An IFNT/FOXO1/PTGS2 axis regulates prostaglandin F2α synthesis in goat uterus during early pregnancy.

In ruminants, IFN-tau (IFNT) regulates the production of prostaglandins (PG) in the endometrium, which is crucial for conceptus adhesion. However, the related molecular regulatory mechanisms remain unclear. Forkhead box O1 (FOXO1), a member of the FOXO subfamily of transcription factors, is known to be important for mouse implantation and decidualization. In this study, we determined the spatiotemporal expression profile of FOXO1 in goat endometrium during early pregnancy. FOXO1 was highly expressed in the glandular epithelium since the onset of conceptus adhesion (d 16 of pregnancy). Then, we validated that FOXO1 could bind to the promoter of prostaglandin-endoperoxide synthase 2 (PTGS2) and increase its transcription. And the expression profile of PTGS2 was similar to that of FOXO1 in the peri-implantation uterus. Moreover, IFNT could upregulate the levels of FOXO1 and PTGS2 in goat uterus and primary endometrial epithelium cells (EEC). In EEC, the intracellular content of PGF2α was positively correlated with the levels of IFNT and FOXO1. Altogether, we found an IFNT/FOXO1/PTGS2 axis that controls the synthesis of PGF2α but not prostaglandin E2 in goat uterine glands. These findings contribute to better understanding the function of FOXO1 in the reproductive physiology of goats and provide more insights into the implantation of small ruminants.

Population growth of Tetranychus truncatus (Acari: Tetranychidae) on different drought-tolerant potato cultivars.

Tetranychus truncatus Ehara (Acari: Tetranychidae) has become one of the major phytophagous pests in China in recent years, and is found on a wide range of host plants. However, little information is available on the population performance of this arthropod pest on potatoes. In this study, we explored the population growth of T. truncatus on two drought-tolerant potato (Solanum tuberosum L.) cultivars under laboratory conditions using the age-stage, two-sex life table. Tetranychus truncatus completed its entire life history on both potato cultivars tested, Holland 15 and Longshu 10. There was no significant difference between two potato cultivars in developmental duration. Tetranychus truncatus had shorter adult longevity (20.61 days), adult female longevity (20.41 days), and total female longevity (33.66 days) on Longshu 10 than Holland 15 (21.16 days, 21.19 days, and 34.38 days, respectively). However, it exhibited a higher preadult survival rate, higher fecundity (F = 88.32 eggs per female), and relatively higher population parameters when reared on Longshu 10 than on Holland 15 (F = 75.70 eggs per female). Growth projection also showed that the population size of T. truncatus on Longshu 10 (expand 750-fold) was larger than that on Holland 15 (expand 273-fold) after 60 days. Our results demonstrate that the drought-sensitive potato variety, Holland 15, is relatively resistant to T. truncatus compared with the drought-tolerant variety, Longshu 10, and suggest that T. truncatus exhibited a trade-off between longevity and reproduction on both potato cultivars. Our findings provide information on population prediction, which may aid the management of this pest mite species of potatoes.

Effect of wrist-ankle acupuncture on propofol dosage during painless colonoscopy: A randomized controlled prospective study.

BACKGROUND: The clinical advantages of painless colonoscopy can reduce the fear and discomfort of patients and increase the detection rate of diseases. Propofol has the characteristics of fast effect and short action time. It is a common choice for painless endoscopic sedation and anesthetics. However, propofol can cause severe respiratory and circulatory depression. Therefore, it is important to find a way to reduce the dose of propofol. AIM: To explore the effect of wrist-ankle acupuncture on propofol dose during colonoscopy. METHODS: Two hundred patients who were going to receive selective painless colonoscopy in Hebei Hospital of Traditional Chinese Medicine were selected and divided into wrist-ankle acupuncture group (WAA group, n = 100) and control group (CON group, n = 100). After entering the operation room, patients were given 0.025 mg/kg nabufine intravenously and propofol at the initial dose of 0.5 mg/kg. In patients who did not fall asleep, propofol (10 mg/time) was given until loss of consciousness. Prior to anesthesia, patients in WAA group were punctured by specialist in the inferior 1, 2 and 3 regions according to the zoning principle of wrist-ankle acupuncture. The primary endpoint was required dose of propofol, and the secondary endpoints were the incidence of hypoxemia and hypotension. Furthermore, the following data were recorded: The operation time, wake-up time, incidence of nausea and vomiting, incidence of abdominal distention, post-colonoscopy pain, examiners' satisfaction, patients' satisfaction and Borg fatigue index. This study has been registered in the Chinese Clinical Trial Registry (Registration Code: ChiCTR1900022177). RESULTS: The induced dose of propofol and the total dose of propofol in WAA group were 80 mg and 110 mg, respectively, which were significantly lower than those in CON group (P < 0.05). The incidences of hypoxemia and hypotension in the WAA group were 2.2% and 3.3%, respectively, significantly lower than those in the CON group (P < 0.05). The incidence of abdominal distension in the WAA group was 8.8%, which was significantly lower than that in the CON group (P < 0.05, 28.9%). The waking time of WAA group was 3.26 ± 0.87 min, which was significantly lower than that of CON group (6.06 ± 0.88 min, P < 0.05). CONCLUSION: Wrist-ankle acupuncture can reduce the induction dose and total dose of propofol as well as the incidence of adverse reactions in painless colonoscopy without affecting the satisfaction of examiners and patients. This procedure is simple in operation and easy to promote in clinical practice.

Expression and hormone regulation of UCP2 in goat uterus.

Pregnancy success is closely related to the molecular mechanisms that control energy metabolism balance. However, the mechanisms have not been fully understood. Uncoupling protein 2 (UCP2) plays a physiological role by regulating energy metabolism in numerous tissues. In this study, we determined the expression and hormone regulation of UCP2 in goat uterus. UCP2 is expressed in the luminal and glandular epithelia of goat uterus during early pregnancy, as revealed by in situ hybridization and immunohistochemistry conducted on pregnant goats. The signals were detected from day 0 (D0) to D30 of pregnancy, though weak on D16 (the adhesion period). The low levels of UCP2 on D16 were confirmed by RT-qPCR and western blot. In goat uterus and endometrial epithelial cells (EECs), UCP2 was up-regulated by progesterone and estrogen. In addition, after goat EECs were treated with genipin (an inhibitor of UCP2), not only UCP2 expression but also cell proliferation was inhibited. Collectively, UCP2 is dynamically expressed in goat uterus and can affect EEC proliferation, suggesting that it may participate in regulating the energy metabolism balance of goat uterus during early pregnancy.

Peri-implantation expression and regulation of ITGB8 in goat uterus.

Ruminants have a superficial implantation pattern. The extended conceptus attaches to the receptive endometrium to form the cotyledonary placenta. During the attachment, a large number of events occur at the maternal-fetal interface. However, the related molecular mechanisms have not been fully understood. Integrin beta8 (ITGB8) is a subunit of integrin beta involved in embryo implantation. In this study, we determined peri-implantation expression and regulation of ITGB8 in goat uterus. The mRNA and protein levels of ITGB8 were both high in goat endometrial luminal epithelium (LE) and superficial glandular epithelium (sGE) during the adhesion period (Days 16-19 of pregnancy). Such expression profile was opposite to that of microRNA-187 (miR-187). Then, we validated that miR-187 targeted the 3' untranslated region (UTR) of ITGB8 in primary goat endometrial epithelial cells (EECs). In EECs, inhibition of miR-187 resulted in not only up-regulated ITGB8 level but also reduced cell proliferation and focal adhesion kinase (FAK) activity. Moreover, ITGB8 and miR-187 were regulated by interferon tau (IFNT). Altogether, in goat, the miR-187/ITGB8 axis may be involved in conceptus attachment and is downstream of IFNT. Our results will help us better understand the mechanisms of ruminant implantation and may provide a useful tool to improve the reproduction ratio for ruminants.

Connective tissue growth factor gene expression in goat endometrium during estrous cycle and early pregnancy.

Embryo implantation is crucial for a successful pregnancy. Although many essential molecular modulators and pathways have been identified, the precise mechanisms of the process in goat remain largely unknown. CCN2 is a connective tissue growth factor participating in many biological processes; however, its presence or function in goat uterus has not yet been reported. In this study, we determined the expression and regulation of CCN2 in goat uterus. CCN2 was not detected by in situ hybridization at ED0 (Day 0 of the estrous cycle), but at ED6 (metestrus), ED12 (dioestrus), and ED16 (proestrus), with high signals in luminal epithelium, superficial glands, and caruncula matrix. During early pregnancy, CCN2 was also detected in these locations on D0 and D6 (pre-receptive uterus). The signals significantly increased on D16 and D19 (receptive uterus), and remained at high levels on D25 and D30. Similarly, the RT-qPCR assays showed that the mRNA level of CCN2 was relatively low on D0 and D6, increased on D16, peaked on D19, and kept high thereafter. Moreover, CCN2 was up-regulated not only in ovariectomized ewes subcutaneously injected with 17ß-estradiol and progesterone (separately or together), but also in cultured goat uterine epithelial cells treated with the two hormones or interferon tau (IFNτ). In conclusion, CCN2 expression may be induced by 17ß-estradiol, progesterone, and IFNτ in the luminal epithelium of goat receptive uterus, suggesting that CCN2 is involved in goat embryo adhesion during early pregnancy.

Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese.

Alzheimer's disease is the most common neurodegenerative disease, and has a high level of genetic heritability and population heterogeneity. In this study, we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer's disease, followed by independent validation, imaging analysis and function characterization. We identified an exome-wide significant rare missense variant rs3792646 (p.K420Q) in the C7 gene in the discovery stage (P = 1.09 × 10-6, odds ratio = 7.853) and confirmed the association in different cohorts and a combined sample (1615 cases and 2832 controls, Pcombined = 2.99 × 10-7, odds ratio = 1.930). The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood, thus resulting in an earlier age of disease onset. Overexpression of the mutant p.K420Q disturbed cell viability, immune activation and ß-amyloid processing. Electrophysiological analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal neurons. These findings suggested that C7 is a novel risk gene for Alzheimer's disease in Han Chinese.

A hyaluronan-based nanosystem enables combined anti-inflammation of mTOR gene silencing and pharmacotherapy.

Accompanied by overproduction of oxidants and reduction of pH, inflammation is closely related to many diseases such as cancer, atherosclerosis, and asthma. Besides chemotherapeutic agents, the potential regulative role of autophagy in inflammation is being actively investigated. RNA interference (RNAi)-based gene therapy is widely explored for clinical therapy but seriously restricted by lack of suitable carriers. In this study, we synthesized a hyaluronan-based ROS-sensitive polymer which was expected to release loaded chemical drugs in inflammatory environment and further developed a stable and nontoxic co-delivery nanosystem of siRNA targeting autophagy suppressive gene and chemotherapeutic agents. The in vitro transfection study of this nanosystem revealed improved intracellular accumulation of siRNA and excellent gene silencing efficacy comparable to that of conventional cationic liposome. Moreover, the mRNA expression of inflammatory cytokines was remarkably decreased by our nanosystem. Considering its biocompatibility, transfection efficacy, and anti-inflammatory capability, this co-delivery nanosystem proclaimed to be a promising combined therapeutic strategy for enhanced anti-inflammatory therapy.

A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer's disease.

INTRODUCTION: Profiling the spatial-temporal expression pattern and characterizing the regulatory networks of brain tissues are vital for understanding the pathophysiology of Alzheimer's disease (AD). METHODS: We performed a systematic integrated analysis of expression profiles of AD-affected brain tissues (684 AD and 562 controls). A network-based convergent functional genomic approach was used to prioritize possible regulator genes during AD development, followed by functional characterization. RESULTS: We generated a complete list of differentially expressed genes and hub genes of the transcriptomic network in AD brain and constructed a Web server (www.alzdata.org) for public access. Seventeen hub genes active at the early stages, especially YAP1, were recognized as upstream regulators of the AD network. Cellular assays proved that early alteration of YAP1 could promote AD by influencing the whole transcriptional network. DISCUSSION: Early expression disturbance of hub genes is an important feature of AD development, and interfering with this process may reverse the disease progression.

The Arc Gene Confers Genetic Susceptibility to Alzheimer's Disease in Han Chinese.

Alzheimer's disease (AD) is the most common form of dementia. The deposition of ß-amyloid (Aß) plaques in the brain was considered one of the main neuropathological hallmarks of AD. As the loss of synapses always occurs during AD progression, AD has been gradually regarded as a "synaptopathy." The activity-regulated cytoskeleton-associated protein (Arc) was recently identified as a key factor for AD due to its active roles in synaptic plasticity, learning, memory, and Aß generation. However, there is little evidence to support the association of the Arc gene with AD. In this study, a two-stage case-control study of 1471 Han Chinese was conducted to investigate the genetic association between the Arc gene and AD. Variant rs10097505 in the 3'UTR region was significantly associated with AD. The whole exons of the Arc gene were also screened in 99 AD patients with a high heritability (familial and/or onset age <55 years old). One missense variant (c.20G>A, p.T7I) was identified in two AD patients but was absent in the controls from the general populations. Both rs10097505 and c.20G>A were predicted to be potentially pathogenic. Further luciferase assay, data mining, and integrative analyses revealed that the AD-risk genotype AA of rs10097505 was associated with an increased Arc mRNA expression and an elevated Aß level. Our results indicated that the Arc gene would confer susceptibility to AD in Han Chinese, probably through changing the protein structure or affecting the Arc expression in brain tissues, which would finally contribute to the pathogenesis and development of AD.

Association between resistin +299A/A genotype and nonalcoholic fatty liver disease in Chinese patients with type 2 diabetes mellitus.

OBJECTIVE: To investigate the relationship between the resistin intronic +299G/A polymorphism and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: We selected 738 T2DM patients, including 395 with NAFLD and 343 without fatty liver disease, as well as 279 healthy control individuals, and analyzed their resistin +299G/A polymorphism genotype by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Plasma resistin levels in T2DM patients with NAFLD were at the highest (P<0.05). The frequency of AA genotype at the +299 site of the resistin gene in patients with concurrent T2DM combined with NAFLD was significantly different from that in the control (P<0.05). The AA genotype was found to be associated with a 1.80-fold increased risk for T2DM combined with NAFLD, 2.05-fold increased risk for obesity and 2.37-fold increased risk for obesity of abdominal type compared to the GG (P<0.05, respectively). The multivariate non-conditional logistic regression model analysis further shows that the AA genotype is a risk factor for the development of NAFLD in T2DM patients (OR, 2.32; 95% CI, 1.05-4.68; P<0.05). CONCLUSION: The resistin +299AA genotype may be associated with increases in the risk of the NAFLD development in T2DM patients.

Advances in murine models of diabetic nephropathy.

Diabetic nephropathy (DN) is one of the microvascular complications of both type 1 and type 2 diabetes, which is also associated with a poor life expectancy of diabetic patients. However, the pathogenesis of DN is still unclear. Thus, it is of great use to establish appropriate animal models of DN for doing research on pathogenesis and developing novel therapeutic strategies. Although a large number of murine models of DN including artificially induced, spontaneous, and genetically engineered (knockout and transgenic) animal models have been developed, none of them develops renal changes sufficiently reflecting those seen in humans. Here we review the identified murine models of DN from the aspects of genetic background, type of diabetes, method of induction, gene deficiency, animal age and gender, kidney histopathology, and phenotypic alterations in the hope of enhancing our comprehension of genetic susceptibility and molecular mechanisms responsible for this disease and providing new clues as to how to choose appropriate animal models of DN.

Common underlying diseases do not contribute in determining the causes of sudden unexplained death.

BACKGROUND: Underlying diseases have a statistically significant positive correlation to sudden death. However, sudden unexplained death (SUD) is different from sudden death, as there is no clinical evidence to support the sudden death due to the original underlying disease, nor a lethal pathological basis to be found during autopsy. In addition, SUD are more common in young, previously healthy individuals, usually without any signs of disease, with no positive lesions found after autopsy. Therefore, a causal relationship between SUD and the underlying disease needs to be further explored. This study aimed to explore the role that common underlying diseases play in patients with SUD and to reveal the correlation between them. METHODS: The medical records, history and case information of 208 patients with SUD were collected for the survey. All these SUD occurred in the emergency room of Peking University Third Hospital from January 2006 to December 2009. The patients were stratified by with and without common underlying diseases. To examine possible associations between the underlying diseases and the cause of unexplained sudden death, the chi-squared and Fisher's exact tests were used. RESULTS: Among the 208 patients, 65 were diagnosed with common underlying diseases while 143 were not. Within these two groups, there were 45 patients for whom the clear cause of death was determined. However, there were no statistically significant differences or strong associations (χ(2) = 1.238, P > 0.05) between the 11 patients with (16.90%) and 34 without (23.78%) common underlying disease among these 45 patients. We also found that occurrence of the common underlying diseases, such as neurological system, cardiovascular and pulmonary system diseases, are not statistically significant (P > 0.05) in the diagnosis of the SUD. CONCLUSION: Common underlying diseases make no obvious contributions to SUD and are not useful in diagnosing the underlying reasons for death.

Binary and Ternary Heterometallic (La3+, Gd3+, Y3+)-Eu3+ Functionalized SBA-15 Mesoporous Hybrids: Chemically Bonded Assembly and Photoluminescence.

A novel kind of organic-inorganic monomer SUASi has been achieved by modifying 5-sulfosalicylic acid (SUA) with 3-aminopropyltrimethoxysilane (APS), subsequently binary and ternary Eu3+ mesoporous hybrid materials with 5-sulfosalicylic acid (SUA)-functionalized SBA-15 and 1,10-phenanthroline (phen) are synthesized by co-condensation of SUASi and TEOS in the presence of Eu3+ complex and Pluronic P123 as a template. Finally, luminescent hybrid mesoporous materials consisting of active rare earth ions (Eu3+)-inert rare earth ions (Y3+, La3+, Gd3+) complex covalently bonded to the mesoporous materials network have been obtained via this sol-gel approach. The physical characterization and photoluminescence of all these resulting materials are studied in detail. Especially the luminescent behavior has been studied with the different ratios of Eu3+-(Y3+, La3+, Gd3+), which suggests that the existence of inert rare earth ions can enhance the luminescence intensity of Eu3+. This may be due to the intramolecular energy transfer between Y3+, La3+, Gd3+, and Eu3+ through the covalently bonded mesoporous framework.

2,2'-[p-Phenyl-enebis(methyl-idene-aza-ne-di-yl)]dipyridinium bis-(hydrogensulfate) dihydrate.

The cation of the title salt, C(18)H(20)N(4) (2+)·2HSO(4) (-)·2H(2)O, lies on a center of inversion with the mid-point directly in the middle of the p-phenyl-ene ring. Within the hydrogensulfate ion, the S-O(H) bond is the longest of the S-O bonds. The dihedral angle between the central and terminal ring of the cation is 78.6 (2)°. In the crystal, the cation, anion and water mol-ecule inter-act by O-H⋯O and N-H⋯O hydrogen bonds, generating a three-dimensional network.

Aqua(4-hydroxy-benzoato-κO)(4-hydroxy-benzoato-κO,O')(1,10-phenanthroline-κN,N')zinc(II) monohydrate.

The Zn atom in the title compound, [Zn(C(7)H(5)O(3))(2)(C(12)H(8)N(2))(H(2)O)]·H(2)O, exists in a distorted cis-ZnN(2)O(4) octa-hedral coordination geometry. One of the 4-hydroxy-benzoate anions chelates in a bidentate manner whereas the other is monodentate. The complex mol-ecules are linked through the uncoordinated water mol-ecules into a hydrogen-bonded sheet structure.

Aqua-chloridobis(1,10-phenanthroline-κN,N')zinc(II) chloride N,N-dimethyl-formamide solvate.

The Zn atom in the title salt, [ZnCl(C(12)H(8)N(2))(2)(H(2)O)]Cl·C(3)H(7)NO, is chelated by two phenanthroline mol-ecules and is bonded to one chloride ion and one water mol-ecule, resulting in a ZnN(4)ClO octa-hedral coordination environment with the Cl and O atoms in a cis conformation. The cations and anions are linked by O-H⋯Cl hydrogen bonds across a center of inversion, forming a hydrogen-bonded dimeric association. The dimethyl-formamide solvent mol-ecule is disordered over two orientations in a 0.56 (1):0.44 (1) ratio.

Poly[[di-mu3-acetato-di-mu2-aqua-diaqua-di-mu3-hydroxo-tricopper(II)] naphthalene-1,5-disulfonate].

The crystal structure of the title complex, {[Cu3(C2H3O2)2(OH)2(H2O)4](C10H6O6S2)}n, is built of infinite polymeric cationic {[Cu3(C2H3O2)2(H2O)4(OH)2]2+}n chains stretching along the a axis, with naphthalene-1,5-disulfonate (1,5-nds) anions in between. One independent Cu(II) cation and the 1,5-nds anion occupy special positions on crystallographic inversion centres. Each Cu(II) cation has an octahedral coordination environment formed by two carboxyl O atoms, two hydroxo O atoms and two water molecules. The carboxylate and hydroxo groups perform a bridging function, linking adjacent Cu atoms in the chain, with a shortest Cu...Cu distance of 2.990 (3) A. The chains are further linked into a three-dimensional supramolecular framework via hydrogen-bonding interactions involving the sulfonate groups of the 1,5-nds dianions.