Melatonin decreases excessive polyspermy for single oocyte in pigs through the MT2 receptor.

Melatonin supplementation during in vitro maturation (IVM) improves porcine oocyte maturation and embryonic development by exerting antioxidative effects. Nevertheless, the mechanism by which melatonin prevents polyspermy after in vitro fertilization (IVF) remains unclear. Here, we examined the effects of melatonin on cytoplasmic maturation and the incidence of polyspermic penetration in porcine oocytes. No statistically significant difference was observed in the rate of first polar body formation between the groups (Control, Melatonin, Melatonin + Luzindole, and Melatonin + 4-P-PDOT). Interestingly, melatonin supplementation significantly improved the cytoplasmic maturation of porcine oocytes by enhancing the normal distribution of organelles (Golgi apparatus, endoplasmic reticulum and mitochondria) and upregulating organelle-related gene expressions (P < 0.05). However, these promotional effects were counteracted by melatonin antagonists, suggesting that melatonin enhances cytoplasmic maturation through its receptors in porcine oocytes. Melatonin supplementation also significantly improved the rate of diploid and blastocyst formation after IVF by promoting the normal distribution of cortical granules (P < 0.05). In conclusion, melatonin supplementation during in vitro maturation of porcine oocyte improves fertilization efficiency and embryonic developmental competence by enhancing cytoplasmic maturation.

Gastric cancer metastatic to the breast: A case report.

BACKGROUND: Metastatic breast cancer originating in the gastrointestinal tract is a rare occurrence. The limited number of cases has resulted in incomplete understanding of the disease, making it challenging to differentiate from primary breast cancer. While clinical history and immunohistochemical studies can aid in distinguishing between the two, the management principles and pathogenesis of gastrointestinal metastatic breast cancer remain controversial. The scarcity of data has hampered comprehensive knowledge. Our objective is to shed light on this rare disease through our case study. CASE SUMMARY: Here, we report a case of breast metastasis from gastric cancer in a 43-year-old woman. This patient was admitted to our hospital with complaints of discomfort in the upper and middle abdomen persisting for two months, as well as black stools for over ten days. She underwent radical distal gastrectomy for gastric cancer, followed by postoperative chemotherapy. Three years later, the patient developed bilateral breast nodules. Imaging studies indicated a high probability of malignancy. She subsequently underwent a right modified radical mastectomy and excision of a left breast mass. Postoperative pathology revealed the right breast tumor was consistent with primary gastric cancer. CONCLUSION: We present a case of breast metastasis from gastric cancer to contribute to the limited foundation of research into this rare disease.

Thermosensitive curcumin/silver/montmorillonite-F127 hydrogels with synergistic photodynamic/photothermal/silver ions antibacterial activity.

Bacterial infections and the emergence of super-resistant bacteria pose a significant risk to human health. Effective sterilization to prevent the development of bacterial drug resistance remains a challenge. Herein, curcumin/silver/montmorillonite (Cur/Ag/Mt) was prepared through a green chemical reduction method with montmorillonite as the carrier, curcumin as the reducing agent and the capping agent, and citric acid as the structure guide agent. Then, a novel dual light-responsive and thermosensitive Pluronic F127-based hydrogel (CAM-F) was prepared by encapsulating Cur/Ag/Mt within the F127 hydrogel. The Cur/Ag/Mt showed strong absorption in the near-infrared region that efficiently converts light into heat for photothermal therapy when the molar ratio of curcumin to silver nitrate was 2 : 1. Specifically, triangular silver nanoparticles reduced by curcumin were immobilized on the Mt layers, which could enhance photodynamic therapy by the metal-enhanced singlet oxygen and metal-enhanced fluorescence mechanisms. Upon combining 405 nm and 808 nm laser irradiation, the CAM-F hydrogel could simultaneously generate reactive oxygen species, increase the local temperature, and sustain the release of Ag+, thus displaying excellent bactericidal performance against Gram-negative and Gram-positive bacteria. The antibacterial rates of CAM-F hydrogels were 99.26 ± 0.95% and 99.95 ± 0.98% for Escherichia coli and Staphylococcus aureus, respectively. The findings suggest the potential of the CAM-F hydrogel as a stable, biologically safe, and broad-spectrum antimicrobial material. The thermosensitive CAM-F hydrogels for synergetic phototherapy may provide a promising strategy for solving clinical problems caused by pathogenic infections.

FGF13 enhances the function of TRPV1 by stabilizing microtubules and regulates acute and chronic itch.

Itching is an aversive somatosensation that triggers the desire to scratch. Transient receptor potential (TRP) channel proteins are key players in acute and chronic itch. However, whether the modulatory effect of fibroblast growth factor 13 (FGF13) on acute and chronic itch is associated with TRP channel proteins is unclear. Here, we demonstrated that conditional knockout of Fgf13 in dorsal root ganglion neurons induced significant impairment in scratching behaviors in response to acute histamine-dependent and chronic dry skin itch models. Furthermore, FGF13 selectively regulated the function of the TRPV1, but not the TRPA1 channel on Ca2+ imaging and electrophysiological recordings, as demonstrated by a significant reduction in neuronal excitability and current density induced by TRPV1 channel activation, whereas TRPA1 channel activation had no effect. Changes in channel currents were also verified in HEK cell lines. Subsequently, we observed that selective modulation of TRPV1 by FGF13 required its microtubule-stabilizing effect. Furthermore, in FGF13 knockout mice, only the overexpression of FGF13 with a tubulin-binding domain could rescue TRP channel function and the impaired itch behavior. Our findings reveal a novel mechanism by which FGF13 is involved in TRPV1-dependent itch transduction and provide valuable clues for alleviating pathological itch syndrome.

Exposure to high concentrations of triphenyl phosphate altered functional performance, liver metabolism and intestinal bacterial composition of aquatic turtles.

Organophosphorus flame retardants, such as triphenyl phosphate (TPhP), exist ubiquitously in various environments owing to their widespread usage. Potential toxic effects of residual flame retardants on cultured non-fish species are not concerned commonly. TPhP-induced physiological and biochemical effects in an aquatic turtle were evaluated here by systematically investigating the changes in growth and locomotor performance, hepatic antioxidant ability and metabolite, and intestinal microbiota composition of turtle hatchlings after exposure to different TPhP concentrations. Reduced locomotor ability and antioxidant activity were only observed in the highest concentration group. Several metabolic perturbations that involved in amino acid, energy and nucleotide metabolism, in exposed turtles were revealed by metabolite profiles. No significant among-group difference in intestinal bacterial diversity was observed, but the composition was changed markedly in exposed turtles. Increased relative abundances of some bacterial genera (e.g., Staphylococcus, Vogesella and Lawsonella) probably indicated adverse outcomes of TPhP exposure. Despite having only limited impacts of exposure at environmentally relevant levels, our results revealed potential ecotoxicological risks of residual TPhP for aquatic turtles considering TPhP-induced metabolic perturbations and intestinal bacterial changes.

Synthesis of 2,3-Dialkyl-5-hydroxybenzofurans via a One-pot, Three-step Reaction Sequence of 2-Monosubstituted 1,3-Diketones and 1,4-Benzoquinones.

An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K2CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration processes under mild conditions in a practical manner. Additionally, an interesting phenomenon was observed during the derivatization studies, where the dihydroquinoline was converted into tetrahydroquinoline and quinoline products, respectively, via a disproportionation process.

Tunable Colloidal Properties of Lauramidopropyl Betaine and Li Co-modified Montmorillonite in Ethanol/Water.

Montmorillonite (Mt) is a hydrophilic clay mineral with a generally high cationic exchange capacity and a remarkable swellability in water. Yet the application of Mt in cosmetics, paints, polymer nanocomposites, drug delivery systems, and tissue engineering are limited due to its unfavorable swelling and dispersion in alcohol/water mixtures. Improving the swellability and dispersibility of Mt in mixtures of ethanol and water remains challenging. Here, we showed that the swellability and dispersibility of Mt in ethanol/water could be significantly enhanced when lithium-Mt (Li-Mt) was intercalated by zwitterionic surfactant lauramidopropyl betaine (LPB). The binding mechanism of the LPB intercalate to Li-Mt originated from a combination of van der Waals forces, ion-dipole interaction, and electrostatic attraction. Due to the synergistic effect of Li+ and LPB, the comodified Mt (LPB-Li-Mt) exhibited excellent swellability, dispersibility, and rheological properties. The structure, morphology, zeta potential, dispersibility, and gel-forming performance of LPB-Li-Mt can be modulated by the concentrations of ethanol in ethanol/water mixtures. When the ethanol concentration increased to 75% v/v ethanol solution, the free swelling of LPB-Li-Mt remained above 80%. The results from X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, X-ray photoemission spectrometry, and small-angle X-ray scattering confirmed the full exfoliation of LPB-Li-Mt at 75% (v/v) ethanol solution. The formation of a stable colloidal LPB-Li-Mt dispersion in a mixture of ethanol/water might be derived from the association between water molecules and the Li+, the hydrophobic interaction, and the ion-dipole of ethanol with the LPB molecules. The findings provide a guide for improving dispersion and swelling of Mt and modified ones in water-miscible organic solvents.

Dynamic foraging strategy adaptation to heterogeneous environments contributes to social aggregation in snub-nosed monkeys.

The dynamics of animal social structures are heavily influenced by environmental patterns of competition and cooperation. In folivorous colobine primates, prevailing theories suggest that larger group sizes should be favored in rainforests with a year-round abundance of food, thereby reducing feeding competition. Yet, paradoxically, larger groups are frequently found in high-altitude or high-latitude montane ecosystems characterized by a seasonal scarcity of leaves. This contradiction is posited to arise from cooperative benefits in heterogeneous environments. To investigate this hypothesis, we carried out a six-year field study on two neighboring groups of golden snub-nosed monkey ( Rhinopithecus roxellana), a species representing the northernmost distribution of colobine primates. Results showed that the groups adjusted their movement and habitat selection in response to fluctuating climates and spatiotemporal variability of resources, indicative of a dynamic foraging strategy. Notably, during the cold, resource-scarce conditions in winter, the large group occupied food-rich habitats but did not exhibit significantly longer daily travel distances than the smaller neighboring group. Subsequently, we compiled an eco-behavioral dataset of 52 colobine species to explore their evolutionary trajectories. Analysis of this dataset suggested that the increase in group size may have evolved via home range expansion in response to the cold and heterogeneous climates found at higher altitudes or latitudes. Hence, we developed a multi-benefits framework to interpret the formation of larger groups by integrating environmental heterogeneity. In cold and diverse environments, even smaller groups require larger home ranges to meet their dynamic survival needs. The spatiotemporal distribution of high-quality resources within these expanded home ranges facilitates more frequent interactions between groups, thereby encouraging social aggregation into larger groups. This process enhances the benefits of collaborative actions and reproductive opportunities, while simultaneously optimizing travel costs through a dynamic foraging strategy.

Variations of pollen concentration in urban alleys of park city and the transmission pattern during the period of high allergenic risk: Taking Qingyang District of Chengdu City as an example.

Pollen (spores and pollen) allergy caused by green areas is one of the most serious environmental epidemics endangering urban public health. The pollen allergy rate in China reached 17.8% in 2022, characterized by a wide age range of onset, severity and diversity of symptoms. The aims of this study were to verify the consistency of the prediction results of pollen concentration and the index of allergenicity of urban green zones (IUGZA) equation, and to clarify the dispersal pattern of tree pollen in the urban alleys of cities with high density of static wind. We selected representative high, medium and low allergenic areas based on the allergenic stress in urban alleys of Qingyang District, Chengdu calculated by IUGZA equation, and monitored the pollen concentrations by selecting points and indicator species within the three allergenic areas. There was a consistency in the variation of pollen concentration in urban alleys of the three areas, with the highest pollen concentration in March. Mean pollen concentration showed a pattern of spring > autumn > summer > winter. The main pollen sources belonged to Ginkgo, Platanus, Firmiana and Cedrus, accounting for 42.4%, 16.3%, 9.0% and 6.5% of the total pollen, respectively. Wind speed had the greatest effect on pollen concentration and its dispersal distance in the urban alley. The horizontal dispersal distance of pollen was up to 260 m, and the number of pollen showed a significant negative linear correlation with the distance away from the pollen sources. The concentration of exotic pollen collected at the high site (4.5 m above ground) was much lower than that at the near-ground site (1.5 m above ground), but without difference in the types of pollen. The results of allergenic risk predicted by the IUGZA equation were consistent with the actual measured pollen concentration, which could be used in high-density static wind city.

Exposure to low levels of antidiabetic glibenclamide had no evident adverse effects on intestinal microbial composition and metabolic profiles in amphibian larvae.

Unmetabolized human pharmaceuticals may enter aquatic environments, and potentially exert adverse effects on the survival of non-target organisms. Here, Pelophylax nigromaculatus tadpoles were exposed to different concentrations of antidiabetic glibenclamide (GLB) for 30 days to evaluate its potential ecotoxicological effect in amphibians using intestinal microbiomic and metabolomic profiles. The mortality rate of GLB-exposed groups appeared to be lower than that of the control group. Despite not being statistically significant, there was a tendency for a decrease in intestinal microbial diversity after exposure. The relative abundance of bacteria phylum Firmicutes was shown to decrease, but those of other phyla did not in GLB-exposed tadpoles. Some potentially pathogenic bacteria (e.g., Clostridium, Bilophila, Hafnia) decrease unexpectedly, while some beneficial bacteria (e.g., Akkermansia, Faecalibacterium) increased in GLB-exposed tadpoles. Accordingly, GLB-induced changes in intestinal microbial compositions did not seem harmful to animal health. Moreover, minor changes in a few intestinal metabolites were observed after GLB exposure. Overall, our results suggested that exposure to low levels of GLB did not necessarily exert an adverse impact on amphibian larvae.

Metformin exposure altered intestinal microbiota composition and metabolites in amphibian larvae.

The antidiabetic pharmaceutical metformin (MET) is largely unmetabolized by the human body. Its residues are readily detectable in various aquatic environments and may have adverse impacts on the growth and survival of aquatic species. To date, its toxicological effects have scarcely been explored in non-fish species. Here, we exposed the tadpoles of black-spotted pond frog (Pelophylax nigromaculatus) to different concentrations (0, 1, 10 and 100 µg/L) of MET for 30 days and measured the body size, intestinal microbiota and metabolites to evaluate potential effects of MET exposure in amphibian larvae. MET exposure did not affect the growth and intestinal microbial diversity of tadpoles. However, intestinal microbial composition changed significantly, with some pathogenic bacteria (e.g., bacterial genera Salmonella, Comamonas, Stenotrophomonas, Trichococcus) increasing and some beneficial bacteria (e.g., Blautia, Prevotella) decreasing in MET-exposed tadpoles. The levels of some intestinal metabolites associated with growth and immune performance also changed significantly following MET exposure. Overall, our results indicated that exposure to MET, even at environmentally relevant concentrations, would cause intestinal microbiota dysbiosis and metabolite alteration, thereby influencing the health status of non-target aquatic organisms, such as amphibians.

Embryonic development, hatchling performance and metabolic profile after egg exposure to environmentally relevant levels of chlorpyrifos in an aquatic turtle.

The extensive use of organophosphorus insecticides poses a threat to the survival of non-target organisms. Ecotoxicological outcomes of embryonic exposure to insecticides are rarely evaluated in various oviparous species. In this study, soft-shelled turtle (Pelodiscus sinensis) eggs were incubated in moist substrate containing different levels (0, 2, 20 and 200 µg/kg) of chlorpyrifos to investigate its toxic effects on embryonic development and survival, and hatchling physiological performance. Chlorpyrifos exposure had no significant impacts on embryonic development rate and egg survival in P. sinensis. Similarly, embryonic chlorpyrifos exposure neither obviously affected the size and locomotor performance of hatchlings, nor changed the activities of superoxide dismutase and catalase, and content of malondialdehyde in their erythrocytes. Based on liquid chromatography-mass spectrometry analysis, minor metabolic perturbations related to amino acid, lipid and energy metabolism in hatchlings after embryonic chlorpyrifos exposure were revealed by hepatic metabolite profiling. Overall, our results suggested that embryonic exposure to environmentally relevant levels of chlorpyrifos had only a limited impact on physiological performances of hatchlings, although it would result in a potential risk of hepatotoxicity in P. sinensis.

Dearomative [4 + 2] Annulation of Electron-Poor N-Heteroarenes with Azoalkenes for Access to Polycyclic Tetrahydro-1,2,4-triazines.

A direct dearomative [4 + 2] annulation of electron-poor N-heteroarenes with azoalkenes generated in situ from α-halogeno hydrazones was developed under mild conditions. Accordingly, a series of fused polycyclic tetrahydro-1,2,4-triazines with potential biological activity were obtained in up to 96% yield. Various α-halogeno hydrazones and N-heteroarenes, such as pyridines, quinolines, isoquinolines, phenanthridine, and benzothiazole, were tolerated by this reaction. The general applicability of this method was shown by upscale synthesis and product derivatization.

Hypoglycemic and H2O2-induced oxidative injury protective effects and the phytochemical profiles of the ethyl acetate fraction from Radix Paeoniae Alba.

Radix Paeonia Alba (RPA) is often used as food and medicine. This study aimed to enrich and identify the antioxidant and hypoglycemic bioactive compounds from RPA. The results indicated that the ethyl acetate fraction (EAF) showed the highest total phenolic content, DPPH, ABTS+ scavenging ability, and α-glucosidase inhibition ability (IC50 = 7.27 µg/ml). The EAF could alleviate H2O2-induced oxidative stress in HepG2 cells by decreasing the MDA and ROS levels, improving cell apoptosis, increasing the enzyme activity of GPX-Px, CAT, SOD, Na+/K+-ATP, and Ca2+/Mg2+-ATP, and stimulating T-AOC expression, which also enhanced the glucose uptake of insulin-resistant HepG2 cells. In addition, the EAF significantly reduced the fasting blood glucose level and improved glucose tolerance in diabetic mice. An HPLC-QTOF-MS/MS analysis displayed that procyanidin, digallic acid isomer, methyl gallate, tetragalloylglucose isomer, dimethyl gallic acid, and paeoniflorin were the major compounds in the EAF. These findings are meaningful for the application of the EAF in the medicinal or food industry to prevent and treat oxidative stress and diabetes mellitus.

Mitigation of Paeoniae Radix Alba extracts on H2O2-induced oxidative damage in HepG2 cells and hyperglycemia in zebrafish, and identification of phytochemical constituents.

Paeoniae Radix Alba (PRA), as a Traditional Chinese Medicine, is widely used in Chinese cuisine due to high health-benefits and nutrition, but the effect of different polarity of solvents on the extraction of antioxidant and hypoglycemic constituents, as well as the major active compounds remain unclear. In this research, 40, 70, and 95% ethanol were firstly applied to extract the polyphenols from PRA, the extraction yields, total phenolics, and total flavonoids content, free radical scavenging ability, α-glucosidase inhibition ability, and anti-glycation ability of extracts were evaluated spectroscopically. The oxidative damage protection, hypoglycemic activity, and alleviation on peripheral nerve damage were evaluated by H2O2-induced HepG2 cells and hyperglycemic zebrafish models. UPLC-QTOF-MS/MS was used to identify the major chemical constituents. The results showed that 40, 70, and 95% ethanol exhibited insignificant difference on the extraction of phenolics and flavonoids from PRA. All extracts showed promising DPPH⋅ and ABTS⋅+ scavenging ability, α-glucosidase inhibition and anti-glycation ability. In addition, PRA extracts could restore the survival rate of HepG2 cells induced by H2O2, and alleviate the oxidative stress by reducing the content of MDA and increasing the levels of SOD, CAT, and GSH-Px. The 70% ethanol extract could also mitigate the blood glucose level and peripheral motor nerve damage of hyperglycemic zebrafish. Thirty-five compounds were identified from 70% ethanol extract, gallotannins, gallic acid and its derivatives, and paeoniflorin and its derivatives were the dominant bioactive compounds. Above results could provide important information for the value-added application of PRA in functional food and medicinal industry.

The impact of circulating IGF-1 and IGFBP-2 on cardiovascular prognosis in patients with acute coronary syndrome.

Background: While insulin-like growth factor 1 (IGF-1) exerts a cardioprotective effect in the setting of atherosclerosis, insulin-like growth factor binding protein 2 (IGFBP-2) is involved in metabolic syndrome. Although IGF-1 and IGFBP-2 are known to be predictors for mortality in patients with heart failure, their use in clinic as prognostic biomarkers for acute coronary syndrome (ACS) requires investigation. We evaluated the relationship between IGF-1 and IGFBP-2 levels at admission and the risk of major adverse cardiovascular events (MACEs) in patients with ACS. Methods: A total of 277 ACS patients and 42 healthy controls were included in this prospective cohort study. Plasma samples were obtained and analyzed at admission. Patients were followed for MACEs after hospitalization. Results: Among patients who suffered acute myocardial infarction, plasma levels of IGF-1 and IGFBP-2 were lower and higher, respectively, as compared to healthy controls (both p < 0.05). The mean follow-up period was 5.22 (1.0-6.0) months and MACEs incidence was 22.4% (62 of 277 patients). Kaplan-Meier survival analysis revealed that patients with low IGFBP-2 levels had a greater event-free survival rate than patients with high IGFBP-2 levels (p < 0.001). Multivariate Cox proportional hazards analysis revealed IGFBP-2, but not IGF-1, to be a positive predictor of MACEs (hazard ratio 2.412, 95% CI 1.360-4.277; p = 0.003). Conclusion: Our findings suggest that high IGFBP-2 levels are associated with the development of MACEs following ACS. Moreover, IGFBP-2 is likely an independent predictive marker of clinical outcomes in ACS.

Insights into the mechanisms of triptolide nephrotoxicity through network pharmacology-based analysis and RNA-seq.

Introduction: Triptolide (TPL) is a promising plant-derived compound for clinical therapy of multiple human diseases; however, its application was limited considering its toxicity. Methods: To explore the underlying molecular mechanism of TPL nephrotoxicity, a network pharmacology based approach was utilized to predict candidate targets related with TPL toxicity, followed by deep RNA-seq analysis to characterize the features of three transcriptional elements include protein coding genes (PCGs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) as well as their associations with nephrotoxicity in rats with TPL treatment. Results & Discussion: Although the deeper mechanisms of TPL nephrotoxcity remain further exploration, our results suggested that c-Jun is a potential target of TPL and Per1 related circadian rhythm signaling is involved in TPL induced renal toxicity.

Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model.

Ménière's disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière's disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière's disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1ß production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk-/- mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière's disease pathogenesis.