An immune cell atlas reveals the dynamics of human macrophage specification during prenatal development.

Macrophages are heterogeneous and play critical roles in development and disease, but their diversity, function, and specification remain inadequately understood during human development. We generated a single-cell RNA sequencing map of the dynamics of human macrophage specification from PCW 4-26 across 19 tissues. We identified a microglia-like population and a proangiogenic population in 15 macrophage subtypes. Microglia-like cells, molecularly and morphologically similar to microglia in the CNS, are present in the fetal epidermis, testicle, and heart. They are the major immune population in the early epidermis, exhibit a polarized distribution along the dorsal-lateral-ventral axis, and interact with neural crest cells, modulating their differentiation along the melanocyte lineage. Through spatial and differentiation trajectory analysis, we also showed that proangiogenic macrophages are perivascular across fetal organs and likely yolk-sac-derived as microglia. Our study provides a comprehensive map of the heterogeneity and developmental dynamics of human macrophages and unravels their diverse functions during development.

Efficacy and Mechanisms of Oleuropein in Postmenopausal Osteoporosis.

Background: Postmenopausal osteoporosis (PMOP) has a supernal morbidity rate in elderly females. Objective: To appraise the effects of oleuropein on bone densitometry, bone metabolic index, oxidative stress, and inflammatory index in PMOP. In addition, the mechanism of olive bittersweet preventing bone loss was explored. Methods: We grouped 80 salubrious female Sprague-Dawley rats into four teams: (1) sham operation team (sham, N = 20), (2) ovariectomy (OVX, N = 20), (3) castrated mice fed with oleuropein (OVX+ole, N = 20), and (4) castrated mice fed with estrogen (OVX+E2, N = 20). The ovariectomized SD rats were continuously raised with 200 µg/kg/dose of oleuropein. Bone mineral density and bone metabolism indexes were recorded. In order to assess the effectiveness of oleuropein on osteopenia, an enzyme-linked immunosorbent assay (ELISA) was devoted to examining the bone marrow indexes. The bone metabolism standards of PMOP rats were appraised by assessing serum levels of calcium, alkaline phosphatase (ALP), phosphorus, malondialdehyde (MDA), and nitrate content by experimental detection methods and levels of osteoclastogenesis inhibitory factor (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) by ELISA. The OPG-RANK-RANKL signal passage was examined by Western blot (WB). We measured bone mineral density using dual-energy X-rays. Results: Our animal experimental results indicated that oleuropein could significantly improve the bone mineral density of ovariectomized SD rats. In the meantime, it could reduce ending interleukin-6 (IL-6), malondialdehyde (MDA), nitrate, alkaline phosphatase (ALP), and phosphorus (P) serum concentration and would not affect Ca2+ concentration. In cell experiments, oleuropein also can promote the proliferation of osteoblasts. Furthermore, it can promote the expression of OPG protein and mRNA. In reverse, it inhibits the expression of RANKL protein and mRNA. Conclusion: Oleuropein can not only improve the inflammatory and oxidative indexes of castrated rats but also prevent osteoporosis. Oleuropein avoids bone resorption by regulating OPG/RANKL expression.

Deep learning for denoising in a Mueller matrix microscope.

The Mueller matrix microscope is a powerful tool for characterizing the microstructural features of a complex biological sample. Performance of a Mueller matrix microscope usually relies on two major specifications: measurement accuracy and acquisition time, which may conflict with each other but both contribute to the complexity and expenses of the apparatus. In this paper, we report a learning-based method to improve both specifications of a Mueller matrix microscope using a rotating polarizer and a rotating waveplate polarization state generator. Low noise data from long acquisition time are used as the ground truth. A modified U-Net structured network incorporating channel attention effectively reduces the noise in lower quality Mueller matrix images obtained with much shorter acquisition time. The experimental results show that using high quality Mueller matrix data as ground truth, such a learning-based method can achieve both high measurement accuracy and short acquisition time in polarization imaging.

Transmission Mueller matrix imaging with spatial filtering.

In this Letter, we report a study on the effects of spatial filtering for a transmission Mueller matrix imaging system. A spatial filter (SF) is placed on the back Fourier plane of the imaging lens in a dual-rotating-retarders Mueller matrix imaging system to select photons within a certain scattering angle. The system is then applied to three types of human cancerous tissues. When imaging with a small-aperture SF, some polarimetry basis parameters show sharp changes in contrast in the cancerous regions. Monte Carlo simulations using a simple sphere-cylinder scattering model also show that spatial filtering of the scattered photons provides extra information on the size and shape of the scattering particles. The results indicate that spatial filtering enhances the capability of polarization imaging as a powerful tool for biomedical diagnosis.

A Polarization-Imaging-Based Machine Learning Framework for Quantitative Pathological Diagnosis of Cervical Precancerous Lesions.

Polarization images encode high resolution microstructural information even at low resolution. We propose a framework combining polarization imaging and traditional microscopy imaging, constructing a dual-modality machine learning framework that is not only accurate but also generalizable and interpretable. We demonstrate the viability of our proposed framework using the cervical intraepithelial neoplasia grading task, providing a polarimetry feature parameter to quantitatively characterize microstructural variations with lesion progression in hematoxylin-eosin-stained pathological sections of cervical precancerous tissues. By taking advantages of polarization imaging techniques and machine learning methods, the model enables interpretable and quantitative diagnosis of cervical precancerous lesion cases with improved sensitivity and accuracy in a low-resolution and wide-field system. The proposed framework applies routine image-analysis technology to identify the macro-structure and segment the target region in H&E-stained pathological images, and then employs emerging polarization method to extract the micro-structure information of the target region, which intends to expand the boundary of the current image-heavy digital pathology, bringing new possibilities for quantitative medical diagnosis.

High NOV/CCN3 expression during high-fat diet pregnancy in mice affects GLUT3 expression and the mTOR pathway.

We investigated the expression levels of nephroblastoma overexpressed [NOV or CCN3 (cellular communication network factor 3)] in the serum and placenta of pregnant women and of pregnant mice fed a high-fat diet (HFD), and its effect on placental glucose transporter 3 (GLUT3) expression, to examine its role in gestational diabetes mellitus (GDM). NOV/CCN3 expression was increased in the mouse serum during pregnancy. At gestational day 18, NOV/CCN3 protein expression was increased in the serum and placenta of the HFD mice compared with that of mice fed a normal diet. Compared with non-GDM patients, the patients with GDM had significantly increased serum NOV/CCN3 protein expression and placental NOV/CCN3 mRNA expression. Therefore, we hypothesized that NOV/CCN3 signaling may be involved in the pathogenesis of GDM. We administered NOV/CCN3 recombinant protein via intraperitoneal injections to pregnant mice fed HFD or normal diet. NOV/CCN3 overexpression led to glucose intolerance. Combined with the HFD, NOV/CCN3 exacerbated glucose intolerance and caused insulin resistance. NOV/CCN3 upregulates GLUT3 expression and affects the mammalian target of rapamycin (mTOR) pathway in the GDM environment in vivo and in vitro. In summary, our results demonstrate, for the first time, the molecular mechanism of NOV/CCN3 signaling in maternal metabolism to regulate glucose balance during pregnancy. NOV/CCN3 may be a potential target for detecting and treating GDM.NEW & NOTEWORTHY NOV/CCN3 regulates glucose homeostasis in mice during pregnancy. NOV/CCN3 upregulates GLUT3 expression and affects the mTOR pathway in the GDM environment in vivo and in vitro.

Surface Antifouling Modification on Polyethylene Filtration Membranes by Plasma Polymerization.

Surface modification on microporous polyethylene (PE) membranes was facilitated by plasma polymerizing with two hydrophilic precursors: ethylene oxide vinyl ether (EO1V) and diethylene oxide vinyl ether (EO2V) to effectively improve the fouling against mammalian cells (Chinese hamster ovary, CHO cells) and proteins (bovine serum albumin, BSA). The plasma polymerization procedure incorporated uniform and pin-hole free ethylene oxide-containing moieties on the filtration membrane in a dry single-step process. The successful deposition of the plasma polymers was verified by Fourier-transform infrared (FTIR), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) analyses. Water contact angle measurements and permeation experiments using cell and protein solutions were conducted to evaluate the change in hydrophilicity and fouling resistance for filtrating biomolecules. The EO1V and EO2V plasma deposited PE membranes showed about 1.45 fold higher filtration performance than the pristine membrane. Moreover, the flux recovery reached 80% and 90% by using deionized (DI) water and sodium hydroxide (NaOH) solution, indicating the efficacy of the modification and the good reusability of the modified PE membranes.

LncRNA MAGI2-AS3 Affects Cell Invasion and Migration of Cervical Squamous Cell Carcinoma (CSCC) via Sponging miRNA-233/EPB41L3 Axis.

INTRODUCTION: The incidence of cervical squamous cell carcinoma (CSCC) has expanded in recent years. However, the function of long non-coding RNA (lncRNA) MAGI2-AS3 in the occurrence and progression of CSCC remains unclear. Therefore, the role of lncRNA MAGI2-AS3 in cervical squamous cell carcinoma (CSCC) was investigated in our study. METHODS: We used qRT-PCR analysis to identify the level of MAGI2-AS3 mRNA expression in CSCC clinical samples and cell lines. We investigated cell migration and invasion of CSCC cells transfected with MAGI2-AS3, miR-233 mimic, or EPB41L3 with transwell assays. Bioinformatics analysis and a luciferase reporter assay were employed to predict the interaction between MAGI2-AS3 and miR-233. RESULTS: We found that MAGI2-AS3 and EPB41L3 were both downregulated in CSCC and the expression of this two was positively correlated. Bioinformatics analysis showed that MAGI2-AS3 might bind to miR-233, which could directly target EPB41L3. In CSCC cells, overexpression of MAGI2-AS3 led to upregulated, while overexpression of miRNA-233 led to downregulated expression of EPB41L3. However, MAGI2-AS3 and miR-233 did not affect the expression of each other. In addition, overexpression of MAGI2-AS3 and EPB41L3 led to inhibited cancer cell invasion and migration, while overexpression of miR-233 played an opposite role and attenuated the effects of overexpressing MAGI2-AS3. CONCLUSION: MAGI2-AS3 may sponge miR-233 to upregulate EPB41L3, thereby inhibiting CSCC cell invasion and migration.

LncRNA terminal differentiation-induced ncRNA (TINCR) sponges miR-302 to upregulate cyclin D1 in cervical squamous cell carcinoma (CSCC).

This study aimed to investigate the role of lncRNA terminal differentiation-induced ncRNA (TINCR) in cervical squamous cell carcinoma (CSCC). By informatics analysis, we found that miR-302 may bind TINCR. Expression analysis showed that miR-302 was downregulated, while TINCR was upregulated in CSCC. Correlation analysis showed that they were not significantly correlated. In CSCC cells, miR-302 and TINCR failed to affect the expression of each other. However, miR-302 overexpression led to downregulated and TINCR overexpression led to upregulated cyclin D1 expression in CSCC cells. Interestingly, overexpression of cyclin D1 led to upregulated miR-302 and TINCR. Cell proliferation analysis showed that TINCR and cyclin D1 overexpression led to increased, while miR-302 overexpression led to decreased rate of cell proliferation. Moreover, miR-302 overexpression reduced the effects of TINCR overexpression. Therefore, TINCR sponges miR-302 to upregulate cyclin D1 in CSCC, thereby promoting cell proliferation.

[Expression of SFRP4 and DKK1 in cervical squamous cell carcinoma and the clinicopathological implications].

OBJECTIVE: To investigate the expression of SFRP4 and DKK1 in cervical squamous cell carcinoma and explore the clinicopathological implications. METHODS: Immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to detect the expressions of SFRP4 and DKK1 in 66 cervical squamous cell carcinoma and 26 normal cervical specimens. RESULTS: SFRP4 expression was significantly higher (P<0.01) and DKK1 expression was significantly lower (P<0.05) in the carcinoma tissues than in normal cervical tissues. DKK1 was negatively correlated with SFRP4 in the carcinoma tissues (P<0.01), and their expressions were associated with the clinical stages, tumor differentiation, depth of invasion and lymph node metastasis of the tumors (P<0.05). CONCLUSION: SFRP4 and DKK1, the upstream components of the Wnt pathway, play a key role in the tumorigenesis of cervical squamous cell carcinoma, and their expressions are associated with the clinicopathological features of the malignancy.