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The high level of progesterone and 17β-estradiol ratio (P4/E2) in follicular fluid has been considered as a biomarker of follicular atresia. CYP11A1, the crucial gene encoding the rate-limiting enzyme for steroid hormone synthesis, has been reported differently expressed in the ovary during follicular atresia. However, the regulation mechanism of CYP11A1 expression during follicular atresia still remains unclear. Here, we have demonstrated that lnc2300, a novel pig ovary-specific highly expressed cis-acting long noncoding RNA (lncRNA) transcribed from chromosome 7, has the ability to induce the expression of CYP11A1 and inhibit the apoptosis of porcine granulosa cells (GCs). Mechanistically, lnc2300, mainly located in the cytoplasm of porcine GCs, sponges and suppresses the expression of miR-365-3p through acting as a competing endogenous RNA (ceRNA), which further relieves the inhibitory effects of miR-365-3p on the expression of CYP11A1. Besides, CYP11A1 is validated as a direct functional target of miR-365-3p in porcine GCs. Functionally, lnc2300 is an antiapoptotic lncRNA that reduces porcine GC apoptosis by inhibiting the proapoptotic function of miR-365-3p. In summary, our findings reveal a cis-acting regulation mechanism of CYP11A1 through lncRNA, and define a novel signaling pathway, lnc2300/miR-365-3p/CYP11A1 axis, which is involved in the regulation of GC apoptosis and follicular atresia.

Stress is one of the leading causes of male infertility, but its exact function in testosterone synthesis has scarcely been reported. We found that adult male rats show a decrease in bodyweight, genital index and serum testosterone level after continual chronic stress for 21 days. Two‐dimensional gel electrophoresis (2‐DE) and MALDI‐TOF‐MS analysis identified 10 differentially expressed proteins in stressed rats compared with controls. A strong protein interaction network was found to be centred on Atp5a1 among these proteins. Atp5a1 expression significantly decreased in Leydig cells after chronic stress. Transfection of Atp5a1 siRNAs decreased StAR, CYP11A1, and 17β‐HSD expression by damaging the structure of mitochondria in TM3 cells. This study confirmed that chronic stress plays an important role in testosterone synthesis by regulating Atp5a1 expression in Leydig cells.

To overcome high toxicity, low bioavailability and poor water solubility of chemotherapeutics, a variety of drug carriers have been designed. However, most carriers are severely limited by low drug loading capacity and adverse side effects. Here, a new type of metal-drug nanoparticles (MDNs) was designed and synthesized. The MDNs self-assembled with Fe(III) ions and drug molecules through coordination, resulting in nanoparticles with high drug loading. To assist systemic delivery and prolong circulation time, the obtained MDNs were camouflaged with red blood cell (RBCs) membranes (RBCs@Fe-DOX MDNs) to improve their stability and dispersity. The RBCs@Fe-DOX MDNs presented pH-responsive release functionalities, resulting in drug release accelerated in acidic tumor microenvironments. The outstanding in vitro and in vivo antitumor therapeutic outcome was realized by RBCs@Fe-DOX MDNs. This study provides an innovative design guideline for chemotherapy and demonstrates the great capacity of nanomaterials in anticancer treatments.

Congenital hydrocephalus is one of the symptoms of Walker-Warburg syndrome that is attributed to the disruptions of the genes, among which the B3GALNT2 gene is rarely reported. A diagnosis of the Walker-Warburg syndrome depends on the clinical manifestations and the whole-exome sequencing after birth, which is unfavorable for an early diagnosis.Walker-Warburg Syndrome was suspected in two families with severe fetal congenital hydrocephalus. Whole-exome sequencing and Sanger sequencing were performed on the affected fetuses.The compound heterozygous variants c.1AG p.(Met1Val) and c.1151+1GA, and c.1068dupT p.(D357*) and c.1052 TA p.(L351*) in the B3GALNT2 gene were identified, which were predicted to be pathogenic and likely pathogenic, respectively. Walker-Warburg syndrome was prenatally diagnosed on the basis of fetal imaging and whole-exome sequencing.Our findings expand the spectrum of pathogenic mutations in Walker-Warburg syndrome and provide new insights into the prenatal diagnosis of the disease.

Summary Co‐infection of apple trees with several viruses/viroids is common and decreases fruit yield and quality. Accurate and rapid detection of these viral pathogens helps to reduce losses and prevent virus spread. Current molecular detection assays used for apple viruses require specialized and expensive equipment. Here, we optimized a CRISPR/Cas12a‐based nucleic acid detection platform for the diagnosis of the most prevalent RNA viruses/viroid in apple, namely Apple necrotic mosaic virus (ApNMV), Apple stem pitting virus (ASPV), Apple stem grooving virus (ASGV), Apple chlorotic leaf spot virus (ACLSV) and Apple scar skin viroid (ASSVd). We detected each RNA virus/viroid directly from crude leaf extracts after simultaneous multiplex reverse transcription‐recombinase polymerase amplification (RT‐RPA) with high specificity. Positive results can be distinguished by the naked eye via oligonucleotide‐conjugated gold nanoparticles. The CRISPR/Cas12a‐RT‐RPA platform exhibited comparable sensitivity to RT‐qPCR, with limits of detection reaching 250 viral copies per reaction for ASPV and ASGV and 2500 copies for the others. However, this protocol was faster and simpler, requiring an hour or less from leaf harvest. Field tests showed 100% agreement with RT‐PCR detection for 52 samples. This novel Cas12a‐based method is ideal for rapid and reliable detection of apple viruses in the orchard without the need to send samples to a specialized laboratory.

BACKGROUND: Photocatalysis is one of the effective ways to solve the problem of water and gas pollution. An excellent photocatalyst should have the following advantages: efficient photocatalytic activity for gas and water pollutants, recyclable and stable characteristics, non‐toxic and low‐cost. Constructing heterojunctions and introducing oxygen vacancies (OVs) are two effective measures to achieve these targets. RESULTS: It is found that the 1.0% Pd/PdO/β‐Bi₂O₃ exhibits the best photocatalytic activity with an efficiency of 97.4% for Bisphenol A (BPA) degradation and 47.6% for nitric oxide (NO) removal within 30 min. The 1.0% Pd/PdO/β‐Bi₂O₃ composite shows 23.3% efficiency in the photodegradation of BPA under 595 nm monochromatic light irradiation, while β‐Bi₂O₃ tends to be invalid. Moreover, the OVs promote the removal of NO without irradiation. CONCLUSION: In this work, a novel ternary Pd/PdO/β‐Bi₂O₃ material as high‐performance photocatalyst for the BPA degradation and NO removal was synthesized. The presence of OVs promotes the activation of the oxygen molecule, thereby facilitating the photocatalytic process. The p‐n junction of PdO/β‐Bi₂O₃ and the Schottky barrier of Pd/β‐Bi₂O₃ significantly limit the recombination of photoinduced electron–hole pairs in the composite. Furthermore, an artifact in the electron spin resonance (ESR) spectrum obtained by spin trapping with 5,5‐dimethyl‐1‐pyrroline N‐oxide (DMPO) as adducts confirms that both hydroxyl radical (•OH) and superoxide radical (•O₂⁻) species are involved in the photocatalytic process. The present work offers a new perspective for developing the composite photocatalysts with high efficiency through loading of metal nanoparticles and creating an heterojunction. © 2019 Society of Chemical Industry

Background Bladder cancer is one of the most common urological cancers all over the world, and NMIBC occupies almost 80% of recently diagnosed bladder cancer cases. Progress and recurrence of bladder cancer are the main problems during the disease. The level of TP53 mutation is obviously higher in the high stage than the lower. This meta‐analysis is to evaluate the potential diagnosis feature of TP53 mutation by the expression of TP53 mutation of Ta stage vs high stage in bladder cancer. Methods A systematic search of databases was conducted, and some relevant articles were selected. Next, the meta‐analysis was carried out according to the standard guidelines. Results There were seven researches in which 677 participants were selected at the basis of inclusion standard. TP53 mutation was associated highly with increased diagnosis of bladder cancer. We found that the high stage of bladder cancer has obviously higher level of TP53 mutation than the lower stage, and these patients of MIBC have higher expression of TP53 mutation compared with NMIBC. No significant publication bias has been observed in this meta‐analysis. The expression of TP53 mutation might be a diagnose‐related biomarker for lots of patients with bladder cancer. Conclusions The results of this meta‐analysis provided further evidences that the expression of TP53 mutation was associated with the diagnosis efficiency of advanced bladder cancer. Higher expression of TP53 mutation was observed in the high stage of bladder cancer or the MIBC, and lower expression of TP53 mutation in the Ta stage of bladder cancer or the NMIBC. The expression level of TP53 mutation was probably a critical diagnosed biomarker in advanced bladder cancer., Flowchart of selecting process for meta‐analysis.

The indoor environment and dietary intake are considered to be major human exposure pathways to per- and polyfluoroalkyl substances (PFASs). Cats have similar exposures to humans by sharing their residential environments, although they have different diet, body sizes, and indoor activities. In the present study, we report PFAS levels in the serum of 2 groups of Northern California cats (>10 yr old) collected during 2 time periods: 2008 to 2010 (n = 21) and 2012 to 2013 (n = 22). Levels of ∑PFAS (geometric mean) were lower in the second period (geometric mean = 8.10 ng/mL) than the first time period (geometric mean = 15.8 ng/mL), although PFAS profiles remained similar. We also analyzed PFAS levels in human serum collected in the same time period (2008-2010) and geographic area, and compared the profiles and ∑PFAS levels (15.8 vs 14.3 ng/mL for cat and human, respectively). Long chain perfluorinated carboxylic acids, especially perfluorononanoic acid and perfluoroundecanoic acid, were significantly higher in cat serum than in humans. Furthermore, serum from hyperthyroid cats in the second time period showed higher ∑PFAS level (9.50 ng/mL) compared to nonhyperthyroid cats (7.24 ng/mL), and it is the perfluorooctanoic acid levels that were statistically significantly higher in hyperthyroid cats' serum (p < 0.05). This result may indicate a possible link between PFAS levels and cat hyperthyroid, warranting a larger study for further investigation. Environ Toxicol Chem 2018;37:2523-2529. © 2018 SETAC.

Newborn assessments, including gestational age (GA) and anthropometric measurements (birth weight, crown-heel length, head circumference) are routinely performed in pediatric settings, being used as important indicators in assessing neonatal development. Close associations of these birth indicators with later cognitive abilities were also reported. However, specific associations of these indicators with white matter (WM) development during the neonatal period remain unclear, as well as the extent to which they influence WM maturation. To address this issue, 51 full-term neonates (GA range, 37-42 weeks) with no abnormalities on MRI were retrospectively recruited. Specific correlations between birth indicators and WM maturation, quantified by diffusion tensor imaging (DTI)-metrics (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity), were identified by using DTI tract-based spatial statistics and automated fiber-tract quantification. Our findings suggest that (a) higher GA, birth weight, and crown-heel length may indicate greater WM maturation in full-term neonates, while head circumference presented weak correlation with WM maturation during early newborn period; (b) among the four indicators examined, GA was the one most associated with WM maturation. We believe that this study advances our knowledge of specific correlations between birth indicators and neonatal brain development and provides a valuable reference for future neonatal studies.

Classical swine fever virus (CSFV) is one of the most important pathogens affectingswine. After infection with a moderate virulence strain at 8 hours after birth, CSFV isable to induce viral persistence. These animals may appear clinically healthy or showedunspecific clinical signs despite the permanent viremia and high viral shedding, inabsence of immune response to the virus. Given the role played by this infection in dis-ease control, we aimed to evaluate the capacity of CSFV to induce postnatal persistentinfection at 3 weeks after birth. Nine pigs were CSFV infected and sampled weekly dur-ing 6 weeks and viral, clinical, pathological and immunological tests were carried out.Also, the CD4/CD8 ratio was calculated with the purpose to relate this marker with theCSFV persistent infection. The IFN‐αresponse was detected mainly 1 week after infec-tion, being similar in all the infected animals. However, 44.4% of animals were CSFVpersistently infected, 33.3% died and 22.2% developed specific antibody response.Interestingly, in persistently infected pigs, the T‐CD8 population was increased, the T‐CD4 subset was decreased and lower CD4/CD8 ratios were detected. This is the firstreport of CSFV capacity to confer postnatal persistent infection in pigs infected at3 weeks after birth, an age in which the weaning could be carried out in some swineproduction systems. This type of infected animals shed high amounts of virus and aredifficult to evaluate from the clinical and anatomopathological point of view. Therefore,the detection of this type of infection and its elimination in endemic areas will be rele-vant for global CSF eradication. Finally, the low CD4/CD8 ratios found in persistentlyinfected animals may be implicated in maintaining high CSFV replication during persis-tence and further studies will be performed to decipher the role of these cells in CSFVimmunopathogenesis. info:eu-repo/semantics/publishedVersion

BACKGROUND Capsaicin, as a food additive, has attracted worldwide concern owing to its pungency and multiple pharmacological effects. However, poor water solubility and low bioavailability have limited its application. This study aims to develop a capsaicin-loaded microemulsion to enhance the oral bioavailability of the anti-neuropathic-pain component, capsaicin, which is poorly water soluble. RESULTS In this study, the microemulsion consisting of Cremophor EL, ethanol, medium-chain triglycerides (oil phase) and water (external phase) was prepared and characterized (particle size, morphology, stability and encapsulation efficiency). The gastric mucosa irritation test of formulated capsaicin was performed in rats to evaluate its oral feasibility, followed by the pharmacokinetic study in vivo. Under these conditions, the encapsulated capsaicin revealed a faster capsaicin release in vitro coupled with a greater absorption in vivo when compared to the free capsaicin. The oral bioavailability of the formulated capsaicin-loaded microemulsions was 2.64-fold faster than that of free capsaicin. No significant irritation was observed on the mucosa from the pathological section of capsaicin-loaded microemulsion treated stomach. CONCLUSION These results indicate that the developed microemulsion represents a safe and orally effective carrier for poorly soluble substances. The formulation could be used for clinical trials and expand the application of capsaicin. © 2014 Society of Chemical Industry

A broad range of materials is currently being studied for possible use as the insulating layer in next generation metal-oxide-semiconductor transistors. Inelastic electron tunneling spectroscopy (IETS) has become a powerful tool to characterize both the structural and electrical properties of the resulting device structures made from these materials. IETS can address issues related to reactions and intermixing at interfaces, as well as properties related to carrier mobility, such as phonon modes and charge traps, for structures that are difficult to characterize accurately by other techniques.

The development of underwater mechanically robust oil-repellent materials is important due to the high demand for these materials with the increase in underwater activities. Based on the previous study, a new strategy is demonstrated to prepare underwater mechanically robust oil-repellent materials by combining conflicting properties using a heterostructure, which has a layered hydrophobic interior structure with a columnar hierarchical micro/nanostructure on the surface and a hydrophilic outer structure. The surface hydrophilic layer imparts underwater superoleophobicity and low oil adhesion to the material, which has oil contact angle of larger than 150° and adhesion of lower than 2.8 µN. The stability of the mechanical properties stemming from the interior hydrophobic-layered structure enables the material to withstand high weight loads underwater. The tensile stress and the hardness of such a heterostructure film after 1 month immersion in seawater and pH solution are in the range from 83.92 ± 8.22 to 86.73 ± 7.8 MPa and from 83.88 ± 6.8 to 86.82 ± 5.64 MPa, respectively, which are superior to any underwater oil-repellent material currently reported.