Remarkable Toughening of Plastic with Monodispersed Nano-CaCO3: From Theoretical Predictions to Experimental Validation.

The structure-property relationship of poly(vinyl chloride) (PVC)/CaCO3 nanocomposites is investigated by all-atom molecular dynamics (MD) simulations. MD simulation results indicate that the dispersity of nanofillers, interfacial bonding, and chain mobility are imperative factors to improve the mechanical performance of nanocomposites, especially toughness. The tensile behavior and dissipated work of the PVC/CaCO3 model demonstrate that 12 wt % CaCO3 modified with oleate anion and dodecylbenzenesulfonate can impart high toughness to PVC due to its good dispersion, favorable interface interaction, and weak migration of PVC chains. Under the guidance of MD simulation, we experimentally prepared a transparent PVC/CaCO3 nanocomposite with good mechanical properties by in situ polymerization of monodispersed CaCO3 in vinyl chloride monomers. Interestingly, experimental tests indicate that the optimum toughness of a nanocomposite (a 368% increase in the elongation at break and 204% improvement of the impact strength) can be indeed realized by adding 12 wt % CaCO3 modified with oleic acid and dodecylbenzenesulfonic acid, which is remarkably consistent with the MD simulation prediction. In short, this work provides a proof-of-concept of using MD simulation to guide the experimental synthesis of PVC/CaCO3 nanocomposites, which can be considered as an example to develop other functional nanocomposites.

Angelicin inhibits cell growth and promotes apoptosis in oral squamous cell carcinoma by negatively regulating DUSP6/cMYC signaling pathway.

Angelicin has been reported to have antitumor effects on many types of cancer. However, few studies on angelicin in oral squamous cell carcinoma (OSCC) have been performed. We performed cell cycle and apoptosis analyses to assess the effect of angelicin on OSCC cells. We conducted RNA-seq studies to reveal differentially expressed genes (DEGs). Dual-specificity phosphatase 6 (DUSP6) and c-MYC were strongly down-regulated differential genes. Silencing RNA (siRNA) was used to knockdown DUSP6. The mouse xenograft model was used to mimic OSCC. Angelicin inhibited OSCC in vitro. We found that DUSP6 interacted with c-MYC. DUSP6 knockdown group and DUSP6 knockdown + angelicin group had similar effects of OSCC cells. Angelicin could reduce tumor formation, DUSP6, and c-MYC expression in vivo. Compared with paclitaxel, the tumor inhibition effect of the two drugs was similar. However, angelicin did not cause weight loss and had lower toxicity. In sum, Angelicin has antitumor effects on OSCC in vitro and vivo by negatively regulating the DUSP6 mediated c-MYC signaling pathway.

Chlorogenic acid improves the development of porcine parthenogenetic embryos by regulating oxidative stress and ameliorating mitochondrial function.

Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA-induced porcine parthenogenetic activation (PA) in early-stage embryos were investigated. Our results showed that 50 µM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early-stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early-stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early-stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis-related gene NRF-1 in porcine PA early-stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early-stage embryos by regulating oxidative stress and improving mitochondrial function.

Dynamically Visualized Mechano-Responsive Supramolecular Self-Assembly System for Small Molecule Release.

The mechano-responsiverelease of small molecules has received extensive attention in ultrasound (US)-controlled drug release in recent years because it can achieve non-invasive, spatiotemporally controlled precise drug release. However, the vast majority of small molecules mechano-release reported so far are based on polymer systems, which suffer from complex preparations and single mechano-response. Here, an isoguanosine (isoG) visualized mechano-responsive supramolecular self-assembly (isoG-VMRSS) system was successfully constructed by a one-pot reaction. It is completely composed of small molecules, which allows for multiple mechano-responsive releases of isoG (at least 9 times) and ultimately has potential for application in US drug release. A combined experimental-computational approach reveals the supramolecular network structure (formed by the joint action of related metal coordination bonds, boronate ester bonds and hydrogen bonds mediated by isoG) gradually formed inside the system is the underlying internal mechanism. Therefore, it provides a new and effective idea of small molecule release in the field of mechanochemistry.

Ferulic Acid Enhances Oocyte Maturation and the Subsequent Development of Bovine Oocytes.

Improving the quality of oocytes matured in vitro is integral to enhancing the efficacy of in vitro embryo production. Oxidative stress is one of the primary causes of quality decline in oocytes matured in vitro. In this study, ferulic acid (FA), a natural antioxidant found in plant cell walls, was investigated to evaluate its impact on bovine oocyte maturation and subsequent embryonic development. Bovine cumulus-oocyte complexes (COCs) were treated with different concentrations of FA (0, 2.5, 5, 10, 20 µM) during in vitro maturation (IVM). Compared to the control group, supplementation with 5 µM FA significantly enhanced the maturation rates of bovine oocytes and the expansion of the cumulus cells area, as well as the subsequent cleavage and blastocyst formation rates after in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT). Furthermore, FA supplementation was observed to effectively decrease the levels of ROS in bovine oocytes and improve their mitochondrial function. Our experiments demonstrate that FA can maintain the levels of antioxidants (GSH, SOD, CAT) in oocytes, thereby alleviating the oxidative stress induced by H2O2. RT-qPCR results revealed that, after FA treatment, the relative mRNA expression levels of genes related to oocyte maturation (GDF-9 and BMP-15), cumulus cell expansion (HAS2, PTX3, CX37, and CX43), and embryo pluripotency (OCT4, SOX2, and CDX2) were significantly increased. In conclusion, these findings demonstrate that FA supplementation during bovine oocyte IVM can enhance oocyte quality and the developmental potential of subsequent embryos.

[Anti-inflammatory and hemostatic effects of total extract, saponins, and flavonoids of Clinopodium chinense in female rats with abnormal uterine bleeding and mechanism].

This study aims to explore the anti-inflammatory and hemostatic effects of the total extract of Clinopodium chinense(TEC), total saponins of C. chinense(TSC), and total flavonoids of C. chinense(TFC) in female rats with abnormal uterine bleeding(AUB), and the possible mechanism. Mifepristone(i.g., 12.4 mg·kg~(-1)) and misoprostol(i.g., 130 µg·kg~(-1)) were used to induce AUB in SD female rats conceiving on the same day. Then the AUB rats were randomized into model group, TEC group, TSC group, TFC group, Yimucao Granules(LG) group, and estradiol valerate(EV) group, with 8 rats in each group. Another 8 non-pregnant female rats were selected as normal group. During the experiment, each group was given the corresponding drug by gavage once a day for 7 days. After the administration, blood and uterine tissue were collected. The uterine bleeding volume was measured by ultraviolet spectrophotometry and the pathological changes of endometrium were observed based on hematoxylin-eosin(HE) staining. In addition, the microvessel density of endometrium was determined by immunohistochemistry, and the content of thromboxane B2(TXB2), 6-keto-PGF_(1α), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in plasma and levels of lutenizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E_2), and progesterone in serum were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of estrogenreceptor α(ERα), progesterone receptor(PR), matrix metalloproteinase(MMP)-2, MMP-9, and vascular endothelial growth factor(VEGF) in uterine tissue was determined by Western blot. Compared with the model group, TEC, TSC, and TFC can reduce uterine bleeding volume, alleviate the pathological damage of endometrium, and increase the microvessel density in endometrium. Moreover, TEC and TSC can significantly raise plasma TXB2 level and ratio of TXB2 to 6-keto-PGF_(1α), and TEC and TFC can significantly reduce the levels of IL-6 and TNF-α. In addition, TEC significantly elevated serum progesterone level and TFC significantly increased serum levels of E_2, FSH, and LH. TSC can significantly raise serum progesterone and FSH levels. In addition, TEC can significantly down-regulate the protein expression of PR, MMP-2, and VEGF and TSC significantly reduced the expression of MMP-9. TFC significantly decreased the expression of PR, MMP-9, and VEGF, and up-regulated the expression of ERα. In conclusion, TEC, TSC, and TFC all show therapeutic effects on AUB, particularly TEC. TSC exerts the effects by enhancing the coagulation function and promoting endometrial repair, and TFC by regulating estrogen levels and reducing inflammatory response. This study reveals the mechanism of C. chinense against AUB and also explains the holistic characteristics of Chinese medicine.

[Simultaneous determination and pharmacokinetic study of five compounds from total extract of Clinopodium chinense in abnormal uterine bleeding rat plasma by UPLC-MS/MS].

Clinopodium chinense, a traditional folk medicinal herb, has been used to treat abnormal uterine bleeding(AUB) for many years. Saponins and flavonoids are the main active components in C. chinense. To study the pharmacokine-tics of multiple components from the total extract of C. chinense(TEC), we established a sensitive and rapid method of ultra-perfor-mance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS) for simultaneous determination of five compounds in the plasma of AUB rats. After validation, the AUB model was established with SD female rats which got pregnant on the same day by gavage with mifepristone(12.4 mg·kg~(-1)) and misoprostol(130 µg·kg~(-1)). The established method was applied to the detection of hesperidin, naringenin, apigenin, saikosaponin a, and buddlejasaponin Ⅳb in AUB rats after the administration of TEC. The pharmacokinetic parameters were calculated by DAS 2.0. The five compounds showed good linear relationship within the detection range. The specificity, accuracy, precision, recovery, matrix effect, and stability of the method all matched the requirements of biolo-gical sample detection. The above 5 compounds were detected in the plasma of AUB rats after the administration of TEC. The C_(max) va-lues of hesperidin, naringenin, apigenin, saikosaponin a, and clinoposide A were 701.6, 429.5, 860.7, 75.1, and 304.1 ng·mL~(-1), respectively. All the compounds owned short half-life and quick elimination rate in vivo, and the large apparent volume of distribution indicated that they were widely distributed in tissues. Being rapid, accurate, and sensitive, this method is suitable for the pharmacokinetic study of extracts of Chinese herbal medicines and provides a reference for the study of pharmacodynamic material basis of C. chinense in treating AUB.

Glycine alleviates fluoride-induced oxidative stress, apoptosis and senescence in a porcine testicular Sertoli cell line.

Glycine is a well-known free radical scavenger in the cellular antioxidant system that prevents oxidative damage and apoptosis. Excessive fluoride exposure is associated with multiple types of cellular damage in humans and animals. The objective of the present study was to investigate the protective effects of glycine on sodium fluoride (NaF) exposure and the possible underlying mechanisms in a porcine testicular Sertoli cell line model. Cellular viability and proliferation were examined following NaF exposure and glycine supplementation, and glycine dramatically ameliorated the decreases in NaF-induced porcine testicular Sertoli cell viability and proliferation. Further investigations revealed that glycine decreased NaF-induced intracellular reactive oxygen species production, DNA fragment accumulation and the apoptosis incidence in the porcine testicular Sertoli cell line; in addition, glycine improved mitochondrial function and ATP production. Notably, results of the SPiDER-ß-Gal analysis suggested that glycine alleviated NaF-induced cellular senescence and downregulated P53, P21, HMGA2 and P16INK4a gene expression in the porcine testicular Sertoli cell line. Collectively, the beneficial effects of glycine alleviate NaF-induced oxidative stress, apoptosis and senescence, and together with our previous findings, support the hypothesis that glycine plays an important role in protecting against NaF exposure-induced impairments in the porcine testicular Sertoli cell line.

Intrinsic Contributions of 2'-Hydroxyl to the Hydration of Nucleosides at the Monomeric Level.

Although many reports have revealed structural differences between DNA and RNA at the polymeric level, there are no comparative studies with 2'-deoxyribonucleoside and ribonucleoside to explore the role of the 2'-OH group at the monomeric level under the same conditions. Inspired by this, herein, the intrinsic contributions of the 2'-OH group in the nucleoside have been systematically investigated by directly solving the single-crystal structures of 2'-deoxy-2-aminoadenosine (1), 2-aminoadenosine (2), and 2-aminoarabinofuranosyladenine (3) in water. The 2'-OH group not only influenced the conformation and base-pair pattern of the single-nucleoside molecule, but also played a fundamental role in the entire supramolecular structure. Interestingly, compound 1, which did not contain the 2'-OH group, displayed strong hydration, whereas 2 and 3 (with the 2'-OH group in the opposite direction) exhibited no hydration, which was completely different from that observed in nucleic acids. Meanwhile, compound 1 trapped water molecules to form unique trihydrol moieties, which further served as the backbone to construct the simplest double-chain DNA-like structures. To this end, to investigate the effect of the biological environment on these unique structures, the solvent was changed from water to phosphate-buffered saline (PBS). Surprisingly, such a subtle adjustment led to entirely different superstructures, consisting of 2D lamellar structures in water and 3D porous structures in PBS. These large morphological differences could be attributed to delicate ion hydration, which was also confirmed through variable-temperature X-ray analysis, SEM, and intermolecular interaction energy calculations. In summary, this study comprehensively investigated the intrinsic contributions of 2'-hydroxyl to the hydration of nucleosides at the monomeric level; this is helpful to further understand the differences in DNA/RNA and the impact of their surrounding environment.

Inhibition of glycolysis ameliorate arthritis in adjuvant arthritis rats by inhibiting synoviocyte activation through AMPK/NF-кB pathway.

OBJECTIVE: This study aimed to evaluate glycolysis inhibitor which can effectively ameliorate arthritis by inhibiting synoviocyte activation through AMPK/NF-кB pathway in AA rats. METHODS: Adjuvant arthritis (AA) rats were treated with 2-deoxyglucose (2-DG), glycolysis inhibitor. HE staining and radiological Examination were used for histopathology analysis and evaluation of joint destruction. HKII expression was quantified by immunostaining. Proliferation and migration of synoviocytes were assessed by synovicyte scores of joint, CCK8 and transwell assay. Inflammatory factors and levels of AMPK, p65 and IκBα were quantified by ELISA analysis and WB. RESULTS: We observed that HKII expression was positively correlated with synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction, and glycolysis inhibitor reduces the joint swelling degree, alleviates bone destruction, inhibits the proliferation and migration of synoviocyte, and reduces secretory function of synoviocytes in AA rats. In addition, we investigated that glycolysis inhibitor may inhibit activation of the NF-κB signaling pathway by activating the AMPK pathway. CONCLUSION: This study suggests the involvement of energy metabolism in the pathological inflammation process in RA joints. Glycolysis inhibitors might, therefore, provide an opportunity for therapeutic intervention.

Identification of Major Sources of Atmospheric NH3 in an Urban Environment in Northern China During Wintertime.

To assess the relative contributions of traffic emission and other potential sources to high levels of atmospheric ammonia (NH3) in urban areas in the wintertime, atmospheric NH3 and related pollutants were measured at an urban site, ∼300 m from a major traffic road, in northern China in November and December 2015. Hourly average NH3 varied from 0.3 to 10.8 ppb with an average of 2.4 ppb during the campaign. Contrary to the common perspective in literature, traffic emission was demonstrated to be a negligible contributor to atmospheric NH3. Atmospheric NH3 correlated well with ambient water vapor during many time periods lasting from tens of hours to several days, implying NH3 released from water evaporation is an important source. Emissions from local green space inside the urban areas were identified to significantly contribute to the observed atmospheric NH3 during ∼60% of the sampling times. Evaporation of predeposited NHx through wet precipitation combined with emissions from local green space likely caused the spikes of atmospheric NH3 mostly occurring 1-4 h after morning rush hours or after and during slight shower events. There are still ∼30% of the data samples with appreciable NH3 level for which major contributors are yet to be identified.

Lysine-specific demethylase 1 (LSD1) participate in porcine early embryonic development by regulating cell autophagy and apoptosis through the mTOR signaling pathway.

Lysine-specific demethylase 1 (LSD1) stands as the pioneering histone demethylase uncovered, proficient in demethylating H3K4me1/2 and H3K9me1/2, thereby governing transcription and participating in cell apoptosis, proliferation, or differentiation. Nevertheless, the complete understanding of LSD1 during porcine early embryonic development and the underlying molecular mechanism remains unclear. Thus, we investigated the mechanism by which LSD1 plays a regulatory role in porcine early embryos. This study revealed that LSD1 inhibition resulted in parthenogenetic activation (PA) and in vitro fertilization (IVF) embryo arrested the development, and decreased blastocyst quality. Meanwhile, H3K4me1/2 and H3K9me1/2 methylase activity was increased at the 4-cell embryo stage. RNA-seq results revealed that autophagy related biological processes were highly enriched through GO and KEGG pathway analyses when LSD1 inhibition. Further studies showed that LSD1 depletion in porcine early embryos resulted in low mTOR and p-mTOR levels and high autophagy and apoptosis levels. The LSD1 deletion-induced increases in autophagy and apoptosis could be reversed by addition of mTOR activators. We further demonstrated that LSD1 inhibition induced mitochondrial dysfunction and mitophagy. In summary, our research results indicate that LSD1 may regulate autophagy and apoptosis through the mTOR pathway and affect early embryonic development of pigs.

Thyroxine regulates pig Sertoli cell line proliferation and maturation through the IKK/NFκB and p38 MAPK signaling pathways.

The aim of this study was to investigate the signaling pathways involved in the proliferation and differentiation of pig Sertoli cells (SCs) mediated by thyroid hormone (T3) to provide a theoretical and practical basis for enhancing pig semen production. The effects of different concentrations of T3 on the proliferation of pig SCs were evaluated using the CCK8 assay. The impact of T3 on the proliferation and differentiation of pig SCs was further examined using RNA-seq, qPCR, and Western Blotting techniques. Additionally, the involvement of the p38 MAPK and NFκB pathways in mediating the effects of T3 on SCs proliferation and differentiation was investigated. Our findings revealed a strong correlation between the dosage of T3 and the inhibition of pig SCs proliferation and promotion of maturation. T3 regulated the activation state of the NFκB signaling pathway by upregulating IKKα, downregulating IKKß, and promoting IκB phosphorylation. Furthermore, T3 facilitated SCs maturation by upregulating AR and FSHR expression while downregulating KRT-18. In conclusion, T3 inhibits pig SCs proliferation and promote pig SCs maturation through the IKK/NFκB and p38 MAPK pathways. These findings provide valuable insights into the mechanisms by which T3 influences the proliferation and maturation of pig SCs.

A simple method for fabricating drugs containing a cis-o-diol structure into guanosine-based supramolecular hydrogels for drug delivery.

Supramolecular hydrogels are attractive biomaterials for local drug delivery owing to their excellent self-healing, injectable, biodegradable, and biocompatible properties. However, traditional drug-loading approaches based on non-covalent encapsulation and covalent bonding have shown problems such as rapid or difficult drug release, complex reaction processes, low reaction efficiency, and decreased drug activity. Therefore, there is a need to find a simple and efficient method to load drugs into hydrogels, which possess stable drug release ability without impairing drug efficacy. In this study, we introduce dynamic borate ester bonds via a simple one-pot method to load cis-o-diol-containing drugs into guanosine (G)-based supramolecular hydrogels. The experimental results confirm that the dynamic covalent borate ester bonds are formed based on the cis-o-diol groups of the drug and the G in these hydrogels. Meanwhile, the as-prepared G-based hydrogels not only possess self-healing properties and injectability but also have satisfactory biodegradability and biocompatibility. Additionally, the drug can be released from the G-based hydrogel according to the pH-responsive cleavage of the borate ester bonds without affecting drug activity. Overall, these results indicate that the simple one-pot method of utilizing the dynamic borate bond can provide a valuable reference for the design of hydrogel dosage forms.

Protective effect of the total flavonoids from Clinopodium chinense against LPS-induced mice endometritis by inhibiting NLRP3 inflammasome-mediated pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinopodium chinense (Benth.) O. Kuntze (C. chinense) is a Chinese herbal medicine used in treating gynecological hemorrhagic diseases for hundreds of years. Flavonoids are one kind of the major components in C. chinense. The flavonoids of C. chinense (TFC) have a vital role in treating endometritis but the underlying therapeutic mechanisms of TFC against endometritis have been rarely reported. AIM OF THE STUDY: To elucidate the therapeutic effect and possible mechanisms of TFC against lipopolysaccharide (LPS)-induced endometritis in vivo and LPS-induced primary mouse endometrial epithelial cells (MEECs) injury in vitro. MATERIALS AND METHODS: The holistic phytochemicals of the TFC and TFC-contained serum were screened and identified using UPLC-Q-TOF-MS. The model of endometritis was established by intrauterine injection of LPS (5 mg/mL) into female BALB/c mice, and the model mice were treated with TFC for 7 days. The value of MPO was measured by Myeloperoxidase assay kit, the pathological changes in the endometrium were evaluated using H&E staining and transmission electron microscope (TEM), the secretions of IL-18, IL-1ß and TNF-α were determined by ELISA kits, the mRNA expressions of IL-18, IL-1ß and TNF-α were determined by RT-PCR assay, and the protein levels of TLR4, IKBα, p-IKBα, p65, p-p65, caspase-1, ASC, NLRP3 and GSDMD were measured by Western blot. Subsequently, MEECs were isolated from the uterus of pregnant female mice, injured by LPS for 24 h and incubated with the TFC-contained serum. Finally, cell viability, LDH release, hoechst 33342/PI staining, immunofluorescence staining, scanning electron microscope observation, ELISA assay, RT-PCR detection and Western blot analysis were carried out to further validate the therapeutic effect and the underlying mechanisms of TFC. RESULTS: A total of 6 compounds in the plasma of mice after being intragastric administrated of TFC were identified. The results in vivo showed that TFC significantly reduced MPO value and alleviated pathological injury of the endometrium. Furthermore, TFC significantly decreased the serum IL-18, IL-1ß and TNF-α levels, and the mRNA levels of IL-18, IL-1ß and TNF-α. TFC also inhibited the expressions of TLR4, p-IKBα, p-p65, caspase-1, ASC, NLRP3 and GSDMD. Besides, compared with the model group in MEECs cells, TFC-contained serum prevented pyroptosis, decreased the levels of IL-18 and IL-1ß, and inhibited the mRNA expressions of IL-18, IL-1ß and GSDMD. TFC-contained serum also reversed the activation of NLRP3 inflammasome caused by nigericin, and restrainted the translocation of NF-κB into nuclear. CONCLUSIONS: TFC protects mice endometritis from the injury of LPS via suppressing the activation of NLRP3 inflammasome and pyroptosis, the underlying mechanisms of which were related to restraining the TLR4/NF-κB/NLRP3 pathway activation.

Puerarin inhibited oxidative stress and alleviated cerebral ischemia-reperfusion injury through PI3K/Akt/Nrf2 signaling pathway.

Introduction: Puerarin (PUE) is a natural compound isolated from Puerariae Lobatae Radix, which has a neuroprotective effect on IS. We explored the therapeutic effect and underlying mechanism of PUE on cerebral I/R injury by inhibiting oxidative stress related to the PI3K/Akt/Nrf2 pathway in vitro and in vivo. Methods: The middle cerebral artery occlusion and reperfusion (MCAO/R) rats and oxygen-glucose deprivation and reperfusion (OGD/R) were selected as the models, respectively. The therapeutic effect of PUE was observed using triphenyl tetrazolium and hematoxylin-eosin staining. Tunel-NeuN staining and Nissl staining to quantify hippocampal apoptosis. The reactive oxygen species (ROS) level was detected by flow cytometry and immunofluorescence. Biochemical method to detect oxidative stress levels. The protein expression related to PI3K/Akt/Nrf2 pathway was detected by using Western blotting. Finally, co-immunoprecipitation was used to study the molecular interaction between Keap1 and Nrf2. Results: In vivo and vitro studies showed that PUE improved neurological deficits in rats, as well as decreased oxidative stress. Immunofluorescence and flow cytometry indicated that the release of ROS can be inhibited by PUE. In addition, the Western blotting results showed that PUE promoted the phosphorylation of PI3K and Akt, and enabled Nrf2 to enter the nucleus, which further activated the expression of downstream antioxidant enzymes such as HO-1. The combination of PUE with PI3K inhibitor LY294002 reversed these results. Finally, co-immunoprecipitation results showed that PUE promoted Nrf2-Keap1 complex dissociation. Discussion: Taken together, PUE can activate Nrf2 via PI3K/Akt and promote downstream antioxidant enzyme expression, which could further ameliorate oxidative stress, against I/R-induced Neuron injury.

Maslinic Acid Supplementation during the In Vitro Culture Period Ameliorates Early Embryonic Development of Porcine Embryos by Regulating Oxidative Stress.

As a pentacyclic triterpene, MA exhibits effective free radical scavenging capabilities. The purpose of this study was to explore the effects of MA on porcine early-stage embryonic development, oxidation resistance and mitochondrial function. Our results showed that 1 µM was the optimal concentration of MA, which resulted in dramatically increased blastocyst formation rates and improvement of blastocyst quality of in vitro-derived embryos from parthenogenetic activation (PA) and somatic cell nuclear transfer (SCNT). Further analysis indicated that MA supplementation not only significantly decreased the abundance of intracellular reactive oxygen species (ROS) and dramatically increased the abundance of intracellular reductive glutathione (GSH) in porcine early-stage embryos, but also clearly attenuated mitochondrial dysfunction and inhibited apoptosis. Moreover, Western blotting showed that MA supplementation upregulated OCT4 (p < 0.01), SOD1 (p < 0.0001) and CAT (p < 0.05) protein expression in porcine early-stage embryos. Collectively, our data reveal that MA supplementation exerts helpful effects on porcine early embryo development competence via regulation of oxidative stress (OS) and amelioration of mitochondrial function and that MA may be useful for increasing the in vitro production (IVP) efficiency of porcine early-stage embryos.

Guanosine-based Hydrogel Integrating Photothermal Effect of PDA-AuNPs through Dynamic Borate Bond for Photothermal Therapy of Cancer.

Photothermal therapy (PTT) has drawn extensive attention owing to its noninvasive and great tissue penetration depth. However, the physical encapsulation of photothermal agents may lead to their rapid release. Dual-functional hydrogel systems that integrate functions and carriers can potentially solve this problem. In this work, we successfully developed a dual-functional guanosine(G)-based hydrogel integrating the photothermal effect and localized delivery by introducing dynamic borate ester utilizing the photothermal property of PDA-AuNPs and the self-assembly ability of G. Both in vitro and in vivo results confirmed that the GBPA hydrogel not only exhibited excellent photothermal toxicity, stability, injectability, and biocompatibility, but also possessed high photothermal antitumor activity. These results suggested that the GBPA hydrogel could be used as a dual-functional hydrogel integrating photothermal effect and localized delivery in one system, which would possibly provide a new opportunity for the design of new dual-functional hydrogels for highly efficient cancer therapy.

Spectrum-effect relationship between UPLC-Q-TOF-MS fingerprint and anti-AUB effect of Clinopodium chinense (Benth.) O. Kuntze.

Clinopodium chinense (Benth.) O. Kuntze (C. chinense), a traditional Chinese medicine with significant astringent and hemostatic properties, is mainly used to treat abnormal uterine bleeding (AUB) with remarkable curative effect, but the active ingredients of which remain unclear. This study aimed to screen and identify the main anti-AUB components of C. chinense via spectrum-effect relationship analysis and experiment validation. Firstly, total extract of C. chinense (TEC) of 12 batches samples was prepared by Chinese Pharmacopoeia. The fingerprint chromatogram of TEC was established by UPLC-Q-TOF-MS. The AUB model was established by intragastric administration of mifepristone and misoprostol to pregnant rats, followed by the treatment with TEC. After drug administration lasting 7 days, metrorrhagia volume was measured, pathological changes in uterine tissue were evaluated by HE staining, the levels of TXB-2, TNF-α, and IL-6 were measured by ELISA. The spectrum-effect relationship was investigated by grey relational analysis (GRA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Finally, the potential active ingredients of TEC screened by spectrum-effect relationship analysis were subsequently verified both in vitro and in vivo. A total of 25 common peaks were obtained from the fingerprint chromatogram of the 12 bathes TEC samples, 12 peaks were identified according to the reference substances. Comparing with the model group, TEC significantly reduced the uterine bleeding volume, alleviated endometrial injury, increased plasma TXB2 level, and decreased plasma IL-6 and TNF-α levels. Furthermore, seven components including kaempferol, quercetin, buddlejasaponin Ⅳb, hesperidin, naringenin, apigenin, and saikosaponin a were identified via spectrum-effect relationship analysis. In vitro and in vivo verification indicated that buddlejasaponin Ⅳb, hesperidin, naringenin, apigenin, and saikosaponin a were responsible for the anti-AUB activity of TEC. In conclusion, the present study established a spectrum-effect relationship for C. chinense and identified the main anti-AUB compounds in TEC, which provides insight for the exploration of bioactive components and quality control of C. chinense.

A multifunctional supramolecular hydrogel for infected wound healing.

Bacterial infection poses a significant threat to wound healing, and the preparation of novel wound dressings is very important. However, currently reported dressings serve as traditional physical barriers or functional ones with limited effects, such as antibacterial effect or adhesion. There is growing demand for developing wound dressing materials with antibacterial effect, good adhesion, proper degradation within the wound recovery time, and simple synthesis. In this study, based on a natural plant extract - tannic acid (TA) and natural guanosine (G), a supramolecular soft hydrogel (G-TA hydrogel) was successfully synthesized based on dynamic borate esters in a one-pot reaction. The hydrogel showed excellent antibacterial and adhesive properties and could be degraded within three days in vivo. In addition, the G-TA hydrogel also showed remarkable antioxidant capability, excellent injectability, a long in vitro lifespan, and good cytocompatibility on L929 cells. Furthermore, the hydrogel could accelerate the healing of full-thickness wounds on the back skin of mice, indicating its promising applications in wound repair.