The walnut-derived peptide TW-7 improves mouse parthenogenetic embryo development of vitrified MII oocytes potentially by promoting histone lactylation.

BACKGROUND: Previous studies have shown that the vitrification of metaphase II (MII) oocytes significantly represses their developmental potential. Abnormally increased oxidative stress is the probable factor; however, the underlying mechanism remains unclear. The walnut-derived peptide TW-7 was initially isolated and purified from walnut protein hydrolysate. Accumulating evidences implied that TW-7 was a powerful antioxidant, while its prospective application in oocyte cryopreservation has not been reported. RESULT: Here, we found that parthenogenetic activation (PA) zygotes derived from vitrified MII oocytes showed elevated ROS level and delayed progression of pronucleus formation. Addition of 25 µmol/L TW-7 in warming, recovery, PA, and embryo culture medium could alleviate oxidative stress in PA zygotes from vitrified mouse MII oocytes, furtherly increase proteins related to histone lactylation such as LDHA, LDHB, and EP300 and finally improve histone lactylation in PA zygotes. The elevated histone lactylation facilitated the expression of minor zygotic genome activation (ZGA) genes and preimplantation embryo development. CONCLUSIONS: Our findings revealed the mechanism of oxidative stress inducing repressed development of PA embryos from vitrified mouse MII oocytes and found a potent and easy-obtained short peptide that could significantly rescue the decreased developmental potential of vitrified oocytes, which would potentially contribute to reproductive medicine, animal protection, and breeding.

Lead-free Perovskite with Distorted [InX6]3- Octahedron Induced by Organic Cation and Enhanced PLQY by Sb Doping.

In-based halide perovskites have attracted a lot of attention because of their unique broadband emission properties. Herein, a series of In-based hybrid perovskites of (H2MP)2InCl7·H2O (1), (H2EP)2InCl7·H2O (2), (H2MP)2InBr7·H2O (3), and (H2EP)2InBr7·H2O (4) were synthesized under the control of halogen ions and organic cations. 1, 2, and 4 exhibit obvious photoluminescence properties with peaks at 392, 442, and 652 nm, respectively. The effects of the different components on the crystal structure and photoluminescence properties are discussed by calculating the structural distortion of the [InX6]3- octahedron. The photoluminescence properties of 1 and 4 were significantly improved after Sb3+ doping with PLQY values of 57.12 and 41.53%. Finally, a white LED was successfully fabricated with the two doped compounds coated onto the 365 nm blue LED chip.

Seeking environmentally friendly halide perovskite photocatalysts: synthesis, structure and photocatalytic performance exploration.

Halide perovskites have high photoelectric conversion efficiency, making them promising candidates for photocatalysis. However, their toxic and unstable nature limits their applications. Here, we successfully synthesised three hybrid Bi-based halide perovskites: (HTMG)3Bi2Br9 (1), (HEI)2BiBr5 (2) and (HTMA)3Bi2Br9 (3). X-ray single-crystal diffraction analysis shows that they all contained 0D structures composed of isolated Bi-Br clusters. The three compounds showed excellent degradability and cycling stability for Sudan III dissolved in ethanol under simulated sunlight. In addition, the photocatalytic degradation performance of four Bi-based halide perovskites previously reported by our group is also characterised and summarised in this work.

Melatonin promotes parthenogenetic development of vitrified-warmed mouse MII oocytes, potentially by reducing oxidative stress through SIRT1.

Previous studies have demonstrated that melatonin could ameliorate oxidative stress during the cryopreservation of mouse MII oocytes and their in vitro culture after parthenogenetic activation. However, the underlying molecular mechanism remained poorly understood. This study was conducted to investigate whether melatonin could modulate the oxidative stress in the parthenogenetic 2-cell embryos derived from vitrified-warmed oocytes through SIRT1. The results showed that the reactive oxygen species levels increased, the glutathione levels and SIRT1 expression decreased significantly in parthenogenetic 2-cell embryos derived from cryopreserved oocyte, and the parthenogenetic blastocyst formation rates significantly decreased when compared to those derived from control oocytes. These unfavorable phenomena were prevented by the addition of either 10-9 mol/L melatonin or 10-6 mol/L SRT-1720 (SIRT1 agonist), and it was restored by the supplementation of 10-9 mol/L melatonin in combination with 2 × 10-5 mol/L EX527 (SIRT1 inhibitor). Therefore, the findings from the present study concluded that melatonin may reduce oxidative stress via regulating SIRT1, and potentially promote the parthenogenetic development of vitrified-warmed mouse MII oocytes.

A ROS-response hyaluronic acid-coated/chitosan polymer prodrug for enhanced tumour targeting efficacy of SN38.

Ethyl-10-hydroxycamptothecin (SN38) is a camptothecin derivative with significant anti-tumour therapeutic potential, while the clinical application of SN38 was limited by its poor water solubility and low stability. Herein, a core-shell polymer prodrug hyaluronic acid @chitosan-S-SN38 (HA@CS-S-SN38) was designed by CS-S-SN38 as the core and the HA as the shell, which aims to overcome the limitations of the clinical application of SN38, while realising the high tumour targeting of polymer prodrug and the controllable release of drug in tumour cells. HA@CS-S-SN38 showed the high responsiveness of the tumour microenvironment and the safe stability of blood circulation. Furthermore, HA@CS-S-SN38 exhibited the begin uptake efficiency and favourable apoptosis in the 4T1 cells. More importantly, compared with irinotecan hydrochloride trihydrate (CPT-11), HA@CS-S-SN38 significantly improved the conversion efficiency of the prodrug to SN38, and showed excellent tumour targeting and retention in vivo by combining passive and active targeting strategies. In tumour-bearing mice treatment, HA@CS-S-SN38 showed the perfect anti-tumour effect and therapeutic safety. These results indicated that the polymer prodrug designed by ROS-response/HA-modification strategy is a safe and efficient drug delivery system, which provides a new idea for clinical utilisation of SN38 and warrants further evaluation.

Structural Regulation and Oxygen Reduction Reaction Activity of [Co(bpy)2BO2(OH)] and [Cu(bpy)(OH)]2- Complex Templated Borates.

Two templated borates, [Co(bpy)2BO2(OH)]·[B5O6(OH)4]·H3BO3·H3O·H2O (1) and [Cu(bpy)(OH)]2·[B5O6(OH)4]2·H2O (2), have been synthesized successfully and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and Fourier transform infrared. The [Co(bpy)2BO2(OH)] complex in 1 shows a very rare coordination mode between Co2+ and BO2(OH)2-. The structures of 1 and 2 can be adjusted by changing the reagent. The oxygen reduction reaction activity of these Co- and Cu-based catalysts was studied. The E1/2 values of Co-C-750 and Cu-C-750 are 0.864 and 0.837 V, respectively.

Oxidative Stress and Oocyte Cryopreservation: Recent Advances in Mitigation Strategies Involving Antioxidants.

Oocyte cryopreservation is widely used in assisted-reproductive technology and animal production. However, cryopreservation not only induces a massive accumulation of reactive oxygen species (ROS) in oocytes, but also leads to oxidative-stress-inflicted damage to mitochondria and the endoplasmic reticulum. These stresses lead to damage to the spindle, DNA, proteins, and lipids, ultimately reducing the developmental potential of oocytes both in vitro and in vivo. Although oocytes can mitigate oxidative stress via intrinsic antioxidant systems, the formation of ribonucleoprotein granules, mitophagy, and the cryopreservation-inflicted oxidative damage cannot be completely eliminated. Therefore, exogenous antioxidants such as melatonin and resveratrol are widely used in oocyte cryopreservation to reduce oxidative damage through direct or indirect scavenging of ROS. In this review, we discuss analysis of various oxidative stresses induced by oocyte cryopreservation, the impact of antioxidants against oxidative damage, and their underlying mechanisms. We hope that this literature review can provide a reference for improving the efficiency of oocyte cryopreservation.

Melatonin Promotes in vitro Development of Vitrified-Warmed Mouse GV Oocytes, Potentially by Modulating Phosphorylation of Drp1.

Previous studies have shown that melatonin can mitigate cryopreservation-induced mitochondrial dysfunction in oocytes; however, the underlying molecular mechanism remains unclear. The objective of the present study was to investigate whether melatonin can improve the mitochondrial function during in vitro maturation of vitrified-warmed mouse germinal vesicle (GV) oocytes by modulating phosphorylation of dynamin related protein 1 (Drp1). Vitrification/warming procedures resulted in the following: (1) After cryopreservation of mouse GV oocytes, the phosphorylation level of Drp1 at Ser616 (p-Drp1 Ser616) in metaphase II (MII) oocytes was increased (P < 0.05). Furthermore, the rates of in vitro maturation, cleavage and blastocyst formation after parthenogenetic activation were decreased (P < 0.05). (2) In MII oocytes, the expression levels of translocase of the mitochondrial outer membrane 20 (TOMM20), mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, and mRNA levels of mitochondrial biogenesis-related genes (Sirt1, Pgc-1α, Tfam) were all decreased (P < 0.05), and (3) Reactive oxygen species (ROS) level, early apoptosis level, Cytochrome C release and mRNA levels of pro-apoptotic related genes (Bax, Caspase9, Caspase3) in MII oocytes were all increased (P < 0.05). The results of this study further revealed that negative impacts of GV oocyte cryopreservation were mitigated by supplementation of warming and in vitro maturation media with 10-7mol /L melatonin or 2 x 10-5mol/L Mdivi-1 (Drp1 inhibitor). Therefore, we concluded that 10-7mol/L melatonin improved mitochondrial function, reduced oxidative stress and inhibited apoptosis by regulating phosphorylation of Drp1, thereby enhancing in vitro development of vitrified-warmed mouse GV oocytes.

Melatonin Promotes In Vitro Maturation of Vitrified-Warmed Mouse Germinal Vesicle Oocytes, Potentially by Reducing Oxidative Stress through the Nrf2 Pathway.

Previously it was reported that melatonin could mitigate oxidative stress caused by oocyte cryopreservation; however, the underlying molecular mechanisms which cause this remain unclear. The objective was to explore whether melatonin could reduce oxidative stress during in vitro maturation of vitrified-warmed mouse germinal vesicle (GV) oocytes through the Nrf2 signaling pathway or its receptors. During in vitro maturation of vitrified-warmed mouse GV oocytes, there were decreases (p < 0.05) in the development rates of metaphase I (MI) oocytes and metaphase II (MII) and spindle morphology grades; increases (p < 0.05) in the reactive oxygen species (ROS) levels; and decreases (p < 0.05) in expressions of Nrf2 signaling pathway-related genes (Nrf2, SOD1) and proteins (Nrf2, HO-1). However, adding 10-7 mol/L melatonin to both the warming solution and maturation solutions improved (p < 0.05) these indicators. When the Nrf2 protein was specifically inhibited by Brusatol, melatonin did not increase development rates, spindle morphology grades, genes, or protein expressions, nor did it reduce vitrification-induced intracellular oxidative stress in GV oocytes during in vitro maturation. In addition, when melatonin receptors were inhibited by luzindole, the ability of melatonin to scavenge intracellular ROS was decreased, and the expressions of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1) were not restored to control levels. Therefore, we concluded that 10-7 mol/L melatonin acted on the Nrf2 signaling pathway through its receptors to regulate the expression of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1), and mitigate intracellular oxidative stress, thereby enhancing in vitro development of vitrified-warmed mouse GV oocytes.

Melatonin improves the first cleavage of parthenogenetic embryos from vitrified-warmed mouse oocytes potentially by promoting cell cycle progression.

BACKGROUND: This study investigated the effect of melatonin (MT) on cell cycle (G1/S/G2/M) of parthenogenetic zygotes developed from vitrified-warmed mouse metaphase II (MII) oocytes and elucidated the potential mechanism of MT action in the first cleavage of embryos. RESULTS: After vitrification and warming, oocytes were parthenogenetically activated (PA) and in vitro cultured (IVC). Then the spindle morphology and chromosome segregation in oocytes, the maternal mRNA levels of genes including Miss, Doc1r, Setd2 and Ythdf2 in activated oocytes, pronuclear formation, the S phase duration in zygotes, mitochondrial function at G1 phase, reactive oxygen species (ROS) level at S phase, DNA damage at G2 phase, early apoptosis in 2-cell embryos, cleavage and blastocyst formation rates were evaluated. The results indicated that the vitrification/warming procedures led to following perturbations 1) spindle abnormalities and chromosome misalignment, alteration of maternal mRNAs and delay in pronucleus formation, 2) decreased mitochondrial membrane potential (MMP) and lower adenosine triphosphate (ATP) levels, increased ROS production and DNA damage, G1/S and S/G2 phase transition delay, and delayed first cleavage, and 3) increased early apoptosis and lower levels of cleavage and blastocyst formation. Our results further revealed that such negative impacts of oocyte cryopreservation could be alleviated by supplementation of warming, recovery, PA and IVC media with 10- 9 mol/L MT before the embryos moved into the 2-cell stage of development. CONCLUSIONS: MT might promote cell cycle progression via regulation of MMP, ATP, ROS and maternal mRNA levels, potentially increasing the first cleavage of parthenogenetic zygotes developed from vitrified-warmed mouse oocytes and their subsequent development.

Melatonin promotes in vitro maturation of vitrified-warmed mouse GV oocytes potentially by modulating MAD2 protein expression of SAC component through MTRs.

Previous studies have shown that melatonin (MT) can ameliorate vitrification-inflicted damage in mouse germinal vesicle (GV) oocytes, however, the key mechanistic basis of this improvement still remains poorly understood. This study was conducted to investigate whether MT can improve in vitro developmental potential of vitrified-warmed GV oocytes through its receptors. The fresh oocytes were randomly divided into four groups: untreated (control group, F), vitrified by open-pulled straw method (vitrification group, V), vitrification group with 100 nmol/L MT supplementation (vitrification + MT group, VM), and with 100 nmol/L MT plus 100 nmol/L luzindole administration (vitrification + MT + luzindole group, VML) or with 50 nmol/L ramelteon addition (vitrification + ramelteon group; VR). After warming, oocytes were cultured in vitro, and MT receptors (MTRs), MAD2 (mitotic arrest deficient 2), Securin and CyclinB1 protein levels and spindle morphology were evaluated. The ratio of oocytes developed to the metaphase I (MI) and metaphase II (MII) stages was also assessed. The results showed that after vitrification-warming, the in vitro maturation rate of GV oocytes was significantly lower compared to the control (F) group. Vitrification also significantly impaired the spindle morphology, decreased the protein level of MTRs and Securin, and decreased MAD2 levels in MI oocytes. However, when MT or ramelteon (MTRs agonist) were added (group wise) to warming and maturation media, the maturation rate of GV oocytes was significantly increased, the normal proportion of the spindle morphology increased, and the expression level of MAD2 increased in their resulting MI oocytes compared to the vitrification group. However, following addition of both MT and ramelteon, the maturation rate of GV oocyte showed no significant difference between VML and vitrification groups. The spindle morphology and MAD2 levels in MI oocytes were comparable to the vitrification group but differed significantly from the VM group. Taken together, finding of the present study shows that MT (100 nmol/L) can ameliorate the in vitro maturation of vitrified-warmed mouse GV oocytes, potentially by improving the spindle morphology, modulating MAD2 protein level and promoting the development of MI stage oocytes through MTRs.