CMOS-compatible 6-inch wafer integration of photonic waveguides and uniformity analysis.

In this work, we demonstrate photonic fabrication by integrating waveguide resonators and groove structures using cost-effective i-line stepper lithography on a 6-inch full wafer. Low-loss silicon nitride (SiN) waveguide can be realized with the quality (Q) factor of waveguide resonators up to 105. In addition, groove structures are also integrated by the full-wafer process, providing long-term stability of coupling and package solutions. The uniformity of different die locations is verified within the full wafer, showing the good quality of the fabricated photonic devices. This process integration of photonic devices provides the potential for mass-productive, high-yield, and high-uniformity manufacturing.

Preparation of Multifunctional Hydrogels with In Situ Dual Network Structure and Promotion of Wound Healing.

As an emerging biomedical material, wound dressings play an important therapeutic function in the process of wound healing. It can provide an ideal healing environment while protecting the wound from a complex external environment. A hydrogel wound dressing composed of tilapia skin gelatin (Tsg) and fucoidan (Fuc) was designed in this article to enhance the microenvironment of wound treatment and stimulate wound healing. By mixing horseradish peroxidase (HRP), hydrogen peroxide (H2O2), tilapia skin gelatin-tyramine (Tsg-Tyr), and carboxylated fucoidan-tyramine in agarose (Aga), using the catalytic cross-linking of HRP/H2O2 and the sol-gel transformation of Aga, a novel gelatin-fucoidan (TF) double network hydrogel wound dressing was constructed. The TF hydrogels have a fast and adjustable gelation time, and the addition of Aga further enhances the stability of the hydrogels. Moreover, Tsg and Fuc are coordinated with each other in terms of biological efficacy, and the TF hydrogel demonstrated excellent antioxidant properties and biocompatibility in vitro. Also, in vivo wound healing experiments showed that the TF hydrogel could effectively accelerate wound healing, reduce wound microbial colonization, alleviate inflammation, and promote collagen deposition and angiogenesis. In conclusion, TF hydrogel wound dressings have the potential to replace traditional dressings in wound healing.

Predicting in-hospital mortality risk for perforated peptic ulcer surgery: the PPUMS scoring system and the benefit of laparoscopic surgery: a population-based study.

BACKGROUND: The major treatment for perforated peptic ulcers (PPU) is surgery. It remains unclear which patient may not get benefit from surgery due to comorbidity. This study aimed to generate a scoring system by predicting mortality for patients with PPU who received non-operative management (NOM) and surgical treatment. METHOD: We extracted the admission data of adult (≥ 18 years) patients with PPU disease from the NHIRD database. We randomly divided patients into 80% model derivation and 20% validation cohorts. Multivariate analysis with a logistic regression model was applied to generate the scoring system, PPUMS. We then apply the scoring system to the validation group. RESULT: The PPUMS score ranged from 0 to 8 points, composite with age (< 45: 0 points, 45-65: 1 point, 65-80: 2 points, > 80: 3 points), and five comorbidities (congestive heart failure, severe liver disease, renal disease, history of malignancy, and obesity: 1 point each). The areas under ROC curve were 0.785 and 0.787 in the derivation and validation groups. The in-hospital mortality rates in the derivation group were 0.6% (0 points), 3.4% (1 point), 9.0% (2 points), 19.0% (3 points), 30.2% (4 points), and 45.9% when PPUMS > 4 point. Patients with PPUMS > 4 had a similar in-hospital mortality risk between the surgery group [laparotomy: odds ratio (OR) = 0.729, p = 0.320, laparoscopy: OR = 0.772, p = 0.697] and the non-surgery group. We identified similar results in the validation group. CONCLUSION: PPUMS scoring system effectively predicts in-hospital mortality for perforated peptic ulcer patients. It factors in age and specific comorbidities is highly predictive and well-calibrated with a reliable AUC of 0.785-0.787. Surgery, no matter laparotomy or laparoscope, significantly reduced mortality for scores < = 4. However, patients with a score > 4 did not show this difference, calling for tailored approaches to treatment based on risk assessment. Further prospective validation is suggested.

Laparoscopic proximal gastrectomy with right-sided overlap and single-flap valvuloplasty (ROSF): a case-series study.

BACKGROUND: There is no standard reconstruction method following proximal gastrectomy, of which gastroesophageal reflux and anastomotic complications are of great concern. Though several techniques have been devised to overcome these postoperative complications, such as double tract reconstruction, double-flap technique and side overlap fundoplication by Yamashita, none of them is considered a perfect solution. Herein, we designed a novel method of esophagogastrostomy after laparoscopic proximal gastrectomy (LPG), named right-sided overlap and single-flap valvuloplasty (ROSF). METHODS: Between March 2021 and December 2021, 20 consecutive patients underwent LPG-ROSF at Department of Gastrointestinal Surgery, Second Affiliated Hospital of Soochow University. Surgical outcomes and postoperative complications were recorded. All patients were followed-up until December 2022. Endoscopy and assessment of gastrointestinal symptoms were performed 1 year after surgery. Nutrition-related parameters including total body weight, hemoglobin, lymphocyte count, serum total protein, serum albumin and serum prealbumin were evaluated 1 year after surgery and compared with those before surgery. RESULTS: The mean surgery time and anastomosis time was 285.3 ± 71.3 and 61.3 ± 11.2 min respectively. None of the patients had gastrointestinal early postoperative complications. Symptomatic reflux was observed in one patient (5%) while reflux esophagitis (Los Angeles Grade A) was observed in another patient (5%). Four patients (20%) had mild dysphagia (Visick score = II) but none of them had anastomotic stenosis. There were no significant changes in nutritional status postoperatively. CONCLUSIONS: ROSF can be safely performed after LPG and has satisfactory outcomes in preventing reflux and stenosis, and maintaining nutritional status. This technique requires further validation.

Esophagus two-step-cut overlap method in esophagojejunostomy after laparoscopic gastrectomy.

PURPOSE: Esophagojejunostomy is a challenging step in laparoscopic gastrectomy. Although the overlap method is a safe and feasible approach for esophagojejunostomy, it has several technical limitations. We developed novel modifications for the overlap method to overcome these disadvantages. METHODS: Forty-eight consecutive gastric cancer patients underwent totally laparoscopic total gastrectomy or laparoscopic proximal gastrectomy with double-tract reconstruction at our institution from January 2019 to April 2020 using the overlap method with the following modifications. The esophagus was initially rotated by 90° counterclockwise, followed by transection of two-thirds of the esophageal diameter. The unstapled esophagus was then transected with a harmonic ultrasonic scalpel to enable esophagostomy at the posterior side of the esophagus. A side-to-side esophagojejunostomy was then formed at the posterior side of the esophagus using an endoscopic linear stapler through the right lower trocar. The common entry hole was closed via hand sewing method using V-Loc suture. This procedure was termed "esophagus two-step-cut overlap method." RESULTS: Only one patient suffered from esophagojejunal anastomotic leakage but subsequently recovered after conservative treatment. Patients did not experience anastomotic bleeding or stricture. CONCLUSION: Our modified overlap method provides satisfactory surgical outcomes and overcomes several technical limitations, such as entering the false lumen of the esophagus, unnecessary pollution caused by nasogastric tube, and unintended left crus stapling during anastomosis.

Feature Fusion of a Deep-Learning Algorithm into Wearable Sensor Devices for Human Activity Recognition.

This paper presents a wearable device, fitted on the waist of a participant that recognizes six activities of daily living (walking, walking upstairs, walking downstairs, sitting, standing, and laying) through a deep-learning algorithm, human activity recognition (HAR). The wearable device comprises a single-board computer (SBC) and six-axis sensors. The deep-learning algorithm employs three parallel convolutional neural networks for local feature extraction and for subsequent concatenation to establish feature fusion models of varying kernel size. By using kernels of different sizes, relevant local features of varying lengths were identified, thereby increasing the accuracy of human activity recognition. Regarding experimental data, the database of University of California, Irvine (UCI) and self-recorded data were used separately. The self-recorded data were obtained by having 21 participants wear the device on their waist and perform six common activities in the laboratory. These data were used to verify the proposed deep-learning algorithm on the performance of the wearable device. The accuracy of these six activities in the UCI dataset and in the self-recorded data were 97.49% and 96.27%, respectively. The accuracies in tenfold cross-validation were 99.56% and 97.46%, respectively. The experimental results have successfully verified the proposed convolutional neural network (CNN) architecture, which can be used in rehabilitation assessment for people unable to exercise vigorously.

The polycomb group protein Yaf2 regulates the pluripotency of embryonic stem cells in a phosphorylation-dependent manner.

The polycomb group (PcG) proteins are key epigenetic regulators in stem cell maintenance. PcG proteins have been thought to act through one of two polycomb repressive complexes (PRCs), but more recent biochemical analyses have challenged this model in the identification of noncanonical PRC1 (nc-PRC1) complexes characterized by the presence of Rybp or Yaf2 in place of the canonical Chromobox proteins. However, the biological significance of these nc-PRC1s and the potential mechanisms by which they mediate gene repression are largely unknown. Here, we explore the functional consequences of Yaf2 disruption on stem cell regulation. We show that deletion of Yaf2 results in compromised proliferation and abnormal differentiation of mouse embryonic stem cells (mESCs). Genome-wide profiling indicates Yaf2 functions primarily as a transcriptional repressor, particularly impacting genes associated with ectoderm cell fate in a manner distinct from Rybp. We confirm that Yaf2 assembles into a noncanonical PRC complex, with deletion analysis identifying the region encompassing amino acid residues 102-150 as required for this assembly. Furthermore, we identified serine 166 as a Yaf2 phosphorylation site, and we demonstrate that mutation of this site to alanine (S166A) compromises Ring1B-mediated H2A monoubiquitination and in turn its ability to repress target gene expression. We therefore propose that Yaf2 and its phosphorylation status serve as dual regulators to maintain the pluripotent state in mESCs.

Essential Role for Polycomb Group Protein Pcgf6 in Embryonic Stem Cell Maintenance and a Noncanonical Polycomb Repressive Complex 1 (PRC1) Integrity.

The Polycomb group (PcG) proteins have an important role in controlling the expression of key genes implicated in embryonic development, differentiation, and decision of cell fates. Emerging evidence suggests that Polycomb repressive complexes 1 (PRC1) is defined by the six Polycomb group RING finger protein (Pcgf) paralogs, and Pcgf proteins can assemble into noncanonical PRC1 complexes. However, little is known about the precise mechanisms of differently composed noncanonical PRC1 in the maintenance of the pluripotent cell state. Here we disrupt the Pcgf genes in mouse embryonic stem cells by CRISPR-Cas9 and find Pcgf6 null embryonic stem cells display severe defects in self-renewal and differentiation. Furthermore, Pcgf6 regulates genes mostly involved in differentiation and spermatogenesis by assembling a noncanonical PRC1 complex PRC1.6. Notably, Pcgf6 deletion causes a dramatic decrease in PRC1.6 binding to target genes and no loss of H2AK119ub1. Thus, Pcgf6 is essential for recruitment of PRC1.6 to chromatin. Our results reveal a previously uncharacterized, H2AK119ub1-independent chromatin assembly associated with PRC1.6 complex.

Polycomb group RING finger proteins 3/5 activate transcription via an interaction with the pluripotency factor Tex10 in embryonic stem cells.

Polycomb group (PcG) proteins are epigenetic transcriptional repressors that orchestrate numerous developmental processes and have been implicated in the maintenance of embryonic stem (ES) cell state. More recent evidence suggests that a subset of PcG proteins engages in transcriptional activation in some cellular contexts, but how this property is exerted remains largely unknown. Here, we generated ES cells with single or combined disruption of polycomb group RING finger protein 3 (Pcgf3) and Pcgf5 with the CRISPR-Cas9 technique. We report that although these mutant cells maintained their self-renewal and colony-forming capacity, they displayed severe defects in mesoderm differentiation in vitro and in vivo Using RNA-seq to analyze transcriptional profiles of ES cells with single or combined Pcgf3/5 deficiencies, we found that in contrast to the canonical role of the related polycomb repressive complex 1 (PRC1) in gene repression, Pcgf3/5 mainly function as transcriptional activators driving expression of many genes involved in mesoderm differentiation. Proteomic approaches and promoter occupancy analyses helped to establish an extended Pcgf3/5 interactome and identified several novel Pcgf3/5 interactors. These included testis-expressed 10 (Tex10), which may directly contribute to transcriptional activation via the transcriptional co-activator p300. Furthermore, Pcgf3/5 deletion in ES cells substantially reduced the occupancy of Tex10 and p300 at target genes. Finally, we demonstrated that Pcgf3/5 are essential for regulating global levels of the histone modifier H2AK119ub1 in ES cells. Our findings establish Pcgf3/5 as transcriptional activators that interact with Tex10 and p300 in ES cells and point to redundant activity of Pcgf3/5 in pluripotency maintenance.

C. Elegans Fatty Acid Two-Hydroxylase Regulates Intestinal Homeostasis by Affecting Heptadecenoic Acid Production.

BACKGROUND/AIMS: The hydroxylation of fatty acids at the C-2 position is the first step of fatty acid α-oxidation and generates sphingolipids containing 2-hydroxy fatty acyl moieties. Fatty acid 2-hydroxylation is catalyzed by Fatty acid 2-hydroxylase (FA2H) enzyme. However, the precise roles of FA2H and fatty acid 2-hydroxylation in whole cell homeostasis still remain unclear. METHODS: Here we utilize Caenorhabditis elegans as the model and systemically investigate the physiological functions of FATH-1/C25A1.5, the highly conserved worm homolog for mammalian FA2H enzyme. Immunostaining, dye-staining and translational fusion reporters were used to visualize FATH-1 protein and a variety of subcellular structures. The "click chemistry" method was employed to label 2-OH fatty acid in vivo. Global and tissue-specific RNAi knockdown experiments were performed to inactivate FATH-1 function. Lipid analysis of the fath-1 deficient mutants was achieved by mass spectrometry. RESULTS: C. elegans FATH-1 is expressed at most developmental stages and in most tissues. Loss of fath-1 expression results in severe growth retardation and shortened lifespan. FATH-1 function is crucially required in the intestine but not the epidermis with stereospecificity. The "click chemistry" labeling technique showed that the FATH-1 metabolites are mainly enriched in membrane structures preferable to the apical side of the intestinal cells. At the subcellular level, we found that loss of fath-1 expression inhibits lipid droplets formation, as well as selectively disrupts peroxisomes and apical endosomes. Lipid analysis of the fath-1 deficient animals revealed a significant reduction in the content of heptadecenoic acid, while other major FAs remain unaffected. Feeding of exogenous heptadecenoic acid (C17: 1), but not oleic acid (C18: 1), rescues the global and subcellular defects of fath-1 knockdown worms. CONCLUSION: Our study revealed that FATH-1 and its catalytic products are highly specific in the context of chirality, C-chain length, spatial distribution, as well as the types of cellular organelles they affect. Such an unexpected degree of specificity for the synthesis and functions of hydroxylated FAs helps to regulate protein transport and fat metabolism, therefore maintaining the cellular homeostasis of the intestinal cells. These findings may help our understanding of FA2H functions across species, and offer potential therapeutical targets for treating FA2H-related diseases.

Controlling the metal to semiconductor transition of MoS2 and WS2 in solution.

Lithiation-exfoliation produces single to few-layered MoS2 and WS2 sheets dispersible in water. However, the process transforms them from the pristine semiconducting 2H phase to a distorted metallic phase. Recovery of the semiconducting properties typically involves heating of the chemically exfoliated sheets at elevated temperatures. Therefore, it has been largely limited to sheets deposited on solid substrates. Here, we report the dispersion of chemically exfoliated MoS2 sheets in high boiling point organic solvents enabled by surface functionalization and the controllable recovery of their semiconducting properties directly in solution. This process connects the scalability of chemical exfoliation with the simplicity of solution processing, ultimately enabling a facile method for tuning the metal to semiconductor transitions of MoS2 and WS2 within a liquid medium.

The Role of Camellia Shell Substrates in Modulating the Nutritional Characteristics of Pleurotus pulmonarius.

Camellia shells are the main by-product of camellia seed processing and are usually incinerated or disposed of as agricultural waste. In this study, camellia shells were employed in the Pleurotus pulmonarius cultivation process using five distinct formulae substituting for cottonseed shells. Our results show that as the substitution rate of camellia shells increased from 0% to 35%, the protein content in P. pulmonarius significantly increased from 34.05% to 53.35%. The polysaccharide content reached a peak value of 5.62% at 30% substitution of camellia shells. The DPPH free radical scavenging rate reached its maximum of 82.70% at 20% substitution of camellia shells. Furthermore, increases in the total amino acid contents in P. pulmonarius were positively correlated with the substitution rate of camellia shells. Considering the yield characteristics, the formula of 20% camellia shell substitution tested in this study appears to be optimal for P. pulmonarius cultivation. These findings not only provide a substrate to enhance the nutritional quality of P. pulmonarius but also demonstrate a novel approach for the ecological utilization of camellia shells.

Effect of non-covalent binding of tannins to sodium caseinate on the stability of high-internal-phase fish oil emulsions.

In this study, we designed the noncovalent binding of sodium caseinate (SC) to tannic acid (TA) to stabilize high internal phase emulsions (HIPEs) used as fish oil delivery systems. Hydrogen bonding was the dominant binding force, followed by weak hydrophobic interaction and weak van der Waals forces, as demonstrated by FTIR, fluorescence spectroscopy, and molecular docking experiments, with a binding constant of 3.25 × 106, a binding site of 1.2, and a static quenching of the binding. Increasing SC:TA from SC to 2:1 decreased the particle size from 107.37 ± 10.66 to 76.07 ± 2.77 nm and the zeta potential from -6.99 ± 2.71 to -22 ± 2.42 mV. TA increased the interfacial tension of SC, decreased the surface hydrophobicity from 1.3 × 104 to 1.6 × 103 and improved the oxidation resistance of SC. The particle size of high internal phase emulsions stabilized by complexes with different mass ratios (SC:TA from 1:0 to 2:1) increased from 4.9 ± 0.02 to 12.9 µm, the potential increased from -32.37 ± 2.7 to -35.07 ± 2.58 mV, and the instability index decreased from 0.75 to 0.02. Thicker interfacial layers could be observed by laser confocal microscopy, and an increase in the storage modulus indicated a formation of a stronger gel network. SC:TA of 1:0 showed emulsion breakage after 14 d of storage at room temperature. SC:TA of 2:1 showed the lowest degree of oil-water separation after freeze-thaw treatment. Especially, the most stable high endo-phase emulsion (at SC:TA of 2:1) prepared at each mass ratio was selected for further stability exploration. The emulsion particle size increased only from 15.63 ± 0.06 to 22.27 ± 0.35 µm at salt ion concentrations of 50-200 mM and to 249.33 ± 31.79 µm at 300 mM. The instability index and storage modulus of the high endo-phase emulsions increased gradually with increasing salt ion concentrations. At different heating temperatures (55-85 °C), the instability index of the high internal phase emulsion gradually decreased and the storage modulus gradually increased. Meanwhile, at 50 °C for 15 d of accelerated oxidation, the content of hydroperoxide decreased from 53.32 ± 0.18 to 37.48 ± 0.77 nmol/g, about 29.7 %, and the thiobarbituric acid value decreased from 1.06 × 103 to 0.8 × 103, about 24.5 %, in the high endo-phase emulsions prepared by 2:1 SC:TA compared to the fish oils, and the SC-stabilized high endo-phase only emulsion broke at the sixth day of oxidation. From the above findings, it was concluded that the high internal phase emulsion prepared with SC:TA of 2:1 can be used as a good delivery system for fish oil.

Effects of phenolic acid grafted-chitosan hydrocolloids on the aldehyde contents from lipid oxidation in golden pompano (Trachinotus blochii) fillets during pan-frying.

The effects of phenolic acid grafted-chitosan hydrocolloids (CS-g-GA/FA) on aldehyde contents from lipid oxidation in golden pompano fillets during pan-frying was investigated with an established high-performance liquid chromatography-mass spectrum method. Results indicated that pan-frying induced profound lipid oxidation and aldehydes generation with propanal, hexanal, nonanal, trans, trans-2,4-decadienal, and 4-hydroxy-2-nonenal as the abundant species. CS-g-FA and CS-g-GA effectively decreased their contents by 23.74-27.42 %, 61.69-67.42 %, 41.83-53.91 %, 29.91-48.79 %, and 61.57-65.39 % after 3 min. Most aldehyde contents decreased with the extension of pan-frying time due to the volatilization and reaction. In terms of substrate depletion, CS-g-phenolic acids effectively inhibited unsaturated fatty acids oxidation due to their decent antioxidant activity than CS. The significant lower retention rates of aldehydes in the CS-g-phenolic acids groups compared with control in chemical mode confirmed the carbonyl ammonia condensation. These results suggested that CS-g-phenolic acids serve as novel coating to reduce hazardous compounds during aquatic products thermal processing.

Enhanced field-emission behavior of layered MoS2 sheets.

Field emission studies are reported for the first time on layered MoS2 sheets at the base pressure of ∼1 × 10⁻8 mbar. The turn-on field required to draw a field emission current density of 10 µA/cm² is found to be 3.5 V/µm for MoS2 sheets. The turn-on values are found to be significantly lower than the reported MoS2 nanoflowers, graphene, and carbon nanotube-based field emitters due to the high field enhancement factor (∼1138) associated with nanometric sharp edges of MoS2 sheet emitter surface. The emission current-time plots show good stability over a period of 3 h. Owing to the low turn-on field and planar (sheetlike) structure, the MoS2 could be utilized for future vacuum microelectronics/nanoelectronic and flat panel display applications.

2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors.

2,4-Di-tert-butylphenol (2,4-DTBP) is an important commercial antioxidant and a toxic natural secondary metabolite that has been detected in humans. However, there is scant information regarding its toxicological effects. We asked whether 2,4-DTBP is a potential obesogen. Using a human mesenchymal stem cell adipogenesis assay, we found that exposure to 2,4-DTBP led to increased lipid accumulation and expression of adipogenic marker genes. Antagonist assays revealed that 2,4-DTBP increased lipid accumulation by activating the peroxisome proliferator-activated receptor (PPAR) γ-retinoid X receptor (RXR) heterodimer. 2,4-DTBP likely activated the PPARγ/RXRα heterodimer by activating RXRα but not directly binding to PPARγ. We confirmed that 2,4-DTBP directly bound to RXRα by solving the crystal structure of this complex, then predicted and demonstrated that related compounds could also activate RXRα. Our study demonstrated that 2,4-DTBP and related chemicals could act as obesogens and endocrine disruptors via RXRs. These data showed that 2,4-DTBP belongs to a family of compounds whose endocrine-disrupting and obesogenic effects can be strongly modulated by their chemical composition. Structure-activity studies such as the present one could help guide the rational development of safer antioxidants that do not interact with important nuclear receptors having broad effects on human development and physiology.

Synergistic and Antagonistic Antiproliferative Effects of Ribociclib (Lee011) and Irinotecan (SN38) on Colorectal Cancer Cells.

BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most common malignancies and cause of cancer-related deaths worldwide. The combination of chemotherapeutics working with different mechanisms enhances the therapeutic effects and delays the development of resistance. This study investigated the anticancer effect of the combination of ribociclib (LEE011) and irinotecan (SN38) on CRC cells. MATERIALS AND METHODS: HT-29 and SW480 cells were treated with LEE011, SN38, or the combination of LEE011 and SN38. Cell viability and cell cycle distribution were analyzed. The expression of cell cycle- and apoptosis-related proteins was determined using western blot. RESULTS: The combination of LEE011 and SN38 elicited a synergistic antiproliferative effect on HT-29 (PIK3CAP449T mutation) cells, and an antagonistic antiproliferative effect on SW480 (KRASG12V mutation) cells. LEE011 inhibited retinoblastoma protein (Rb) phosphorylation and led to G1 arrest in HT-29 and SW480 cells. SN38 treatment caused a significant increase in the phosphorylation levels of Rb, cyclin B1, and CDC2 in SW480 cells and induced S phase arrest. Furthermore, SN38 treatment increased the phosphorylation levels of p53 and activated caspase-3 and caspase-8 in HT-29 and SW480 cells. LEE011-induced G1 arrest contributed to its synergistic antiproliferative effect with SN38 in HT-29 cells through the down-regulation of the phosphorylation of Rb. In addition, it elicited an antagonistic effect with SN38 in SW480 cells by changing the phosphorylation levels of Rb and activating caspase-8. CONCLUSION: The effects of the combination of LEE011 and conventional chemotherapy drugs on CRC depend on the chemotherapy drug and the specific gene mutation harbored by tumor cells.

Steam etched porous graphene oxide network for chemical sensing.

Oxidative etching of graphene flakes was observed to initiate from edges and the occasional defect sites in the basal plane, leading to reduced lateral size and a small number of etch pits. In contrast, etching of highly defective graphene oxide and its reduced form resulted in rapid homogeneous fracturing of the sheets into smaller pieces. On the basis of these observations, a slow and more controllable etching route was designed to produce nanoporous reduced graphene oxide sheets by hydrothermal steaming at 200 °C. The degree of etching and the concomitant porosity can be conveniently tuned by etching time. In contrast to nonporous reduced graphene oxide annealed at the same temperature, the steamed nanoporous graphene oxide exhibited nearly 2 orders of magnitude increase in the sensitivity and improved recovery time when used as chemiresistor sensor platform for NO(2) detection. The results underscore the efficacy of the highly distributed nanoporous network in the low temperature steam etched GO.

Mga safeguards embryonic stem cells from acquiring extraembryonic endoderm fates.

Polycomb group (PcG) proteins form multiprotein complexes that affect stem cell identity and fate decisions by still largely unexplored mechanisms. Here, by performing a CRISPR-based loss-of-function screen in embryonic stem cells (ESCs), we identify PcG gene Mga involved in the repression of endodermal transcription factor Gata6 We report that deletion of Mga results in peri-implantation embryonic lethality in mice. We further demonstrate that Mga-null ESCs exhibit impaired self-renewal and spontaneous differentiation to primitive endoderm (PE). Our data support a model in which Mga might serve as a scaffold for PRC1.6 assembly and guide this multimeric complex to specific genomic targets including genes that encode endodermal factors Gata4, Gata6, and Sox17. Our findings uncover an unexpected function of Mga in ESCs, where it functions as a gatekeeper to prevent ESCs from entering into the PE lineage by directly repressing expression of a set of endoderm differentiation master genes.

Rbbp4 Suppresses Premature Differentiation of Embryonic Stem Cells.

Polycomb group (PcG) proteins exist in distinct multi-protein complexes and play a central role in silencing developmental genes, yet the underlying mechanisms remain elusive. Here, we show that deficiency of retinoblastoma binding protein 4 (RBBP4), a component of the Polycomb repressive complex 2 (PRC2), in embryonic stem cells (ESCs) leads to spontaneous differentiation into mesendodermal lineages. We further show that Rbbp4 and core PRC2 share an important number of common genomic targets, encoding regulators involved in early germ layer specification. Moreover, we find that Rbbp4 is absolutely essential for genomic targeting of PRC2 to a subset of developmental genes. Interestingly, we demonstrate that Rbbp4 is necessary for sustaining the expression of Oct4 and Sox2 and that the forced co-expression of Oct4 and Sox2 fully rescues the pluripotency of Rbbp4-null ESCs. Therefore, our study indicates that Rbbp4 links maintenance of the pluripotency regulatory network with repression of mesendoderm lineages.