Poly(ethylene oxide)- and Polyzwitterion-Based Thermoplastic Elastomers for Solid Electrolytes.

In this article, ABA triblock copolymer (tri-BCP) thermoplastic elastomers with poly(ethylene oxide) (PEO) middle block and polyzwitterionic poly(4-vinylpyridine) propane-1-sulfonate (PVPS) outer blocks were synthesized. The PVPS-b-PEO-b-PVPS tri-BCPs were doped with lithium bis-(trifluoromethane-sulfonyl) imide (LiTFSI) and used as solid polyelectrolytes (SPEs). The thermal properties and microphase separation behavior of the tri-BCP/LiTFSI hybrids were studied. Small-angle X-ray scattering (SAXS) results revealed that all tri-BCPs formed asymmetric lamellar structures in the range of PVPS volume fractions from 12.9% to 26.1%. The microphase separation strength was enhanced with increasing the PVPS fraction (fPVPS) but was weakened as the doping ratio increased, which affected the thermal properties of the hybrids, such as melting temperature and glass transition temperature, to some extent. As compared with the PEO/LiTFSI hybrids, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids could achieve both higher modulus and higher ionic conductivity, which were attributed to the physical crosslinking and the assistance in dissociation of Li+ ions by the PVPS blocks, respectively. On the basis of excellent electrical and mechanical performances, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids can potentially be used as solid electrolytes in lithium-ion batteries.

The comparision among euploidy of preimplantation blastocysts in different controlled ovary stimulation (COH) protocols.

PURPOSE: To compare differences in euploidy rates for blastocysts in preimplantation genetic testing for aneuploidy (PGT-A) cycles after gonadotropin-releasing hormone agonist (GnRH-a) long and short protocols, GnRH-antagonist (GnRH-ant) protocol, progestin-primed ovarian stimulation and mild stimulation protocols, and other ovary stimulation protocols. METHODS: This was a retrospective cohort study from the Assisted Reproductive Medicine Department of Shanghai First Maternity and Infant Hospital. A total of 1657 PGT-A cycles with intracytoplasmic sperm injection after different controlled ovary hyperstimulation protocols were analyzed, and a total of 3154 embryos were biopsied. Differences in euploidy rate per embryo biopsied, embryo euploidy rate per oocyte retrieved and cycle cancellation rate were compared. RESULTS: For the PGT-A cycles, the euploidy rate per embryo biopsied was lower in the GnRH-ant protocol than in the GnRH-a long protocol (53.26 vs. 58.68%, respectively). Multiple linear regression showed that the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied (ß = -0.079, p = 0.011). The euploidy rate per embryo biopsied was not affected by total gonadotropin dosage, duration of stimulation and number of oocytes retrieved. The embryo euploidy rate per oocyte retrieved was similar in all protocols and was negatively correlated with the total number of oocytes retrieved (ß = -0.003, p = 0.003). CONCLUSION: Compared with the GnRH-a long protocol, the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied. The total gonadotropin dosage, duration of stimulation and number of oocytes retrieved did not appear to significantly influence euploidy rates.

Ficolin 3 promotes ferroptosis in HCC by downregulating IR/SREBP axis-mediated MUFA synthesis.

BACKGROUND: Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown. METHODS: Cell viability, BODIPY-C11 staining, and MDA assay were carried out to detect ferroptosis. Primary hepatocellular carcinoma (HCC) and xenograft models were utilized to investigate the effect of FCN3 on the development of HCC in vivo. A metabonomic analysis was conducted to assess alterations in intracellular and HCC intrahepatic lipid levels. RESULTS: Our study elucidates a substantial decrease in the expression of FCN3, a component of the complement system, leads to MUFA accumulation in human HCC specimens and thereby significantly promotes ferroptosis resistance. Overexpression of FCN3 efficiently sensitizes HCC cells to ferroptosis, resulting in the inhibition of the oncogenesis and progression of both primary HCC and subcutaneous HCC xenograft. Mechanistically, FCN3 directly binds to the insulin receptor ß (IR-ß) and its pro-form (pro-IR), inhibiting pro-IR cleavage and IR-ß phosphorylation, ultimately resulting in IR-ß inactivation. This inactivation of IR-ß suppresses the expression of sterol regulatory element binding protein-1c (SREBP1c), which subsequently suppresses the transcription of genes related to de novo lipogenesis (DNL) and lipid desaturation, and consequently downregulates intracellular MUFA levels. CONCLUSIONS: These findings uncover a novel regulatory mechanism by which FCN3 enhances the sensitivity of HCC cells to ferroptosis, indicating that targeting FCN3-induced ferroptosis is a promising strategy for HCC treatment.

The Inflammatory State of Follicular Fluid Combined with Negative Emotion Indicators can Predict Pregnancy Outcomes in Patients with PCOS.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder syndrome with an incidence of 6% to 10% in women of reproductive age. Women with PCOS not only exhibit abnormal follicular development and fertility disorders, but also have a greater tendency to develop anxiety and depression. Our aim was to evaluate the ability of inflammatory factors in follicular fluid to predict embryonic developmental potential and pregnancy outcome and to construct a machine learning model that can predict IVF pregnancy outcomes based on indicators such as basic sex hormones, embryonic morphology, the follicular microenvironment, and negative emotion. In this study, inflammatory factors (CRP, IL-6, and TNF-α) in follicular fluid samples obtained from 225 PCOS and 225 non-PCOS women were detected via ELISA. For patients with PCOS, the levels of CRP and IL-6 in the follicular fluid in the pregnant group were significantly lower than those in the nonpregnant group. For non-patients with PCOS, only the level of IL-6 in the follicular fluid was significantly lower in the pregnant group than in the nonpregnant group. In addition, for both PCOS and non-patients with PCOS, compared with those in the pregnant group, patients in the nonpregnant group showed more pronounced signs of anxiety and depression. Finally, the factors that were significantly different between the two subgroups (pregnancy and nonpregnancy) of patients with or without PCOS were identified by an independent sample t test first and further analysed by multilayer perceptron (MLP) and random forest (RF) models to distinguish the two clinical pregnancy outcomes according to the classification function. The accuracy of the RF model in predicting pregnancy outcomes in patients with or without PCOS was 95.6% and 91.1%, respectively. The RF model is more suitable than the MLP model for predicting pregnancy outcomes in IVF patients. This study not only identified inflammatory factors that can affect embryonic development and assessed the anxiety and depression tendencies of PCOS patients, but also constructed an AI model that predict pregnancy outcomes through machine learning methods, which is a beneficial clinical tool.

Coagulation Factor VII Fine-tunes Hepatic Steatosis by Blocking AKT-CD36-Mediated Fatty Acid Uptake.

Nonalcoholic fatty liver disease (NAFLD) is considered a risk factor for cardiovascular and cerebrovascular disease owing to its close association with coagulant disturbances. However, the precise biological functions and mechanisms that connect coagulation factors to NAFLD pathology remain inadequately understood. Herein, with unbiased bioinformatics analyses followed by functional testing, we demonstrate that hepatic expression of coagulation factor VII (FVII) decreases in patients and mice with NAFLD/nonalcoholic steatohepatitis (NASH). By using adenovirus-mediated F7-knockdown and hepatocyte-specific F7-knockout mouse models, our mechanistic investigations unveil a noncoagulant function of hepatic FVII in mitigating lipid accumulation and lipotoxicity. This protective effect is achieved through the suppression of fatty acid uptake, orchestrated via the AKT-CD36 pathway. Interestingly, intracellular FVII directly interacts with AKT and PP2A, thereby promoting their association and triggering the dephosphorylation of AKT. Therapeutic intervention through adenovirus-mediated liver-specific overexpression of F7 results in noteworthy improvements in liver steatosis, inflammation, injury, and fibrosis in severely afflicted NAFLD mice. In conclusion, our findings highlight coagulation factor FVII as a critical regulator of hepatic steatosis and a potential target for the treatment of NAFLD and NASH.

Multiblock Poly-ε-Caprolactones: One-Step Synthesis toward Programmable Properties.

Control of monomer sequence enables predictable structure-property relationships in versatile polymeric materials. The facile synthesis of multiblock copolymers (MBCPs) with controlled chain structure is highly challenging, particularly for those prepared via one-pot copolymerization of mixed monomers. Herein, poly-ε-caprolactone MBCPs, a series of thermoplastic elastomers with tailored thermal, mechanical, rheological, and degradable properties, are synthesized by Janus polymerization. Melting temperature, tensile strength, ductility, viscosity, and enzymatic degradability are governed by block length which is in turn dictated by the monomer-to-catalyst feed ratio. The relationships between the physicochemical properties and the architectures are investigated in detail.

Microphase Separation with Sub-3 nm Microdomains in Comb-Like Poly(n-alkyl acrylate) Homopolymers Facilitated by Charged Junction Groups between the Main Chains and Side Chains.

The phase structure with a small domain size in polymers is expected to provide a template for lithography to fabricate electronic devices, while the uniformity and thermal stability of the phase structure are vital in lithography. In this work, we report an accurately microphase-separated system of comb-like poly(ionic liquid) (PIL)-based homopolymers containing imidazolium cation junctions between the main chain parts and the long alkyl side chains, poly(1-((2-acryloyloxy)ethyl)-3-alkylimidazolium bromide) (P(AOEAmI-Br)). The ordered hexagonally packed cylinder (HEX) and lamellar (LAM) structures with small domain sizes (sub-3 nm) were successfully achieved. Since the microphase separation was induced by the incompatibility between the main chain parts and the hydrophobic alkyl chains, the microdomain spacing of the ordered structure was independent of the molecular weight and molecular weight distribution of P(AOEAmI-Br) homopolymers and could be precisely regulated by changing the length of the alkyl side chains. Importantly, the microphase separation was promoted by the charged junction groups; thus, the phase structure and domain size of P(AOEAmI-Br) exhibited excellent thermal stability.

Betaine-homocysteine methyltransferase promotes adipocyte commitment and insulin resistance via p38 MAPK/Smad signaling.

OBJECTIVE: Betaine-homocysteine methyltransferase (Bhmt) belongs to the family of methyltransferases and is involved in the one-carbon metabolic cycle, which is associated with the risk of diabetes and adiposity. This study aimed to explore whether Bhmt participated in the development of obesity or its associated diabetes, as well as the mechanism involved. METHODS: The expression levels of Bhmt were examined in stromal vascular fraction cells and mature adipocytes in obesity and nonobesity. Knockdown and overexpression of Bhmt in C3H10T1/2 cells were used to investigate Bhmt's function in adipogenesis. Bhmt's role in vivo was analyzed using an adenovirus-expressing system and a high-fat diet-induced obesity mouse model. RESULTS: Bhmt was highly expressed in stromal vascular fraction cells rather than mature adipocytes of adipose tissue and was upregulated in adipose tissue in obesity and C3H10T1/2-commited preadipocytes. Overexpression of Bhmt promoted adipocyte commitment and differentiation in vitro and exacerbated adipose tissue expansion in vivo, with a concomitant increase in insulin resistance, whereas Bhmt silencing exhibited opposite effects. Mechanistically, Bhmt-induced adipose expansion was mediated by stimulating the p38 MAPK/Smad pathway. CONCLUSIONS: The findings of this study highlight the obesogenic and diabetogenic role of adipocytic Bhmt and propose Bhmt as a promising therapeutic target for obesity and obesity-related diabetes.

Relationship of the levels of reactive oxygen species in the fertilization medium with the outcome of in vitro fertilization following brief incubation.

Embryo selection in in vitro fertilization-embryo transfer (IVF-ET) mostly relies on morphological assessment using a conventional microscope or the time-lapse monitoring system, which is not comprehensive. Inappropriate levels of reactive oxygen species (ROS) in the fertilization medium may cause damage to gametes, eventually leading to adverse IVF outcomes. The present study aimed to identify the optimal oxidation-reduction level in the fertilization medium for IVF outcomes by measuring the static oxidation-reduction potential (sORP) using a highly accurate and sensitive MiOXSYS system. A total of 136 patients undergoing IVF following brief incubation were divided equally into 4 groups in this prospective cohort study. The sORP value in the fertilization medium was detected using the MiOXSYS system, and its relationship with IVF outcomes was analyzed. The primary outcome was pregnancy outcomes, including live birth rate (LBR), clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), and implantation rate (IR). The secondary outcome was embryo quality, including fertilization rate (FR), cleavage rate (CR), available embryo rate (AER), and good-quality embryo rate (GQER). Group II (sORP: 228.7-235.3 mV) showed a higher LBR, CPR, BPR, and IR compared with Group III (sORP: 235.4-242.7 mV), presented as follows: LBR (32.0% for Group II vs 3.6% for Group III, P = 0.033), CPR (32.0% for Group II vs 3.6% for Group III, P = 0.033), BPR (36.0% for Group II vs 3.6% for Group III, P = 0.019), and IR (31.3% for Group II vs 2.7% for Group III, P = 0.003). The FR in Groups I and II had lower significant differences compared with that in Groups III and IV (71.7% and 70.3% for Groups I and II vs 83.5% and 80.4% for Groups III and IV, P = 0.000). The GQER in Group I to Group IV was 32.7%, 37.4%, 26.5%, and 33.3%, respectively (P = 0.056). This study indicated that the sORP value in the fertilization medium might be a potential indicator of embryo quality and pregnancy outcome.

Electrostatic crosslinking-enabled highly asymmetric lamellar nanostructures of polyzwitterionic block copolymers for lithography.

For the bulk self-assembly of traditional diblock copolymers (di-BCPs), lamellar structures only occur when two constituents have similar volume fractions (f) and two alternating layers tend to have similar thicknesses. Highly asymmetric lamellar (A-LAM) structures, in which the thickness of one layer is several times higher than the other, are hardly formed in di-BCPs, while they have potential applications in nanolithography. In this work, A-LAM structures with different dimensions were constructed using a type of simple linear di-BCP, polystyrene-b-poly(4-vinylpyridine)propane-1-sulfonate (PS-b-PVPS) with the polyzwitterionic block PVPS in minority. The origin of the A-LAM structure was ascribed to the electrostatic crosslinking and confirmed by doping PS-b-PVPS block copolymers (BCPs) with N-butyl pyridinium methane sulfonate (BPMS). The morphology of compositionally asymmetric PS-b-PVPS BCPs changed from A-LAM to cylindrical structures upon salt-doping, i.e. the phase behavior of common BCPs was recovered. In addition, the morphologies of PS-b-PVPS BCPs with similar molecular weights but varied compositions were also studied, and only two kinds of structures (lamellar or ill-defined spherical structure) were observed when the volume fraction of PVPS (fPVPS) was less than 0.5, and the composition range for the formation of the lamellar structure was found to be fPVPS ≥ 0.188.

The alterations of circulating mucosal-associated invariant T cells in polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting reproductive age females and an important cause of infertility. Although the etiology is complex and its pathogenesis remains unclear, the pathological process of PCOS is tightly related with the immune dysfunction and gut microbial dysbiosis. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells which can regulate inflammation through the production of cytokines and play a role in regulating the gut microbiota. We aim to evaluate the correlation between characteristics of PCOS and MAIT cells as well as their impact on cytokine secretion. Methods: Peripheral blood samples were taken from PCOS patients (n=33) and healthy controls (n=30) during 2-5 days of the menstrual period. The frequencies of MAIT cells and T cells were measured by flow cytometry. Cytokines interleukin 17 (IL-17), interleukin 22(IL-22), interferon γ (IFN-γ) and granzyme B were determined by Enzyme-linked immunosorbent assay (ELISA). Results: The frequency of MAIT cells was significantly reduced in the blood of PCOS patients compared with the controls, and negatively correlated with Body Mass Index (BMI), Homeostatic model assessment- insulin resistance (HOMA-IR) index, and Anti Miillerian Hormone (AMH). Thus, the frequencies of MAIT cells decreased in PCOS patients with abnormal weight (BMI≥24kg/m2), higher HOMA-IR (≥1.5), and excessive AMH (≥8ng/ml). The Cytokine IL-17 was significantly higher in PCOS patients and negatively correlated with the frequency of MAIT cells. Even though the IL-22 was lower in PCOS Patients, no correlation with MAIT cells was detected. In subgroup, CD4+MAIT cells correlated with BMI, AMH, and testosterone (T) levels. Conclusion: The frequency change of MAIT cells may play a significant role in the pathogenesis of PCOS. Exploring these interactions with MAIT cells may provide a new target for PCOS treatment and prevention.

PEO-Based Block Copolymer Electrolytes Containing Double Conductive Phases with Improved Mechanical and Electrochemical Properties.

In this work, the advanced all solid-state block copolymer electrolytes (SBCPEs) for lithium-ion batteries with double conductive phases, poly(ethylene oxide)-b-poly(trimethyl-N-((2-(dimethylamino)ethyl methacrylate)-7-propyl)-ammonium bis(trifluoromethanesulfonyl) imide) (PEO-b-PDM-dTFSI)/LiTFSI, were fabricated, in which the charged PDM-dTFSI block contained double quaternary ammonium cations and the PEO block was doped with LiTFSI. The disordered (DIS) and ordered lamellae (LAM) phase structures were achieved by adjusting the composition of the block copolymer and the doping ratio r. In addition, the presence of the hard PDM-dTFSI block and the formation of the LAM phase structure resulted in a good mechanical strength of the solid PEO-b-PDM-dTFSI/LiTFSI electrolyte, and it could maintain a high level of 104 Pa at 100 °C, which was around 10,000 times stronger than that of the PEO/LiTFSI electrolyte. Based on the good mechanical and electrochemical properties, the PEO-b-PDM-dTFSI/LiTFSI SBCPE exhibited excellent long-term galvanostatic cycle performance, indicating the strong ability to suppress lithium dendrites.

The impact of different endometrial preparation protocols on obstetric and neonatal complications in frozen-thawed embryo transfer: a retrospective cohort study of 3,458 singleton deliveries.

BACKGROUND: Frozen-thawed embryo transfer (FET) is thought to be associated with obstetric and neonatal complications after in vitro fertilization/intracytoplasmic single sperm injection (IVF/ICSI) treatment. The study aimed to determine whether the endometrial preparation protocol is an influencing factor for these complications. METHODS: We conducted a retrospective cohort study of 3,458 women who had singleton deliveries after IVF/ICSI-FET treatment at the Centre for Reproductive Medicine of Shanghai First Maternity and Infant Hospital between July 2016 and April 2021. The women were divided into three groups according to the endometrial preparation protocols: 2,029 women with programmed cycles, 959 with natural cycles, and 470 with minimal ovarian stimulation cycles. The primary outcomes were the incidence rates of obstetric and neonatal complications, namely, hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), placenta previa, preterm rupture of membranes (PROM), preterm delivery, postpartum haemorrhage, large for gestational age (LGA), small for gestational age (SGA), and macrosomia. RESULTS: After adjustments for confounding variables by multivariate logistic regression analysis, the results showed that programmed cycles had an increased risk of HDP (aOR = 1.743; 95% CI, 1.110-2.735; P = 0.016) and LGA (aOR = 1.269; 95% CI, 1.011-1.592; P = 0.040) compared with natural cycles. Moreover, programmed cycles also increased the risk of LGA (aOR = 1.459; 95% CI, 1.083-1.965; P = 0.013) but reduced the risk of SGA (aOR = 0.529; 95% CI, 0.348-0.805; P = 0.003) compared with minimal ovarian stimulation cycles. There were no significant differences between natural cycles and minimal ovarian stimulation cycles. CONCLUSIONS: During IVF/ICSI-FET treatment, the risk of HDP and LGA was increased in women with programmed cycles. Therefore, for patients with thin endometrium, irregular menstruation or no spontaneous ovulation, minimal ovarian stimulation cycles may be a relatively safer option than programmed cycles.

Binary Promoter Improving the Moderate-Temperature Adhesion of Addition-Cured Liquid Silicone Rubber for Thermally Conductive Potting.

The strong adhesion of thermally conductive silicone encapsulants on highly integrated electronic devices can avoid external damages and lead to an improved long-term reliability, which is critical for their commercial application. However, due to their low surface energy and chemical reactivity, the self-adhesive ability of silicone encapsulants to substrates need to be explored further. Here, we developed epoxy and alkoxy groups-bifunctionalized tetramethylcyclotetrasiloxane (D4H-MSEP) and boron-modified polydimethylsiloxane (PDMS-B), which were synthesized and utilized as synergistic adhesion promoters to provide two-component addition-cured liquid silicone rubber (LSR) with a good self-adhesion ability for applications in electronic packaging at moderate temperatures. The chemical structures of D4H-MSEP and PDMS-B were characterized by Fourier transform infrared spectroscopy. The mass percentage of PDMS-B to D4H-MSEP, the adhesion promoters content and the curing temperature on the adhesion strength of LSR towards substrates were systematically investigated. In detail, the LSR with 2.0 wt% D4H-MSEP and 0.6 wt% PDMS-B exhibited a lap-shear strength of 1.12 MPa towards Al plates when curing at 80 °C, and the cohesive failure was also observed. The LSR presented a thermal conductivity of 1.59 W m-1 K-1 and good fluidity, which provided a sufficient heat dissipation ability and fluidity for potting applications with 85.7 wt% loading of spherical α-Al2O3. Importantly, 85 °C and 85% relative humidity durability testing demonstrated LSR with a good encapsulation capacity in long-term processes. This strategy endows LSR with a good self-adhesive ability at moderate temperatures, making it a promising material requiring long-term reliability in the encapsulation of temperature-sensitive electronic devices.

Suppression of RIP1 activity via S415 dephosphorylation ameliorates obesity-related hepatic insulin resistance.

OBJECTIVE: Receptor-interacting serine/threonine-protein kinase 1 (RIP1) is a well-documented key regulator of TNFα-mediated inflammation, apoptosis, and necroptosis, which contribute to the development of obesity-related metabolic diseases such as nonalcoholic steatohepatitis. However, the mechanism regarding how RIP1 influences obesity-related insulin resistance remains elusive. METHODS: Primary hepatocytes with necrostatin 1 treatment or RIP1 expression were exposed to palmitic acid (PA), prior to the examination of cellular insulin signaling. Phosphorylation sites of RIP1 were detected by liquid chromatography with tandem mass spectrometry, and RIP1 variants with mutated phosphorylation sites were overexpressed in hepatocytes to identify the specific residue that influenced the RIP1-mediated insulin resistance. Adenovirus expressing RIP1 (S415A) mutant were administered into diet-induced obese mice to assess the effects on insulin sensitivity. RESULTS: This study uncovered an aberrant increase in RIP1 activity during the development of obesity-induced insulin resistance. Inhibition of RIP1 activity with necrostatin 1 ameliorated PA- or high-fat diet-caused hepatic insulin resistance. With liquid chromatography with tandem mass spectrometry analysis and mutagenesis screening, S415, a novel phosphorylation site of RIP1, was identified to be responsible for RIP1-mediated insulin resistance. Loss-of-function mutation of S415 efficiently blunted RIP1-evoked insulin resistance in PA-treated hepatocytes or diet-induced obese mice. CONCLUSIONS: These findings highlight the diabetogenic role of RIP1 S415 and propose RIP1 as a promising therapeutic target for type 2 diabetes.

Promoters for Improved Adhesion Strength between Addition-Cured Liquid Silicone Rubber and Low-Melting-Point Thermoplastic Polyurethanes.

A polydimethylsiloxane armed with epoxy, alkoxy and acrylate groups was synthesized from silanol terminated-PDMS and epoxy and acrylate groups functionalized silane coupling agents, and utilized as the adhesion promoter (AP) to prepare addition-cured liquid silicone rubber that exhibited self-adhesion ability (SA-LSR) with biocompatible thermoplastic polyurethanes (TPU) sheets. The structural characteristics of AP were characterized by Fourier transform infrared (FTIR) spectroscopy, which demonstrated the strong adhesion to polyester-based TPU sheets due to a sufficient amount of acrylate groups, epoxy groups and silanol groups obtained by the hydrolysis of alkoxy groups. In detail, the peel-off strength of SA-LSR and TPU joints reached up to 7.63 N mm-1 after the optimization of adhesion promoter including type and content, and curing condition including time and temperature. The cohesive failure was achieved during the sample breakage process. Moreover, the SA-LSR showed a good storage stability under proper storage conditions. This design strategy provided the feasibility to combine the advantages of addition-cured liquid silicone rubber and plastics with low melting points, promoting the potential application range of those silicone-based materials.

Reversible Photo-, Thermal-, and pH-Responsive Functionalized Wood with Fluorescence Emission.

A reversible photo-, thermal-, and pH-responsive high-performance functional wood with fluorescence has been prepared. The properties, structure, multi-response, fluorescence, water resistance, and corrosion resistance of original wood (ORW) and functional wood (FUW) were investigated with an X-ray photoelectron spectroscopy (XPS) spectrometer, a Fourier-transform infrared (FTIR) spectrometer, a N2 adsorption-desorption analyzer, an atomic force microscope (AFM), tensile tests, a scanning electron microscope (SEM), an ultraviolet-visible (UV-Vis) spectrophotometer, a fluorescence spectrometer, the equilibrium swelling ratio (ESR), and corrosion tests. The results of XPS, FTIR, N2 adsorption-desorption, and AFM exhibited that FUW was successfully prepared. Additionally, the results of the tensile test and SEM revealed that FUW had better mechanical properties than ORW, due to the filling of epoxy resin in the pores of the wood. Moreover, the UV-Vis and fluorescence spectra demonstrated that the introduction of epoxy resin induced multi-response and fluorescence functions to FUW. Furthermore, the data of ESR and corrosion test showed that the introduction of epoxy resin greatly improved the water and corrosion resistance of wood. This study provides ideas and methods for preparing novel high-performance multi-response FUW.

A homozygous variant in TBPL2 was identified in women with oocyte maturation defects and infertility.

STUDY QUESTION: What are the genetic causes of oocyte maturation defects? SUMMARY ANSWER: A homozygous splicing variant (c.788 + 3A>G) in TATA-box binding protein like 2 (TBPL2) was identified as a contributory genetic factor in oocyte maturation defects. WHAT IS KNOWN ALREADY: TBPL2, a vertebrate oocyte-specific general transcription factor, is essential for oocyte development. TBPL2 variants have not been studied in human oocyte maturation defects. STUDY DESIGN, SIZE, DURATION: Two infertile families characterized by oocyte maturation defects were recruited for whole-exome sequencing (WES). PARTICIPANTS/MATERIALS, SETTING, METHODS: Genomic DNA was extracted from peripheral blood for WES analysis. Sanger sequencing was performed for data validation. Pathogenicity of variants was predicted by in silico analysis. Minigene assay and single-oocyte RNA sequencing were performed to investigate the effects of the variant on mRNA integrity and oocyte transcriptome, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: A homozygous splicing variant (c.788 + 3A>G) in TBPL2 was identified in two unrelated families characterized by oocyte maturation defects. Haplotype analysis indicated that the disease allele of Families 1 and 2 was independent. The variant disrupted the integrity of TBPL2 mRNA. Transcriptome sequencing of affected oocytes showed that vital genes for oocyte maturation and fertilization were widely and markedly downregulated, suggesting that a mutation in the transcriptional factor, TBPL2, led to global gene alterations in oocytes. LIMITATIONS, REASONS FOR CAUTION: Limitations include the lack of direct functional evidence. Owing to the scarcity of human oocyte samples, only two immature MI oocytes were obtained from the patients, and we could only investigate the effect of the mutation at the transcriptional level by high-throughput sequencing technology. No extra oocytes were obtained to assess the transcriptional activity of the mutant oocytes by immunofluorescence, or investigate the effects on the binding of TBPL2 caused by the mutation. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight a critical role of TBPL2 in female reproduction and identify a homozygous splicing mutation in TBPL2 that might be related to defects in human oocyte maturation. This information will facilitate the genetic diagnosis of infertile individuals with repeated failures of IVF, providing a basis for genetic counseling. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2018YFC1004000, 2017YFC1001504 and 2017YFC1001600), the National Natural Science Foundation of China (81871168, 31900409 and 31871509), the Foundation for Distinguished Young Scholars of Shandong Province (JQ201816), the Innovative Research Team of High-Level Local Universities in Shanghai (SSMU-ZLCX20180401) and the Fundamental Research Funds of Shandong University. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Cetrimonium bromide promotes the clearance of lipids by activating the TFEB-mediated autophagosome-lysosome pathway in hepatic cells.

Autophagy plays a key role in the metabolism of macromolecules via the degradative abilities of the lysosome. Transcription factor EB (TFEB) regulates autophagosome biogenesis and lysosome function, and promoting TFEB activity has emerged as a potential strategy for the treatment of metabolic disorders. Herein, we report that cetrimonium bromide (CTAB; a quaternary ammonium compound) promotes autophagy and lysosomal biogenesis by inducing the nuclear translocation of TFEB in hepatic cells. Knockdown of TFEB mediated by short hairpin RNA inhibits CTAB-induced autophagy and lysosomal biogenesis. Mechanistically, CTAB treatment inhibits the Akt-mTORC1 signaling pathway. Moreover, CTAB treatment significantly increases lipid metabolism in both palmitate- and oleate-treated HepG2 cells, and this increase was attenuated by knockdown of TFEB. Collectively, our results indicate that CTAB activates the autophagosome-lysosome pathway via inducing the nuclear translocation of TFEB by inhibiting the mTORC1 signaling pathway. These results add to the collective understanding of TFEB function and provide new insights into CTAB-mediated lipid metabolism.

Icarisid II promotes proliferation and neuronal differentiation of neural stem cells via activating Wnt/ß-catenin signaling pathway.

Adult neurogenesis plays a vital role in maintaining cognitive functions in mammals and human beings. Mobilization of hippocampal neurogenesis has been regarded as a promising therapeutic approach to restore injured neurons in neurodegenerative diseases including Alzheimer's disease (AD). Icarisid II (ICS II), an active ingredient derived from Epimedii Folium, has been reported to exhibit multiple neuroprotective effects. In the present study, we investigated the effects of ICS II on the proliferation and differentiation of neural stem cells (NSCs) and amyloid precusor protein (APP)-overexpressing NSCs (APP-NSCs) in vitro. Our results demonstrated that ICS II dose-dependently suppressed apoptosis and elevated viability of APP-NSCs. ICS II (1 µM) potently promoted proliferation and neuronal differentiation of NSCs and APP-NSCs. ICS II (1 µM) significantly upregulated Wnt-3a expression, increased the phosphorylation of glycogen synthase kinase-3ß and enhanced the nuclear transfer of ß-catenin. Moreover, ICS II also promoted astrocytes to secrete Wnt-3a, which positively modulates Wnt/ß-catenin signaling pathway. These findings demonstrate that ICS II promotes NSCs proliferation and neuronal differentiation partly by activating the Wnt/ß-catenin signaling pathway.