Computational optical sectioning via near-field multi-slice ptychography.

We introduce a method for the computational sectioning of optically thick samples based on a combination of near-field and multi-slice ptychography. The method enables a large field-of-view 3D phase imaging of samples that is an order of magnitude thicker than the depth of field of bright-field microscopy. An axial resolution for these thick samples is maintained in the presence of multiple scattering, revealing a complex structure beyond the depth of the field limit. In this Letter, we describe the new, to the best of our knowledge, approach and demonstrate its effectiveness using a range of samples with diverse thicknesses and optical properties.

In vitro study to identify ligand-independent function of estrogen receptor-α in suppressing DNA damage-induced chondrocyte senescence.

In osteoarthritis (OA), chondrocytes undergo many pathological alternations that are linked with cellular senescence. However, the exact pathways that lead to the generation of a senescence-like phenotype in OA chondrocytes are not clear. Previously, we found that loss of estrogen receptor-α (ERα) was associated with an increased senescence level in human chondrocytes. Since DNA damage is a common cause of cellular senescence, we aimed to study the relationship among ERα levels, DNA damage, and senescence in chondrocytes. We first examined the levels of ERα, representative markers of DNA damage and senescence in normal and OA cartilage harvested from male and female human donors, as well as from male mice. The influence of DNA damage on ERα levels was studied by treating human chondrocytes with doxorubicin (DOX), which is an often-used DNA-damaging agent. Next, we tested the potential of overexpressing ERα in reducing DNA damage and senescence levels. Lastly, we explored the interaction between ERα and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Results indicated that the OA chondrocytes contained DNA damage and displayed senescence features, which were accompanied by significantly reduced ERα levels. Overexpression of ERα reduced the levels of DNA damage and senescence in DOX-treated normal chondrocytes and OA chondrocytes. Moreover, DOX-induced the activation of NF-κB pathway, which was partially reversed by overexpressing ERα. Taken together, our results demonstrated the critical role of ERα in maintaining the health of chondrocytes by inhibiting DNA damage and senescence. This study also suggests that maintaining the ERα level may represent a new avenue to prevent and treat OA.

Dual Pigment Epithelium-derived Factor and Hepatocyte Growth Factor Overexpression: A New Therapy for Pulmonary Hypertension.

Pulmonary hypertension (PH) is a disease characterized by advanced pulmonary vasculature remodeling that is thought to be curable only through lung transplantation. The application of angiogenic hepatocyte growth factor (HGF) is reported to be protective in PH through its anti-vascular remodeling effect, but excessive HGF-mediated immature neovascularization is not conducive to the restoration of pulmonary perfusion because of apparent vascular leakage. As a canonical antiangiogenic molecule, pigment epithelium-derived factor (PEDF) inhibits angiogenesis and reduces vascular permeability in a variety of diseases. However, the effect of PEDF on HGF-based PH treatment remains to be determined. In this study, monocrotaline-induced PH rats and endothelial cells isolated from rat and human PH lung tissues were used. We assessed PH progression, right cardiac function, and pulmonary perfusion in HGF- and/or PEDF-treated rats with PH. Additionally, the receptor and mechanism responsible for the role of PEDF in HGF-based PH therapy were investigated. In this study, we found that HGF and PEDF jointly prevent PH development and improve right cardiac function in rats with PH. Moreover, PEDF delivery increases the pulmonary perfusion in PH lungs and inhibits immature angiogenesis and vascular endothelial (VE)-cadherin junction disintegration induced by HGF without affecting the therapeutic inhibition of pulmonary vascular remodeling by HGF. Mechanistically, PEDF targets VE growth factor receptor 2 and suppresses its phosphorylation at Y951 and Y1175 but not Y1214. Finally, VE growth factor receptor 2/VE protein tyrosine phosphatase/VE-cadherin complex formation and Akt and Erk1/2 inactivation were observed in rat and human PH lung endothelial cells. Collectively, our data indicate that PEDF additively enhances the efficacy of HGF against PH, which may provide new insights into treatment strategies for clinical PH.

Near-field multi-slice ptychography: quantitative phase imaging of optically thick samples with visible light and X-rays.

Ptychography is a form of lens-free coherent diffractive imaging now used extensively in electron and synchrotron-based X-ray microscopy. In its near-field implementation, it offers a route to quantitative phase imaging at an accuracy and resolution competitive with holography, with the added advantages of extended field of view and blind deconvolution of the illumination beam profile from the sample image. In this paper we show how near-field ptychography can be combined with a multi-slice model, adding to this list of advantages the unique ability to recover high-resolution phase images of larger samples, whose thickness places them beyond the depth of field of alternative methods.

Efficient Communications in V2V Networks with Two-Way Lanes Based on Random Linear Network Coding.

Vehicle-to-vehicle (V2V) communication has gained significant attention in the field of intelligent transportation systems. In this paper, we focus on communication scenarios involving vehicles moving in the same and opposite directions. Specifically, we model a V2V network as a dynamic multi-source single-sink network with two-way lanes. To address rapid changes in network topology, we employ random linear network coding (RLNC), which eliminates the need for knowledge of the network topology. We begin by deriving the lower bound for the generation probability. Through simulations, we analyzed the probability distribution and cumulative probability distribution of latency under varying packet loss rates and batch sizes. Our results demonstrated that our RLNC scheme significantly reduced the communication latency, even under challenging channel conditions, when compared to the non-coding case.

ciRS-7 Enhances the Progression of Hepatocellular Carcinoma through miR-944/NOX4 Pathway.

Recently, increasing numbers of non-coding RNA have been uncovered in research. As a new class of non-coding RNA, circular RNA has been identified to be involved in various diseases including many cancers. The circular RNA ciRS-7 is reported to play critical roles in tumorigenesis. However, the role of ciRS-7 in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression and function of ciRS-7 in HCC cells and cancer tissues. CCK8 was applied to detect the influence of ciRS-7 on proliferation. Wound heal assay and invasion assay were used to identify the effects on migration and invasion. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, RNA pull-down, and luciferase reporter assay were used to investigate the downstream targets of ciRS-7. The results showed that ciRS-7 was highly expressed in both hepatocellular carcinoma cells and tissues. Overexpression of ciRS-7 could promote the proliferation, migration, and invasion of HCC. Further study showed that ciRS-7 regulated the miR-944 level through acting as a microRNA sponge. q-RT-PCR, Western blot, RNA pull-down and dual luciferase activity assays showed that miR-944 targeted and regulated the expression of NOX4. Furthermore, the tumor-promoting effect of ciRS-7 could be blocked by inhibition of miR-944/NOX4. Our study demonstrated that ciRS-7 enhanced the proliferation, migration, and invasion of HCC through miR-944/NOX4 pathway. ciRS-7 could be a promising therapeutic target for HCC.

Focus on the classical and non-classical functions of EZH2: Guide the development of inhibitors and degraders.

Enhancer of zeste homologue 2 (EZH2, also known as KMT6A) is found to be a member of the histone lysine methyltransferase family. An increasing number of studies have shown that in addition to methylating histones, EZH2 plays a vital role in a variety of ways. The methylated substrates of EZH2 also include GATA4, AR/AR-related proteins, STAT3, Talin protein, and RORα. Meanwhile, EZH2 has been reported to form complexes with some proteins to perform other important biological functions as well as methylation. These complexes include: the EZH2-RelA-RelB complex, EZH2-ER-ß-catenin complex, and ß-catenin-PAF-EZH2-Mediator complex. Herein, we focus on the classical and non-classical functions of EZH2, and summarize anti-EZH2 therapeutic strategies. Finally, we highlight that understanding the physiological and pathological functions of EZH2 in specific indications can help the development of inhibitors or degraders.

Ptycho-cam: a ptychographic phase imaging add-on for optical microscopy.

Near field ptychography uses diffraction data collected at large Fresnel numbers, together with iterative reconstruction algorithms, to realize quantitative phase imaging of transmissive samples. It delivers excellent phase sensitivity with a wide field of view from a simple optical system using a relatively small number of measured diffraction patterns. In this paper, we develop an add-on to a standard optical microscope that implements near-field ptychography. The add-on is self-contained and attaches to the microscope camera port, requiring no modification to the microscope itself. Unlike conventional ptychography, it does not involve sample translation, making it more suitable for delicate samples or samples in liquid.

Identification of Important Factors Causing Developmental Arrest in Cloned Pig Embryos by Embryo Biopsy Combined with Microproteomics.

The technique of pig cloning holds great promise for the livestock industry, life science, and biomedicine. However, the prenatal death rate of cloned pig embryos is extremely high, resulting in a very low cloning efficiency. This limits the development and application of pig cloning. In this study, we utilized embryo biopsy combined with microproteomics to identify potential factors causing the developmental arrest in cloned pig embryos. We verified the roles of two potential regulators, PDCD6 and PLK1, in cloned pig embryo development. We found that siRNA-mediated knockdown of PDCD6 reduced mRNA and protein expression levels of the pro-apoptotic gene, CASP3, in cloned pig embryos. PDCD6 knockdown also increased the cleavage rate and blastocyst rate of cloned porcine embryos. Overexpression of PLK1 via mRNA microinjection also improved the cleavage rate of cloned pig embryos. This study provided a new strategy to identify key factors responsible for the developmental defects in cloned pig embryos. It also helped establish new methods to improve pig cloning efficiency, specifically by correcting the expression pattern of PDCD6 and PLK1 in cloned pig embryos.

Integrating ecosystem services modeling into effectiveness assessment of national protected areas in a typical arid region in China.

Protected areas (PAs) are essential for biodiversity conservation and for the delivery of ecosystem services (ESs). However, little is known about their effectiveness in providing ESs and contribution to species richness, especially in arid regions. Effectiveness evaluation is fundamental to understanding the extent of management enhancement required to fulfill conservation targets. In this study, we analyzed the supply of six ESs (water yield, nutrient retention, soil retention, sand fixation, carbon storage, and biodiversity richness) by landscapes in China's arid region of Xinjiang Uygur Autonomous Region (hereafter Xinjiang). The aim was to identify distribution of ESs hotspots and the extent of hotspots located within or outside national PAs. The results showed significant spatial heterogeneity and coverage differences in six types of ESs hotspots. Hotspots coverage of six ESs on average accounted for 10.45 % of the total area, distributed mainly in mountains and oases covered by vegetation and wetlands. Among these ESs hotspots, over 50 % fell within PAs. This suggested that although PAs delivered moderately well outcomes in preserving ESs and biodiversity in Xinjiang, conservation gaps needed to be addressed. Our study also revealed substantial differences in ESs supplied by different PAs, and serious deficiency existed in some PAs in protecting either biodiversity or key ESs outlined in their conservation objectives. Our study illustrated the priority areas for future conservation expansion and stressed the urgent shift toward broadening the goals of PAs from a dominant focus to ones that encompass multiple ESs for human well-being.