Discrete wavelet transform assisted convolutional neural network equalizer for PAM VLC system.

With the deepening of research and the further differentiation of damage types, and to compensate for both linear and nonlinear damage in visible light communication systems (VLCs), we propose a novel discrete wavelet transform-assisted convolutional neural network (DWTCNN) equalizer that combines the advantages of wavelet transform and deep learning methods. More specifically, wavelet transform is used in DWTCNN to decompose the signal into diverse coefficient series and employ an adaptive soft-threshold method to eliminate redundant information in the signal. The coefficients are then reconstructed to achieve complete signal compensation. The experimental results show that the proposed DWTCNN equalizer can significantly reduce nonlinear impairment and improve system performance with the bit error rate (BER) under the 7% hard-decision forward error correction (HD-FEC) limit of 3.8 × 10-3. We also experimentally compared DWTCNN with the Long Short-Term Memory (LSTM) and entity extraction neural network (EXNN) equalizer, the Q factor has been improved by 0.76 and 0.53 dB, and the operating ranges of the direct current (DC) bias have increased by 4.76% and 23.5%, respectively.

Mir-629 Repressed LATS2 Expression and Promoted the Proliferation of Prostate Cancer Cells.

MicroRNAs (miRNAs) have been discovered to play critical role in regulating prostate cancer (PC) progression. The function role of miR-629 in tumor progression of PC has not been studied. Here, we found that miR-629 was markedly upregulated in PC as determined using the cancer genome atlas (TCGA) dataset, clinical tissues, and cell lines. Functional analysis (MTT assays, colony formation assays, soft agar growth assay and BrdU incorporation assay) indicated that overexpression of miR-629 was drastically promoted, while miR-629-in significantly suppressed cell proliferation. LATS2 was predicted as a direct target of miR-629 and was confirmed by western blot and dual luciferase assay. Through downregulation of large tumor suppressor 2 (LATS2) by overexpression of miR-629, the p21 mRNA and protein were decreased while the Cyclin D3 mRNA and protein were enhanced, suggesting promoting of cell proliferation process. Additionally, knockdown of LATS2 reversed the inhibitory effect by miR-629-in in PC. Our study indicated that miR-629 might serve as a new promising target for PC treatment.

Morroniside ameliorates glucocorticoid-induced osteoporosis and promotes osteoblastogenesis by interacting with sodium-glucose cotransporter 2.

CONTEXT: Morroniside (MOR) possesses antiosteoporosis (OP) effects, but its molecular target and relevant mechanisms remain unknown. OBJECTIVE: We investigated the effects of MOR on glucocorticoid-induced OP and osteoblastogenesis and its underlying mechanisms. MATERIALS AND METHODS: The effects of MOR (10-100 µM) on the proliferation and differentiation of MC3T3-E1 cells were studied in vitro. The glucocorticoid-induced zebrafish OP model was treated with 10, 20 and 40 µM MOR for five days to evaluate its effects on vertebral bone density and related osteogenic markers. In addition, molecular targets prediction and molecular docking analysis were carried out to explore the binding interactions of MOR with the target proteins. RESULTS: In cultured MC3T3-E1 cells, 20 µM MOR significantly increased cell viability (1.64 ± 0.12 vs. 0.95 ± 0.16; p < 0.01) and cell differentiation (1.57 ± 0.01 vs. 1.00 ± 0.04; p < 0.01) compared to the control group. MOR treatment significantly ameliorated vertebral bone loss in the glucocorticoid-induced OP zebrafish model (0.86 ± 0.02 vs. 0.40 ± 0.03; p < 0.01) and restored the expression of osteoblast-specific markers, including ALP, Runx2 and Col-І. Ligand-based target prediction and molecular docking revealed the binding interaction between MOR and the glucose pockets in sodium-glucose cotransporter 2 (SGLT2). DISCUSSION AND CONCLUSIONS: These findings demonstrated that MOR treatment promoted osteoblastogenesis and ameliorated glucocorticoid-induced OP by targeting SGLT2, which may provide therapeutic potential in managing glucocorticoid-induced OP.

Utilizing deep neural networks to extract non-linearity as entities in PAM visible light communication with noise.

Herein, we propose a novel entity extraction neural network (EXNN) with a newly designed sampling convolution kernel approach and a deep learning-based structure to differentiate noise in visible light communication (VLC) systems. In particular, EXNN is used to extract linear and nonlinear distortion in a received signal as an entity and compensate for the signal by removing it. First, we designed a deep learning structure tailored for VLC systems, used experimentation to validate our algorithm's usability, and determined an appropriate range for the hyper-parameters that govern the PAM-8 system. Second, we compared our approach with existing finite impulse response (FIR) linear and Volterra nonlinear compensation algorithms via experiments. Below the hard-decision forward error correction (HD-FEC) threshold limit of 3.8×10-3, experimental results show that the use of the EXNN increased the operating range of the direct current (DC) bias and the voltage by ∼33.3% and by ∼50% under optimal conditions, respectively. Furthermore, under corresponding optimal power conditions, the proposed approach improved the Q factor of the VLC system by 0.36 and 1.57 dB compared with the aforementioned linear and nonlinear equalizers, respectively. To the best of our knowledge, this is the first time that a deep learning operator has been custom-designed for the VLC system and we have named the completely redesigned network with this sampling convolution kernel operator as EXNN.

miR-532-3p inhibits osteogenic differentiation in MC3T3-E1 cells by downregulating ETS1.

BACKGROUND: Many studies had identified that MicroRNAs (miRNAs) could affect bone metabolism by regulating the expression of various proteins. This study explored the effect and mechanism of miR-532-3p on osteogenic differentiation. METHODS: We analyzed the content of miR-532-3p in osteoporosis patients, osteoporosis rats, and osteogenic induced MC3T3-E1 cells. MiR-532-3p mimic or inhibitor utilized to alter intracellular miR-532-3p content. MTT method executed to detect the effect of miR-532-3p on osteoblast proliferation. Real-time qPCR, Western blot, alkaline phosphatase staining, and alizarin red staining utilized to ascertain the influence of miR-532-3p on osteogenic differentiation. Then, databases and a dual-luciferase reporter gene assay used to verify the target of miR-532-3p. Furthermore, the lentiviral vector was utilized to overexpress interesting target gene expression and checked whether the target gene was involved in the regulation of osteogenic differentiation by miR-532-3p. RESULTS: MiR-532-3p expression boosted in low bone mineral density (BMD) patients and rats. In MC3T3-E1 cells, miR-532-3p expression gradually decreased as osteogenic induction matures. MiR-532-3p mimic negatively regulated succinate dehydrogenase (SDH) activity, alkaline phosphatase (ALP) activity, mineralization ability, the osteogenic-associated gene (Col1A1, Runx2, ALP, OPN, and OCN) and E-26 transformation specific-1 (ETS1) expression of MC3T3-E1 cells. Things are the opposite of the miR-532-3p inhibitor. ETS1 identified as the miR-532-3p target gene, and miR-532-3p could inhibit its expression. Besides, improved ETS1 expression could rescue the suppressive effect of miR-532-3p mimic on osteogenic differentiation. CONCLUSION: miR-532-3p can suppress osteogenic differentiation by downregulating ETS1 expression.

Novel promising 4-anilinoquinazoline-based derivatives as multi-target RTKs inhibitors: Design, molecular docking, synthesis, and antitumor activities in vitro and vivo.

4-Anilinoquinazoline derivatives function as tyrosine kinase inhibitors (TKIs). Novel TKIs are needed for cancer mutations and drug-resistant cells. We designed and synthesized 4-anilinoquinazoline derivatives with substitutions at quinazoline positions 6, 7 and 4 using a binding model with multi-target receptor tyrosine kinases, and assessed their antitumor activity against five human tumor cell lines (HepG2, A549, MCF-7, DU145, SH-SY5Y). The majority of the compounds inhibited the proliferation of all the cancer cell types, with some compounds displaying selective inhibition. Compounds 21, 25, 27, and 37 displayed IC50 values of 7.588, 8.619, 6.936, and 8.516 µM, respectively, for A549 cells, which were much lower than that of Gefitinib (14.803 µM). Compound 32 displayed an IC50 value of 2.756 µM for DU145 cells. The representative compound 40 had unexceptionable broad-spectrum inhibition for all cancer cell types, and demonstrate inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFR-ß), and epidermal growth factor receptor (EGFR) with IC50 values of 46.4, 673.6 and 384.8 nM, respectively, which were similar to those of Sorafenib for VEGFR-2 and PDGFR-ß (140.6 and 582.7 nM, respectively). Molecular docking results supported the molecular level assay results. Data for production of reactive oxygen species and assessment of matrix metalloproteinase corroborated the strong anti-proliferative effect of compound 40. The compound also displayed robust antitumor efficacy and relativity lower toxicity in a xenograft model. These attributes were similar to those of Sorafenib. Compound 40 drug warrants further study as a candidate.

LSINCT5 activates Wnt/ß-catenin signaling by interacting with NCYM to promote bladder cancer progression.

Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are critically involved in tumor progression. In current study, we reported a novel lncRNA signature correlated with bladder cancer development. Particularly, the lncRNA long stress-induced noncoding transcript 5 (LSINCT5) is significantly upregulated in human bladder cancer cell lines and tumor specimens. Meanwhile, high LSINCT5 expression correlates with poor prognosis, enhances tumor sphere formation and invasion in vitro. In vivo xenograft tumor growth is also elevated by LSINCT5 overexpression. Mechanistic investigations showed that LSINCT5 could physically interact with NCYM, a de novo gene product from the MYCN cis-antisense RNA and inhibit GSK3ß activity leading to enhanced Wnt/ß-catenin signaling activation and epithelial mesenchymal transition (EMT). Taken together, our findings have created a novel LSINCT5 mediated process which facilitates bladder cancer progression and may provide a potential target for therapeutic intervention.

Synthesis and evaluation of novel 18 F-labeled quinazoline derivatives with low lipophilicity for tumor PET imaging.

Four novel 18 F-labeled quinazoline derivatives with low lipophilicity, [18 F]4-(2-fluoroethoxy)-6,7-dimethoxyquinazoline ([18 F]I), [18 F]4-(3-((4-(2-fluoroethoxy)-7-methoxyquinazolin-6-yl)oxy)propyl)morpholine ([18 F]II), [18 F]4-(2-fluoroethoxy)-7-methoxy-6-(2-methoxyethoxy)quinazoline ([18 F]III), and [18 F]4-(2-fluoroethoxy)-6,7-bis(2-methoxyethoxy)quinazoline ([18 F]IV), were synthesized via a 2-step radiosynthesis procedure with an overall radiochemical yield of 10% to 38% (without decay correction) and radiochemical purities of >98%. The lipophilicity and stability of labeled compounds were tested in vitro. The log P values of the 4 radiotracers ranged from 0.52 to 1.07. We then performed ELISA to measure their affinities to EGFR-TK; ELISA assay results indicated that each inhibitor was specifically bounded to EGFR-TK in a dose-dependent manner. The EGFR-TK autophosphorylation IC50 values of [18 F]I, [18 F]II, [18 F]III, and [18 F]IV were 7.732, 0.4698, 0.1174, and 0.1176 µM, respectively. All labeled compounds were evaluated via cellular uptake and blocking studies in HepG2 cell lines in vitro. Cellular uptake and blocking experiment results indicated that [18 F]I and [18 F]III had excellent cellular uptake at 120-minute postinjection in HepG2 carcinoma cells (51.80 ± 3.42%ID/mg protein and 27.31 ± 1.94%ID/mg protein, respectively). Additionally, biodistribution experiments in S180 tumor-bearing mice in vivo indicated that [18 F]I had a very fast clearance in blood and a relatively high uptake ratio of tumor to blood (4.76) and tumor to muscle (1.82) at 60-minute postinjection. [18 F]III had a quick clearance in plasma, and its highest uptake ratio of tumor to muscle was 2.55 at 15-minute postinjection. These experimental results and experiences were valuable for the further exploration of novel radiotracers of quinazoline derivatives.

MicroRNA-588 is upregulated in human prostate cancer with prognostic and functional implications.

BACKGROUND: Epigenetic factors of microRNAs (miRNAs) are important biomarkers and modulators in human prostate cancer (PCa). In this work, we characterized the expression, biomarker-potential and functional regulation of miR-588 in PCa. METHODS: Endogenous miR-588 levels were quantified by qRT-PCR in both prostate-specific antigen (PSA)-negative and PSA-positive PCa cell lines, as well as human PCa tumors. The associations between endogenous miR-588 and PCa patients' clinical outcomes and postoperative overall survival were statistically examined. Moreover, in both PSA-negative DU145 and PSA-positive LNCaP, downregulation of miR-588 was achived by transduction of miR-588 inhibitor lentivirus. The subsequent effects of miR-588 downregulation on PCa cell developments were investigated both in vitro and in vivo. RESULTS: MiR-588 was profoundly upregulated in both PSA-negative and PSA-positive PCa cells, as well as in PCa tumors. Significant miR-588 upregulation was found to be closely associated with PCa patients' poor clinical outcomes and shorter postoperative overall survivals. In DU145 and LNCaP cell lines, lentiviral transduction markedly downregulated endogenous miR-588 levels. MiR-588 downregulation was shown to profoundly inhibit PCa proliferation in vitro and xenograft in vivo. CONCLUSION: Aberrant upregulation of endogenous miR-588 in PCa patients may be a prognostic biomarker, indicative of their poor clinical outcomes. Inhibiting endogenous miR-588 may also serve as a therapeutic target for PCa treatment. This article is protected by copyright. All rights reserved.

Fluorescent Pdots Facilitate High-Resolution Mapping of the Intact Meningeal Vascular Network and Eye-Brain Connections.

Meningeal vascular network is significant in neurology and neurosurgery. However, high-resolution imaging of intact meningeal vascular network is lacking. In this work, we develop a practical experimental method to ensure that the intact meninges are morphologically unfolded and fixed in an agarose gel. With the help of high-brightness polymer dots (Pdots) as probe, macroscopic and detailed imaging of the vascular network on the intact dorsal meninges can be performed. Meningeal vessels are symmetrically distributed along the superior sagittal sinus, and the distribution of meningeal vessels had a certain degree of hierarchy. The meninges are thicker blood vessels and capillary networks from the outside to the inside. Moreover, the diameter of the capillaries is 3.96 ± 0.89 µm. Interestingly, meningeal primo vessels in the central nervous system of mice is imaged with the diameter of 4.18 ± 1.18 µm, which has not been reported previously. It is worth mentioning that we found that orthotopic xenografts of brain tumors caused the appearance of corneal neovascularization and morphological changes in optic nerve microvessels. In conclusion, our work provides an effective Pdots-based imaging method for follow-up research on meningeal vascular-related diseases, and illustrates that the eye can serve as a window for the prevention and diagnosis of brain diseases.

Evaluation of Fourier deconvolution ion mobility spectrometer as high-performance gas chromatography detector for the analysis of plant extract flavors.

The Fourier deconvolution ion mobility spectrometer (FDIMS) offers multiplexing and improves the resolving power and signal-to-noise ratio. To evaluate the FDIMS as a detector for gas chromatography for the analysis of complex samples, we connected a drift tube ion mobility spectrometer to a commercial gas chromatograph and compared the performance including resolving power, sensitivity, and linear range using 2,6-di­tert-butylpyridine. Mixed standards were also injected into the tandem system to evaluate the performance under optimized conditions. A complex plant extract sample used as natural flavoring was investigated using the resulting system. The results show that the instrument implemented with the Fourier deconvolution multiplexing method demonstrated higher performance over the traditional signal averaging method including higher resolving power, better limit of detection, and wider linear range for a variety of compounds and natural plant extract flavorings.

Longevity extension in rats via improved redox homeostasis with high carbohydrate diet intervention from weaning to adulthood: a comprehensive multi-omics study.

Early dietary patterns potentially influence the health status and lifespan throughout adulthood and the entire lifespan. However, dietary behaviors are difficult for everyone to control during adolescence. It is even more important to study the effects of interventions of early dietary patterns on the lifespan under arbitrary feeding conditions. The research involves observing the survival status and lifespan of rats from weaning to adulthood with three different dietary patterns (a high-carbohydrate diet (HC), a high-protein diet (HP), and a high-fat diet (HF)) under ad libitum feeding conditions. The administration of high-carbohydrate diets leads to a significant extension of both median and maximum survival times (P < 0.05) in Wistar rats. Furthermore, it markedly enhanced the spatial memory capacity, mitigated the occurrence of liver and kidney pathological outcomes in elderly rats, and increased the abundance of gut microbiota improving amino acid metabolism. Additionally, feeding rats a high-carbohydrate diet improved glutathione (GSH) synthesis and recycling and activated the expression and upregulation of the lifespan-related proteins Foxo3a/Sirt3 and the key metabolic enzyme GPX-4. The high-carbohydrate diet from weaning to adulthood may potentially extend the lifespan by enhancing rat systemic glutathione synthesis, recycling, and improving the redox state pathway.

Enhancing osteoporosis treatment using a targeted, sustained-release drug delivery system based on macrocyclic amphiphile.

Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.

Supramolecular 3 in 1: A Lubrication and Co-Delivery System for Synergistic Advanced Osteoarthritis Therapy.

The complexity, heterogeneity, and drug resistance of diseases necessitate a shift in therapeutic paradigms from monotherapy to combination therapy, which could augment treatment efficiency. Effective treatment of advanced osteoarthritis (OA) requires addressing three key factors contributing to its deterioration: chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation. Herein, we present a supramolecular nanomedicine of multifunctionality via molecular recognition and self-assembly. The employed macrocyclic carrier, zwitterion-modified cavitand (CV-2), not only accurately loads various drugs but also functions as a therapeutic agent with lubricating properties for the treatment of OA. Kartogenin (KGN), a drug for articular cartilage regeneration and protection, and flurbiprofen (FP), an anti-inflammatory agent, were coloaded onto CV-2 assembly, forming a supramolecular nanomedicine KGN&FP@CV-2. The three-in-one combination therapy of KGN&FP@CV-2 addresses the three pathological features for treating OA collectively, and thus provides long-term therapeutic benefits for OA through sustained drug release and intrinsic lubrication in vivo. The multifunctional integration of macrocyclic delivery and therapeutics provides a simple, flexible, and universal platform for the synergistic treatment of diseases involving multiple drugs.

Recent advances on catalysts for photocatalytic selective hydrogenation of nitrobenzene to aniline.

Selective hydrogenation of nitrobenzene (SHN) is an important approach to synthesize aniline, an essential intermediate with extremely high research significance and value in the fields of textiles, pharmaceuticals and dyes. SHN reaction requires high temperature and high hydrogen pressure via the conventional thermal-driven catalytic process. On the contrary, photocatalysis provides an avenue to achieve high nitrobenzene conversion and high selectivity towards aniline at room temperature and low hydrogen pressure, which is in line with the sustainable development strategies. Designing efficient photocatalysts is a crucial step in SHN. Up to now, several photocatalysts have been explored for photocatalytic SHN, such as TiO2, CdS, Cu/graphene and Eosin Y. In this review, we divide the photocatalysts into three categories based on the characteristics of the light harvesting units, including semiconductors, plasmonic metal-based catalysts and dyes. The recent progress of the three categories of photocatalysts is summarized, the challenges and opportunities are pointed out and the future development prospects are described. It aims to give a clear picture to the catalysis community and stimulate more efforts in this research area.

Evaluation of enlarged laminectomy with lateral mass screw fixation in relieving nerve root symptoms and correcting kyphosis for cervical myelopathy and radiculopathy.

Purpose: This study aimed to compare the surgical efficacy of enlarged laminectomy with lateral mass screw fixation (EL-LMSF) and anterior cervical decompression and fusion (ACDF) for multilevel cervical myelopathy and radiculopathy (CMR) related to kyphosis. Methods: 75 patients were retrospectively reviewed and divided into ACDF and EL-LMSF group. Clinical results including operative time, blood loss, and postoperative complications were compared. The JOA scoring system was used to evaluate spinal cord function and the VAS score evaluate nerve root pain severity. Cervical alignment a C2-C7 was measured with Cobb method and compared to confirm the reconstruction effect. Results: Data on 75 patients (M/F: 41:34; EL-LMSF/ACDF:42/33) with the mean age of 57.5 years (range 43-72 year old) were reviewed retrospectively. Discectomy and/or sub-toal corpectomy in ACDF group was performed with a mean of 3.24 levels (range, 3-4). Enlarged laminectomy in EL-LMSF group was performed with a mean of 3.89 enlarged levels (range, 3-5). The procedure of ACDF group showed a shorter operation time (103 ± 22 min vs. 125 ± 37 min, P = 0.000) and less blood loss (78 ± 15 ml vs. 226 ± 31 ml, P = 0.000) compared than that of the EL-LMSF group. Patients treated with EL-LMSF indicated lower VAS for upper extremity (1.3 ± 1.7 vs. 3.3 ± 1.3, P = 0.003) and better curvature corrected (10.7 ± 4.2° vs. 8.5 ± 3.5°, P = 0.013). The difference were of statistical significance. No statistical difference was found after surgery in the JOA score (14.1 ± 1.7 vs. 13.5 ± 2.1, P = 0.222). During the follow-up period, 15.2% of patients in the ACDF group had complications including 2 cases with transient dysphagia, 1 case with C5 palsy, 1 case with axial pain, and 1 case with screw pullout 3 month after surgery. However, only 9.5% of cases in the EL-LMSF group experienced complications, including 3 cases of axial pain and 1 case of epidural hematoma. Conclusion: The EL-LMSF procedure requires a longer operation time and more blood loss because of the incision of the stenosed foramen. However, the procedure has obvious advantages in relieving nerve root symptoms and correcting cervical curvature with fewer postoperative complications.

High-Resolution Imaging of the Ocular Vasculature of Conjunctivitis in Mice Using Highly Bright Polymer Dots.

Ocular diseases are mainly caused by vascular aberrations in the eye, and accurate imaging and analysis of the ocular vascular structure is crucial. In this study, poly(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT) polymer dots (Pdots), with the advantages of easy synthesis, high brightness, and low toxicity, are used as nanoprobes to perform high-resolution imaging of the vasculature of the eyeball and optic nerve. Moreover, rapid imaging of the choroidal microvessels is carried out by stereoscopic fluorescence microscopy with a resolution of up to 1.6 µm. The comprehensive 3D vascular information of retinal aorta and optic nerve microvessels is obtained by combining tissue clearing and multiphoton microscopy. In addition, the vascular density of Schlemm's canal and iris blood vessels is compared between the conjunctivitis mice and the normal mice. These results suggest that PFBT Pdots have great application potential in the fast and accurate imaging of ocular diseases.

Analysis of serum fatty acid, amino acid, and organic acid profiles in gestational hypertension and gestational diabetes mellitus via targeted metabolomics.

This study aimed to characterize metabolite differences and correlations between hypertensive disorders of pregnancy (HP) and gestational diabetes mellitus (GDM) using univariate, multivariate analyses, RF, and pathway analyses in a cross-sectional study. Dietary surveys were collected and targeted metabolomics was applied to measure levels of serum fatty acids, amino acids, and organic acids in 90 pregnant women at 24-28 weeks gestation at the First Affiliated Hospital of Harbin Medical University. Principal components analysis (PCA) and partial least squares-discriminatory analysis (PLS-DA) models were established to distinguish HP, GDM, and healthy, pregnant control individuals. Univariate and multivariate statistical analyses and Random Forest (RF) were used to identify and map co-metabolites to corresponding pathways in the disease states. Finally, risk factors for the disease were assessed by receiver operating characteristics (ROC) analysis. Dietary survey results showed that HP and GDM patients consumed a high-energy diet and the latter also consumed a high-carbohydrate and high-fat diet. Univariate analysis of clinical indices revealed HP and GDM patients had glycolipid disorders, with the former possessing more severe organ dysfunction. Subsequently, co-areas with significant differences identified by basic discriminant analyses and RF revealed lower levels of pyroglutamic acid and higher levels of 2-hydroxybutyric acid and glutamic acid in the GDM group. The number of metabolites increased in the HP group as compared to the healthy pregnant control group, including pyroglutamic acid, γ-aminobutyric acid (GABA), glutamic acid, oleic acid (C18:1), and palmitic acid (C16:0). ROC curves indicated that area under curve (AUC) for pyroglutamic acid in the GDM group was 0.962 (95% CI, 0.920-1.000), and the AUC of joint indicators, including pyroglutamic acid and GABA, in the HP group was 0.972 (95% CI, 0.938-1.000). Collectively, these results show that both GDM and HP patients at mid-gestation possessed dysregulated glucose and lipid metabolism, which may trigger oxidative stress via glutathione metabolism and biosynthesis of unsaturated fatty acids.

Multifunctional Imaging of Vessels, Brown Adipose Tissue, and Bones in the Visible and Second Near-infrared Region Using Dual-Emitting Polymer Dots.

Dual-emitting polymer dots (dual-Pdots) in the visible and second near-infrared (NIR-II) region can facilitate the high-resolution imaging of the fine structure and improve the signal-to-noise ratio in in vivo imaging. Herein, combining high brightness of Pdots and multi-scale imaging, we synthesized dual-Pdots using a simple nano-coprecipitation method and performed multi-functional imaging of vessels, brown adipose tissue, and bones. Results showed that in vivo blood vessel imaging had a high resolution of up to 5.9 µm and bone imaging had a signal-to-noise ratio of 3.9. Moreover, dual-Pdots can accumulate in the interscapular brown adipose tissue within 2 min with a signal-to-noise ratio of 5.8. In addition, the prepared dual-Pdots can image the lymphatic valves and the frequency of contraction. Our study provides a feasible method of using Pdots as nanoprobes for multi-scale imaging in the fields of metabolic disorders, skeletal system diseases, and circulatory systems.

[Effects and mechanism of morroniside on osteogenic differentiation and proliferation of mouse MC3T3-E1 cells].

Objective: To study the effects of morroniside (MOR) on the proliferation and osteogenic differentiation of mouse MC3T3-E1 cells. Methods: The 4th generation MC3T3-E1 cells were randomly divided into 6 groups: control group (group A), MOR low dose group (10 µmol/L, group B), MOR medium-low dose group (20 µmol/L, group C), MOR medium dose group (40 µmol/L, group D), MOR medium-high dose group (80 µmol/L, group E), and MOR high dose group (100 µmol/L, group F). The proliferation activity of each group was detected by cell counting kit 8 (CCK-8) assay; the bone differentiation and mineralized nodule formation of each group were detected by alizarin red staining; real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect cyclin-dependent kinase inhibitor 1A (P21), recombinant Cyclin D1 (CCND1), proliferating cell nuclear antigen (PCNA), alkaline phosphatase (ALP), collagen type Ⅰ (COL-1), bone morphogenetic protein 2 (BMP-2), and adenosine A2A receptor (A2AR) mRNA expressions; Western blot was used to detecte the expressions of osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), and adenosine A2AR protein. Results: The CCK-8 assay showed that the absorbance ( A) values of groups B to F were significantly higher than that of group A at 24 hours of culture, with group C significantly higher than the rest of the groups ( P<0.05). The MOR concentration (20 µmol/L) of group C was selected for the subsequent CCK-8 assay; the results showed that the A values of group C were significantly higher than those of group A at 24, 48, and 72 hours of culture ( P<0.05). Alizarin red staining showed that orange-red mineralized nodules were visible in all groups and the number of mineralized nodules was significantly higher in groups B and C than in group A ( P<0.05). RT-qPCR showed that the relative expressions of P21, CCND1, and PCNA mRNAs were significantly higher in group C than in group A ( P<0.05). The expressions of ALP, BMP-2, COL-1, and adenosine A2AR mRNAs in groups B to E were significantly higher than those in group A, with the expressions of ALP, BMP-2, COL-1 mRNAs in group C significantly higher than the rest of the groups ( P<0.05). Compared with group A, the expressions of OPN and RUNX2 proteins in groups B and C were significantly increased, while those in group D and E were significantly inhibited ( P<0.05). There was no significant difference between groups B and C and between groups D and E ( P>0.05). The relative expression of adenosine A2AR protein in groups B to E was significantly higher than that in group A, with group C significantly higher than the rest of the groups ( P<0.05). Conclusion: MOR can promote the proliferation and osteogenic differentiation of MC3T3-E1 cells; the mechanism of MOR may be achieved by interacting with adenosine A2AR.