AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.

AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer disease (AD) by generating the toxic ß-amyloid peptide (Aß). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aß in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aß, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.

The Buerger's rabbit model: a closer step to unravelling thromboangiitis obliterans?

OBJECTIVE: Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. METHODS: Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). RESULTS: The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. CONCLUSION: The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

The mechanisms underlying Li+/Mg2+ separation in ZIF-8 under an electric field from atomistic simulations.

In this study, we explore the mass transfer and separation mechanism of Li+ and Mg2+ confined within the flexible nanoporous zeolite imidazolate framework ZIF-8 under the influence of an electric field, employing molecular dynamics simulation. Our results highlight that the electric field accelerates the dehydration process of ions and underscore the critical importance of ZIF-8 framework flexibility in determining the separation selectivity of the ZIF-8 membrane. The electric field is shown to diminish ion hydration in the confined space of ZIF-8, notably disrupting the orientation of water molecules in the first hydration shells of ions, leading to an asymmetrical ionic hydration structure characterized by the uniform alignment of water dipoles. Furthermore, despite the geometrical constraints imposed by the ZIF-8 framework, the electric field significantly enhances ionic mobility. Notably, the less stable hydration shell of Li+ facilitates its rapid, dehydration-induced transit through ZIF-8 nanopores, unlike Mg2+, whose stable hydration shell impedes dehydration. Further investigation into the structural characteristics of the six-ring windows traversed by Li+ and Mg2+ ions reveals distinct mechanisms of passage: for Mg2+ ions, significant window expansion is necessary, while for Li+ ions, the mechanism involves both window expansion and partial dehydration. These findings reveal the profound impact of the electric field and framework flexibility on the separation of Li+ and Mg2+, offering critical insights for the potential application of flexible nanoporous materials in the selective extraction of Li+ from salt-lake brine.

Associations between adverse childhood experiences and pain in middle-aged and older adults: findings from the China Health and Retirement Longitudinal Study.

OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations. METHODS: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTS: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain. CONCLUSIONS: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics.

Prevalence and genotype/subtype distribution of Enterocytozoon bieneusi and Blastocystis in donkeys in Shanxi Province, north China.

Enterocytozoon bieneusi and Blastocystis may cause diarrhea in humans and various animals. However, little information is available regarding the prevalence and genetic diversity of E. bieneusi and Blastocystis in donkeys. To fill this gap, we molecularly assessed E. bieneusi and Blastocystis in fecal samples from donkeys (n = 815) in Shanxi Province, north China. The overall prevalence of E. bieneusi and Blastocystis in donkeys was 8.1% and 0.2%, respectively. Region and age were risk factors associated with E. bieneusi infection in donkeys. Three internal transcribed spacer (ITS) genotypes of E. bieneusi were identified in the current study, including two previously described genotypes (D and Henan-IV) and one novel genotype (named SXD1). Of which, genotype D was found to be the most prevalent. Phylogenetic analysis demonstrated that the three genotypes belonged to group 1, implying a potential of zoonotic transmission. Multilocus sequence typing showed that 19, 15, 13, and 22 types were identified at the loci MS1, MS3, MS4, and MS7, respectively, forming six multilocus genotypes (MLGs) distributed in the genotype D. One Blastocystis subtype (ST33) was identified, which has previously been reported only in horses. This is the first molecular-based description of E. bieneusi and Blastocystis infections in donkeys in Shanxi Province, north China, contributing to a better understanding of transmission dynamics and molecular epidemiological characteristics of the two intestinal protozoa.

[Identification of a novel variant in a patient with Calsequestrin 1 related myopathy].

OBJECTIVE: To explore the genetic basis of a myopathic patient with pathological characteristics including tubular aggregates and vacuoles. METHODS: Next generation sequencing was carried out for the patient, and candidate variant was verified by Sanger sequencing. RESULTS: Genetic testing revealed that the patient has harbored a heterozygous c.730G>C (p.D244H) variant of Calsequestrin 1 (CASQ1) gene. The same variant was not found in his unaffected parents. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PS1+PM2+PP3). CONCLUSION: The novel c.730G>C (p.D244H) variant of the CASQ1 gene probably underlay the myopathy in this patient. Above finding has enriched the mutational spectrum of the CASQ1 gene.

Graphitic Armor: A Natural Molecular Sieve for Robust Hydrogen Electroxidation.

Carbon coating layers have been found to improve the catalytic performance of transition metals, which is usually explained as an outcome of electronic synergistic effect. Herein we reveal that the defective graphitic carbon, with a unique interlayer gap of 0.342 nm, can be a highly selective natural molecular sieve. It allows efficient diffusion of hydrogen molecules or radicals both along the in-plane and out-of-plane direction, but sterically hinders the diffusion of molecules with larger kinetic diameter (e.g., CO and O2) along the in-plane direction. As a result, poisonous species lager than 0.342 nm are sieved out, even when their adsorption on the metal is thermodynamically strong; at the same time, the interaction between H2 and the metal is not affected. This natural molecular sieve provides a very chance for constructing robust metal catalysts for hydrogen-relevant processes, which are more tolerant to chemical or electrochemical oxidation or CO-relevant poisoning.

Association between ovarian reserve and spontaneous miscarriage and their shared genetic architecture.

STUDY QUESTION: Can potential mechanisms involved in the likely concurrence of diminished ovarian reserve (DOR) and miscarriage be identified using genetic data? SUMMARY ANSWER: Concurrence between ovarian reserve and spontaneous miscarriage was observed, and may be attributed to shared genetic risk loci enriched in antigen processing and presentation and autoimmune disease pathways. WHAT IS KNOWN ALREADY: Previous studies have shown that lower serum anti-Müllerian hormone (AMH) levels are associated with increased risk of embryo aneuploidy and spontaneous miscarriage, although findings have not been consistent across all studies. A recent meta-analysis suggested that the association between DOR and miscarriage may not be causal, but rather a result of shared underlying causes such as clinical conditions or past exposure. Motivated by this hypothesis, we conducted the present analysis to explore the concurrence between DOR and miscarriage, and to investigate potential mechanisms using genetic data. STUDY DESIGN, SIZE, DURATION: Three data sources were used in the study: the clinical IVF data were retrospectively collected from an academically affiliated Reproductive Medicine Center (17 786 cycles included); the epidemiological data from the UK Biobank (UKB), which is a large-scale, population-based, prospective cohort study (35 316 white women included), were analyzed; and individual-level genotype data from the UKB were extracted for further analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were three modules of analysis. First, clinical IVF data were used to test the association between ovarian reserve biomarkers and the subsequent early spontaneous miscarriage risk. Second, the UKB data were used to test the association of spontaneous miscarriage history and early menopause. Third, individual-level genotype data from the UKB were analyzed to identify specific pleiotropic genes which affect the development of miscarriage and menopause. MAIN RESULTS AND THE ROLE OF CHANCE: In the analysis of clinical IVF data, the risk of early spontaneous miscarriage was 1.57 times higher in the group with AMH < 1.1 ng/ml group (P < 0.001), 1.62 times for antral follicular count <5 (P < 0.001), and 1.39 times for FSH ≥10 mIU/ml (P < 0.001) in comparison with normal ovarian reserve groups. In the analysis of UKB data, participants with a history of three or more miscarriages had a one-third higher risk of experiencing early menopause (odds ratio: 1.30, 95% CI 1.13-1.49, P < 0.001), compared with participants without spontaneous miscarriage history. We identified 158 shared genetic risk loci that affect both miscarriage and menopause, which enrichment analysis showed were involved in antigen processing and presentation and autoimmune disease pathways. LIMITATIONS, REASONS FOR CAUTION: The analyses of the UKB data were restricted to participants of European ancestry, as 94.6% of the cohort were of white ethnicity. Further studies are needed in non-white populations. Additionally, maternal age at the time of spontaneous miscarriage was not available in the UKB cohort, therefore we adjusted for age at baseline assessment in the models instead. It is known that miscarriage rate in IVF is higher compared to natural conception, highlighting a need for caution when generalizing our findings from the IVF cohort to the general population. WIDER IMPLICATIONS OF THE FINDINGS: Our findings have implications for IVF clinicians in terms of patient counseling on the prognosis of IVF treatment, as well as for genetic counseling regarding miscarriage. Our results highlight the importance of further research on the shared genetic architecture and common pathophysiological basis of DOR and miscarriage, which may lead to new therapeutic opportunities. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Hunan Youth Science and Technology Innovation Talent Project (2020RC3060), the International Postdoctoral Exchange Fellowship Program (Talent-Introduction Program, YJ20220220), the fellowship of China Postdoctoral Science Foundation (2022M723564), and the Natural Science Foundation of Hunan Province, China (2023JJ41016). This work has been accepted for poster presentation at the 39th Annual Meeting of ESHRE, Copenhagen, Denmark, 25-28 June 2023 (Poster number: P-477). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The influence of force fields on the structure and dynamics of water confined in ZIF-8 from atomistic simulations.

The complexity of modeling flexible crystals, such as ZIF-8, mainly stems from the handling of intramolecular interactions. Numerous force fields have been proposed in the literature to describe the interactions between atoms in ZIF-8. We employ seven force fields to examine the structure and dynamic behavior of water molecules confined in ZIF-8, with the aim of investigating the impact of force fields on simulation results. Various structural characterization methods consistently indicate that the choice of different force fields has quantitative effects but no qualitative effects on the structural characteristics of confined water. Additionally, the force fields do not impact the qualitative description of the diffusion mechanism. Both mean-square displacement and van Hove autocorrelation function reveal two characteristic movements of water molecules diffusing in ZIF-8: a short-time intra-cavity hopping process and a long-time inter-cavity hopping process. However, the framework flexibility is found to play a crucial role in determining the order of spatial arrangement and local structure, self-diffusion coefficient and reorientational dynamics of confined water. Specifically, the DREIDING force field gives rise to an unrealistic stiff framework, enhancing the order of spatial arrangement and diminishing the local ordered structure of confined water. Meanwhile, it results in much slower translational and reorientational dynamics. Hence, the general DREIDING force field cannot be considered for providing a quantitative description of the water structure and dynamics.

Similarity measurements of B cell receptor repertoire in baseline mice showed spectrum convergence of IgM.

BACKGROUND: The B cell receptor (BCR) repertoire is highly diverse among individuals. Poor similarity of the spectrum among inbred baseline mice may limit the ability to discriminate true signals from those involving specific experimental factors. The repertoire similarity of the baseline status lacks intensive measurements. RESULTS: We measured the repertoire similarity of IgH in blood and spleen samples from untreated BALB/c and C57BL/6J mice to investigate the baseline status of the two inbred strains. The antibody pool was stratified by the isotype of IgA, IgG and IgM. Between individuals, the results showed better convergence of CDR3 and clonal lineage profiles in IgM than in IgA and IgG, and better robustness of somatic mutation networks in IgM than in IgA and IgG. It also showed that the CDR3 clonotypes and clonal lineages shared better in the spleen samples than in the blood samples. The animal batch differences were detected in CDR3 evenness, mutated clonotype proportions, and maximal network degrees. A cut-off of 95% identity in the CDR3 nucleotide sequences was suitable for clonal lineage establishment. CONCLUSIONS: Our findings reveal a natural landscape of BCR repertoire similarities between baseline mice and provide a solid reference for designing studies of mouse BCR repertoires.

Single-photon 3D imaging with a multi-stage network.

Active single-photon 3D imaging technology has been applied to 3D imaging of complex scenes in many frontier fields such as biomedicine, remote sensing mapping, etc. However, single-photon 3D imaging with strong background noise is still a major challenge. Several classical algorithms and machine learning methods have been proposed to solve the problem. In this paper, we propose a novel multi-stage synergistic recovery network to reconstruct an accurate depth map. In the model, we first extract multi-scale feature information using encoder and decoder architectures, then combine them with an original resolution network that retains complete spatial location information. Through this way, we can compensate the deficiencies of the original resolution network for multi-scale local feature extraction. Moreover, a self-supervised attention module (SAM) is constructed to weight local features between different stages, optimizing the feature exchange between different stages of the multi-stage architecture network. Our method currently performs the best of all the tested methods.

Structure and dynamics of a water/methanol mixture confined in zeolitic imidazolate framework ZIF-8 from atomistic simulations.

A classical atomistic simulation study is reported for the microscopic structure and dynamics of a water/methanol mixture confined in flexible nanoporous zeolitic imidazolate framework ZIF-8. Both the radial density distribution and vivid two-dimensional density profile demonstrate that methanol molecules can roughly be viewed as "embedded" between two layers of water molecules to form a "sandwich" structure. The reason for the formation of such a specific structure is explained based on the hydrogen-bonding state and the strength of various hydrogen bonds. The investigation of guest molecular diffusion shows that the self-diffusion coefficient of confined water is generally one to two orders of magnitude smaller than that of bulk water. In addition, the dependence of the self-diffusion coefficient on loading is non-monotonic: the self-diffusion coefficient firstly shows a significant increase and then decreases at higher loading. Moreover, both the structure and dynamics of the hydrogen bond (HB) network of confined water molecules are investigated in a spatially resolved manner. The results indicate that both the HB structure and dynamics of water molecules near the ZIF-8 surface deviate significantly from those of bulk water. However, while water molecules located at the pore center are relatively similar to bulk water molecules with respect to the HB structure, they exhibit strong slowdown in HB dynamics when compared with bulk water. This simulation study elucidates in detail the structural and dynamical properties of a water/methanol mixture in nanoscopic ZIF-8 confinement, which is expected to provide a deep insight into the role of porous fillers, such as ZIF-8, in improving the performance of the dehydration of alcohols via pervaporation and other related processes.

First total syntheses of kanjone and its natural analogues.

Kanjone (1), a bioactive furanoflavone and a potent biomolecule, was first isolated from Pongamia pinnata (L.). Herein, we have developed two approaches to synthesize kanjone as well as its natural analogues 6-methoxyisopongaglabol (2) and 6,3'-dimethoxy-[2″,3″:7,8]furanoflavone (3) starting from khellin and 3-hydroxy-4-methoxy-benzaldehyde, respectively.

[Effect of astragaloside â £ on angiotensin â ¡-induced inflammatory response of vascular endothelial cells and mechanism].

This study was designed to determine the inhibitory effect of astragaloside Ⅳ(AS-Ⅳ), a principal bioactive component extracted from the Chinese medicinal Astragali Radix, on the inflammatory response of vascular endothelial cells induced by angiotensin Ⅱ(Ang Ⅱ), the most major pathogenic factor for cardiovascular diseases, and to clarify the role of calcium(Ca~(2+))/phosphatidylinosi-tol-3-kinase(PI3K)/protein kinase B(Akt)/endothelial nitric oxide synthase(eNOS)/nitric oxide(NO) pathway in the process. To be specific, human umbilical vein endothelial cells(HUVECs) were cultured in the presence of AS-Ⅳ with or without the specific inhibitor of NO synthase(NG-monomethyl-L-arginine, L-NMMA), inhibitor of PI3K/Akt signaling pathway(LY294002), or Ca~(2+)-chelating agent(ethylene glycol tetraacetic acid, EGTA) prior to Ang Ⅱ stimulation. The inhibitory effect of AS-Ⅳ on Ang Ⅱ-induced inflammatory response and the involved mechanism was determined with enzyme-linked immunosorbent assay(ELISA), cell-based ELISA assay, Western blot, and monocyte adhesion assay which determined the fluorescently labeled human monocytic cell line(THP-1) adhered to Ang Ⅱ-stimulated endothelial cells. AS-Ⅳ increased the production of NO by HUVECs in a dose-and time-dependent manner(P<0.05) and raised the level of phosphorylated eNOS(P<0.05). The above AS-Ⅳ-induced changes were abolished by pretreatment with L-NMMA, LY294002, or EGTA. Compared with the control group, Ang Ⅱ obviously enhanced the production and release of cytokines(tumor necrosis factor-α, interleukin-6), chemokines(monocyte chemoattractant protein-1) and adhesion molecules(intercellular adhesion molecule-1, vascular cellular adhesion molecule-1), and the number of monocytes adhered to HUVECs(P<0.05), which were accompanied by the enhanced levels of phosphorylated inhibitor of nuclear factor-κBα protein and activities of nuclear factor-κB(NF-κB)(P<0.05). This study also demonstrated that Ang Ⅱ-induced inflammatory response was inhibited by pretreatment with AS-Ⅳ(P<0.05). In addition, the inhibitory effect of AS-Ⅳ was abrogated by pretreatment with L-NMMA, LY294002, or EGTA(P<0.05). This study provides a direct link between AS-Ⅳ and Ca~(2+)/PI3K/Akt/eNOS/NO pathway in AS-Ⅳ-mediated anti-inflammatory actions in endothelial cells exposed to Ang Ⅱ. The results indicate that AS-Ⅳ attenuates endothelial cell-mediated inflammatory response induced by Ang Ⅱ via the activation of Ca~(2+)/PI3K/Akt/eNOS/NO signaling pathway.

Photoinduced NO and HNO Production from Mononuclear {FeNO}6 Complex Bearing a Pendant Thiol.

Light triggers the formation of HNO from a metal-nitrosyl species, facilitated by an intramolecular pendant thiol proton. Two {FeNO}6 complexes (the Enemark-Felthan notation), [Fe(NO)(TMSPS2)(TMSPS2H)] (1, TMSPS2H2 = 2,2'-dimercapto-3,3'-bis(trimethylsilyl)diphenyl)phenylphosphine; H is a dissociable proton) with a pendant thiol and [Fe(NO)(TMSPS2)(TMSPS2CH3)] (2) bearing a pendant thioether, are spectroscopically and structurally characterized. Both complexes are highly sensitive to visible light. Upon photolysis, complex 2 undergoes NO dissociation to yield a mononuclear Fe(III) complex, [Fe(TMSPS2)(TMSPS2CH3)] (3). In contrast, the pendant SH of 1 can act as a trap for the departing NO radical upon irradiation, resulting in the formation of an intermediate A with an intramolecular [SH···ON-Fe] interaction. As suggested by computational results (density functional theory), the NO stretching frequency (νNO) is sensitive to the intramolecular interaction between the pendant ligand and the iron-bound NO, and a shift of νNO from 1833 (1) to 1823 cm-1 (A) is observed experimentally. Subsequent photolysis of the intermediate A results in HNO production and a thiyl group that then coordinates to the Fe center for the formation of [Fe(TMSPS2)2] (4). In contrast with the common acid-base coupling pathway, the HNO is not voluntarily yielded from 1 but rather is generated by the photopromoted pathway. The photogenerated HNO can further react with [MnIII(TMSPS3)(DABCO)] (TMSPS3H3 = (2,2'2''-trimercapto-3,3',3''-tris(trimethylsilyl)triphenylphosphine; DABCO = 1,4-diazabicyclo[2.2.2]octane) in organic media to yield anionic [Mn(NO)(TMSPS3)]- (5-) with a {MnNO}6 electronic configuration, whereas [MnIII(TMSPS3)(DABCO)] reacts with NO gas for the formation of a {MnNO}5 species, [Mn(NO)(TMSPS3)] (6). Effective differentiation of the formation of HNO from complex 1 with the pendant SH versus NO from 2 with the pendant SMe is achieved by the employment of [MnIII(TMSPS3)(DABCO)].

H3.3 impedes zygotic transcriptional program activated by Dux.

During development, fertilization triggers totipotency establishment, featured by zygotic genome activation/embryonic genome activation (ZGA/EGA). Mouse embryonic stem cells (mESCs) occasionally cycle through a two-cell (2C)-like status with activated expression of Dux and its targeted ZGA genes. Here, we demonstrate that deficiency of histone variant H3.3 dramatically stimulates expression of ZGA genes in mESCs. Our analysis revealed that H3.3 directly associates with Dux locus and inhibits Dux expression, therefore it is an important upstream regulator of Dux. Our finding is further supported by transcriptome change in early mouse embryos with H3.3 knockdown. We suggest that proper H3.3 level in early embryos is important to orchestrate ZGA activity for totipotency establishment.

MiR-423-5p may regulate ovarian response to ovulation induction via CSF1.

BACKGROUND: We have previously shown that hsa-miR-423-5p expression in ovarian granulosa cells is decreased in high ovarian response populations. The objective of the present study was to find the target gene and mechanism for miR-423-5p involved in ovarian response regulation. METHODS: (a) TargetScan was used to predict the target gene of hsa-miR-423-5p. (b) A model for hsa-miR-423-5p overexpression or inhibition was constructed by transfecting KGN cells with lentivirus. CSF1 mRNA and protein expression and luciferase activity were measured. (c) The cell cycles of control and lentivirus treated KGN cells were analyzed. Western blot was used to measure the expression of CDKN1A in KGN cells. (d) The concentration of E2 in KGN cell culture medium were measured. RESULTS: (a) TargetScan revealed that the 3' un-translated region of CSF1 matched 11 bases at the 5' end of miR-423-5p, making it a likely target gene. (b) Overexpression or inhibition of miR-423-5p were associated with respective decreases or increases in CSF1 expression (both mRNA and protein) (p < 0.05) and luciferase activity (p < 0.05). (c) When miR-423-5p expression increased, the number of G0/G1 phase cells and the expression of CDKN1A protein increased while estradiol concentrations in the cell culture solution decreased (p < 0.05). However, when miR-423-5p expression decreased, the number of S phase cells increased and E2 concentrations increased while the expression of CDKN1A protein decreased (p < 0.05). CONCLUSIONS: Colony stimulating factor 1 is a target gene of miR-423-5p and that it may regulate ovarian response to ovulation induction by affecting granulosa cells proliferation and estrogen secretion.

Correction to: Value of endometrial echo pattern transformation after hCG trigger in predicting IVF pregnancy outcome: a prospective cohort study.

An amendment to this paper has been published and can be accessed via the original article.

A collective elastic fluctuation mechanism for decoupling and stretched relaxation in glassy colloidal and molecular liquids.

We propose a microscopic theory for the decoupling of self-diffusion and structural relaxation in glass-forming liquids within the Elastically Collective Nonlinear Langevin Equation (ECNLE) activated dynamics framework. Our central hypothesis is that the heterogeneity relevant to this problem is static fluctuations of local density on the scale of 3-4 particle diameters and how this changes local packing correlations. These fluctuations modify the degree of dynamical cage expansion that mechanistically couples intracage large amplitude hopping and longer range collective elasticity in ECNLE theory. Decoupling only emerges in the deeply supercooled regime where the strongly temperature dependent elastic barrier becomes non-negligible relative to its noncooperative local analog. The theory makes predictions for various aspects of the decoupling phenomenon, including apparent fractional power law Stokes-Einstein behavior, that appear to be consistent with experiments and simulations on hard sphere fluids and molecular liquids. Of central importance is a microscopic connection between the barrier fluctuation variance and most probable barrier height. Sensible results are also obtained for the nonexponential stretching of a generic relaxation time correlation function and its temperature evolution. Nonuniversality can arise from the relative importance of the local and collective barriers (related to fragility) and the precise magnitude of the length scale that defines the transition from local cage to elastic physics. Comparison is made with a traplike model based on a Gaussian distribution of barriers.

Acetylome analysis of the feline small intestine following Toxoplasma gondii infection.

Toxoplasma gondii is a protozoan parasite capable of infecting a large number of warm-blooded animals and causes serious health complications in immunocompromised patients. T. gondii infection of the feline small intestine is critical for the completion of the life cycle and transmission of T. gondii. Protein acetylation is an important posttranslational modification, which plays roles in the regulation of various cellular processes. Therefore, understanding of how T. gondii reprograms the protein acetylation status of feline definitive host can help to thwart the production and spread of T. gondii. Here, we used affinity enrichment and high-resolution liquid chromatography with tandem mass spectrometry to profile the alterations of the acetylome in cat small intestine 10 days after infection by T. gondii Prugniuad (Pru) strain. Our analysis showed that T. gondii induced significant changes in the acetylation of proteins in the cat intestine. We identified 2606 unique lysine acetylation sites in 1357 acetylated proteins. The levels of 334 acetylated peptides were downregulated, while the levels of 82 acetylated peptides were increased in the infected small intestine. The proteins with differentially acetylated peptides were particularly enriched in the bioenergetics-related processes, such as tricarboxylic acid cycle, oxidative phosphorylation, and oxidation-reduction. These results provide the first baseline of the global acetylome of feline small intestine following T. gondii infection and should facilitate further analysis of the role of acetylated protein in the pathogenesis of T. gondii infection in its definitive host.