably maintain the overall coherence of the images. Experimental results demonstrate that our approach outperforms other methods, with SSIM, PSNR, and FID metrics reaching 0.8993, 29.6108, and 29.7489, respectively, achieving the state-of-the-art. Furthermore, we conduct visual experiments on the synthesized pseudo-CT images in terms of image structure and texture. The results indicate that the pseudo-CT images synthesized in this study are more similar to real CT images, providing accurate structure information for clinical disease analysis and lesion localization.

Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma.

BACKGROUND: Patients who possess various histological subtypes of early-stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early-stage LUAD due to intratumour intricacy. METHODS: We included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single-cell RNA sequencing (scRNA-seq) was carried out on matched tumour and normal tissue. Three formalin-fixed and paraffin-embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP). RESULTS: Using DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA-seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = -.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD-L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region. CONCLUSIONS: These findings illustrate that assessing patient histological subtypes at the single-cell level is feasible. Additionally, tumour endothelial cells that express PD-L1 in stage IA LUAD suppress immune-responsive CD8+ T cells.

Plasma Lipidomics Profiling to Identify the Biomarkers of Diagnosis and Radiotherapy Response for Advanced Non-Small-Cell Lung Cancer Patients.

Background: Advanced lung cancer that contributes to a heavy burden on medical institutions is the leading cause of cancer-related death and is often accompanied by metabolic disorders. In this study, we aimed to explore the biomarkers of diagnosis and radiotherapy response in non-small-cell lung cancer (NSCLC) patients by plasma lipidomics analysis. Method: Using triple-quadrupole mass spectrometer analysis, our research characterized the plasma lipid metabolomics profile of 25 healthy controls and 31 advanced NSCLC patients in each of three different radiotherapy phases. Results: The results showed altered lipid elements and concentrations among NSCLC patients with different radiotherapy phases, NSCLC subtypes, and different radiotherapeutic responses. We found that compared to the healthy controls, myelin-associated glycoprotein (MAG), phosphatidylinositol (PI), and phosphatidylserine (PS) were mainly and significantly altered lipid elements (> twofold, and p < 0.05) among NSCLC patients with different radiotherapy phases. Through comparison of lipid elements between bad and good responses of NSCLC patients with radiotherapy, the obviously declined phosphatidylglycerol (PG 18 : 0/14 : 0, 18 : 1/18 : 3, and 18 : 0/20 : 1) or markedly elevated PI (20 : 0/22 : 5 and 18 : 2/22 : 4) and phosphatidic acid (PA 14 : 0/20 : 4, 14 : 0/20 : 3, and 18 : 2/22 : 4) could indicate poor therapeutic response for NSCLC patients. The results of ROC curve analysis suggested that PG (18 : 0/20 : 1 and 18 : 0/14 : 0) could clearly predict the radiotherapeutic response for NSCLC patients, and PS (18 : 0/20 : 0) and cholesterol were the first two lipid components with the most potential for the diagnosis of advanced NSCLC. Conclusion: Our results indicated that plasma lipidomics profiling might have a vital value to uncover the heterogeneity of lipid metabolism in healthy people and advanced NSCLC patients with different radiotherapy phase, and further to screen out radiotherapeutic response-specific biomarkers.

Expert consensus on odontogenic maxillary sinusitis multi-disciplinary treatment.

ABSTARCT: Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.

GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases.

Partial endothelial-to-mesenchymal transition (EndMT) is an intermediate phenotype observed in endothelial cells (ECs) undergoing a transition toward a mesenchymal state to support neovascularization during (patho)physiological angiogenesis. Here, we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4 (GTF2H4) as a positive regulator of this process. In addition, we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3 (ERCC3) to co-regulate partial EndMT. Furthermore, by using phosphorylation proteomics and site-directed mutagenesis, we demonstrated that GTF2H4 was involved in the phosphorylation of receptor coactivator 3 (NCOA3) at serine 1330, which promoted the interaction between NCOA3 and p65, resulting in the transcriptional activation of NF-κB and the NF-κB/Snail signaling axis during partial EndMT. In vivo experiments confirmed that GTF2H4 significantly promoted partial EndMT and angiogenesis after ischemic injury. Collectively, our findings reveal that targeting GTF2H4 is promising for tissue repair and offers potential opportunities for treating hypoxic/ischemic diseases.

Aneurysmal Subarachnoid Hemorrhage and Sex Differences: Analysis of Epidemiology, Outcomes, and Risk Factors.

BACKGROUND: The differences in outcomes after aneurysmal subarachnoid hemorrhage (aSAH) between the sexes have not been concretely determined. This study aimed to evaluate the differences in epidemiology, outcomes, and risk factors between male and female patients with aSAH. METHODS: We performed a multicenter, retrospective study of patients with aSAH from 2017 to 2020. We investigated the epidemiological differences between the two sexes. Propensity score matching (PSM) was used to compare short-term outcomes between the sexes. Binary logarithmic regression was performed to investigate the odds ratio (OR) for dependent survival in patients of different sexes. RESULTS: A total of 5,407 consecutive patients with aSAH were included in this study, and the female-to-male ratio was 1.8:1. The peak incidence of aSAH occurred in the 6th and 7th decades in males and females, respectively. There were more female patients with internal carotid artery or posterior communicating artery aneurysms (53.2%), and there were more male patients with anterior cerebral artery or anterior communicating artery aneurysms (43.2%). The incidence of multiple aneurysms was greater in female patients (21.5% vs. 14.2%, P < 0.001). There was no significant difference in outcomes before and after PSM at discharge. The dependent survival risk was related only to the clinical condition on admission in women. In addition, age > 50 years (OR 1.88, 95% confidence interval 1.17-3.02; P = 0.01) and hypertension (OR 1.81, 95% confidence interval 1.25-2.61; P = 0.002) were also risk factors for male patients. CONCLUSIONS: There were more female patients with aneurysms than male patients in this study. Most aneurysm locations were different between the two groups. There was no significant difference in discharge outcomes before and after PSM. The risk factors for dependent survival were different between female and male patients.

Stable nanoscale sea-island structure of biobased polyamide 56/poly (butylene adipate-co-terephthalate) blends compatibilized by interfacial hyperbranched structure: Toward biobased polymer blends with ultrahigh toughness.

Developing biobased materials is a considerably effective approach to save fossil resources and reduce emissions. Biobased polyamide 56 (PA56) is an excellent engineering material, but it has low toughness. Herein, to enhance the toughness of PA56, an ultra-tough biodegradable material, i.e., poly (butylene adipate-co-terephthalate) (PBAT) was introduced into PA56. Moreover, a self-synthesized epoxy-terminated hyperbranched polyester (EHBP) was used to improve the compatibility of the blended materials. The results of differential scanning calorimetry and Fourier-transform infrared spectroscopy indicated that the epoxide group of EHBP could react with PA56 and PBAT to form a block-like polymer structure and limit the crystallization behavior of the blends. The scanning electron microscopy results show that the addition of EHBP considerably reduced the dispersed-phase size in the blends, forming a nanoscale island structure. Moreover, the hydrogen bonds formed between EHBP and PA56/PBAT enhanced the intermolecular interaction between the two materials. Thus, PA56 blends with ultrahigh toughness were successfully prepared. The prepared PA56/PBAT/EHBP blend exhibited a notch impact strength of 20.71 kJ/m2 and a breaking elongation of 38.3 %, which represent increases of 427.3 % and 252.8 %, respectively, compared with those of pure PA56. Thus, the proposed method is suitable for toughening PA56 and broadening its applications.

SCAR: Single-cell and Spatially-resolved Cancer Resources.

Advances in sequencing and imaging technologies offer a unique opportunity to unravel cell heterogeneity and develop new immunotherapy strategies for cancer research. There is an urgent need for a resource that effectively integrates a vast amount of transcriptomic profiling data to comprehensively explore cancer tissue heterogeneity and the tumor microenvironment. In this context, we developed the Single-cell and Spatially-resolved Cancer Resources (SCAR) database, a combined tumor spatial and single-cell transcriptomic platform, which is freely accessible at http://8.142.154.29/SCAR2023 or http://scaratlas.com. SCAR contains spatial transcriptomic data from 21 tumor tissues and single-cell transcriptomic data from 11 301 352 cells encompassing 395 cancer subtypes and covering a wide variety of tissues, organoids, and cell lines. This resource offers diverse functional modules to address key cancer research questions at multiple levels, including the screening of tumor cell types, metabolic features, cell communication and gene expression patterns within the tumor microenvironment. Moreover, SCAR enables the analysis of biomarker expression patterns and cell developmental trajectories. SCAR also provides a comprehensive analysis of multi-dimensional datasets based on 34 state-of-the-art omics techniques, serving as an essential tool for in-depth mining and understanding of cell heterogeneity and spatial location. The implications of this resource extend to both cancer biology research and cancer immunotherapy development.

Interaction of eosinophilic and neutrophilic inflammation in patients with chronic rhinosinusitis.

PURPOSE OF REVIEW: In the past year, the endotype of chronic rhinosinusitis (CRS) has been studied from a new perspective. Eosinophilic and neutrophilic inflammation are not independent processes in the pathogenesis of CRS. In this review, we will focus on recent research on mixed eosinophilic-neutrophilic inflammation in CRS and discuss the mechanism and potential treatments. RECENT FINDINGS: Traditionally, patients with eosinophilic CRS (ECRS) present with severe clinical manifestations, comorbidities, and a higher recurrence rate. Recent studies have found that approximately 40% of patients with ECRS present with neutrophilic infiltration, while patients with predominantly eosinophilic infiltration along with neutrophilic inflammation present with more complex inflammation, clinical manifestations and exhibit refractory characteristics. SUMMARY: The complex inflammatory profile and refractory clinical characteristics of mixed eosinophilic-neutrophilic inflammation in CRS are current challenges for clinicians. We summarize the features of eosinophilic and neutrophilic inflammation and current studies on the mechanisms of mixed eosinophilic-neutrophilic inflammation and suggest potentially effective therapeutic methods. We hope that this review will help with determining precise treatment options for patients.

SCAN: Spatiotemporal Cloud Atlas for Neural cells.

The nervous system is one of the most complicated and enigmatic systems within the animal kingdom. Recently, the emergence and development of spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) technologies have provided an unprecedented ability to systematically decipher the cellular heterogeneity and spatial locations of the nervous system from multiple unbiased aspects. However, efficiently integrating, presenting and analyzing massive multiomic data remains a huge challenge. Here, we manually collected and comprehensively analyzed high-quality scRNA-seq and ST data from the nervous system, covering 10 679 684 cells. In addition, multi-omic datasets from more than 900 species were included for extensive data mining from an evolutionary perspective. Furthermore, over 100 neurological diseases (e.g. Alzheimer's disease, Parkinson's disease, Down syndrome) were systematically analyzed for high-throughput screening of putative biomarkers. Differential expression patterns across developmental time points, cell types and ST spots were discerned and subsequently subjected to extensive interpretation. To provide researchers with efficient data exploration, we created a new database with interactive interfaces and integrated functions called the Spatiotemporal Cloud Atlas for Neural cells (SCAN), freely accessible at http://47.98.139.124:8799 or http://scanatlas.net. SCAN will benefit the neuroscience research community to better exploit the spatiotemporal atlas of the neural system and promote the development of diagnostic strategies for various neurological disorders.

Upregulated LncRNA-Meg3 modulates the proliferation and survival of MEPM cells via interacting with Smad signaling in TCDD-induced cleft palate.

Exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero can result in high rates of cleft palate (CP) formation, yet the underlying mechanisms remain to be characterized. In vivo, the lncRNA Meg3 was upregulated following TCDD treatment in CP-associated murine embryonic palatal tissue, with concomitant changes in proliferative and apoptotic activity in these murine embryonic palatal mesenchymal (MEPM) cells. Meg3 can modulate the TGF-ß/Smad to control the proliferation, survival, and differentiation of cells. Accordingly, TCCD and TGF-ß1 were herein used to treat MEPM cells in vitro, revealing that while TCDD exposure altered the proliferative activity and apoptotic death of these cells, exogenous TGF-ß1 exposure antagonized these effects via TGF-ß/Smad signaling. TCDD promoted Meg3 upregulation, whereas TGF-ß1 suppressed TCDD-driven upregulation of this lncRNA. Meg3 was additionally determined to directly interact with Smad2, with significant Meg3 enrichment in Smad2-immunoprecipitates following TCDD treatment. When Meg3 was silenced, the impact of TCDD on Smad signaling, proliferative activity, and apoptosis were ablated, while the effects of exogenous TGF-ß1 were unchanged. This supports a model wherein Meg3 is upregulated in TCDD-exposed palatal tissue whereupon it can interact with Smad2 to suppress Smad-dependent signaling, thus controlling MEPM cell proliferation and apoptosis, contributing to TCDD-induced CP, which provides a theoretical support for the precautions of cleft palate induced by TCDD.

Characterization and anti-tumor activities of polysaccharide isolated from Brassica rapa L. via activation of macrophages through TLR2-and TLR4-Dependent pathways.

We have previously shown the immunostimulatory effects by Nozawana (Brassica rapa L.). In this report, we determined the characteristics of Nozawana polysaccharide (NPS) and evaluated the immunomodulatory effects and anti-tumor activity of NPS mediated by macrophage activation. The molecular weight of NPS was determined by gel filtration chromatography with an average molecular weight of approximately 100.6 kDa. HPLC analysis showed that NPS contained glucose, galacturonic acid, galactose, and arabinose. NPS increased cytokine and nitric oxide (NO) production by macrophages in a Toll-like receptor (TLR)2 and TLR4-dependent manner. Furthermore, NPS induced apoptosis significantly against 4T1 murine breast cancer cells cultured in conditioned medium from NPS-treated macrophages through tumor necrosis factor-α. In tumor-bearing mouse model, tumor growth was significantly reduced in NPS-treated mice compared with control mice. These results support the potential use of NPS as an immunotherapeutic material found in health food products.