High life satisfaction reported among small-scale societies with low incomes.

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.

Reprogramming efficiency and pluripotency of mule iPSCs over its parents†.

The mule is the interspecific hybrid of horse and donkey and has hybrid vigor in muscular endurance, disease resistance, and longevity over its parents. Here, we examined adult fibroblasts of mule (MAFs) compared with the cells from their parents (donkey adult fibroblasts and horse adult fibroblasts) (each species has repeated three independent individuals) in proliferation, apoptosis, and glycolysis and found significant differences. We subsequently derived mule, donkey, and horse doxycycline (Dox)-independent induced pluripotent stem cells (miPSCs, diPSCs, and hiPSCs) from three independent individuals of each species and found that the reprogramming efficiency of MAFs was significantly higher than that of cells of donkey and horse. miPSCs, diPSCs, and hiPSCs all expressed the high levels of crucial endogenous pluripotency genes such as POU class 5 homeobox 1 (POU5F1, OCT4), SRY-box 2 (SOX2), and Nanog homeobox (NANOG) and propagated robustly in single-cell passaging. miPSCs exhibited faster proliferation and higher pluripotency and differentiation than diPSCs and hiPSCs, which were reflected in co-cultures and separate-cultures, teratoma formation, and chimera contribution. The establishment of miPSCs provides a unique research material for the investigation of "heterosis" and perhaps is more significant to study hybrid gamete formation.

Active control of mid-wavelength infrared non-linearity in silicon photonic crystal slab.

Natural materials' inherently weak nonlinear response demands the design of artificial substitutes to avoid optically large samples and complex phase-matching techniques. Silicon photonic crystals are promising artificial materials for this quest. Their nonlinear properties can be modulated optically, paving the way for applications ranging from ultrafast information processing to quantum technologies. A two-dimensional 15-µm-thick silicon photonic structure, comprising a hexagonal array of air holes traversing the slab's thickness, has been designed to support a guided resonance for the light with a wavelength of 4-µm. At the resonance conditions, a transverse mode of the light is strongly confined between the holes in the "veins" of the silicon component. Owing to the confinement, the structure exhibits a ratio of nonlinear to linear absorption coefficients threefold higher than the uniform silicon slab of the same thickness. A customised time-resolved Z-scan method with provisions to accommodate ultrafast pump-probe measurements was used to investigate and quantify the non-linear response. We show that optically pumping free charge carriers into the structure decouples the incoming light from the resonance and reduces the non-linear response. The time-resolved measurements suggest that the decoupling is a relatively long-lived effect on the scale comparable to the non-radiative recombination in the bulk material. Moreover, we demonstrate that the excited free carriers are not the source of the nonlinearity, as this property is determined by the structure design.

Differential expression and localisation of heat shock protein 70 (HSP70) and glutathione peroxidase 5 (GPX5) in the testis and epididymis of Sonid Bactrian camels.

CONTEXT: Heat shock protein 70 (HSP70) and glutathione peroxidase 5 (GPX5) are biomarkers of oxidative stress and stress in temperate, tropical environments, which are crucial for male reproduction. Their expression and distribution patterns in the testis and epididymis of Bactrian camels are still unknown. AIMS: This study aims to investigate the HSP70 and GPX5 expression and localisation in 3- and 6-year-old Bactrian camel testis and epididymis. METHODS: Reverse transcription quantitative polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry were used to detect HSP70 in the testis and epididymis (caput, corpus and cauda) and GPX5 in the epididymis at two developmental stages (3-year-old puberty group and 6-year-old adult group). KEY RESULTS: HSP70 was upregulated in the testis. Immunohistochemistry results indicated the HSP70 protein was mainly detected in spermatids and Leydig cells of testicular tissue. In the epididymis, HSP70 was located at the luminal spermatozoa, the epithelium lining the epididymal and the epididymal interstitium. GPX5 expression was significantly higher in the caput epididymis than in the corpus and cauda epididymis. GPX5 protein was observed in the epithelium lining the epididymal, interstitium and luminal spermatozoa in the epididymis by immunohistochemistry. CONCLUSIONS: Bactrian camel HSP70 and GPX5 exhibited spatiotemporal expression specificity. IMPLICATIONS: HSP70 and GPX5 may be essential for germ cell development and reproductive success after sexual maturation in Sonid Bactrian camels.

Taming non-radiative recombination in Si nanocrystals interlinked in a porous network.

A range of the distinctive physical properties, comprising high surface-to-volume ratio, possibility to achieve mechanical and chemical stability after a tailored treatment, controlled quantum confinement and the room-temperature photoluminescence, combined with mass production capabilities offer porous silicon unmatched capabilities required for the development of electro-optical devices. Yet, the mechanism of the charge carrier dynamics remains poorly controlled and understood. In particular, non-radiative recombination, often the main process of the excited carrier's decay, has not been adequately comprehended to this day. Here we show, that the recombination mechanism critically depends on the composition of surface passivation. That is, hydrogen passivated material exhibits Shockley-Read-Hall type of decay, while for oxidised surfaces, it proceeds by two orders of magnitude faster and exclusively through the Auger process. Moreover, it is possible to control the source of recombination in the same sample by applying a cyclic sequence of hydrogenation-oxidation-hydrogenation processes, and, consequently switching on-demand between Shockley-Read-Hall and Auger recombinations. Remarkably, irregardless of the recombination mechanism, the rate constant scales inversely with the average volume of individual silicon nanocrystals contained in the material. Thus, the type of the non-radiative recombination is established by the composition of the passivation, while its rate depends on the degree of the charge carriers' quantum confinement.

Comprehensive Analysis of FASN in Tumor Immune Infiltration and Prognostic Value for Immunotherapy and Promoter DNA Methylation.

Fatty acid synthase (FASN) promotes tumor progression in multiple cancers. In this study, we comprehensively examined the expression, prognostic significance, and promoter methylation of FASN, and its correlation with immune cell infiltration in pan-cancer. Our results demonstrated that elevated FASN expression was significantly associated with an unfavorable prognosis in many cancer types. Furthermore, FASN promoter DNA methylation can be used as a tumor prognosis marker. Importantly, high levels of FASN were significantly negatively correlated with tumor immune infiltration in 35 different cancers. Additionally, FASN was significantly associated with tumor mutational burden (TMB) and microsatellite instability (MSI) in multiple malignancies, suggesting that it may be essential for tumor immunity. We also investigated the effects of FASN expression on immunotherapy efficacy and prognosis. In up to 15 tumors, it was significantly negatively correlated with immunotherapy-related genes, such as PD-1, PD-L1, and CTLA-4. Moreover, we found that tumors with high FASN expression may be more sensitive to immunotherapy and have a good prognosis with PD-L1 treatment. Finally, we confirmed the tumor-suppressive effect of mir-195-5p through FASN. Altogether, our results suggested that FASN may serve as a novel prognostic indicator and immunotherapeutic target in various malignancies.

An Adaptive Multi-Target Jamming Waveform Design Based on Power Minimization.

With increasing complexity of electronic warfare environments, smart jammers are beginning to play an important role. This study investigates a method of power minimization-based jamming waveform design in the presence of multiple targets, in which the performance of a radar system can be degraded according to the jammers' different tasks. By establishing an optimization model, the power consumption of the designed jamming spectrum is minimized. The jamming spectrum with power control is constrained by a specified signal-to-interference-plus-noise ratio (SINR) or mutual information (MI) requirement. Considering that precise characterizations of the radar-transmitted spectrum are rare in practice, a single-robust jamming waveform design method is proposed. Furthermore, recognizing that the ground jammer is not integrated with the target, a double-robust jamming waveform design method is studied. Simulation results show that power minimization-based single-robust jamming spectra can maximize the power-saving performance of smart jammers in the local worst-case scenario. Moreover, double-robust jamming spectra can minimize the power consumption in the global worst-case scenario and provide useful guidance for the waveform design of ground jammers.

MicroRNA-448 promotes multiple sclerosis development through induction of Th17 response through targeting protein tyrosine phosphatase non-receptor type 2 (PTPN2).

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system, and its pathogenesis remains largely unclear. Much attention has been paid to the role of microRNAs (miRs) in regulation of autoimmune disease. Here, we found, for the first time, that miR-448 expression was significantly increased in periphery blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) of patients with MS, and its expression positively correlated with the disease severity. We further demonstrated that CD4+ T cells, especially the Th17 lineage, were the major source of miR-448 expression. Using gain- and loss-of-function approaches, we further verified that miR-448 could enhance Th17 differentiation, characterized by up-regulated expression levels of IL-17A and RORγt. Interleukin (IL)-1ß as a potent driver of pathogenic Th17 cells was able to strongly induce miR-448 expression in CD4+ T cells through activating NF-κB pathway. Additionally, we identified that miR-448 directly targeted protein tyrosine phosphatase non-receptor type 2 (PTPN2), which has been known as an anti-inflammatory player with capacity to suppress Th17 differentiation. We also observed markedly decreased expression of PTPN2 in PBMC and CSF of MS patients. Our results suggest that miR-448 might promote Th17 differentiation in MS and thus aggravate the disease through inhibiting PTPN2.

Arbuscular mycorrhizal fungus inoculation reduces the drought-resistance advantage of endophyte-infected versus endophyte-free Leymus chinensis.

Grasses can be infected simultaneously by endophytic fungi and arbuscular mycorrhizal (AM) fungi. In this study, we tested the hypothesis that endophyte-associated drought resistance of a native grass was affected by an AM fungus. In a greenhouse experiment, we compared the performance of endophyte-infected (EI) and endophyte-free (EF) Leymus chinensis, a dominant species native to the Inner Mongolia steppe, under altered water and AM fungus availability. The results showed that endophyte infection significantly increased drought resistance of the host grass, but the beneficial effects were reduced by AM fungus inoculation. In the mycorrhizal-non-inoculated (MF) treatment, EI plants accumulated significantly more biomass, had greater proline and total phenolic concentration, and lower malondialdehyde concentration than EF plants. In the mycorrhizal-inoculation (MI) treatment, however, no significant difference occurred in either growth or physiological characters measured between EI and EF plants. AM fungus inoculation enhanced drought resistance of EF plants but had no significant effect on drought resistance of EI plants, thus AM fungus inoculation reduced the difference between EI and EF plants. Our findings highlight the importance of interactions among multiple microorganisms for plant performance under drought stress.

Late-onset depression in the absence of stroke: associated with silent brain infarctions, microbleeds and lesion locations.

BACKGROUND: Late-onset depression (LOD) is a frequent mood disorder among elderly. Previous studies have proved that LOD is associated with cerebral silent lesions especially white matter lesions (WML) and yielded the "vascular depression" hypothesis to explain the pathogenesis of LOD. However, there were relatively few studies about the association between silent brain infarctions (SBIs), microbleeds (MBs) and the prevalence of LOD. In this study we sought to evaluate the presence, accumulation and locations of SBIs and MBs, and explore the possible association between them and LOD. METHODS: 65 patients of LOD diagnosed according to DSM-IV and 270 subjects of control group were enrolled and scanned by MRI to analyze the presence, numbers and locations of SBIs and MBs. Clinical and radiological characteristics were compared between LOD patients and control group. Logistic regression models were constructed to identify the independent risk factors for LOD. RESULTS: LOD patients had higher prevalence and numbers of both SBIs and MBs. SBIs and MBs in the left hemisphere, SBIs in basal ganglia and lobar MBs were all independent risk factors for LOD. CONCLUSION: The presence of both SBIs and MBs were associated with a higher rate LOD. Lesions in some specific locations might be critical for the presence of LOD.

Depression in silent lacunar infarction: a cross-sectional study of its association with location of silent lacunar infarction and vascular risk factors.

Most previous studies reported a close link between fresh infarcts and post-stroke depression. However, studies on the relation of depression and silent lacunar infarction (SLI) are limited. This study aims to analyze the effects of SLI and the vascular risk factors on depression. A total of 243 patients with SLI were divided into depression and non-depression groups. The presence and location of SLI were evaluated with magnetic resonance imaging. Depression was assessed with the Patient Health Questionnaire-9 and vascular risks factors were collected. We used t tests and χ (2) test to compare the baseline characteristics of the two groups and the multivariate logistic regression model to identify the risk factors for depression. Univariate analysis results showed that the proportion of patients with SLI in basal ganglia was significantly higher in the depression group (65.0 versus 32.8 %; P < 0.001) than in the non-depression group, and multiple prevalent factors had significant differences between the two groups. However, on multivariate logistic analysis, some of these factors were eliminated, and SLI in basal ganglia remained an independent predictor of depression with an odds ratio of 3.128 (P = 0.018). In addition, vascular risk factors, including high body mass index level, presence of inflammation markers (e.g., CRP, TNF-α, Hs-CRP, and IL-6), and lack of physical activity, were associated with depression. Our findings suggest that SLI in basal ganglia is associated with a higher risk of depression. Vascular risk factors, which are intertwined, may propose the pathological basis of depression in SLI.

A meta-analysis of association between cerebral microbleeds and cognitive impairment.

BACKGROUND: The clinical effect of cerebral microbleeds (CMBs) on cognition has been receiving much research attention, but results are often inconsistent. MATERIAL/METHODS: We searched PubMed, Embase, Web of Science, and some Chinese electronic databases. A total of 15 studies were included. RESULTS: Patients with CMBs had higher incidence of cognitive dysfunction (OR 3.14; 95% CI 1.66-5.92) and lower scores of cognitive function (SMD was -0.36 [-0.55, -0.18] in the MMSE group and -0.65 [-0.99, -0.32] in the MoCA [Montreal Cognitive Assessment] group). The results also indicated that a higher number of CMB lesions led to more severe cognitive dysfunction (SMD was -2.41 [-5.04, -0.21] in the mild group and -2.75 [-3.50, -2.01] in the severe group). We also found that cognitive performance was significantly impaired when CMBs were located in deep (-0.4 [-0.69, -0.11]), lobar regions (-0.50 [-0.92, -0.09]), basal ganglia (-0.72 [-1.03, -0.41]), and thalamus brain regions (-0.65 [-0.98, -0.32]). CONCLUSIONS: This meta-analysis showed that CMBs were associated with cognitive dysfunction according to higher number and different locations of CMBs. Future work should focus on long-term prognosis of continuing cognitive decline and specific treatments to reduce the formation of CMBs.

Population Viability Analysis on Chinese Goral Indicates an Extinction Risk for a Local Population in Beijing, China.

The Chinese goral (Naemorhedus griseus) is identified as a vulnerable species on the Red List of China's Biodiversity and listed as a national second-class key protected wild animal in China. It is a representative flagship ungulate in Beijing. Its distribution range is fragmented and small populations are separated by dense infrastructures and tourism sites. Understanding its population status provides a foundation to plan effective conservation strategies. In this study, a population viability analysis was conducted with VORTEX (10.5.6.0) on a Chinese goral population in Beijing Yunmengshan Nature Reserve with the data collected by camera trapping and parameters referenced from other goral populations. The results show that this population will initially increase in the next 20 years and then decrease with a 32% probability of extinction risk. Supplementation with four adults, two females and two males, every 10 years would help minimize the extinction risk of this population. The results highlight the vital limiting factors for Chinese goral, including the initial population size, sex ratio at birth and mortality of infants (especially female infants). To improve the protection efficiency, detailed population parameters should be further acquired through continuous monitoring of this population. A thorough large-scale study should be carried out on other segregated goral populations in Beijing to facilitate the recovery of this endangered species.

AMH inhibits androgen production in human theca cells.

Both excessive ovarian production of AMH and androgen are important features of polycystic ovary syndrome (PCOS). Present study aimed to explore the direct effect of AMH on androgen production in human theca cells. Primary cultured human theca cells were treated with AMH, an ALK2 (the BMP type 1 receptor) inhibitor and an ALK5 (the TGFß type 1 receptor) inhibitor. AMH significantly suppresses the expression of the androgen synthesis-related enzyme CYP17A1 and reduces the production of androstenedione and testosterone in normal human theca cells and PCOS theca cells. Inhibitors of ALK2/3 and ALK5 antagonize the effect of AMH on the expression of CYP17A1. Although both ALK5 and ALK2 interact with AMHR2 in the presence of AMH, AMH activated neither TGFßR-Smads (Smad 2/3) nor BMPR-Smads (Smad 1/5/8). Our data suggested that AMH suppresses androgen synthesis-related enzyme CYP17A1 expression and inhibits androgen production in human theca cells, which process may be mediated by ALK2 and ALK5.

Characterization of Type I and Type III Collagen in the Intramuscular Connective Tissue of Wuzhumuqin Sheep.

Intramuscular connective tissue (IMCT) collagen is an important factor in meat quality. This study analyzed the characteristics of type I and III collagen in the IMCT of the semitendinosus (SD) and longissimus dorsi (LD) of Wuzhumuqin sheep at different growth stages (6, 9, 12, and 18 months). Utilizing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared spectroscopy (FTIR), collagen types I and III were successfully isolated and shown to contain an intact triple helix structure. Immunofluorescence revealed that these collagens were located in the endomysium and perimysium. Collagen-related genes were significantly expressed in sheep aged 9 and 12 months. The amino acid content increased with age in type I collagen whereas it decreased in type III collagen. Furthermore, type III collagen contained more hydroxyproline (Hyd) than type I collagen. Differential scanning calorimetry (DSC) revealed that the thermal stability of collagen increased with age, accompanied by a decrease in solubility. Semitendinosus muscle had more collagen cross-linkages than LD muscle due to the high pyridinoline (Pyr) content in the endomysium. Finally, a correlation analysis highlighted the multiple correlations between characteristics in different types of collagen during sheep growth. In summary, the collagen characteristics in the IMCT of sheep were impacted by collagen type, muscle type, and age. Furthermore, the various correlations between these characteristics may play an important role in the development of IMCT.

Integrated Transcriptome Analysis of miRNAs and mRNAs in the Skeletal Muscle of Wuranke Sheep.

MicroRNAs (miRNAs) are regarded as important regulators in skeletal muscle development. To reveal the regulatory roles of miRNAs and their target mRNAs underlying the skeletal muscle development of Wuranke sheep, we investigated the miRNA and mRNA expression profiles in the biceps femoris of these sheep at the fetal (3 months of gestation) and 3- and 15-month-old postnatal stages. Consequently, a total of 1195 miRNAs and 24,959 genes were identified. Furthermore, 474, 461, and 54 differentially expressed miRNAs (DEMs) and 6783, 7407, and 78 differentially expressed genes (DEGs) were detected among three comparative groups. Functional analysis demonstrated that the target mRNAs of the DEMs were enriched in multiple pathways related to muscle development. Moreover, the interactions among several predicted miRNA-mRNA pairs (oar-miR-133-HDAC1, oar-miR-1185-5p-MYH1/HADHA/OXCT1, and PC-5p-3703_578-INSR/ACTG1) that potentially affect skeletal muscle development were verified using dual-luciferase reporter assays. In this study, we identified the miRNA and mRNA differences in the skeletal muscle of Wuranke sheep at different developmental stages and revealed that a series of candidate miRNA-mRNA pairs may act as modulators of muscle development. These results will contribute to future studies on the function of miRNAs and their target mRNAs during skeletal muscle development in Wuranke sheep.

Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index.

Introduction: Lung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, research on the LUSC-specific prognosis genes is lacking. This study aimed to develop a comprehensive LUSC-specific differentially expressed genes (DEGs) signature for prognosis correlated with tumor progression, immune infiltration,and stem index. Methods: RNA sequencing data for LUSC and lung adenocarcinoma (LUAD) were extracted from The Cancer Genome Atlas (TCGA) data portal, and DEGs analyses were conducted in TCGA-LUSC and TCGA-LUAD cohorts to identify specific DEGs associated with LUSC. Functional analysis and protein-protein interaction network were performed to annotate the roles of LUSC-specific DEGs and select the top 100 LUSC-specific DEGs. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were performed to select prognosis-related DEGs. Results: Overall, 1,604 LUSC-specific DEGs were obtained, and a validated seven-gene signature was constructed comprising FGG, C3, FGA, JUN, CST3, CPSF4, and HIST1H2BH. FGG, C3, FGA, JUN, and CST3 were correlated with poor LUSC prognosis, whereas CPSF4 and HIST1H2BH were potential positive prognosis markers in patients with LUSC. Receiver operating characteristic analysis further confirmed that the genetic profile could accurately estimate the overall survival of LUSC patients. Analysis of immune infiltration demonstrated that the high risk (HR) LUSC patients exhibited accelerated tumor infiltration, relative to low risk (LR) LUSC patients. Molecular expressions of immune checkpoint genes differed significantly between the HR and LR cohorts. A ceRNA network containing 19 lncRNAs, 50 miRNAs, and 7 prognostic DEGs was constructed to demonstrate the prognostic value of novel biomarkers of LUSC-specific DEGs based on tumor progression, stemindex, and immune infiltration. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. Conclusion: Our study demonstrated the potential clinical implication of the 7- DEGs signature for prognosis prediction of LUSC patients based on tumor progression, immune infiltration, and stem index. And the FGG could be an independent prognostic biomarker of LUSC promoting cell proliferation, migration, invasion, THP-1 cell infiltration, and stem cell maintenance.

T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese.

Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere (T2T) version - T2T-CHM13 - reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. Here, to provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we assembled the genome of a male Han Chinese individual, T2T-YAO, which includes T2T assemblies of all the 22 + X + M and 22 + Y chromosomes in both haploid. The quality of T2T-YAO is much better than all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼ 330-Mb exclusive sequences, ∼ 3100 unique genes, and tens of thousands of nucleotide and structural variations as compared with CHM13, highlighting the necessity of a population-stratified reference genome. The construction of T2T-YAO, a truly accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

Synthesis of Fluorescent Copper Nanomaterials and Detection of Bi3.

Based on the aggregation-induced luminescence of glutathione-protected non-noble metal copper nanoparticles (GSH-CuNPs), a fluorescence method for the rapid detection of bismuth (Bi3 +) was developed. The fluorescence intensity of GSH-CuNP solution is good, and the fluorescence can be quenched in the presence of Bi3 +. Based on this principle, a fluorescence mean for the admeasurement of Bi3+was built. The linear range was 0-100 mmol/L, and the detection limit was 10 mmol/L. The method is simple, rapid, and selective and can be used for the qualitative detection of Bi3 +.

Luteinizing hormone stimulates the expression of amphiregulin in human theca cells.

BACKGROUND: Luteinizing hormone (LH) can stimulate mural granulosa cells to produce Amphiregulin (AREG), which can induce the resumption of meiosis in oocytes. Theca cells are present in the outer layer of follicles, providing communication with the pituitary axis through the established vascular system around the follicle. As LH target cells, it is unknown whether theca cells can produce AREG after LH stimulation. METHODS: Primary cultured human theca cells were treated with LH (with or without the inhibitor of PKA, H89), or agonists of adenylate cyclase (forskolin or db-cAMP). The mRNA and protein levels of AREG were evaluated by RT-qPCR, immunochemistry, immunofluorescence, western blotting, and ELISA. RESULTS: Immunohistochemistry of normal ovarian tissue obtained in the early-mid follicle phase showed that AREG expression was absent in both the theca layer and the granulosa cell layer of antral follicles. Double immunofluorescent staining revealed colocalization of AREG and CYP17A1 in human theca cells and colocalization of FSHR and AREG in human granulosa cells isolated from follicular fluid collected during IVF/ICSI after hCG trigger. LH significantly increased the mRNA and protein levels of AREG in human theca cells and the concentration of AREG in the culture medium. Forskolin and db-cAMP, activators of the cAMP/PKA signalling pathway, also significantly increased the mRNA and protein levels of AREG in human theca cells and the concentration of AREG in the culture medium. H89 antagonized the stimulating effect of LH on AREG expression in human theca cells. In addition, the concentration of AREG was lower in polycystic ovarian syndrome (PCOS) follicular fluid than in normal follicular fluid. The mRNA levels of AREG were significantly lower in PCOS granulosa cells and theca cells than in normal granulosa cells and theca cells. CONCLUSION: LH can stimulate the expression of AREG in human theca cells, and the adenylate cyclase/cAMP/PKA cascade may mediate this process. Expression of AREG is decreased in PCOS theca cells compared to normal theca cells, with or without LH stimulation.