Adipose tissue browning and thermogenesis under physiologically energetic challenges: a remodelled thermogenic system.

Metabolic diseases such as obesity and diabetes are often thought to be caused by reduced energy expenditure, which poses a serious threat to human health. Cold exposure, exercise and caloric restriction have been shown to promote adipose tissue browning and thermogenesis. These physiological interventions increase energy expenditure and thus have emerged as promising strategies for mitigating metabolic disorders. However, that increased adipose tissue browning and thermogenesis elevate thermogenic consumption is not a reasonable explanation when humans and animals confront energetic challenges imposed by these interventions. In this review, we collected numerous results on adipose tissue browning and whitening and evaluated this bi-directional conversion of adipocytes from the perspective of energy homeostasis. Here, we propose a new interpretation of the role of adipose tissue browning under energetic challenges: increased adipose tissue browning and thermogenesis under energy challenge is not to enhance energy expenditure, but to reestablish a more economical thermogenic pattern to maintain the core body temperature. This can be achieved by enhancing the contribution of non-shivering thermogenesis (adipose tissue browning and thermogenesis) and lowering shivering thermogenesis and high intensity shivering. Consequently, the proportion of heat production in fat increases and that in skeletal muscle decreases, enabling skeletal muscle to devote more energy reserves to overcoming environmental stress.

From theory to therapy: a bibliometric and visual study of stem cell advancements in age-related macular degeneration.

BACKGROUND AIMS: Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, offer groundbreaking therapeutic potential for degenerative diseases and cellular repair. Despite their significance, a comprehensive bibliometric analysis in this field, particularly in relation to age-related macular degeneration (AMD), is yet to be conducted. This study aims to map the foundational and emerging areas in stem cell and AMD research through bibliometric analysis. METHODS: This study analyzed articles and reviews on stem cells and AMD from 2000 to 2022, sourced from the Web of Science Core Collection. We used VOSviewer and CiteSpace for analysis and visualization of data pertaining to countries, institutions, authors, journals, references and key words. Statistical analyses were conducted using R language and Microsoft Excel 365. RESULTS: In total, 539 publications were included, indicating an increase in global literature on stem cells and AMD from 2000 to 2022. The USA was the leading contributor, with 239 papers and the highest H-index, also the USA had the highest average citation rate per article (59.82). Notably, 50% of the top 10 institutions were from the USA, with the University of California system being the most productive. Key authors included Masayo Takahashi, Michiko Mandai, Dennis Clegg, Pete J. Coffey, Boris Stanzel, and Budd A. Tucker. Investigative Ophthalmology & Visual Science published the majority of relevant papers (n = 27). Key words like "clinical trial," "stem cell therapy," "retinal organoid," and "retinal progenitor cells" were predominant. CONCLUSIONS: Research on stem cells and AMD has grown significantly, highlighting the need for increased global cooperation. Current research prioritizes the relationship between "ipsc," "induced pluripotent stem cell," "cell culture," and "human embryonic stem cell." As stem cell culture and safety have advanced, focus has shifted to prognosis and complications post-transplantation, signifying the movement of stem cell research from labs to clinical settings.

Unveiling the potential of estrogen: Exploring its role in neuropsychiatric disorders and exercise intervention.

Neuropsychiatric disorders shorten human life spans through multiple ways and become major threats to human health. Exercise can regulate the estrogen signaling, which may be involved in depression, Alzheimer's disease (AD) and Parkinson's disease (PD), and other neuropsychiatric disorders as well in their sex differences. In nervous system, estrogen is an important regulator of cell development, synaptic development, and brain connectivity. Therefore, this review aimed to investigate the potential of estrogen system in the exercise intervention of neuropsychiatric disorders to better understand the exercise in neuropsychiatric disorders and its sex specific. Exercise can exert a protective effect in neuropsychiatric disorders through regulating the expression of estrogen and estrogen receptors, which are involved in neuroprotection, neurodevelopment, and neuronal glucose homeostasis. These processes are mediated by the downstream factors of estrogen signaling, including N-myc downstream regulatory gene 2 (Ndrg2), serotonin (5-HT), delta like canonical Notch ligand 1 (DLL1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), etc. In addition, exercise can act on the estrogen response element (ERE) fragment in the genes of estrogenic downstream factors like ß-amyloid precursor protein cleavase 1 (BACE1). However, there are few studies on the relationship between exercise, the estrogen signaling pathway, and neuropsychiatric disorders. Hence, we review how the estrogen signaling mediates the mechanism of exercise intervention in neuropsychiatric disorders. We aim to provide a theoretical perspective for neuropsychiatric disorders affecting female health and provide theoretical support for the design of exercise prescriptions.

Streptomyces virginiae XDS1-5, an antagonistic actinomycete, as a biocontrol to peach brown rot caused by Monilinia fructicola.

BACKGROUND: Peach brown rot, caused by the pathogen Monilinia fructicola, represents a significant postharvest infectious disease affecting peach fruit. This disease is responsible for a substantial increase in fruit decay rates, leading to significant economic losses, often exceeding 50%. Currently, there is a growing interest in identifying biocontrol agents to mitigate peach brown rot, with a predominant interest in Bacillus species. RESULTS: In this investigation, we isolated 410 isolates of actinomycetes from non-farmland ecosystem soil samples. Subsequently, 27 isolates exhibiting superior inhibitory capabilities were selected. Among these, strain XDS1-5 demonstrated the most robust fungistatic effect against brown rot disease, achieving an 80% inhibition rate in vitro and a 66% inhibition rate in vivo. XDS1-5 was identified as belonging to the Streptomyces virginiae species. Furthermore, a fermentation filtrate of XDS1-5 exhibited the ability to metabolize 34.21% of the tested carbon sources and 7.37% of the tested nitrogen sources. Particularly noteworthy was its capacity to disrupt the cell membrane structure directly, leading to increased cell membrane permeability and cytoplasmic leakage. Additionally, our investigation indicated that indoline, a metabolite produced by XDS1-5, played a pivotal role in inhibiting the growth of M. fructicola. CONCLUSION: In summary, our study has identified a biocontrol actinomycete, XDS1-5, with the potential to effectively inhibit postharvest brown rot disease in peaches. This finding holds great significance for the biological control of peach brown rot, offering promising prospects for mitigating the economic losses associated with this devastating disease. © 2024 Society of Chemical Industry.

Tobacco mosaic virus hijacks its coat protein-interacting protein IP-L to inhibit NbCML30, a calmodulin-like protein, to enhance its infection.

Calcium is an important plant immune signal that is essential for activating host resistance, but how RNA viruses manipulate calcium signals to promote their infections remains largely unknown. Here, we demonstrated that tobacco mosaic virus (TMV) coat protein (CP)-interacting protein L (IP-L) associates with calmodulin-like protein 30 (NbCML30) in the cytoplasm and nucleus, and can suppress its expression at the nucleic acid and protein levels. NbCML30, which lacks the EF-hand conserved domain and cannot bind to Ca2+ , was located in the cytoplasm and nucleus and was downregulated by TMV infection. NbCML30 silencing promoted TMV infection, while its overexpression inhibited TMV infection by activating Ca2+ -dependent oxidative stress in plants. NbCML30-mediated resistance to TMV mainly depends on IP-L regulation as the facilitation of TMV infection by silencing NbCML30 was canceled by co-silencing NbCML30 and IP-L. Overall, these findings indicate that in the absence of any reported silencing suppressor activity, TMV CP manipulates IP-L to inhibit NbCML30, influencing its Ca2+ -dependent role in the oxidative stress response. These results lay a theoretical foundation that will enable us to engineer tobacco (Nicotiana spp.) with improved TMV resistance in the future.

MAP30 and luffin-α: Novel ribosome-inactivating proteins induce plant systemic resistance against plant viruses.

Ribosome-inactivating proteins (RIPs) are toxic N-glycosylase that act on eukaryotic and prokaryotic rRNAs, resulting in arrest protein synthesis. RIPs are widely found in higher plant species and display strong antiviral activity. Previous studies have shown that PAP and α-MMC have antiviral activity against TMV. However, the localization of RIPs in plant cells and the mechanism by which RIPs activate plant defense against several plant viruses remain unclear. In this study, we obtained four RIPs (the C-terminal deletion mutant of pokeweed antiviral proteins (PAP-c), alpha-momorcharin (α-MMC), momordica anti-HIV protein of 30 kDa (MAP30) and luffin-α). The subcellular localization results indicated that these four RIPs were located on the plant cell membrane. Heterologous expression of RIPs (PAP-c, α-MMC, MAP30, luffin-α) enhanced tobacco mosaic virus (TMV) resistance in N. benthamiana. Compared with the control treatment, these RIPs significantly reduced the TMV content (149-357 fold) and altered the movement of TMV in the leaves of N. benthamiana. At the same time, heterologous expression of RIPs (MAP30 and luffin-α) could relieve TMV-induced oxidative damage, significantly inducing the expression of plant defense genes including PR1 and PR2. Furthermore, application of these RIPs could inhibit the infection of turnip mosaic virus (TuMV) and potato virus x (PVX). Therefore, this study demonstrated that MAP30 and luffin-α could be considered as new, effective RIPs for controlling plant viruses by activating plant systemic defense.

Fabrication of an alginate-based ZhiNengCong gel showed an enhanced antiviral and plant growth promoting functions.

Tobacco mosaic disease is a worldwide viral disease that can cause huge economic losses. Plant immune inducers have become the main force in the prevention and treatment of viral disease own to their high efficiency and rapid effect. However, since tobacco mosaic disease can occur at any point in the plant growth cycle, a single application period cannot guarantee the completely management. In this study, an extract from Paecilomyces variotii named ZhiNengCong (ZNC), which can fight against tobacco mosaic disease with 65% control effect, and improve the promotion of tobacco stem girth, was selected from five commercial antiviral medicines, and a sustained release sodium alginate (Alg)-based ZNC (ZNC@Alg) was prepared by physical absorption. ZNC@Alg, who contains only 5 mg/mL ZNC, can release ZNC for 7 consecutive days, and displayed an enhanced effect in inducing the PAL-mediated salicylic acid signaling pathway activation to participate in the inhibition of green fluorescent protein (GFP)-tagged tobacco mosaic virus (TMV-GFP) infection, even after 7 days of the application. Notably, field experiments showed that the control effect of ZNC@Alg was up to 88%, which was significantly better than that of ZNC with the same concentration (10 µg per plant). In addition, ZNC@Alg exhibited a stronger growth-promoting effect than ZNC, which significantly increased the wet weight of tobacco. Taken together, we screened out a plant immune inducer ZNC that can effectively inhibit tobacco virus disease, and created ZNC@Alg with higher control effect and growth promotion effect, laying a foundation for effective field management of tobacco mosaic disease.

Silicon-Vacancy Nanodiamonds as High Performance Near-Infrared Emitters for Live-Cell Dual-Color Imaging and Thermometry.

Nanodiamonds (NDs) with color centers are excellent emitters for various bioimaging and quantum biosensing applications. In our work, we explore new applications of NDs with silicon-vacancy centers (SiV) obtained by high-pressure high-temperature (HPHT) synthesis based on metal-catalyst-free growth. They are coated with a polypeptide biopolymer, which is essential for efficient cellular uptake. The unique optical properties of NDs with SiV are their high photostability and narrow emission in the near-infrared region. Our results demonstrate for the first time that NDs with SiV allow live-cell dual-color imaging and intracellular tracking. Also, intracellular thermometry and challenges associated with SiV atomic defects in NDs are investigated and discussed for the first time. NDs with SiV nanoemitters provide new avenues for live-cell bioimaging, diagnostic (SiV as a nanosized thermometer), and theranostic (nanodiamonds as drug carrier) applications.

Codon-optimized FAM132b gene therapy prevents dietary obesity by blockading adrenergic response and insulin action.

BACKGROUND: FAM132b (myonectin) has been identified as a muscle-derived myokine with exercise and has hormone activity in circulation to regulate iron homeostasis and lipid metabolism via unknown receptors. Here, we aim to explore the potential of adeno-associated virus to deliver FAM132b in vivo to develop a gene therapy against obesity. METHODS: Adeno-associated virus AAV9 were engineered to induce overexpression of FAM132b with two mutations, A136T and P159A. Then, AAV9 was delivered into high-fat diet mice through tail vein, and glucose homeostasis and obesity development of mice were observed. Methods of structural biology were used to predict the action site or receptor of the FAM132b mutant. RESULTS: Treatment of high-fat diet-fed mice with AAV9 improved glucose intolerance and insulin resistance, and resulted in reductions in body weight, fat depot, and adipocyte size. Codon-optimized FAM132b (coFAM132b) reduced the glycemic response to epinephrine (EPI) in the whole body and increased the lipolytic response to EPI in adipose tissues. However, FAM132b knockdown by shRNA significantly increased the glycemic response to EPI in vivo and reduced adipocyte response to EPI and adipose tissue browning. Structural analysis predicted that the FAM132b mutant with A136T and P159A may form a weak bond with ß2 adrenergic receptor (ADRB2) and may have more affinity for insulin and insulin-receptor complexes. CONCLUSIONS: Our study underscores the potential of FAM132b gene therapy with codon optimization to treat obesity by modulating the adrenergic response and insulin action. Both structural biological analysis and in vivo experiments suggest that the adrenergic response and insulin action are most likely blockaded by FAM132b mutants.

Trends of overweight and obesity among preschool children from 2013 to 2018: a cross-sectional study in Rhine-Neckar County and the City of Heidelberg, Germany.

BACKGROUND: Early childhood overweight and obesity is a growing public health concern worldwide. Few recent studies have addressed how time trends varied by sociodemographic characteristics at the regional level using large and high-quality data. This study determines how time trends vary in the prevalence of early childhood overweight and obesity by age, gender, and migration background at the regional level. METHODS: We used a Kernel-density curve to describe the BMI distribution, and evaluated the trends of overweight and obesity by age, gender, and migration background using logistic regression. RESULTS: Mean BMI and the overall prevalence of overweight and obesity increased among preschool children aged 4-6 years in the Rhine-Neckar County and the City of Heidelberg. After adjusting for age, sex, and migration background, trends of overweight significantly increased only among male children in the age 5 year group with migration background (P < 0.05), and an upward trend of obesity was observed only among male children in the age 5 year group and female children in the age 6 year group with migration background (P < 0.05). CONCLUSIONS: BMI distribution as well as general prevalence of overweight and obesity are still increasing among preschool children. Children with migration backgrounds, particularly male children in the age 5 year groups and female children in the age 6 year group should be prioritized. Health promotion strategies for children with migration backgrounds will help address this challenge.

Selenium regulates the mitogen-activated protein kinase pathway to protect broilers from hexavalent chromium-induced kidney dysfunction and apoptosis.

Hexavalent chromium [Cr (VI)] is a common environmental pollutant. Although selenium (Se) can antagonize the toxicity of Cr (VI), the specific underlying mechanism has not been identified. To investigate this mechanism, we used potassium dichromate (K2Cr2O7) and selenium-rich yeast (SeY) to construct single Cr (VI)- and combined Se/Cr (VI)-exposed broiler models during a 42-day period. Broilers were randomly assigned to the control (C), SeY (Se), SeY + Cr (VI) (Se/Cr), and Cr (VI) (Cr) groups. The antagonistic mechanisms of Se and Cr (VI) were evaluated using histopathological evaluation, serum and tissue biochemical tests, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The results suggested that Se alleviated the morphological and structural damage to renal tubules and glomeruli, while reducing the organ index, creatinine levels, and blood urea nitrogen levels in the kidneys of Cr (VI)-exposed broilers. Furthermore, Cr (VI) reduced the levels of superoxide dismutase and glutathione, and increased the levels of malondialdehyde, in broiler kidney tissues. However, Se alleviated Cr (VI)-induced oxidative stress by increasing the levels of superoxide dismutase and glutathione, and decreasing the levels of malondialdehyde, within a certain range. Compared to the C group, the levels of p38, JNK, p-p38, p-JNK, p-p38/p38, and p-JNK/JNK significantly increased, whereas those of ERK, p-ERK, and p-ERK/ERK decreased, in the Cr group. Compared to the Cr group, the levels of p38, JNK, p-p38, p-JNK, p-p38/p38, and p-JNK/JNK significantly decreased, whereas those of ERK, p-ERK, and p-ERK/ERK increased, in the Se/Cr group. Furthermore, the levels of p53, c-Myc, Bax, Cyt-c, caspase-9, and caspase-3 significantly increased, and those of Bcl-2 and Bcl-2/Bax significantly decreased, following Cr (VI) exposure, while Se restored the expression of these genes. In conclusion, our findings suggest that SeY can protect against Cr (VI)-induced dysfunction and apoptosis by regulating the mitogen-activated protein kinase pathway activated by oxidative stress in broiler kidney tissues.

Transcription factor McWRKY71 induced by ozone stress regulates anthocyanin and proanthocyanidin biosynthesis in Malus crabapple.

In plants, anthocyanins and proanthocyanidins (PAs) play important roles in plant resistance to abiotic stress. In this study, ozone (O3) treatments caused the up-regulation of Malus crabapple structural genes McANS, McCHI, McANR and McF3H, which promoted anthocyanin and PA accumulation. We identified the WRKY transcription factor (TF) McWRKY71 by screening differentially expressed genes (DEGs) that were highly expressed in response to O3 stress from an RNA sequencing (RNA-seq) analysis. Overexpressing McWRKY71 increased the resistance of 'Orin' apple calli to O3 stress and promoted the accumulation of anthocyanins and PAs, which facilitated reactive oxygen species scavenging to further enhance O3 tolerance. Biochemical and molecular analyses showed that McWRKY71 interacted with McMYB12 and directly bound the McANR promoter to participate in the regulation of PA biosynthesis. These findings provide new insights into the WRKY TFs mechanisms that regulate the biosynthesis of secondary metabolites, which respond to O3 stress, in Malus crabapple.

The Role of Fgf9 in the Antidepressant Effects of Exercise and Fluoxetine in Chronic Unpredictable Mild Stress Mice.

OBJECTIVE: The neurotrophic hypothesis of depression posits that stress and depression decrease neurotrophic factor expression in brain, whereas antidepressants and exercise can contribute to the blockade of stress effects and produce antidepressant effects. Fibroblast growth factor 9 (FGF9), a member of the fibroblast growth factor (FGF) family, has been reported to be dysregulated in depression. The present study aimed to determine whether and how Fgf9 mediates the antidepressant effects of fluoxetine and exercise in chronic unpredictable mild stress (CUMS) mice. METHODS: Male C57BL/6 mice were exposed to CUMS for 7 weeks. From the fourth week, CUMS-exposed mice were subjected to fluoxetine treatment or swimming exercise for 4 weeks. Forced swim test, tail suspension test, and hole-board test were used to assess behaviors of mice. Real-time polymerase chain reaction was used to examine hippocampal messenger RNA levels of Fgf9, Fgf2, FgfR1, FgfR2, and FgfR3. Western blotting was used to examine the protein levels of Fgf9, protein kinase B (Akt), and phosphorylation of Akt at Ser473 in mouse hippocampus. RESULTS: Our results demonstrated that CUMS induced depression-like behaviors, which were reversed by fluoxetine treatment and swimming exercise. Moreover, we found that CUMS resulted in a dysregulation of Fgf9, Fgf2, and FgfR2 expression, whereas fluoxetine and swimming restored the FGF expression in CUMS-exposed mice. An analysis of the proteins suggests that the antidepressant effects of fluoxetine and exercise in CUMS-exposed mice were associated with ameliorated Fgf9/Akt signaling. CONCLUSIONS: Our findings have demonstrated that swimming exercise mimics the antidepressant effects of fluoxetine by regulating Fgf9 in CUMS-exposed mice, which may offer new mechanism-based therapeutic targets for depression.

Associations between BMI and visual impairment of 33 407 preschool children in Germany: a pooled cross-sectional study.

BACKGROUND: Prevalence of overweight and obesity in Germany is increasing. High body weight can affect children's growth and development. This paper aimed to determine the association between body mass index (BMI) and visual impairment among preschool children and explore the potential role of obesity in predicting visual developmental disorder. METHODS: Six consecutive years of data from the School Entry Examination were collected for all preschool children aged from 4 to 6 years residing in Rhine-Neckar County and the City of Heidelberg, Germany from 2013 to 2018. Univariate and multivariate regression were used to analyze the complete data, multiple imputation was used to deal with missing data. RESULTS: Among the group with an immigrant background, children with obesity [OR = 1.20, 99% (1.02-1.42)] were more likely to have visual impairment compared to those with normal body weight (P < 0.01) after adjusting for survey year, age, and gender of children, education and occupation of parents, screen time-frequency, whether a television was in their bedroom, and quality of preschool outdoor environment. CONCLUSION: There were significant associations between obesity and visual impairment among German preschool children with immigrant backgrounds. Strategies to support vulnerable groups were needed across all regional schools.

Decrease in SHP-1 enhances myometrium remodeling via FAK activation leading to labor.

Preterm birth is one of the most common complications during human pregnancy and is associated with a dramatic switch within the uterus from quiescence to contractility. However, the mechanisms underlying uterine remodeling are largely unknown. Protein kinases and phosphatases play critical roles in regulating the phosphorylation of proteins involved in the smooth muscle cell functions. In the present study, we found that Src-homology phosphatase type-1 (SHP-1, PTPN6) was significantly decreased in human myometrium in labor compared with that not in labor. Timed-pregnant mice injected intraperitoneally with the specific SHP-1 inhibitor protein tyrosine phosphatase inhibitor I (PTPI-1) manifested significantly preterm labor, with enriched plasmalemmal dense plaques between myometrial cells and increased phosphorylation at Tyr397 and Tyr576/577 sites of focal adhesion kinase (FAK) in myometrial cells, which remained to the time of labor, whereas the phosphorylation levels of ERK1/2 and phosphatidylinositol 3 kinase (PI3K) showed a rapid increase upon PTPI-1 injection but fell back to normal at the time of labor. The Tyr576/577 in FAK played an important role in the interaction between FAK and SHP-1. Knockdown of SHP-1 dramatically increased the spontaneous contraction of human uterine smooth muscle cells (HUSMCs), which was reversed by coinfection of a FAK-knockdown lentivirus. PGF2α downregulated SHP-1 via PLCß-PKC-NF-κB or PI3K-NF-κB pathways, suggesting the regenerative downregulation of SHP-1 enhances the uterine remodeling and plasticity by activating FAK and subsequent focal adhesion pathway, which eventually facilitates myometrium contraction and leads to labor. The study sheds new light on understanding of mechanisms that underlie the initiation of labor, and interventions for modulation of SHP-1 may provide a potential strategy for preventing preterm birth.

Unraveling In Vivo Brain Transport of Protein-Coated Fluorescent Nanodiamonds.

Nanotheranostics, combining diagnostics and therapy, has the potential to revolutionize treatment of neurological disorders. But one of the major obstacles for treating central nervous system diseases is the blood-brain barrier (BBB) preventing systemic delivery of drugs and optical probes into the brain. To overcome these limitations, nanodiamonds (NDs) are investigated in this study as they are a powerful sensing and imaging platform for various biological applications and possess outstanding stable far-red fluorescence, do not photobleach, and are highly biocompatible. Herein, fluorescent NDs encapsulated by a customized human serum albumin-based biopolymer (polyethylene glycol) coating (dcHSA-PEG) are taken up by target brain cells. In vitro BBB models reveal transcytosis and an additional direct cell-cell transport via tunneling nanotubes. Systemic application of dcHSA-NDs confirms their ability to cross the BBB in a mouse model. Tracking of dcHSA-NDs is possible at the single cell level and reveals their uptake into neurons and astrocytes in vivo. This study shows for the first time systemic NDs brain delivery and suggests transport mechanisms across the BBB and direct cell-cell transport. Fluorescent NDs are envisioned as traceable transporters for in vivo brain imaging, sensing, and drug delivery.

Prostaglandin E2 receptors differentially regulate the output of proinflammatory cytokines in myometrial cells from term pregnant women.

Prostaglandin (PG) E2 plays critical roles during pregnancy and parturition. Emerging evidence indicates that human labour is an inflammatory event. We sought to investigate the effect of PGE2 on the output of proinflammatory cytokines in cultured human uterine smooth muscle cells (HUSMCs) from term pregnant women and elucidate the role of subtypes of PGE2 receptors (EP1, EP2, EP3 and EP4). After drug treatment and/or transfection of each receptor siRNA, the concentrations of inflammatory secreting factors in HUSMCs culture medium were detected by the corresponding ELISA kits. The results showed that, PGE2 increased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) output, decreased chemokine (c-x-c motif) ligand 8 (CXCL8) output in a dose-dependent manner, but had no effect on IL-1ß and chemokine (c-c motif) ligand 2 (CCL-2) secretion of HUSMCs. EP1/EP3 agonist 17-phenyl-trinor-PGE2 stimulated IL-6 and TNFα whilst suppressing IL-1ß and CXCL8 output. The effects of 17-phenyl-trinor-PGE2 on IL-1ß and CXCL8 secretion were remained whereas its effect on IL-6 and TNFα output did not occur in the cells with EP3 knockdown. The stimulatory effects of 17-phenyl-trinor-PGE2 on IL-6 and TNFα were remained whereas the inhibitory effects of 17-phenyl-trinor-PGE2 on IL-1ß secretion was blocked in the cells with EP1 knockdown. Either of EP2 and EP4 agonists stimulated IL-1ß and TNFα output, which was reversed by EP2 and EP4 siRNA, respectively. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked EP1/EP3 modulation of TNFα and CXCL8 output. PI3K inhibitor LY294002 and P38 inhibitor SB202190 blocked 17-phenyl-trinor-PGE2-induced IL-1ß and IL-6 output, respectively. The inhibitors of adenylyl cyclase and PKA prevented EP2 and EP4 stimulation of IL-1ß and TNFα output, whereas PLC and PKC inhibitors blocked EP2- and EP4-induced TNFα output but not IL-1ß output. Our data suggest that PGE2 receptors exhibit different effects on the output of various cytokines in myometrium, which can subtly modulate the inflammatory microenvironment in myometrium during pregnancy.

A Microwave Method for Dielectric Characterization Measurement of Small Liquids Using a Metamaterial-Based Sensor.

We present a microwave method for the dielectric characterization of small liquids based on a metamaterial-based sensor The proposed sensor consists of a micro-strip line and a double split-ring resonator (SRR). A large electric field is observed on the two splits of the double SRRs at the resonance frequency (1.9 GHz). The dielectric property data of the samples under test (SUTs) were obtained with two measurements. One is with the sensor loaded with the reference liquid (REF) and the other is with the sensor loaded with the SUTs. Additionally, the principle of extracting permittivity from measured changes of resonance characteristics changes of the sensor loaded with REF and SUTs is given. Some measurements were carried out at 1.9 GHz, and the calculated results of methanol⁻water mixtures with different molar fractions agree well with the time-domain reflectometry method. Moreover, the proposed sensor is compact and highly sensitive for use of sub-wavelength resonance. In comparison with literature data, relative errors are less than 3% for the real parts and 2% for the imaginary parts of complex permittivity.

Controlling Cellular Uptake and Toxicity of Polyphenylene Dendrimers by Chemical Functionalization.

Polyphenylene dendrimers (PPDs) represent a unique class of macromolecules based on their monodisperse and shape-persistent nature. These characteristics have enabled the synthesis of a new genre of "patched" surface dendrimers, where their exterior can be functionalized with a variety of polar and nonpolar substituents to yield lipophilic binding sites in a site-specific way. Although such materials are capable of complexing biologically relevant molecules, show high cellular uptake in various cell lines, and low to no toxicity, there is minimal understanding of the driving forces to these characteristics. We investigated whether it is the specific chemical functionalities, relative quantities of each moiety, or the "patched" surface patterning on the dendrimers that more significantly influences their behavior in biological media.

Endogenous hydrogen sulfide contributes to uterine quiescence during pregnancy.

Recent evidence suggests that uterine activation for labor is associated with inflammation within uterine tissues. Hydrogen sulfide (H2S) plays a critical role in inflammatory responses in various tissues. Our previous study has shown that human myometrium produces H2S via its generating enzymes cystathionine-γ-lyase (CSE) and cystathionine-ß-synthetase (CBS) during pregnancy. We therefore explored whether H2S plays a role in the maintenance of uterine quiescence during pregnancy. Human myometrial biopsies were obtained from pregnant women at term. Uterine smooth muscle cells (UMSCs) isolated from myometrial tissues were treated with various reagents including H2S. The protein expression of CSE, CBS and contraction-associated proteins (CAPs) including connexin 43, oxytocin receptor and prostaglandin F2α receptor determined by Western blot. The levels of cytokines were measured by ELISA. The results showed that CSE and CBS expression inversely correlated to the levels of CAPs and activated NF-κB in pregnant myometrial tissues. H2S inhibited the expression of CAPs, NF-κB activation and the production of interleukin (IL)-1ß, IL-6 and tumor necrosis factor α (TNFα) in cultured USMCs. IL-1ß treatment reversed H2S inhibition of CAPs. Knockdown of CSE and CBS prevented H2S suppression of inflammation. H2S modulation of inflammation is through KATP channels and phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) signaling pathways. H2S activation of PI3K and ERK signaling is dependent on KATP channels. Our data suggest that H2S suppresses the expression of CAPs via inhibition of inflammation in myometrium. Endogenous H2S is one of the key factors in maintenance of uterine quiescence during pregnancy.