Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency.

Of all known cultured stem cell types, pluripotent stem cells (PSCs) sit atop the landscape of developmental potency and are characterized by their ability to generate all cell types of an adult organism. However, PSCs show limited contribution to the extraembryonic placental tissues in vivo. Here, we show that a chemical cocktail enables the derivation of stem cells with unique functional and molecular features from mice and humans, designated as extended pluripotent stem (EPS) cells, which are capable of chimerizing both embryonic and extraembryonic tissues. Notably, a single mouse EPS cell shows widespread chimeric contribution to both embryonic and extraembryonic lineages in vivo and permits generating single-EPS-cell-derived mice by tetraploid complementation. Furthermore, human EPS cells exhibit interspecies chimeric competency in mouse conceptuses. Our findings constitute a first step toward capturing pluripotent stem cells with extraembryonic developmental potentials in culture and open new avenues for basic and translational research. VIDEO ABSTRACT.

NEK2 promotes the development of ovarian endometriosis and impairs decidualization by phosphorylating FOXO1.

Ovarian endometriosis is a common gynecological disease, and one of its most significant symptoms is infertility. In patients with endometriosis, defects in endometrial decidualization lead to impaired endometrial receptivity and embryo implantation, thus affecting early pregnancy and women's desire to have children. However, the mechanisms underlying the development of endometriosis and its associated defective decidualization are unclear. We find that NEK2 expression is increased in the ectopic and eutopic endometrium of patients with endometriosis. Meanwhile, NEK2 interacts with FOXO1 and phosphorylates FOXO1 at Ser184, inhibiting the stability of the FOXO1 protein. Importantly, NEK2-mediated phosphorylation of FOXO1 at Ser184 promotes cell proliferation, migration, invasion and impairs decidualization. Furthermore, INH1, an inhibitor of NEK2, inhibits the growth of ectopic lesions in mouse models of endometriosis and promotes endometrial decidualization in mouse models of artificially induced decidualization. Taken together, these findings indicate that NEK2 regulates the development of endometriosis and associated disorders of decidualization through the phosphorylation of FOXO1, providing a new therapeutic target for its treatment.

Male, female, and mixed-sex poplar plantations support divergent soil microbial communities.

Males and females of dioecious plants have sex-specific adaptations to diverse habitats. The effects of inter- and intrasexual interactions in poplar plantations on composition, structure, and function of soil microbiota have not been explored in degraded areas. We conducted a series of greenhouse and field experiments to investigate how belowground competition, soil microbial communities, and seasonal variation nitrogen content differ among female, male, and mixed-sex Populus cathayana plantations. In the greenhouse experiment, female neighbors suppressed the growth of males under optimal nitrogen conditions. However, male neighbors enhanced stable isotope ratio of nitrogen (δ15 N) of females under intersexual competition. In the field, the root length density, root area density, and biomass of fine roots were lower in female plantations than in male or mixed-sex plantations. Bacterial networks of female, male, and mixed-sex plantations were characterized by different composition of hub nodes, including connectors, modules, and network hubs. The sex composition of plantations altered bacterial and fungal community structures according to Bray-Curtis distances, with 44% and 65% of variance explained by the root biomass, respectively. The total soil nitrogen content of mixed-sex plantation was higher than that in female plantation in spring and summer. The mixed-sex plantation also had a higher ß-1,4-N-acetyl-glucosaminidase activity in summer and a higher nitrification rate in autumn than the other two plantations. The seasonal soil N content, nitrification rate, and root distribution traits demonstrated spatiotemporal niche separation in the mixed-sex plantation. We argue that a strong female-female competition and limited nitrogen content could strongly impede plant growth and reduce the resistance of monosex plantations to climate change and the mixed-sex plantations constitutes a promising way to restore degraded land.

Enterotoxin-related genes PPFIA4 and SCN3B promote colorectal cancer development and progression.

To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.

Enterotoxigenic Bacteroides fragilis (ETBF) Enhances Colorectal Cancer Cell Proliferation and Metastasis Through HDAC3/miR-139-3p Pathway.

Enterotoxigenic Bacteroides fragilis (ETBF) is believed to promote the malignant process of colorectal cancer (CRC), but the underlying molecular mechanism still needs to be revealed. CRC cells (SW480 and HCT-116) were treated with ETBF strain. Cell proliferation, invasion and, migration were evaluated by cell counting kit 8 assay, EdU assay, colony formation assay, transwell assay, and wound healing assay. Protein expression was analyzed by western blot. MicroRNA (miR)-139-3p and histone deacetylase 3 (HDAC3) expression levels in tissues and cells were determined by qRT-PCR. Xenograft tumor model was conducted to evaluate the effect of miR-139-3p on CRC tumor growth. ETBF treatment could promote CRC cell proliferation, invasion and migration. MiR-139-3p expression was decreased by ETBF, and its overexpression reversed the effect of ETBF on CRC cell progression. HDAC3 negatively regulated miR-139-3p expression, and its overexpression facilitated CRC cell behaviors via reducing miR-139-3p expression. Moreover, HDAC3 expression was increased by ETBF, and its knockdown also abolished ETBF-mediated CRC cell progression. Additionally, miR-139-3p overexpression could reduce CRC tumor growth in vivo. ETBF aggravated CRC proliferation and metastasis via the regulation of HDAC3/miR-139-3p axis. The discovery of ETBF/HDAC3/miR-139-3p axis may provide a new direction for CRC treatment.

Long wavelength mid-infrared multi-gases spectroscopy using tunable single-mode slot waveguide quantum cascade laser.

Single-mode tunable quantum cascade lasers (QCLs) are promising for high-resolution and highly sensitive trace gases sensing across the mid-infrared (MIR) region. We report on the development of a tunable single-mode slot waveguide QCL array in the long wavelength part of the MIR regime (>12 µm). This laser array exhibits a tuning range of around 12 cm-1, from 735.3 to 747.3 cm-1. Using this developed single-mode tunable QCL, we demonstrate individual gas sensing, yielding the detection limit of 940 ppb and 470 ppb for acetylene and o-xylene, respectively. To verify the potential of the developed QCL array in multi-species gas detection, laser absorption measurements of two mixed gases of acetylene and o-xylene were conducted, showing the absorption features of the corresponding gases agree well with the theoretical predictions.

Allicin protects against LPS-induced cardiomyocyte injury by activating Nrf2-HO-1 and inhibiting NLRP3 pathways.

BACKGROUND: Allicin is a bioactive compound with potent antioxidative activity and plays a protective effect in myocardial damage and fibrosis. The role and mechanism of Allicin in septic cardiomyopathy are unclear. In this study, we investigated the effects and underlying mechanisms of Allicin on lipopolysaccharide (LPS) induced injury in H9c2 cardiomyocytes. METHODS: H9c2 cardiomyocyte cells were pretreated with Allicin (0, 25, 50, and 100 µM) for 2 h, followed by incubation with LPS (10 µg/mL) for 24 h at 37 °C. Cell viability (cell counting kit-8 [CCK-8]), apoptosis (TUNEL staining), oxidative stress (malondialdehyde [MDA] and superoxide dismutase [SOD]), and cytokines release (Interleukin beta [IL-ß], Interleukin 6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) were determined. The mRNA and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NLR family pyrin domain containing 3 (NLRP3) signaling pathway molecules were quantified by real-time quantitative PCR (RT-qPCR) and western blot, respectively. RESULTS: Allicin had no effect on H9c2 cell viability but attenuated LPS-induced injury, with increased cell viability, reduction in inflammatory cytokines release, apoptosis, reduced MDA, and increased SOD (P < 0.05). Additionally, Allicin increased Nrf2 and cellular HO-1 expressions in LPS-treated H9c2 cells. Moreover, Allicin modulated the NLRP3 inflammasome, increased the cleaved caspase-1 (p10) protein, and attenuated the LPS-induced increase in NLRP3, pro-IL-1ß, and IL-1ß proteins. Silencing of Nrf2 by siRNA (siNrf2) significantly attenuated Allicin-induced increase in cell viability and HO-1 and decrease in NLRP3 protein in LPS-stimulated H9c2 cells. CONCLUSIONS: Allicin protects cardiomyocytes against LPS­induced injury through activation of Nrf2/HO-1 and inhibition of NLRP3 signaling pathways.

CHIP induces ubiquitination and degradation of HMGB1 to regulate glycolysis in ovarian endometriosis.

Ovarian endometriosis is a common gynecological condition that can cause infertility in women of childbearing age. However, the pathogenesis is still unknown. We demonstrate that the carboxyl terminus of Hsc70-interacting protein (CHIP) is a negative regulator in the development of endometriosis and reduces HMGB1 expression in endometriotic cells. Meanwhile, CHIP interacts with HMGB1 and promotes its ubiquitinated degradation, thereby inhibiting aerobic glycolysis and the progression of endometriosis. Furthermore, the CHIP agonist YL-109 effectively suppresses the growth of ectopic endometrium in endometriosis mouse model, which could be a potential therapeutic approach for endometriosis. In conclusion, our data suggest that CHIP may inhibit the development of endometriosis by suppressing the HMGB1-related glycolysis.

Widely tunable single-mode slot waveguide quantum cascade laser array.

We report designs and experimental demonstrations of a widely tunable single-mode quantum cascade laser array based on slot waveguide structures in the mid-infrared region. The laser array device realized a continuous tuning range of 71 cm-1 from 9.66 µm to 10.37 µm at 300 K only using the current tuning without any external heatsink temperature adjustments, in good agreement with the design. Stable single-mode operations free of undesired mode-hops have been obtained over the whole tuning range. Another slot waveguide QCL array with a 41 cm-1 continuous tuning range around 7.3 µm has also been realized with the same design principle, demonstrating the universal applicability of the array design. The broadly continuous tuning with simple processing makes the array device a suitable candidate for mid-infrared sensing and spectroscopy application.

Large-scale flexible-resonators with temperature insensitivity employing superoleophobic substrates.

Whispering gallery mode polymer resonators are becoming competitive with devices made of other materials, however, the inherent thermal sensitivity of the materials and the small size limit their applications, such as high-precision optical gyroscope. Here, a method is proposed for fabricating large-scale NOA65 resonators with quality factors greater than 105 on a chip employing superoleophobic. The sandwich structure as the core layer of resonator is used to present the flexible remodeling characteristics, the surface roughness remains below 1 nm when the diameter changes by more than 25%. Importantly, theoretical and experimental results show that under the tuning action of external pressure, the equivalent thermal expansion coefficient of the resonator gradually approaches the glass sheet on both sides with the variation of 2 × 10-4 /°C∼0.9 × 10-4 /°C, and the corresponding temperature response range of 0.12 nm/°C∼-0.056 nm/°C shows the promise of temperature insensitivity resonators on a chip.

Beam combining of a broadly and continuously tunable quantum cascade laser.

We report a cost-efficient method to demonstrate the beam combining of five laser elements in an array of tunable slot waveguide quantum cascade lasers in the mid-infrared region at around 10 µm. An aspherical lens with five fine-tuned mini mirrors was employed to collimate the individual beams from the laser array. To verify the feasibility of this beam combining approach, the combined beams were coupled into a hollow-core fiber gas cell with a low numerical aperture (N.A.) of 0.03 and a coupling efficiency >= 0.82, for gas sensing of binary compound gases of ammonia and ethylene simultaneously.

Thyroid hormone levels as a predictor marker predict the prognosis of patients with sepsis.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome with high mortality. There is an upward trend in sepsis prevalence and mortality worldwide. Early and accurate prediction of outcome in sepsis is important. There remains a great need to improve a reliable prognostic model for sepsis patients with widely available variables. The aim of this study was to explore the correlation between serum thyroid hormone levels and prognosis in sepsis patients. METHODS: Septic patients were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Factors that were found to contribute to the outcome in the uni-variate analysis at P value <0.1 were included in the multivariate. Multivariate analysis was performed by binary logistic regression analysis, which allows adjust for confounding factors. We combined an assessment of thyroid hormone and some variables together, which improve the accurate prediction of outcome. The accuracy of the test was assessed measuring the area under the ROC curve (AUROC). RESULTS: A total of 929 eligible septic patients were included in the data analysis. Seventy hundred and three patients had a good functional outcome, whereas 226 patients had a bad functional outcome. Thyroxin (T4) level was significantly decreased in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome (P < 0.01). Binary logistic regression analyses revealed that lower thyroxin concentrations on admission were associated with a risk for poor outcomes (OR 0.556, 95% CI 0.41-0.75; P < 0.01). In addition, in ROC curve analysis, the combined model AUROC was 0.82 for ICU survival, which was significantly higher than the AUROCs of original fT4 (0.65 and 0.65), T4 (0.71 and 0.71) and SAPSII (0.70 and 0.72) (all P < 0.05). CONCLUSIONS: Low serum thyroxin levels can be a predictive marker of short-term outcome after sepsis. A combined model (fT4, T4 and SAPSII score) can add significant additional predictive information to the clinical score of the SAPSII.

Spatial-light-modulator-based dual shearing direction shearography.

We propose a dual shearing shearography system based on a spatial light modulator (SLM). Compared to spatial phase shift shearography, the advantages of this system include its simple structure, relatively high light efficiency, and good phase map quality. Digital shearography is a fast, practical, non-contact, whole-field, and anti-turbulent optical approach to non-destructive testing (NDT) and strain measurement. Because the shearing direction determines the strain direction being measured, tests using multiple shearing directions are sometimes required to obtain strain in different directions and detect all defects. Various setups, based on the spatial phase shift method, have been proposed to solve the issue. While some of these setups perform well, they may also introduce new problems, such as poor phase map quality and low light efficiency. We present a sequential dual shearing shearographic system with good phase map quality and high light efficiency. Due to the SLM's high-speed response, capable of reaching hundreds of hertz, SLM-based dual shearing direction shearography allows for fast temporal phase shifting and shearing direction switching while providing very good phase map quality. Unlike the spatial phase shift method, which has low light efficiency due to its need for a small aperture to enable a relatively large speckle size to cover multiple pixels, the proposed method is based on a fast temporal phase shift and does not have this limitation. In addition, SLM can provide a programmable and adjustable shearing method in any direction and distance, which is beneficial for strain measurements and NDT requiring strain measurements in different directions using a small and precise shearing distance. We describe in detail the theory derivation and non-destructive testing application results for the SLM-based dual shearing direction shearography system.

Method to eliminate thermal disturbance errors in digital image correlation measurement based on projection speckle.

Digital image correlation (DIC) technology is an optical measurement method of material strain displacement based on visible light illumination. With the increasing application of DIC technology in the field of high-temperature measurement, however, the effect of thermal disturbance on measurement accuracy becomes more and more serious. To solve this problem, a method to eliminate thermal disturbance in material measurements based on projection speckle is proposed. First, the gray surface information of two different colors is assigned to the surface of the test piece by artificial splashing and projector projection. The pictures are collected using a color camera, and the channels are separated for each frame of the picture. After that, the displacement field recorded by different channels can be obtained by DIC calculation so the thermal disturbance error can be separated from the real displacement and eliminated. Subsequently, an experimental system is built. Finally, the corrected results are compared with the true displacement value of the stage. The results show that the two sets of values are highly consistent, which verifies the feasibility and accuracy of the proposed method.

Risk Factors of Multidrug-Resistant Bacteria in Lower Respiratory Tract Infections: A Systematic Review and Meta-Analysis.

BACKGROUND: Multidrug-resistant (MDR) bacteria are the main cause of lower respiratory tract infections (LRTIs) with high mortality. The purpose of this study is to identify the risk factors associated with MDR by performing a systematic review and meta-analysis. METHODS: PubMed, EMBASE (via Ovid), and Cochrane Library were systematically searched for studies on the risk factors for MDR bacteria in LRTIs as of November 30, 2019. Literature screening, data abstraction, and quality assessment of the eligible studies were performed independently by two researchers. RESULTS: A total of 3,607 articles were retrieved, of which 21 articles representing 20 cohort studies published in English were included after title/abstract and full-text screening. Among the 21 articles involving 7,650 patients and 1,360 MDR organisms, ten reported the risk factors for MDR Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), ten for MDR GNB, and one for MDR GPB. The meta-analysis results suggested that prior antibiotic treatment, inappropriate antibiotic therapy, chronic lung disease, chronic liver disease and cerebral disease, prior MDR and PA infection/colonization, recent hospitalization, longer hospitalization stay, endotracheal tracheostomy and mechanical ventilation, tube feeding, nursing home residence, and higher disease severity score were independent risk factors for MDR bacteria. CONCLUSIONS: This review identified fourteen clinical factors that might increase the risk of MDR bacteria in patients with LRTIs. Clinicians could take into account these factors when selecting antibiotics for patients and determine whether coverage for MDR bacteria is required. More well-designed studies are needed to confirm the various risk factors for MDR bacteria in the future.

Loss tailoring of high-power broad-area diode lasers.

Broad-area diode lasers (BALs) with high power are highly desirable for a variety of applications. However, such lasers suffer from strongly deteriorated beam quality due to multimode behavior in the lateral direction. In this Letter, we present an approach to flexibly tailor the optical loss of different-order lateral modes by etching micro-holes on the laser mesa with controlled position and numbers. Through arranging the micro-holes at the peak positions of high-order lateral modes with an increasing number from the mesa center to both edges, high-order modes are suppressed due to a larger propagation loss than the fundamental mode. As a result of enhanced mode discrimination, we demonstrate that this technique provides a greatly improved beam quality and about two times higher brightness for 100 µm wide BAL, while maintaining high power and slope efficiency output.

Simultaneous 3D measurement of deformation and its first derivative with speckle pattern interferometry and shearography.

Digital speckle pattern interferometry and digital shearography are widely used in nondestructive testing due to their advantages of high speed, full field, and high sensitivity. However, traditional speckle pattern interferometry and shearography can only measure a single variable of deformation or strain. This study presents a modified common measurement setup that can simultaneously measure deformation and its first derivative. In the optical setup, a reference beam is introduced behind the shearing device to interfere with the object beams, thereby simplifying the spectrum and improving the quality of the phase maps. Then the spatial carrier technology is used to extract phase and achieve dynamic measurements. The proposed system also expands the measurement range using a ${4}f$4f system. This study also presents a 3D optical setup based on the 1D system, which is more suitable for practical measurement applications in industrial areas. Theoretical derivation and experimental results are described and presented.

Long-term outcomes of per-oral endoscopic myotomy in a patient with distal esophageal spasm followed up for 2.5 years: two sides of the same coin - A Case Report and Literature Review.

INTRODUCTION: Distal esophageal spasm (DES), a relatively rare condition, is characterized by simultaneous contractions of the distal esophagus and manifested by dysphagia and chest pain. Several treatment options are recommended, such as pharmacological therapy, endoscopic interventions, and surgical myotomy. Recently, per-oral endoscopic myotomy (POEM) has been adopted as an effective and less-invasive treatment due to its excellent short-term clinical outcomes. Nevertheless, few reports describe its long-term effects. CASE PRESENTATION: A 65-year-old woman complained of chest pain accompanied with dysphagia and weight loss for 4 months. A series of examinations suggested that she was suffering from DES and then POEM was performed. During the 2.5-year follow-up, we observed an exciting long-term outcome. Interestingly, hematoxylin and eosin staining verified a large number of eosinophils in the muscularis externa, which was absent in the mucosa of the esophagus of the patient. CONCLUSIONS: We herein report a case of DES who underwent POEM to eliminate persistent esophageal contractions. Eckardt score, esophageal emptying test, and high-resolution manometry were assumed to monitor the efficacy of POEM. During treatment and 2.5 years after operation, esophageal muscle biopsies and/or mucosal tissues were obtained. This case has been presented to describe that POEM could be a strategy for DES with a long-term curative effect and that eosinophils in the muscle layer of the esophagus might be involved in the pathogenesis of DES. What is more, we reviewed literature to find similar cases reported in the past.

Pixelated Carrier Phase-Shifting Shearography Using Spatiotemporal Low-Pass Filtering Algorithm.

Shearography has been widely used in non-destructive testing due to its advantages in providing full-field, high precision, real-time measurement. The study presents a pixelated carrier phase-shifting shearography using a pixelated micropolarizer array. Based on the shearography, a series of shearograms are captured and phase maps corresponding to deformation are measured dynamically and continuously. Using the proposed spatiotemporal filtering algorithm in the complex domain, the set of phase maps are simultaneously low-pass filtered in the spatial and temporal domains, resulting in better phase quality than spatial low-pass filtering. By accumulating the temporally adjacent phase, the phase corresponding to large deformation can be evaluated; thus, large deformations can be accurately measured and protected from speckle noise, allowing internal defects to be easily identified. The capability of the proposed shearography is described by theoretical discussions and experiments.