Study on the tissue clearing process using different agents by Mueller matrix microscope

In this paper, we monitor the in vitro tissue clearing process of mouse dorsal skin immersed into two types of agents using Mueller matrix microscope. By Mueller matrix polar decomposition, we can see that the major difference between polarization changes due to two kinds of agents is the opposite trend of phase retardance with clearing. For the insight of the connection between different agents with the microstructural and optical changes of cleared tissues, we establish various models to mimic the dynamic process of microphysical features of tissues with clearing time. The mechanisms considered include refractive index matching, collagen shrinkage, more orderly fibers and birefringence variation. We compare the experimental results with simulations based on a single mechanism model and a combined model, respectively, which confirms that an individual possible mechanism cannot explain the polarization phenomena due to clearing. Also by simulations of various clearing models involving two possible mechanisms, we can speculate that formamide and saturated sucrose as agents have respective impacts on tissue features and then cause different polarization changes with clearing. Specifically, collagen shrinkage plus birefringence reduction can better explain the tissue cleared by formamide, and refractive index match plus increased birefringence model is likely to be a proper description of tissue cleared by sucrose. Both simulations and experiments also validate the potential of Mueller matrix microscope as a good tool to understand the interaction between clearing agents and tissues

Inhibitory Effect of Ginsenoside Rg1 on Vascular Smooth Muscle Cell Proliferation Induced by PDGF-BB Is Involved in Nitric Oxide Formation

Ginsenoside Rg1 (Rg1) has been reported to suppress the proliferation of vascular smooth muscle cells (VSMCs). This study aimed to observe the role of nitric oxide (NO) in Rg1-antiproliferative effect. VSMCs from the thoracic aorta of SD rats were cultured by tissue explant method, and the effect of Rg1 (20 mg·L−1, 60 mg·L−1, and 180 mg·L−1) on platelet-derived growth factor-BB (PDGF-BB)-induced proliferation was evaluated by MTT assay. The cell cycle was analyzed by flow cytometry. For probing the mechanisms, the content of NO in supernatant and cGMP level in VSMCs was measured by nitric oxide kit and cGMP radio-immunity kit, respectively; the expressions of protooncogene c-fos and endothelial NO synthase (eNOS) mRNA in the VSMCs were detected by real-time RT-PCR; the intracellular free calcium concentration ([Ca2+]i) was detected with Fura-2/AM-loaded VSMCs. Comparing with that in normal group, Rg1 180 mg·L−1 did not change the absorbance of MTT and cell percent of G0/G1, G2/M, and S phase in normal cells (P > 0.05). Contrarily, PDGF-BB could increase the absorbance of MTT (P < 0.01) and the percent of the S phase cells but decrease the G0/G1 phase cell percent in the cell cycle, accompanied with an upregulating c-fos mRNA expression (P < 0.01), which was reversed by additions of Rg1(20 mg·L−1, 60 mg·L−1, and 180 mg·L−1). Rg1 administration could also significantly increase the NO content in supernatant and the cGMP level in VSMCs, as well as the eNOS mRNA expression in the cells, in comparison of that in the group treated with PDGF-BB alone (P < 0.01). Furthermore, Rg1 caused a further increase in the elevated [Ca2+]i induced by PDGF-BB. It was concluded that Rg1 could inhibit the VSMC proliferation induced by PDGF-BB through restricting the G0/G1 phase to S-phase progression in cell cycle. The mechanisms may be related to the upregulation of eNOS mRNA and the increase of the formation of NO and cGMP

Reconfigurable two-dimensional optoelectronic devices enabled by local ferroelectric polarization.

Ferroelectric engineered pn doping in two-dimensional (2D) semiconductors hold essential promise in realizing customized functional devices in a reconfigurable manner. Here, we report the successful pn doping in molybdenum disulfide (MoS2) optoelectronic device by local patterned ferroelectric polarization, and its configuration into lateral diode and npn bipolar phototransistors for photodetection from such a versatile playground. The lateral pn diode formed in this way manifests efficient self-powered detection by separating ~12% photo-generated electrons and holes. When polarized as bipolar phototransistor, the device is customized with a gain ~1000 by its transistor action, reaching the responsivity ~12 A W-1 and detectivity over 1013 Jones while keeping a fast response speed within 20 μs. A promising pathway toward high performance optoelectronics is thus opened up based on local ferroelectric polarization coupled 2D semiconductors

Structural analysis of inhibition of E. coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes

Background: Methionine aminopeptidase is a potential target of future antibacterial and anticancer drugs. Structural analysis of complexes of the enzyme with its inhibitors provides valuable information for structure-based drug design efforts. Results: Five new X-ray structures of such enzyme-inhibitor complexes were obtained. Analysis of these and other three similar structures reveals the adaptability of a surface-exposed loop bearing Y62, H63, G64 and Y65 (the YHGY loop) that is an integral part of the substrate and inhibitor binding pocket. This adaptability is important for accommodating inhibitors with variations in size. When compared with the human isozymes, this loop either becomes buried in the human type I enzyme due to an N-terminal extension that covers its position or is replaced by a unique insert in the human type II enzyme. Conclusion: The adaptability of the YHGY loop in E. coli methionine aminopeptidase, and likely in other bacterial methionine aminopeptidases, enables the enzyme active pocket to accommodate inhibitors of differing size. The differences in this adaptable loop between the bacterial and human methionine aminopeptidases is a structural feature that can be exploited to design inhibitors of bacterial methionine aminopeptidases as therapeutic agents with minimal inhibition of the corresponding human enzymes

Structural analysis of inhibition of E. coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes

<p>Abstract</p> <p>Background</p> <p>Methionine aminopeptidase is a potential target of future antibacterial and anticancer drugs. Structural analysis of complexes of the enzyme with its inhibitors provides valuable information for structure-based drug design efforts.</p> <p>Results</p> <p>Five new X-ray structures of such enzyme-inhibitor complexes were obtained. Analysis of these and other three similar structures reveals the adaptability of a surface-exposed loop bearing Y62, H63, G64 and Y65 (the YHGY loop) that is an integral part of the substrate and inhibitor binding pocket. This adaptability is important for accommodating inhibitors with variations in size. When compared with the human isozymes, this loop either becomes buried in the human type I enzyme due to an N-terminal extension that covers its position or is replaced by a unique insert in the human type II enzyme.</p> <p>Conclusion</p> <p>The adaptability of the YHGY loop in <it>E. coli </it>methionine aminopeptidase, and likely in other bacterial methionine aminopeptidases, enables the enzyme active pocket to accommodate inhibitors of differing size. The differences in this adaptable loop between the bacterial and human methionine aminopeptidases is a structural feature that can be exploited to design inhibitors of bacterial methionine aminopeptidases as therapeutic agents with minimal inhibition of the corresponding human enzymes.</p

Effects of Gualou Guizhi Decoction Aqueous Extract on Axonal Regeneration in Organotypic Cortical Slice Culture after Oxygen-Glucose Deprivation

Gualou Guizhi decoction (GLGZD) is effective for the clinical treatment of limb spasms caused by ischemic stroke, but its underlying mechanism is unclear. Propidium iodide (PI) fluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunohistochemistry, western blot, and real-time qPCR were used to observe the axonal regeneration and neuroprotective effects of GLGZD aqueous extract on organotypic cortical slices exposed to oxygen-glucose deprivation (OGD) and further elucidate the potential mechanisms. Compared with the OGD group, the GLGZD aqueous extract decreased the red PI fluorescence intensity; inhibited neuronal apoptosis; improved the growth of slice axons; upregulated the protein expression of tau and growth-associated protein-43; and decreased protein and mRNA expression of neurite outgrowth inhibitor protein-A (Nogo-A), Nogo receptor 1 (NgR1), ras homolog gene family A (RhoA), rho-associated coiled-coil-containing protein kinase (ROCK), and phosphorylation of collapsin response mediator protein 2 (CRMP2). Our study found that GLGZD had a strong neuroprotective effect on brain slices after OGD injury. GLGZD plays a vital role in promoting axonal remodeling and functional remodeling, which may be related to regulation of the expression of Nogo-A and its receptor NgR1, near the injured axons, inhibition of the Rho-ROCK pathway, and reduction of CRMP2 phosphorylation

An increase in early cancer detection rates at a single cancer center: Experiences from Sun Yat-sen University Cancer Center

Cancer has become a major fatal disease in China. The relatively lower early detection rates for multiple cancer types have been one of the main reasons for a relatively lower cancer curative rate in China compared with the developed countries. To investigate trends in the early cancer detection rate over the past 5 years in a major city of China, 45,260 patients with newly diagnosed cancers of the nasopharynx, lung, thyroid, colorectum, liver, breast, uteral cervix, stomach, esophagus, blood, and kidney from 2016 to 2020 at Sun Yat-sen University Cancer Center were evaluated. The early detection rate (stage I disease) for all cancer types in combination significantly increased from 14.4 to 23.07%. Among the studied cancer types, a significant increase in stage I cancers was proportionally seen in cancers of the lung, thyroid, colorectum, and uterine cervix. While for cancers of the liver and stomach, a significant proportional increment was only observed when combining stage I and stage II diseases. No significant alteration in early cancer detection of the nasopharynx, breast, esophagus, blood, or kidney was observed. Three limitations of this present study include relatively small cohorts of cancer patients, relatively short observation periods, and limited sample representativeness. Further efforts are anticipated to validate our findings with larger patient cohorts from different parts of China and enhance early cancer detection rates by promoting public awareness, applying better health care policies, and improving insurance coverage and medical resources

METTL14-mediated Epitranscriptome Modification of Mn1 Mrna Promote Tumorigenicity and All-trans-retinoic Acid Resistance in Osteosarcoma

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. The molecular mechanism behind OS progression and metastasis remains poorly understood, which limits the effectiveness of current therapies. RNA N METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS), dot blotting, and colorimetric ELISA were used to detect m FINDINGS: We observed the abundance of m INTERPRETATION: Our study revealed that METTL14 contributes to OS progression and ATRA resistance as an m FUNDING: This work was supported by the National Natural Science Foundation of China (Grants 81972510 and 81772864)