Amorphous Calcium Phosphate (ACP) is an essential mineral phase formed in mineralized tissues and the first commercial product as artificial hydroxyapatite. ACP is unique among all forms of calcium phosphates in that it lacks long-range, periodic atomic scale order of crystalline calcium phosphates. The X-ray diffraction pattern is broad and diffuse with a maximum at 25 degree 2 theta, and no other different features compared with well-crystallized hydroxyapatite. Under electron microscopy, its morphological form is shown as small spheroidal particles in the scale of tenths nanometer. In aqueous media, ACP is easily transformed into crystalline phases such as octacalcium phosphate and apatite due to the growing of microcrystalline. It has been demonstrated that ACP has better osteoconductivity and biodegradability than tricalcium phosphate and hydroxyapatite in vivo. Moreover, it can increase alkaline phosphatase activities of mesoblasts, enhance cell proliferation and promote cell adhesion. The unique role of ACP during the formation of mineralized tissues makes it a promising candidate material for tissue repair and regeneration. ACP may also be a potential remineralizing agent in dental applications. Recently developed ACP-filled bioactive composites are believed to be effective anti-demineralizing/remineralizing agents for the preservation and repair of tooth structures. This review provides an overview of the development, structure, chemical composition, morphological characterization, phase transformation and biomedical application of ACP in dentistry.

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Osseointegrated implants are a common therapy for the elderly population as lifespan increases. Understanding the effects of age and sex on osseointegration is important for successful implant therapy. Therefore, the response of primary human osteoblasts (HOB) to implant materials was studied. HOBs were obtained by outgrowth of cells from bone from orthopaedic procedures and categorized as Young (Y), <15; Middle (M), 30-50; and Old (0), >60 years old. Initially the HOB phenotype was determined on tissue culture plastic. Alkaline phosphatase (ALP) staining and activity were significantly increased in HOBs from older patients. Message levels of type I collagen (COL), bone sialoprotein (BSP) and ALP were significantly higher (from 2.3-to 3.8-fold) in Y subjects compared to M and 0 patients at 2 weeks. Studies of the response of HOBs to implant materials were undertaken using Ti-6A14V disks prepared in a manner similar to orthopaedic implants. A I . '!-fold (p < 0.05) increase in cell attachment was found inHOBs from Y compared with 0 in female subjects but not in male subjects. Cell proliferation at 24 h was not significantly different by age or sex, nor was DNA content different at 2 and 4 weeks. Mineralization in HOB-implant cultures was 2.3-fold higher in Y than in 0, and 1.7-fold higher in Y compared to M HOBs from female but not male subjects at 4 weeks. Northern blot and RT-PCR analysis at 2 weeks of culture showed significantly higher levels (1.6-2.3-fold) of COL, BSP, and osteocalcin (OC) mRNAs in Y HOBs compared to M and 0 HOBs from female subjects. We conclude that human osteoblasts from older female patients have a decreased ability to form bone on implants.

STUDY QUESTION What is the relationship between abnormal BMI and semen quality? SUMMARY ANSWER Underweight was significantly associated with lower sperm concentration, total sperm number and total motile sperm count, while overweight was significantly associated with lower semen volume, total sperm number and total motile sperm count. WHAT IS KNOWN ALREADY Abnormal BMI has been associated with lower semen quality, but the results remain somewhat controversial. In addition, most previous studies have focused on the influence of obesity or overweight on semen quality, and evidence on the association between underweight and semen quality is rare. STUDY DESIGN, SIZE, DURATION This research was an observational study investigating 3966 sperm donors from a large sperm bank in Wuhan city, China. These donors passed the screening for sperm donation and underwent 29 949 semen examinations between 1 January 2013 and 9 April 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS BMI was categorized into four groups: underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (≥30 kg/m2). Semen volume, sperm concentration, total sperm number, total motility, progressive motility and total motile sperm count were determined by trained clinical technicians. Linear mixed models were used to conduct dose–response analyses between BMI and semen quality parameters. MAIN RESULTS AND THE ROLE OF CHANCE Underweight was significantly associated with a 3.0% (95% CI: 0.1%, 5.8%), 6.7% (1.9%, 11.3%) and 7.4% (2.2%, 12.4%) reduction in sperm concentration, total sperm number and total motile sperm count, respectively. Overweight was significantly associated with a 4.2% (1.6%, 6.8%), 3.9% (0.9%, 6.9%) and 3.6% (0.2%, 6.9%) reduction in semen volume, total sperm number and total motile sperm count, respectively. Non-linear models including continuous BMI as a natural cubic spline function yielded similar results. LIMITATIONS, REASONS FOR CAUTION Our study subjects were sperm donors who are typically young and healthy, and therefore not representative of the general male population. Caution should be paid in generalizing our results to other populations. Furthermore, we did not measure the donors’ weight repeatedly along with each semen donation; instead, we only measured it once during the screening, which may cause bias due to the variations of weight across time. WIDER IMPLICATIONS OF THE FINDINGS Our study provides evidence that underweight and overweight are associated with lower semen quality, and highlights the importance of maintaining a normal weight for men. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Health and Family Planning Commission of Hubei Province (Grant number WJ2015MA027), the Hubei Provincial Committee of the Communist Youth League of China, and Center for Global and Regional Environmental Research at the University of Iowa. The authors declare that there are no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Hypofunction of the serotonergic (5-HT) system has close relationship with the symptoms in major depressive disorders (MDD), however, the underlying neural circuitry mechanisms are not fully understood. Lateral habenula (LHb) plays a crucial role in aversive behaviors and is activated in conditions of depression. It has been reported that 5-HT inhibits the excitability of LHb neurons, leading to the hypothesis that decreased transmission of 5-HT would elevate the activity of LHb and therefore mediates depressive symptoms. Using retrograde tract tracing with cholera toxin subunit B, we find that dorsal raphe nucleus (DRN) sends primary 5-HT projection to the LHb. In vitro slice patch-clamp recording reveals that opto-stimulation of DRN inputs to the LHb suppresses the frequency of miniature excitatory postsynaptic current, while increases paired pulse ratio in LHb neurons, indicating 5-HT projection presynaptically suppresses the excitability of LHb neurons. In chronic unpredictable mild stress (CUMS) rat model of depression, optogenetic stimulation of DRN-LHb projection alleviates the depressive symptoms in CUMS models. Meanwhile, opto-inhibition of this circuit results in elevated c-fos expression in LHb and induces depression-like behaviors. This study demonstrates that the 5-HT projection from DRN to LHb suppresses the excitability of LHb neurons, and hypofunction of 5-HT transmission induces depressive behavior via the activation of LHb. Our results reveal the functional connectivity of DRN-LHb circuit and its antidepressant action, which may provide a novel target for the treatment of depression.

Dopamine, an important neurotransmitter in brain, exerts its action via dopamine receptors, which are known to belong to the G-protein-coupled receptor family. Calcium plays a critical role in mediating neuronal excitability and neuroplasticity. Regulation of calcium content in neuronal cells by dopamine has been reported in different experimental systems (Bergson et al. 2003;Lee et al. 2004;Neve et al. 2004). Both protein kinase A (PKA)-dependent and independent mechanisms have been proposed to mediate dopamine receptor-stimulated calcium signals (Tang et al. 2003;Neve et al. 2004). Recent evidence indicates that activation of dopamine receptors also activates phospholipase Cb (PLC b ) through coupling to the Gq protein, resulting in hydrolysis of phosphatidylinositol into diacylglycerol and inositol triphosphate (IP3;Felder et al. 1989;Frail et al. 1993;Pacheco and Jope 1997; Lezano & Bergson., 2001;Lee et al. 2004;Wirtshafter and Osborn, 2005;Panchalingam and Undie 2005;Zhang et al. 2005). This stimulation of phosphatidylinositol hydrolysis appears to be mediated by a D1-like receptor as only selective D1 receptor agonist but not D2 receptor agonist can elicit this action, which is blocked by SCH23390, a selective D1 receptor antagonist (Undie et al. 1994). However, the stimulation of phosphatidylinositol hydrolysis by the D 1 -like receptor appears to be distinct from the D 1A receptor because in D 1A transfected PC12 cells there is no detectable D1 receptor-stimulated IP3 generation (Jin et al. 2002), and in D 1A knock-out mice the stimulation of IP 3 by D1 agonist in brain was still present even though the effect can be blunted by a D1 antagonist (Friedman et al.

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The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.