Mbd3, a Component of NuRD/Mi-2 Complex, Helps Maintain Pluripotency of Mouse Embryonic Stem Cells by Repressing Trophectoderm Differentiation

Embryonic stem cells (ES cells) can differentiate into cells derived from all three germ layers and extraembryonic tissues. While transcription factors such as, Oct4 and Nanog are well known for their requirements for undifferentiated ES cell growth, mechanisms of epigenetic repression of germ layer specific differentiation in ES cells are not well understood. Here, we investigate functions of Mbd3, a component of nucleosome remodeling and histone deacetylation complex (NuRD/Mi-2) in mouse ES cells. We find that compared to wild type ES cells, Mbd3 knockdown cells show elevated RNA expression of trophectoderm markers, including Cdx2, Eomesodermin, and Hand1. In parallel, these cells show an increased acetylation level of histone 3 in promoters of the respective genes, suggesting Mbd3 plays a role in repression of these genes in undifferentiated ES cells. However, these changes are not sufficient for definitive differentiation to trophectoderm (TE) in chimeric embryos. When further cultured in ES medium without LIF or in trophoblast stem (TS) cell medium, Mbd3 knockdown cells differentiate into TE cells, which express Cdx2 and, at later stages, trophoblast lineage specific marker Cadherin 3. These results suggest that Mbd3 helps restrict ES cells from differentiating towards the trophectoderm lineage and is an important epigenetic player in maintaining full pluripotency of mouse ES cells

An exploratory study of the effect of labor pain management on postpartum depression among Chinese women

Objectives: The purpose of this study was to investigate the effects of pain relief during labor on the occurrence of potential postpartum depression in early postpartum among Chinese women.Material and methods: A quasi-experimental study used, with a convenience sample of 565 women who delivered at the Women’s Hospital, School of Medicine. Three types of pain relief were administered based on the women’s preference (doula, n = 301; transcutaneous electrical nerve stimulation, n = 51; epidural analgesia, n = 213). Pain scores of participants were assessed using a 10-point visual analog scale during labor. The Edinburgh Postnatal Depression Scale was administered in person and by phone at three days and two to four weeks after delivery, respectively. All data were analyzed using SPSS 20.0.Results: Visual analog scale pain scores in the epidural analgesia group decreased significantly during labor compared to those of the other two groups. The occurrence of potential postpartum depression at three days was 6.6% in the epidural analgesia group, 1.3% in the doula group, and 2% in the transcutaneous electrical nerve stimulation group (P = 0.04). Furthermore, potential postpartum depression occurred at two to four weeks after childbirth in 16% (34/213) of the participants in the epidural analgesia group, 7.3% (22/301) of those who received doula support, and in 7.8% (4/51) of those in the transcutaneous electrical nerve stimulation group (P = 0.006).Conclusions: The results indicated that epidural analgesia was an effective pain relief method during labor. However, it did not reduce the occurrence of potential postpartum depression and was associated with higher postnatal depression scores

Neuron with Steady Response Leads to Better Generalization

Regularization can mitigate the generalization gap between training and inference by introducing inductive bias. Existing works have already proposed various inductive biases from diverse perspectives. However, none of them explores inductive bias from the perspective of class-dependent response distribution of individual neurons. In this paper, we conduct a substantial analysis of the characteristics of such distribution. Based on the analysis results, we articulate the Neuron Steadiness Hypothesis: the neuron with similar responses to instances of the same class leads to better generalization. Accordingly, we propose a new regularization method called Neuron Steadiness Regularization (NSR) to reduce neuron intra-class response variance. Based on the Complexity Measure, we theoretically guarantee the effectiveness of NSR for improving generalization. We conduct extensive experiments on Multilayer Perceptron, Convolutional Neural Networks, and Graph Neural Networks with popular benchmark datasets of diverse domains, which show that our Neuron Steadiness Regularization consistently outperforms the vanilla version of models with significant gain and low additional computational overhead.Comment: Accepted by NeurIPS'2

Bis[2-(1H-benzimidazol-2-yl)benzoato]copper(II) dihydrate

In the title compound, [Cu(C14H9N2O2)2]·2H2O, the Cu(II) ion lies on a centre of symmetry and is four-coordinated by two N atoms and two O atoms from two 2-(1H-benzimidazol-2-yl)benzoate ligands in a square-planar environment. The benzimidazol and benzyl rings form a dihedral angle of 42.8 (5)°. The mol­ecule contains two H-bonded carboxyl O acceptors and two H-bonded N—H donors in the benzimidazol groups, which inter­act with two symmetry-related uncoordinated water mol­ecules so that neighboring mol­ecular units are linked by (O—H)water⋯Ocarbox­yl hydrogen bonds with an R 2 4(8) graph-set motif, generating a helical chain in the a-axis direction. These chains are, in turn, inter­connected by (N—H)benzimidazol⋯Owater hydrogen bonds, forming a three-dimensional supra­molecular network

Solving the Batch Stochastic Bin Packing Problem in Cloud: A Chance-constrained Optimization Approach

This paper investigates a critical resource allocation problem in the first party cloud: scheduling containers to machines. There are tens of services and each service runs a set of homogeneous containers with dynamic resource usage; containers of a service are scheduled daily in a batch fashion. This problem can be naturally formulated as Stochastic Bin Packing Problem (SBPP). However, traditional SBPP research often focuses on cases of empty machines, whose objective, i.e., to minimize the number of used machines, is not well-defined for the more common reality with nonempty machines. This paper aims to close this gap. First, we define a new objective metric, Used Capacity at Confidence (UCaC), which measures the maximum used resources at a probability and is proved to be consistent for both empty and nonempty machines, and reformulate the SBPP under chance constraints. Second, by modeling the container resource usage distribution in a generative approach, we reveal that UCaC can be approximated with Gaussian, which is verified by trace data of real-world applications. Third, we propose an exact solver by solving the equivalent cutting stock variant as well as two heuristics-based solvers -- UCaC best fit, bi-level heuristics. We experimentally evaluate these solvers on both synthetic datasets and real application traces, demonstrating our methodology's advantage over traditional SBPP optimal solver minimizing the number of used machines, with a low rate of resource violations.Comment: To appear in SIGKDD 2022 as Research Track pape

Therapeutic potential of Ganoderma lucidum polysaccharide peptide in Doxorubicin-induced nephropathy: modulation of renin-angiotensin system and proteinuria

Introduction: In the Doxorubicin (DOX)-induced nephropathy model, proteinuria is a manifestation of progressive kidney injury. The pathophysiology of renal illness is heavily influenced by the renin-angiotensin system (RAS). To reduce renal RAS activation and proteinuria caused by DOX, this study evaluated the effectiveness of Ganoderma lucidum polysaccharide peptide (GL-PP), a new glycopeptide produced from Ganoderma lucidum grown on grass.Methods: Three groups of BALB/c male mice were created: control, DOX, and DOX + GL-PP. GL-PP (100 mg/kg) was administered to mice by intraperitoneal injection for 4 weeks following a single intravenous injection of DOX (10 mg/kg via the tail vein).Results: After 4 weeks, full-length and soluble pro(renin) receptor (fPRR/sPRR) overexpression in DOX mouse kidneys, which is crucial for the RAS pathway, was dramatically inhibited by GL-PP therapy. Additionally, GL-PP successfully reduced elevation of urinary renin activity and angiotensin II levels, supporting the idea that GL-PP inhibits RAS activation. Moreover, GL-PP showed a considerable downregulation of nicotinamide adenine nucleotide phosphate oxidase 4 (NOX4) expression and a decrease in hydrogen peroxide (H2O2) levels. GL-PP treatment effectively reduced glomerular and tubular injury induced by DOX, as evidenced by decreased proteinuria, podocyte damage, inflammation, oxidative stress, apoptosis, and fibrosis.Discussion: GL-PP inhibits intrarenal PRR/sPRR-RAS activation and upregulation of NOX4 and H2O2, suggesting potential therapeutic approaches against DOX-induced nephropathy

Binding Features and Functions of ATG3

Autophagy is an evolutionarily conserved catabolic process that is essential for maintaining cellular, tissue, and organismal homeostasis. Autophagy-related (ATG) genes are indispensable for autophagosome formation. ATG3 is one of the key genes involved in autophagy, and its homologs are common in eukaryotes. During autophagy, ATG3 acts as an E2 ubiquitin-like conjugating enzyme in the ATG8 conjugation system, contributing to phagophore elongation. ATG3 has also been found to participate in many physiological and pathological processes in an autophagy-dependent manner, such as tumor occurrence and progression, ischemia–reperfusion injury, clearance of pathogens, and maintenance of organelle homeostasis. Intriguingly, a few studies have recently discovered the autophagy-independent functions of ATG3, including cell differentiation and mitosis. Here, we summarize the current knowledge of ATG3 in autophagosome formation, highlight its binding partners and binding sites, review its autophagy-dependent functions, and provide a brief introduction into its autophagy-independent functions