Boswellianols A-I, Structurally Diverse Diterpenoids from the Oleo-Gum Resin of Boswellia carterii and Their TGF-ß Inhibition Activity.

Olibanum, a golden oleo-gum resin from species in the Boswellia genus (Burseraceae family), is a famous traditional herbal medicine widely used around the world. Previous phytochemical studies mainly focused on the non-polar fractions of olibanum. In this study, nine novel diterpenoids, boswellianols A-I (1-9), and three known compounds were isolated from the polar methanolic fraction of the oleo-gum resin of Boswellia carterii. Their structures were determined through comprehensive spectroscopic analysis as well as experimental and calculated electronic circular dichroism (ECD) data comparison. Compound 1 is a novel diterpenoid possessing an undescribed prenylmaaliane-type skeleton with a 6/6/3 tricyclic system. Compounds 2-4 were unusual prenylaromadendrane-type diterpenoids, and compounds 5-9 were new highly oxidized cembrane-type diterpenoids. Compounds 1 and 5 showed significant transforming growth factor ß (TGF-ß) inhibitory activity via inhibiting the TGF-ß-induced phosphorylation of Smad3 and the expression of fibronectin and N-cadherin (the biomarker of the epithelial-mesenchymal transition) in a dose-dependent manner in LX-2 human hepatic stellate cells, indicating that compounds 1 and 5 should be potential anti-fibrosis agents. These findings give a new insight into the chemical constituents of the polar fraction of olibanum and their inhibitory activities on the TGF-ß/Smad signaling pathway.

Can Media Literacy Intervention Improve Fake News Credibility Assessment? A Meta-Analysis.

Fake news impacts individuals' behavior and decision-making while also disrupting political processes, perceptions of medical advice, and societal trends. Improving individuals' ability to accurately assess fake news can reduce its harmful effects. However, previous research on media literacy interventions designed for improving fake news credibility assessments has yielded inconsistent results. We systematically collected 33 independent studies and performed a meta-analysis to examine the effects of media literacy interventions on assessing fake news credibility (n = 36,256). The results showed that media literacy interventions significantly improved fake news credibility assessments (Hedges' g = 0.53, 95% confidence interval [0.29-0.78], p < 0.001). Gaming interventions were the most effective intervention form. Conversely, the intervention channel, outcome measurement, and subject characteristics (age, gender, and country development level) did not influence the intervention effects.

Cevanine-type alkaloids from the bulbs of Fritillaria unibracteata var. wabuensis and their antifibrotic activities in vitro.

Steroidal alkaloids are the main bioactive components of the bulbs of Fritillaria, which have been used as traditional Chinese medicine, known as "Beimu", for the treatment of cough for thousands of years in China. Cough and dyspnea are the most common symptoms observed in patients with pulmonary fibrosis. However, the antifibrotic activity of steroidal alkaloids has not been reported yet. In this study, two previously unreported cevanine-type steroidal alkaloids (1 and 2), four previously undescribed cevanine-type alkaloid glycosides (3-6), and 19 known steroidal alkaloids (7-25) were isolated from the bulbs of Fritillaria unibracteata var. wabuensis. The structures of these compounds were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, as well as DP4+ NMR calculations. The biological evaluation showed that compounds 2, 7-10, 14, 15, and 17 downregulated fibrotic markers induced by transforming growth factor-ß (TGF-ß) in MRC-5 cells. Moreover, compounds 14 and 17 dose dependently inhibited TGF-ß-induced epithelial-mesenchymal transition in A549 cells, alleviated TGF-ß-induced migration and proliferation of fibroblasts, and decreased the expression of fibrotic markers, fibronectin, and N-cadherin in TGF-ß-induced MRC-5 cells. The research showed the potential of cevanine-type alkaloids as a class of natural antifibrotic agents.

[Gly14]-humanin exerts a protective effect against D-galactose-induced primary ovarian insufficiency in mice.

RESEARCH QUESTION: Is there a protective effect of the humanin derivative [Gly14]-humanin (HNG) on a D-gal-induced mouse model of primary ovarian insufficiency (POI), and what is the underlying mechanism? DESIGN: D-gal (200 mg/kg/day) was injected subcutaneously for 6 weeks to induce the mouse POI model. Mice treated with HNG were injected intraperitoneally with different concentrations for 6 weeks. Ovarian morphology, function, levels of sex hormones and states of oxidative stress in the ovary and body were evaluated. RESULTS: Compared with the D-gal group, 10 mg/kg HNG improved the abnormal ovarian morphology and oestrous cycle (P = 0.0036), increased the number of ovarian follicles (P = 0.0016) and litters (P = 0.0127), and increased the levels of oestrogen (P = 0.0043) and AMH (P = 0.0147). Antioxidant indicators in the ovaries and serum of mice, including total antioxidant capacity (P = 0.0004 and P = 0.0032, respectively), catalase (P = 0.0173 and P = 0.0103, respectively) and glutathione (both P < 0.0001) were significantly increased. The oxidation indicator malondialdehyde decreased significantly (all P < 0.01). Apoptosis of ovarian granulosa cells was significantly reduced (P = 0.0140) as was the expression of senescence-related proteins p53, p21 and p16 (all P < 0.01). The level of autophagy in ovarian tissue of mice treated with high increased (significantly increased LC3 protein [P < 0.0001] and significantly reduced p62 protein [P = 0.0007]). CONCLUSIONS: HNG inhibited D-gal-induced oxidative stress, apoptosis and ovarian damage, promoting ovarian autophagy. HNG may be a potential prophylactic agent against POI.

[Neuropsychological development of large for gestational age infants at the age of 12 months]. / 大于胎龄儿12æœˆé¾„ç¥žç»å¿ƒç†å‘è‚²çŠ¶å†µç ”ç©¶.

OBJECTIVES: To investigate the level of neuropsychological development in large for gestational age (LGA) infants at the age of 12 months. METHODS: The infants, aged 12 to <13 months, who attended the Outpatient Service of Child Care in the First Affiliated Hospital of Shandong First Medical University from December 2021 to June 2023, were enrolled as subjects. According to the gestational age and birth weight, they were divided into preterm appropriate for gestational age (AGA) group, preterm LGA group, early term AGA group, early term LGA group, full-term AGA group, and full-term LGA group. A modified Poisson regression analysis was used to investigate the association between LGA and neuropsychological development outcome at 12 months of age. RESULTS: After adjustment for confounding factors, compared with the full-term AGA group at the age of 12 months, the full-term LGA group had a significant increase in the risk of language deficit (RR=1.364, 95%CI: 1.063-1.750), the early term LGA group had significant increases in the risk of abnormal gross motor, fine motor, language, and the preterm LGA group had significant increases in the risk of abnormal language, social behavior, and total developmental quotient (P<0.05); also, the early term AGA group had higher risks of developmental delay across all five attributes and in total developmental quotient at the age of 12 months (P<0.05); except for the language attribute, the preterm AGA group had higher risks of developmental delay in the other 4 attributes (P<0.05). CONCLUSIONS: The neuropsychological development of LGA infants with different gestational ages lags behind that of full-term AGA infants at 12 months of age, and follow-up and early intervention of such infants should be taken seriously in clinical practice.

Wavefront coding image reconstruction via physical prior and frequency attention.

Wavefront coding (WFC) is an effective technique for extending the depth-of-field of imaging systems, including optical encoding and digital decoding. We applied physical prior information and frequency domain model to the wavefront decoding, proposing a reconstruction method by a generative model. Specifically, we rebuild the baseline inspired by the transformer and propose three modules, including the point spread function (PSF) attention layer, multi-feature fusion block, and frequency domain self-attention block. These models are used for end-to-end learning to extract PSF feature information, fuse it into the image features, and further re-normalize the image feature information, respectively. To verify the validity, in the encoding part, we use the genetic algorithm to design a phase mask in a large field-of-view fluorescence microscope system to generate the encoded images. And the experimental results after wavefront decoding show that our method effectively reduces noise, artifacts, and blur. Therefore, we provide a deep-learning wavefront decoding model, which improves reconstruction image quality while considering the large depth-of-field (DOF) of a large field-of-view system, with good potential in detecting digital polymerase chain reaction (dPCR) and biological images.

Molecular simulation on compatibility and mechanisms of SBS and PTW polymer modifiers in asphalt binder.

CONTEXT: Ultrathin overlays are preventive maintenance measures; the tensile and shear stresses generated inside a structural layer under vehicle load are greater than those of conventional thickness asphalt pavement. Therefore, asphalt binders must use high-viscosity and elasticity unique cementing materials to ensure stability. To investigate the modification mechanism of styrene-butadiene-styrene (SBS)/ethylene-butyl acrylate-glycidyl methacrylate copolymer (PTW) high-viscosity modified asphalt binder suitable for ultrathin overlays, the compatibility and molecular behavior of SBS/PTW high-viscosity modified asphalt binder were analyzed by the molecular dynamics (MD) method. These research results provide a reference for preparing ultrathin overlay high-performance composite modified asphalt binder. METHODS: SBS molecular models, PTW molecular models, asphalt binder molecular models, SBS/asphalt binder blend systems, and SBS/PTW/asphalt binder blend systems were sequentially constructed using Materials Studio (MS) software. The compatibility of SBS, PTW, and SBS/PTW with asphalt binder and the diffusion coefficients of SBS, PTW, and SBS/PTW in the asphalt binder were investigated separately using the MD method. The mechanical properties and molecular behavior of SBS, PTW, and SBS/PTW blended with asphalt binder were studied. The research results indicate that the compatibility of PTW with asphalt binder is better than that of SBS with asphalt binder. PTW can effectively decrease the solubility parameter of asphalt binder and improve the compatibility between SBS and asphalt binder. PTW effectively improves the diffusion coefficient and interaction energy of SBS in asphalt binder by up to 29% and 83%. In addition, SBS/PTW had a significant positive effect on the mechanical properties of the asphalt binders, increasing the elastic modulus (E), bulk modulus (K), and shear modulus (G) of the asphalt binder by 4.6%, 9.5%, and 3.5%, respectively, compared to SBS. The results indicate that the SBS/PTW modified asphalt binder composite can significantly improve the high-temperature shear resistance of asphalt binder. Meanwhile, SBS and PTW improve the self-aggregation behavior between asphalt binder component molecules. The distance between the center of mass of asphalt binder and resin system molecules is increased. PTW enhances the extensibility of the branched chains of asphalt binder component molecules and improves the interaction between asphalt binder components and the chains. This further enhances the density and stability of the asphalt binder molecular structure system, improving the physical properties of the asphalt binder.

Sesquiterpenoids from the roots of Aucklandia costus and their anti-inflammatory activities.

Five undescribed sesquiterpenoid dimers, aucklandiolides A-E (1-5), one new sesquiterpenoid glycoside, ß-cyclocostunolide-15-ß-D-glucopyranoside (6), and seventeen known analogues (7-23) were isolated from the roots of Aucklandia costus. Their structures were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, and their configurations were confirmed by the computational calculations of ECD and NMR chemical shifts. Aucklandiolides A and B are the first examples of dimeric sesquiterpenoids with a unique 6/6/6/5/6/6 ring system originated from a proposed Diels-Alder cycloaddition between two eudesmane sesquiterpenoids. Besides, compounds 9-11, 20, and 22 showed significant inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells at a concentration of 20 µM.

The effect of herbal medicine in innate immunity to Candida albicans.

Candida albicans (C. albicans) is an opportunistic pathogenic fungus that often causes mucosal and systemic infections. Several pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs), have been implicated in the host recognition of C. albicans. These PRRs recognize the pathogen-associated molecular patterns (PAMPs) of C. albicans to activate innate immune cells, thereby rapidly inducing various inflammatory responses by activating intracellular signaling cascades. Herbal medicine and its active components deserve priority development due to their low toxicity and high antibacterial, antiviral and antifungal activities. This review discussed the activities of herbal compounds against C. albicans and their related mechanisms, especially their regulatory role on innate immune cells such as neutrophils, macrophages, and dendritic cells (DCs) implicated in C. albicans infections. Our work aims to find new therapeutic drugs and targets to prevent and treat diseases caused by C. albicans infection with the mechanisms by which this fungus interacts with the innate immune response.

Endoplasmic reticulum stress promotes endometrial fibrosis through the TGF-ß/SMAD pathway.

In brief: Intrauterine adhesion (IUA) is one of the main causes of female infertility. This study reveals that endoplasmic reticulum stress activation upregulates the TGF-ß/SMAD pathway to induce epithelial-mesenchymal transition and promote endometrial fibrosis in an IUA model. Abstract: IUA is a common gynecological disease and is a leading cause of female infertility. Mechanical or infectious damage to the endometrial basal layer can lead to endometrial fibrosis, which is the most common cause of IUA. Endoplasmic reticulum stress (ERS), the transforming growth factor beta signaling pathway (TGF-ß/SMAD) and epithelial-mesenchymal transition (EMT) are important factors promoting endometrial fibrosis. The purpose of this study was to determine the up- and downstream regulatory relationships of the above three in the process of endometrial fibrosis. The rat IUA model was induced by double injury method and prophylactic injection of the ERS inhibitor 4-phenylbutyric acid (4-PBA) was given in vivo. The ERS activator tunicamycin and the TGF-ß/SMAD pathway inhibitor A 83-01 were used in human endometrial epithelial cells (HEECs) in vitro. Masson's trichrome, Sirius red staining, immunohistochemistry, immunofluorescence and Western blot analyses were used to determine ERS, TGF-ß/SMAD pathway, EMT and fibrosis markers in the uterine tissue and HEECs of the different treatment groups. In animal experiments, ERS and the TGF-ß/SMAD pathway had been activated and EMT occurred in an in vivo model of IUA but was suppressed in animals treated with prophylactic 4-PBA. In in vitro experiments, tunicamycin-treated HEECs had increased the activation of ERS, the abundance of TGF-ß/SMAD pathway and fibrosis markers while EMT occurred, but the TGF-ß/SMAD pathway and EMT were significantly inhibited in the tunicamycin+A 83-01 group. Our data suggest that increased ERS can induce EMT and promote endometrial fibrosis through the TGF-ß/SMAD pathway.

Toxicity of polystyrene nanoparticles for mouse ovary and cultured human granulosa cells.

The issue of global environmental contamination of microplastics has recently been receiving widespread attention. However, the effects of polystyrene nanoparticles (Nano-PS) on the female reproductive system remain unclear. We investigated the toxicity and explored the potential underlying mechanisms of Nano-PS in both mouse ovarian tissue in vivo and human ovarian granulosa cell lines in vitro. In vivo experiments: Mice were fed different concentrations of Nano-PS for 8 weeks. In vitro experiments: COV434 cells were treated with increasing concentrations of Nano-PS. In the present study, ovarian reserve was found to decrease significantly, while oxidative stress and apoptosis levels increased. Nano-PS increased the proportion of metestrum and diestrus periods, and decreased the proportion of estrous period. The implantation rates and the number of pups per litter decreased. In COV434 cells, Nano-PS reduced cell viability and mitochondrial membrane potential, increased the expression of apoptotic and oxidative stress markers and led to subsequent cell cycle arrest. Specifically, Nano-PS exert their toxic effects on mouse ovarian tissue and COV434 cells by inducing oxidative stress. A potential strategy to overcome this could be to activate the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway to mitigate Nano-PS-induced oxidative stress.

Targeting Virulence Factors of Candida albicans with Natural Products.

Natural products derived from natural resources, including nutritional functional food, play an important role in human health. In recent years, the study of anti-fungal and other properties of agri-foods and derived functional compounds has been a hot research topic. Candida albicans is a parasitic fungus that thrives on human mucosal surfaces, which are colonized through opportunistic infection. It is the most prevalent cause of invasive fungal infection in immunocompromised individuals, resulting in a wide variety of clinical symptoms. Moreover, the efficacy of classical therapeutic medications such as fluconazole is often limited by the development of resistance. There is an ongoing need for the development of novel and effective antifungal therapy and medications. Infection of C. albicans is influenced by a great quantity of virulence factors, like adhesion, invasion-promoting enzymes, mycelial growth, and phenotypic change, and among others. Furthermore, various natural products especially from food sources that target C. albicans virulence factors have been researched, providing promising prospects for C. albicans prevention and treatment. In this review, we discuss the virulence factors of C. albicans and how functional foods and derived functional compounds affect them. Our hope is that this review will stimulate additional thoughts and suggestions regarding nutritional functional food and therapeutic development for patients afflicted with C. albicans.

[Changes in Carbonaceous Aerosol in the Northern Suburbs of Nanjing from 2015 to 2019].

Carbonaceous aerosol is an important component of atmospheric fine particles that has an important impact on air quality, human health, and climate change. In order to explore the long-term changes in carbonaceous aerosol under the background of emission reduction, this study measured the mass concentrations of organic carbon (OC) and elemental carbon (EC) of PM2.5, which collected in the northern suburbs of Nanjing for five years (December 17, 2014 to January 5, 2020). The results showed that the five-year average ρ(OC) and ρ(EC) were (10.2±5.3) µg·m-3 and (1.6±1.1) µg·m-3, accounting for 31.1% and 5.2% of PM2.5, respectively. OC and EC concentrations were both high in winter and low in summer. According to the nonparametric Mann-Kendall test and Sen's slope, the mass concentrations of OC and PM2.5 decreased significantly[OC:P<0.0001, -0.79 µg·(m3·a)-1, -0.29%·a-1; PM2.5:P<0.0001, -4.59 µg·(m3·a)-1, -1.58%·a-1]. Although EC had an upward trend, the significance and range of change were not obvious[P=0.02, 0.05 µg·(m3·a)-1, 0.02%·a-1]. OC and EC decreased significantly during winter from 2014 to 2019[OC:P<0.0001, -2.05 µg·(m3·a)-1, -0.74%·a-1; EC:P=0.001, -0.15 µg·(m3·a)-1, -0.05%·a-1], and the decline was more obvious than the whole. The correlation between OC and EC showed that the sources in winter and summer were more complex than those in spring and autumn. According to the characteristic ratio of OC and EC, the contribution of coal combustion and biomass burning decreased from 2015 to 2019, whereas the impact of industrial sources and vehicle emissions became more significant. Corresponding to this was the obvious decline in OC and the slight recovery of EC. The OC/EC ratio was over 2.0, indicating that there was secondary pollution in the study area. Further calculation revealed that the variation in SOC was consistent with that in OC, showing a significant decrease[P<0.0001, -0.47 µg·(m3·a)-1, -0.17%·a-1]. The average mass concentration of SOC was (5.0±3.5) µg·m-3, accounting for 49.2% of OC. These changes indicate clear effects of the prevention and control of air pollution in Nanjing in recent years. Furthermore, future control can focus on the emissions of VOCs to reduce secondary pollution.

EndMT: New findings on the origin of myofibroblasts in endometrial fibrosis of intrauterine adhesions.

BACKGROUND: Intrauterine adhesion (IUA) is one of the leading causes of infertility and the main clinical challenge is the high recurrence rate. The key to solving this dilemma lies in elucidating the mechanisms of endometrial fibrosis. The aim of our team is to study the mechanism underlying intrauterine adhesion fibrosis and the origin of fibroblasts in the repair of endometrial fibrosis. METHODS: Our experimental study involving an animal model of intrauterine adhesion and detection of fibrosis-related molecules. The levels of molecular factors related to the endothelial-to-mesenchymal transition (EndMT) were examined in a rat model of intrauterine adhesion using immunofluorescence, immunohistochemistry, qPCR and Western blot analyses. Main outcome measures are levels of the endothelial marker CD31 and the mesenchymal markers alpha-smooth muscle actin (α-SMA) and vimentin. RESULTS: Immunofluorescence co-localization of CD31 and a-SMA showed that 14 days after moulding, double positive cells for CD31 and a-SMA could be clearly observed in the endometrium. Decreased CD31 levels and increased α-SMA and vimentin levels indicate that EndMT is involved in intrauterine adhesion fibrosis. CONCLUSIONS: Endothelial cells promote the emergence of fibroblasts via the EndMT during the endometrial fibrosis of intrauterine adhesions.

Cold-inducible RNA-binding protein regulates cyclin B1 against spermatogenesis arrest caused by heat stress.

BACKGROUND: Spermatogenesis arrest and spermatogenic cell apoptosis occur in the testes of heat-stressed mice. Although heat stress-induced spermatogenic cell apoptosis is due to the decreased expression of cold-inducible RNA-binding protein (CIRBP), it remains unclear whether spermatogenesis arrest is also affected by CIRBP. Additionally, the specific mechanism by which CIRBP regulates spermatogenic cell apoptosis or inhibits spermatogenesis remains to be elucidated. OBJECTIVES: To investigate the mechanism by which CIRBP contributes to heat stress-induced testicular spermatogenesis arrest. MATERIALS AND METHODS: Target mRNAs downstream of CIRBP in testicular tissue of BALB/c mice, exposed or not to heat stress, were sequenced. Sequencing data were subjected to bioinformatics analysis to identify key mRNAs and pathways associated with heat stress-induced spermatogenic damage. The link between CIRBP and its target mRNA Ccnb1 (cyclin B1) was verified by western blotting, flow cytometry, and RNA pulldown assays, and the ability of CIRBP to inhibit germ cell cycle arrest by regulating cyclin B1 expression was investigated in a mouse spermatocyte cell line (GC-2spd). RESULTS: Changes in mRNA expression downstream of CIRBP were mainly associated with the cell cycle and RNA binding, transport and splicing. Cyclin B1 was found to regulate the G2/M transition during the first meiotic division of spermatogenic cells. Further, CIRBP was shown to bind directly to the 3'-untranslated region of Ccnb1 mRNA and was associated with cyclin B1-induced inhibition of spermatogenesis arrest. DISCUSSION AND CONCLUSION: In conclusion, our results provide strong evidence that CIRBP may exert its key function in heat stress-induced testicular spermatogenic cell injury partly by regulating the expression of Ccnb1, the product of which inhibits spermatogenesis arrest.

Cold exposure prevents fat accumulation in striped hamsters refed a high-fat diet following food restriction.

BACKGROUND: In mammals, body mass lost during food restriction is often rapidly regained, and fat is accumulated when ad libitum feeding is resumed. Studies in small cold-acclimated mammals have demonstrated significant mobilization of fat deposits during cold exposure to meet the energy requirements of metabolic thermogenesis. However, no studies to our knowledge have examined the effect of cold exposure on fat accumulation during body mass recovery when refed ad libitum. In this study, striped hamsters restricted to 80% of their regular food intake were then refed ad libitum and exposed to one of three conditions: Intermittent cold temperature (5 °C) for 2 h per day (ICE-2 h/d), intermittent cold temperature (5 °C) for 12 h per day (ICE-12 h/d), or persistent cold exposure (PCE) for four weeks. We measured energy intake, fat deposit mass, serum thyroid hormone levels, and uncoupling protein 1 expression in brown adipose tissue. RESULTS: There was no significant effect of intermittent or persistent cold exposure on body mass regain, whereas energy intake increased significantly and total fat deposit decreased in the ICE-12 h/d and PCE groups compared to the ICE-2 h/d group and control group maintained at 23 °C (CON). In the ICE-12 h/d and PCE groups, hamsters had 39.6 and 38.3% higher serum 3,3',5-triiodothyronine levels, respectively, and 81.6 and 71.3% up-regulated expression of uncoupling protein 1, respectively, in brown adipose tissue compared to their counterparts in the CON group. The rate of mitochondrial state III and state IV respiration O2 consumption and the activity of cytochrome c oxidase in BAT and liver were significantly higher in the ICE-12 h/d and PCE groups than in the ICE-2 h/d and CON groups. CONCLUSIONS: Our findings suggest thyroid hormone-mediated heat production in brown adipose tissue and liver may be involved in preventing fat accumulation during refeeding in animals frequently or persistently exposed to cold conditions.

Differential expression of microRNAs in human endometrium after implantation of an intrauterine contraceptive device containing copper.

Intrauterine devices containing copper placement will release a large amount of Cu2+ into the uterine fluid, leading to local endometrial damage and inflammation, which is considered to be one of the causes of abnormal uterine bleeding. Studies have shown that the metabolism and function of metal ions are related to the regulation of microRNA. The aims of this study were to investigate changes in endometrial microRNA levels after implantation of an intrauterine device containing copper and to preliminarily explore the signalling pathways involved in abnormal uterine bleeding. The subjects were fertile women, aged 25-35, without major obstetrics and gynaecology diseases. Human endometrial tissues were collected before implantation or removal of the intrauterine device containing copper. High-throughput microRNA sequencing was performed on human endometrial tissues, and real-time quantitative PCR, western blotting and immunohistochemistry were used to detect the expression of relevant genes. MicroRNA sequencing results showed that 72 miRNAs were differentially expressed in the endometrial tissue after the insertion of the intrauterine device containing copper. Implantation of an intrauterine device containing copper implantation can up-regulate the expression of miR-144-3p in endometrial tissue, and therefore, decreases the mRNA and protein expression levels of genes related to endometrial injury and tissue repair, including the MT/NF-κB/MMP damage pathway and the THBS-1/TGF-ß/SMAD3 repair pathway. In this study, the molecular mechanisms of abnormal uterine bleeding due to an intrauterine device containing copper were preliminarily investigated. The information will be beneficial for the clinical treatment of abnormal uterine bleeding caused by intrauterine device.

The effect of aggression II: Acclimation to a high ambient temperature reduces territorial aggression in male striped hamsters (Cricetulus barabensis).

Thyroid hormones have a profound influence on development, cellular differentiation and metabolism, and are also suspected of playing a role in aggression. We measured territorial aggression, body temperature (Tb) and serum thyroid hormones levels of male striped hamsters (Cricetulus barabensis) acclimated to either cold (5 °C), cool (21 °C) or hot (34 °C) ambient temperatures. The effects of methimazole on territorial aggression, food intake, metabolic rate and serum thyroid hormone levels, were also examined. Territorial aggression was significantly lower in male hamsters acclimated to the hot temperature compared to those acclimated to the cool or cold temperatures. Tb significantly increased during aggressive territorial interactions with intruders but did not significantly differ among the three temperature treatments. Serum T3, T4 and cortisol levels of hamsters acclimated to 34 °C were significantly lower than those acclimated to 21 °C. In addition to significantly reducing territorial aggression, treatment with methimazole also significantly reduced serum T3 and T4 levels, Tb and metabolic rate. These results suggest that exposure to high temperatures reduces the capacity of hamsters to dissipate heat causing them to lower their metabolic rate, which, in turn, causes them to reduce territorial aggression to prevent hyperthermia. The lower metabolic rate mediated by down-regulated thyroid hormones inhibits territorial aggression and could thereby determine the outcome of territorial conflicts.

Influenza A Viruses Enter Host Cells via Extracellular Ca2+ Influx-Involved Clathrin-Mediated Endocytosis.

Influenza A virus (IAV) is internalized into its host cells by endocytosis, which involves many cellular proteins and molecules. In this study, we focus on the function of calcium ion (Ca2+) in IAV endocytosis. We have found that IAV infection is accompanied by the increase in concentration of cytosolic Ca2+, which is mainly attributed to the influx of extracellular Ca2+. When Ca2+ influx is abolished, IAV internalization will be markedly suppressed, but the virus attachment to its host cells will be unaffected. Extracellular Ca2+ influx is essential to the clathrin-mediated endocytosis (CME) of IAVs but dispensable to the clathrin-independent endocytosis of the virus and is dispensable to the CME of transferrin or low-density lipoprotein as a control. Ca2+ influx might participate in the dynamin-promoted membrane fission in the CME of IAVs. Our study highlights that IAVs enter host cells via extracellular Ca2+ influx-involved clathrin- and dynamin-dependent endocytosis, which will facilitate better understanding of IAV infection and development of anti-influenza drugs.