Targeting Estrogen Receptor Beta Ameliorates Diminished Ovarian Reserve via Suppression of the FOXO3a/Autophagy Pathway.

Diminished ovarian reserve (DOR) refers to a decrease in the number and/or quality of oocytes, leading to infertility, poor ovarian response and adverse pregnancy outcomes. Currently, the pathogenesis of DOR is largely unknown, and the efficacy of existing therapeutic methods is limited. Therefore, in-depth exploration of the mechanism underlying DOR is highly important for identifying molecular therapeutic targets for DOR. Our study showed that estrogen receptor beta (ERß) mRNA and protein expression was upregulated in granulosa cells (GCs) from patients with DOR and in the ovaries of DOR model mice. Mechanistically, elevated ERß promotes forkhead transcription factor family 3a (FOXO3a) expression, which contributes to autophagic activation in GCs. Activation of FOXO3a/autophagy signalling leads to decreased cell proliferation and increased cell apoptosis and ultimately leads to DOR. In a cyclophosphamide (Cy)-induced DOR mouse model, treatment with PHTPP, a selective ERß antagonist, rescued fertility by restoring normal sex hormone secretion, estrus cycle duration, follicle development, oocyte quality and litter size. Taken together, these findings reveal a pathological mechanism of DOR based on ERß overexpression and identify PHTPP as a potential therapeutic agent for DOR.

Glucose metabolism reprogramming promotes immune escape of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a complex process that plays an important role in its progression. Abnormal glucose metabolism in HCC cells can meet the nutrients required for the occurrence and development of liver cancer, better adapt to changes in the surrounding microenvironment, and escape the attack of the immune system on the tumor. There is a close relationship between reprogramming of glucose metabolism and immune escape. This article reviews the current status and progress of glucose metabolism reprogramming in promoting immune escape in liver cancer, aiming to provide new strategies for clinical immunotherapy of liver cancer.

Alpha fetoprotein promotes polarization of macrophages towards M2-like phenotype and inhibits macrophages to phagocytize hepatoma cells.

Alpha-fetoprotein(AFP) is a cancer biomarker for the diagnosis of hepatocellular carcinoma(HCC); however, its role in macrophage polarization and phagocytosis remains unclear. In the present study, we explored the correlation between AFP regulation of macrophage function and the possible regulatory mechanisms. Human mononuclear leukemia cells (THP-1) and monocytes from healthy donors were used to analyze the effect of AFP on the macrophages' phenotype and phagocytosis. THP-1 cells and healthy human donor-derived monocytes were polarized into M0 macrophages induced by phorbol ester (PMA), and M0 macrophages were polarized into M1 macrophages induced by lipopolysaccharide(LPS) and interferon-γ(IFN-γ). Interleukin-4(IL-4) and interleukin-13(IL-13) were used to induce M0 macrophage polarization into M2 macrophages. Tumor-derived AFP(tAFP) stimulated M0 macrophage polarization into M2 macrophages and inhibited M1 macrophages to phagocytize HCC cells. The role of AFP in promoting macrophage polarization into M2 macrophages and inhibiting the M1 macrophages to phagocytize HCC cells may be involved in activating the PI3K/Akt signaling pathway. AFP could also enhanced the migration ability of macrophages and inhibited the apoptosis of HCC cells when co-cultured with M1-like macrophages. AFP is a pivotal cytokine that inhibits macrophages to phagocytize HCC cells.

Funeral arrangements requested by suicide decedents in Shanghai and Wuhan, China.

This qualitative study analyzed suicide notes left by 591 decedents in Shanghai and Wuhan, in China. General guidelines and detailed requests with regard to funeral service were coded. In general, suicide decedents preferred untraditional funerals, which were simple and speedy rather than grand and costly funeral arrangements. These choices suggested that suicide decedents could fear stigmatization and discrimination. Some suicide decedents regarded suicides as vicious deaths, and thus wished their families to dispose of the cursed bodily remains and tombs as swiftly as possible.

Self-Stigma and Its Relationship With Rates of Depression Diagnosis.

Background: Self-stigma about suicide might impede people seeking help from mental health professionals. There is little research about self-stigma expressed by suicide decedents. Aims: We aimed to explore (a) self-stigma about suicide through examination of suicide notes; and (b) whether the expression of self-stigma was associated with the formal diagnoses of depression. Method: Data were extracted from notes left by people who died by suicide in two major Chinese cities (Shanghai, 2004-2017; Wuhan, 2005-2019). Note content was examined and self-stigma items were coded. Demographics associated with self-stigma were reported. Rates of depression were compared between note-leavers who expressed self-stigma, and those who did not. Results: Notes were left by 567 suicide decedents (representing about 19% all suicides). Approximately 25% notes contained at least one self-stigma item. Older people made fewer self-stigma references, as did people from Wuhan. Depression was not associated with self-stigma. Limitations: Not all people dying from suicide leave notes, and suicide notes variably report self-stigma, thus self-stigma about suicide may be underestimated. Conclusion: Self-stigma items varied across regions and age groups, but not with depression. Therefore, self-stigma expressed by suicide decedents may not reflect help-seeking behaviours from professional mental health services.

Mortalities of methamphetamine, opioid, and ketamine abusers in Shanghai and Wuhan, China.

Studies on the mortalities of drug abusers in China are scarce. This study explores the deaths of methamphetamine, opioid, and ketamine abusers in Shanghai (2004-2017) and Wuhan (2005-2017). Chi-square/Fisher's exact tests were used to compare the differences in terms of region, gender, age, cause of death, and the method used in the last drug abuse. Poisson regression models were used to estimate the rate ratios ("RRs") and annual percentage changes ("APCs"). 314 heroin, 43 methamphetamine, and 4 ketamine abusers were included. Furthermore, simultaneously, 6 abusers used heroin and methamphetamine, and 7 abusers used methamphetamine and ketamine. Heroin-related deaths have declined in Shanghai (APC, -16.1; 95 % CI, -18.4 to -11.3) and Wuhan (APC, -16.0; 95 % CI, -18.9 to -10.6), whereas methamphetamine-related deaths have increased in Wuhan (APC, 12.8; 95 % CI, 0.0 to 29.2). On the whole, in the two cities, males were more frequently observed than females in heroin-related deaths (4.4, 230/52). However, the gender ratios for methamphetamine- (1.8, 34/19) and ketamine-related deaths (1.2, 6/5) were close to one. In view of the mortality rates of the drug abusers in most Chinese cities were still unclear, it is thus important to improve mortality surveillance of the drug abusers at the national level.

Adsorption and Diffusion of Fluids in Defective Carbon Nanotubes: Insights from Molecular Simulations.

Single-walled carbon nanotubes (SWNTs) have been shown from both simulations and experiments to have remarkably low resistance to gas and liquid transport. This has been attributed to the remarkably smooth interior surface of pristine SWNTs. However, real SWNTs are known to have various defects that depend on the synthesis method and procedure used to activate the SWNTs. In this paper, we study adsorption and transport properties of atomic and molecular fluids in SWNTs having vacancy point defects. We construct models of defective nanotubes that have either unrelaxed defects, where the overall structure of the SWNT is not changed, or reconstructed defects, where the bonding topology and therefore the shape of the SWNT is allowed to change. Furthermore, we include partial atomic charges on the SWNT carbon atoms due to the reconstructed defects. We consider adsorption and diffusion of Ar atoms and CO2 and H2O molecules as examples of a noble gas, a linear quadrupolar fluid, and a polar fluid. Adsorption isotherms were found to be fairly insensitive to the defects, even for the case of water in the charged, reconstructed SWNT. We have computed both the self-diffusivities and corrected diffusivities (which are directly related to the transport diffusivities) for each of these fluids. In general, we found that at zero loading that defects can dramatically reduce the self- and corrected diffusivities. However, at high, liquidlike loadings, the self-diffusion coefficients for pristine and defective nanotubes are very similar, indicating that fluid-fluid collisions dominate the dynamics over the fluid-SWNT collisions. In contrast, the corrected diffusion coefficients can be more than an order of magnitude lower for water in defective SWNTs. This dramatic decrease in the transport diffusion is due to the formation of an ordered structure of water, which forms around a local defect site. It is therefore important to properly characterize the level and types of defects when accurate transport diffusivities are needed.

Experimental and theoretical investigations on the MMOF selectivity for CO2 vs. N2 in flue gas mixtures.

The adsorption capacity and selectivity of carbon dioxide and nitrogen at 298 K have been evaluated for two series of MMOFs built on metal paddle-wheel building units, including non-interpenetrated Zn(BDC)(TED)(0.5) (1), Zn(BDC-OH)(TED)(0.5) (2), Zn(BDC-NH(2))(TED)(0.5) (3), and interpenetrated Zn(BDC)(BPY)(0.5) (4), Zn(BDC)(DMBPY)(0.5) (5), Zn(NDC)(BPY)(0.5) (6) and Zn(NDC)(DMBPY)(0.5) (7) framework structures. The ideal adsorbed solution theory (IAST) has been employed to predict the adsorption selectivity of CO(2)-N(2) binary mixtures on all seven MMOFs using single-component experimental adsorption isotherm data. The applicability of IAST to these systems is verified by GCMC simulations performed on both single- and multi-component gases.

Testing the accuracy of correlations for multicomponent mass transport of adsorbed gases in metal-organic frameworks: diffusion of H2/CH4 mixtures in CuBTC.

Mass transport of chemical mixtures in nanoporous materials is important in applications such as membrane separations, but measuring diffusion of mixtures experimentally is challenging. Methods that can predict multicomponent diffusion coefficients from single-component data can be extremely useful if these methods are known to be accurate. We present the first test of a method of this kind for molecules adsorbed in a metal-organic framework (MOF). Specifically, we examine the method proposed by Skoulidas, Sholl, and Krishna (SSK) ( Langmuir, 2003, 19, 7977) by comparing predictions made with this method to molecular simulations of mixture transport of H 2/CH 4 mixtures in CuBTC. These calculations provide the first direct information on mixture transport of any species in a MOF. The predictions of the SSK approach are in good agreement with our direct simulations of binary diffusion, suggesting that this approach may be a powerful one for examining multicomponent diffusion in MOFs. We also use our molecular simulation data to test the ideal adsorbed solution theory method for predicting binary adsorption isotherms and a method for predicting mixture self-diffusion coefficients.

Unusual hydrogen bonding in water-filled carbon nanotubes.

We present the first experimental vibrational spectroscopy study providing direct evidence of a water phase inside single-walled carbon nanotubes that exhibits an unusual form of hydrogen-bonding due to confinement. Water adopts a stacked-ring structure inside nanotubes, forming intra- and inter-ring hydrogen bonds. The intra-ring hydrogen bonds are bulk-like while the inter-ring hydrogen bonds are relatively weak, having a distorted geometry that gives rise to a distinct OH stretching mode. The experimentally observed infrared mode at 3507 cm(-1) is assigned to vibrations of the inter-ring OH-groups based on detailed atomic-level modeling. The direct observation of unusual hydrogen bonding in nanotubes has potential implications for water in other highly confined systems, such as biological channels and nanoporous media.

Spectroscopic measurement of diffusion kinetics through subnanometer and larger Al2O3 particles by a new method: the interaction of 2-chloroethylethyl sulfide with gamma-Al2O3.

A new method to study the diffusion properties of molecules into porous materials using transmission IR spectroscopy is employed. A measurement of the diffusion of the 2-chloroethylethyl sulfide (2-CEES) molecule into two types of gamma-Al2O3 powder is performed, showing that the diffusion rate into subnanometer crystallite particle size gamma-Al2O3 powders (subnano-Al2O3) is higher than that into the larger crystallite particle size powder. It is shown that a surface diffusion mechanism can be used to model the diffusion process giving good agreement with the experimental results, where Dsubnano-Al2O3 is approximately 5 times larger than Dmultinano-Al2O3 at 170 K for the 2-CEES molecule.